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Biomedical subjects

M Shibuya

Publications and source records attributed to M Shibuya.

At least 145 records · Page 8Linked to original sources

Benign osteoblastoma of the odontoid process of the axis: a case report.

BACKGROUND: The majority of benign spinal osteoblastomas arise from the posterior elements of the spine; there have been no published reports of the tumor in the odontoid process of the axis. Accurate preoperative localization of the tumor is important for planning minimally invasive surgery on such benign tumors. However, the magnetic resonance imaging (MRI) findings may be misleading, because peritumoral changes may be confusing. CASE DESCRIPTION: We report the case of a 20-year-old man, who presented with a 4-year history of protracted left posterior neck pain. Preoperative computed tomography (CT) revealed a discrete mixed-density mass within the odontoid process. MRI showed diffusely abnormal signal intensity and enhancement both in the odontoid process and the body of the axis, including regions from which biopsy specimens were normal or had minimal inflammatory changes. Precise preoperative localization of the tumor margins using CT and biopsy allowed for successful resection of the tumor via a transoral approach with preservation of a part of the axis and the odontoid process. Consequently, stabilization of the spine was unnecessary, and the patient remained symptom-free for 3.5 years. CONCLUSION: We reported a rare case of benign osteoblastoma of the odontoid process of the axis. The tumor was successfully resected via a transoral approach, preserving a part of the axis and the odontoid process. We have emphasized an advantage of CT over MRI for accurate localization of the tumor.

Adult↗

Isolation and characterization of mouse ovarian surface epithelial cell lines.

The incidence of ovarian malignancies has significantly increased in the past decades in many countries, however, an appropriate animal model system enabling the study of ovarian cancer such as stable mouse ovarian epithelial cell lines has not yet been developed. Here we report the establishment of cell lines derived from mouse ovarian surface epithelium (MOSE) by two procedures--one, through the introduction of SV40 large T antigen DNA into C3H/He MOSE (T-Ag-MOSE) and another through spontaneous immortalization of cells from p53-deficient MOSE (p53-def-MOSE). p53-def-MOSE cell line did not show any transformed phenotype either in vitro culture system nor in vivo tumorigenicity assay, whereas T-Ag-MOSE formed tumors in nude mice. Tumors formed by the injection of T-Ag-MOSE were undifferentiated malignancies associated with heterologous mesothelial tissues such as those of the osteoid phenotype. The established MOSE cell lines are useful in the molecular analysis of the multistep carcinogenesis of ovarian tissues in humans.

Animals↗

Tumorigenicity depends on angiogenic potential of tumor cells: dominant role of vascular endothelial growth factor and/or fibroblast growth factors produced by tumor cells.

The aim of this study was to determine the role of tumor-derived angiogenic factors in solid tumor formation. We compared the angiogenic potential of tumorigenic and non-tumorigenic human tumor cell lines. All tumorigenic cell lines induced angiogenesis in vivo and their angiogenesis-inducing abilities were higher than those of the other non-tumorigenic cell lines. This in vivo angiogenic potential was well correlated with the in vitro endothelial cell growth-stimulating activity contained in the cell extract or conditioned medium of each cell line. The endothelial cell growth-stimulating activities of these cell lines were completely inhibited by neutralizing antibodies to basic fibroblast growth factor (bFGF), acidic FGF (aFGF) or vascular endothelial growth factor (VEGF). Furthermore, the levels of tumor-derived endothelial cell growth-stimulating activities depended on the amounts of angiogenic factors such as VEGF and bFGF produced by tumor cells. Although VEGF transcripts were detected in all of the cell lines by RT-PCR assay, the non-tumorigenic cell lines showed poor productivity of VEGF as well as FGFs and had less or non-potency for endothelial cell growth stimulation. These findings suggest that the increase in production of angiogenic factors by tumor cells is necessary for their in vivo angiogenic and tumorigenic potentials, and that VEGF and FGFs are the major mediators of tumor-induced angiogenesis.

