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Biomedical subjects

Jun Yoshida

Publications and source records attributed to Jun Yoshida.

79 records · Page 5Linked to original sources

Antitumor effect of an adeno-associated virus vector containing the human interferon-beta gene on experimental intracranial human glioma.

We constructed an adeno-associated virus (AAV) vector containing the human interferon-beta (HuIFN-b ) gene (AAV-IFN-beta) and investigated its antitumor effect against human glioma cells (U251-SP) inoculated into the brain of nude mice. Prior to this, we examined human glioma cells transduced with AAV-IFN-beta using video-enhanced contrast differential interference contrast (VEC-DIC) microscopy. Infection of AAV-IFN-beta induced apoptosis and secondary necrosis in human glioma cells. In in vivo experiments, we confirmed production of HuIFN-beta and induction of heat-shock protein (HSP) in glioma cells transduced with AAV-IFN-beta. Growth of the experimental gliomas was completely inhibited by six injections of AAV-IFN-beta, starting 7 days after transplantation of glioma cells. In addition, the survival of mice treated with AAV-IFN-beta was remarkably prolonged. These results indicate that AAV-IFN-beta induces apoptosis of glioma cells and