Journal Article↗

Flt-1, a receptor for vascular endothelial growth factor, has transforming and morphogenic potentials.

A paradox of Flt-1, a tyrosine kinase receptor for vascular endothelial growth factor (VEGF), is that the ligand cannot activate the receptor to stimulate growth of cells that exogenously overexpress the receptor. In order to find Flt-1 kinase-dependent biological systems, we obtained for the first time activated forms of the Flt-1 kinase in a ligand-independent manner. Replacement of the ABL sequences in the human leukemia oncoprotein BCR-ABL with the cytoplasmic domain of Flt-1 (BCR-FLT) followed by a retroviral random mutagenesis scheme gave constitutively active artificial chimera BCR-FLTm with mutations within the Flt-1 sequence. Like BCR-ABL it could, but not the original BCR-FLT, transform Rat1 fibroblasts, abrogate cytokine dependence in Ba/F3 cells, and induce neurite-like structures in neuronal PC12 cells. Interestingly, Rat1 cells transformed by BCR-FLTm formed tube-like structures in basement membrane matrix. BCR-FLTm retroviruses may be a very useful tool to investigate an as yet uncovered functions of the Flt-1 kinase.

Animals↗

Effect of a balanced biventricular bypass system on left ventricular energies.

Left dominant biventricular failure is a common type of heart failure after cardiac surgery. We developed a biventricular bypass (BVB) system for treatment of postcardiotomy ventricular failure, and we previously reported that the clinical results of the BVB system were superior to those obtained with venoarterial bypass (VAB). The purpose of this study was to evaluate the effect of the BVB system on left ventricular (LV) performance in comparison to that of VAB by means of the LV pressure-volume relationship (PVR). Eight adult mongrel dogs (14-21 kg) underwent VAB with right atrial and aortic cannulation. Left atrial cannulation was added for BVB, and both atrial drainage tubes were joined with a Y-shaped connector. The bypass flow was maintained at half of the baseline cardiac output (0.7-1.0 L/min), and the hemodynamic parameters were monitored. A high fidelity microtip catheter and a conductance catheter were used to evaluate LV function. The slope of the LV end-systolic pressure-volume relation (Emax), the slope of the LV end-systolic pressure-stroke-volume relation (Ea), the LV stroke work (SW), LV potential energy (PE), LV pressure-volume area (PVA), the slope of the SW end-diastolic volume relation (PRSW), and an index of the LV energizing charge (ratio of PE/PVA) were assessed during transient occlusion of the inferior vena cava. LV contractility (Emax) showed no significant change during each experiment. Standardized LV work (PRSW) was reduced by BVB in comparison to the baseline and in comparison to VAB. The rate of LV energy charge (PE/PVA) significantly increased only during BVB. These results suggested that the BVB system might be an effective circulatory support for reducing LV work and improving the LV energizing charge in patients with severe heart failure after cardiac operation.

Animals↗

Expression of vascular endothelial growth factor and its receptors in rats with protein-overload nephrosis.

BACKGROUND: Based on the fact that vascular endothelial growth factor (VEGF) increases vascular permeability, it is speculated that VEGF might be involved in the development of proteinuria, although this remains unconfirmed. The production and site of action of VEGF remains unclear in nephrotic renal diseases. METHODS: Non-radioactive in situ hybridization was performed to examine the expression of VEGF mRNA and its receptors, flt-1 and KDR/flk-1, in a rat model of nephrosis induced by intraperitoneal injection of bovine serum albumin (BSA). Saline injected rats were served as control animals. RESULTS: Neither morphological changes nor deposition of immunoglobulin or complement were observed in our model. Proteinuria developed, reaching a maximum level in rats injected with BSA for 3 days, followed by persistent proteinuria until day 14. The expression of mRNA for VEGF and the two receptors was markedly upregulated in glomeruli of BSA-induced nephritis compared with the control group. VEGF mRNA was localized in glomerular cells, including cells in mesangium, visceral and parietal epithelial cells. In contrast, flt-1 mRNA and KDR/flk-1 mRNA were expressed on glomerular endothelial cells and cells in mesangium. The ratio of glomerular cells positive for VEGF mRNA and its receptors mRNA increased proportionately with the severity of proteinuria. Immunohistochemistry for ED-1 and proliferating cell nuclear antigen showed no significant increase in infiltrating macrophage or cellular proliferation. CONCLUSIONS: Our results suggest that altered glomerular expression of VEGF and its receptors is not associated with proliferation of endothelial cells, but rather with proteinuria in BSA-induced nephritis in rats. VEGF may play a different role in different renal diseases.

Animals↗

Clotrimazole, an imidazole antimycotic, is a potent inhibitor of angiogenesis.

Clotrimazole, an imidazole antimycotic, interferes with the rise in cytosolic Ca2+ and inhibits cell proliferation in a reversible manner. Here we describe the effect of clotrimazole on vascular endothelial cells (ECs). Clotrimazole inhibited the proliferation of ECs stimulated with typical angiogenic growth factors; vascular endothelial growth factor and basic fibroblast growth factor (bFGF). This inhibitory effect of clotrimazole was dose-dependent and the maximal inhibition was observed at a concentration of 10 mM. We did not observe any increase in 51Cr release from ECs during treatment with 10 microM clotrimazole. Moreover, clotrimazole inhibited the basal and bFGF-stimulated migration of ECs. As clotrimazole inhibited two principle components of angiogenesis; the proliferation and migration of ECs, we examined whether clotrimazole inhibited angiogenesis. Tube formation by ECs in type 1 collagen gel was investigated, and clotrimazole was found to be significantly inhibitory. The inhibitory effect of clotrimazole on angiogenesis was further confirmed in an in vivo angiogenesis model of murine Matrigel plug assay. These results demonstrate that clotrimazole is a potent inhibitor of angiogenesis.

Animals↗

Benefit of in-phase chest wall vibration on the pulmonary hemodynamics in patients with chronic obstructive pulmonary disease.

OBJECTIVE: Chest wall vibration of contracting intercostal muscles (in-phase vibration, (IPV)) improves O2 saturation in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate the effect of IPV on the pulmonary hemodynamics in patients with COPD. METHODOLOGY: Twelve patients with COPD (FEV1%, 43.7 +/- 14.4%) underwent pulmonary artery catheterization in the supine position; hemodynamic variables as well as arterial and mixed venous gas tension were measured at baseline and after 15 min of IPV with IPV continued during the measurement. RESULTS: Mean pulmonary arterial pressure (Ppa, 21.3 +/- 5.0-19.1 +/- 4.8 mmHg and pulmonary vascular resistance (PVR, 294.6 +/- 196.0-228.5 +/- 101.7 dyne.sec.cm-5) decreased significantly, but there was no change in heart rate, cardiac index or systemic blood pressure. PaO2 increased (66.5 +/- 10.3-70.0 +/- 9.7 Torr) and PaCO2 decreased (46.6 +/- 8.9-45.0 +/- 10.1 Torr) significantly. Minute ventilation and tidal volume increased significantly in five out of the eight patients in whom ventilation was monitored throughout the study. CONCLUSION: IPV improves gas exchange and pulmonary circulation without affecting systemic circulation.

Aged↗

Effects of chest wall vibration on breathlessness during hypercapnic ventilatory response.

Vibratory stimulation applied to the chest wall during inspiration reduces the intensity of breathlessness, whereas the same stimulation during expiration has no effect or may increase breathlessness. The purpose of the present study was to determine whether vibration reduced the intensity of breathlessness during progressive hypercapnia with and without the addition of an external resistive load. A second objective was to see whether the mouth occlusion pressure at 0.2 s (P0.2) was reduced by the vibratory stimulation. Hypercapnic ventilatory response was conducted in 10 healthy male volunteers with simultaneous measurement of visual analog scale, P0.2, and minute ventilation. Hypercapnic ventilatory response was performed and randomly combined with or without vibratory stimulation (100 Hz) as well as with or without inspiratory load. With inspiratory load, in-phase vibration did not cause any significant changes in the slopes of P0.2 and minute ventilation to CO2, whereas the slope of visual analog scale to CO2 significantly decreased from 0.47 +/- 0.15 to 0.34 +/- 0.11 (SE) cm/Torr (P < 0.05). We conclude that in-phase vibration could decrease the slope of breathlessness elicited by inspiratory load combined with hypercapnia without changing motor output.

Adult↗

ELISA for the determination of saikosaponin a, an active component of Bupleuri Radix.

In order to quantify saikosaponin a (SSA), one of the major active components of Bupleuri Radix, a competitive and indirect ELISA method was developed. High titer rabbit polyclonal antibodies (pAbs) were raised against a conjugate of SSA and bovine serum albumin, coupled with a periodate oxidation method. SSA competitively inhibited the binding of rabbit anti-SSA pAbs to SSA-ovalbumin on the solid phase, a coated antigen on the well. The quantity of pAbs bound to the well was monitored using a peroxidase-conjugated anti-rabbit IgG as a secondary antibody, and tetramethylbenzidine solution as a substrate. The measuring range extended from 50 pg/ml to 20 ng/ml of SSA, with a detection limit of 40 pg/ml (5.13 pM). Antibodies showed some cross-reactivity with saikosaponin c (12.74%). However, the antibodies showed only slight cross-reactivities with saikosaponin d (0.3%), which differs from SSA only in the stereochemistry of the 16-hydroxyl group, and the artificial saikosaponins, saikosaponin b1 (2.1%) and saikosaponin g (0.53%). The specific and sensitive ELISA is especially suited for determination of SSA in samples when only small quantities of materials can be extracted for analysis.

Animals↗

Fatal alveolar hemorrhage in a patient with mixed connective tissue disease presenting polymyositis features.

A 22-year-old female with Raynaud's phenomenon, swollen hands and a high titer of anti-RNP antibodies developed fever and myositis. Prednisolone (40 mg/day) was considered effective for myositis since circulating myogenic enzymes rapidly decreased. However, she suddenly developed respiratory distress with bilateral pulmonary infiltrates and bloody sputum. Under the diagnosis of alveolar hemorrhage (AH), intravenous methylprednisolone pulse therapy was given, but she died of respiratory failure. Autopsy findings demonstrated massive AH with hematoma formation, and myositis in the iliopsoas muscle. Depositions of immune complex and vasculitic lesions were not recognized in her lungs.

Adult↗

In-phase chest wall vibration decreases dyspnea during arm elevation in chronic obstructive pulmonary disease patients.

In-phase chest wall vibration (IPV) is known to decrease dyspnea in patients with chronic obstructive pulmonary disease (COPD) at rest and during leg exercise. In the present study, the effects of IPV (100 Hz) on dyspnea and arm fatigue during upper extremity activity were studied in 9 patients with COPD (mean FEV1, 0.95 l). Dyspnea and arm fatigue (modified Borg scale) and ventilatory variables were measured during arm elevation (AE) with weights lifted straight above the head with and without IPV. Mean dyspnea during AE was 3.3 without IPV and 2.1 with IPV (p<0.05), but, arm fatigue, oxygen saturation and end-tidal FCO2 were not affected by IPV. Minute ventilation during AE was significantly increased with IPV in 5 of 9 patients. The results suggest that IPV decreases dyspnea during AE.

Afferent Pathways↗

Titanium aneurysm clips: mechanical characteristics and clinical trial.

Titanium clip is well documented to reduce the artifact observed in computed tomography (CT) or magnetic resonance (MR) imaging and improve the quality of these images. There are, however, some demerits based on metallic characteristics including large spring portions, lack of long and fenestration clips, and difficulties to produce. We examined the mechanical characteristics of Sugita titanium aneurysm clips (product of 6 aluminium-4 vanadium-titanium) and investigate the safety in clinical use and the imaging quality compared with those of cobalt (Co) alloy clips. On mechanical test, Sugita titanium clips showed no significant difference in closing force compared with the conventional Co alloy clips. The closing force reduced about 10% after 100 times repeated opening in titanium clips in contrast with no remarkable changes in Co alloy clips. Sixty-four patients with ruptured or unruptured cerebral aneurysms (total number of 71 aneurysms) were treated with Sugita titanium clips through the microsurgical technique. None of the unfavorable outcome occurred in related to the titanium clips. Neither clip dislocation nor deformation was experienced in this series during the follow-up period. The clip artifacts seen in CT and MR image were markedly reduced, however, MR angiography had less quality to resolve anatomical structures due to an existence of vessel gap. These results indicate that in spite of some disadvantages, Sugita titanium clips allow safe and beneficial use routinely in aneurysm surgery insofar as the complete clipping is obtained.

Biomechanical Phenomena↗

Dietary protein as a factor affecting vitamin B6 requirement.

Rats were fed 20 or 70% casein diets with varying amounts of vitamin B6 (B6), and the B6 content and B6-dependent enzymatic activity in their tissues were examined to determine the minimum requirement of B6 for animals subjected to different levels of dietary protein (i.e., 20%: 0, 1.45, 2.90, 5.80 mg pyridoxine (PN)/kg diet; 70%: 0, 2.90, 5.80, 8.70 mg PN/kg diet). B6 requirements for the rats were almost met in the 1.45 mg PN/kg 20% casein diet and the 2.90 mg PN/kg 70% casein diet when judged from the hepatic B6 content. However, almost twice the PN was required in both 20 and 70% casein diets when judged from PLP-enzymatic activity. The content of B6 vitamers in plasma appeared to be most sensitive to B6 status, though the satisfactory level is not known. It was confirmed that, in any case tested, a high-protein diet increased the requirement of B6.

Animals↗

[Two cases of subarachnoid hemorrhage associated with neurofibromatosis type I: a case of multiple cerebral aneurysms and arteriovenous malformation, and another case of an anterior communicating artery aneurysm].

Two cases of subarachnoid hemorrhage associated with neurofibromatosis type I (von Recklinghausen's disease) are reported. A 30-year-old male patient (case 1) had been diagnosed as having neurofibromatosis type I due to neurofibroma and café-au-lait spot. He suffered from subarachnoid hemorrhage and angiography showed multiple aneurysms in the right and left middle cerebral arteries and left internal carotid artery. He also had arteriovenous malformation in the left temporal lobe. Case 2 was that of a 62-year-old female patient with neurofibroma and café-au-lait spot. She suffered from subarachnoid hemorrhage and angiography showed an aneurysm in the anterior communicating artery. Both patients were discharged with no deficits after neck clipping, however they both suffered from large-sized hematoma in the punctured site of the femoral artery after angiography. The cerebral aneurysms associated with neurofibromatosis type I are often multiple and may coexist with arteriovenous malformation.

Adult↗

[Improvement of cognition after trepanation for the chronic subdural hematoma].

The cognitive functions were examined in the pre- and post-operative stages about the 16 cases of the chronic subdural hematoma. The evaluation was performed with MMS (mini-mental state) test. Although the average of the total score was 16.6 in the preoperative stage, it increased to 22.7 in the postoperative stage. Orientation of time and place, recall and the ability of writing a sentence, which were impaired prominently in the preoperative stage, improved significantly in the postoperative stage. The improvement was poorer in the patients with gait instability and in those older than 80 years. Trepanation surgery seems to be efficient for the improvement of cognition.

Aged↗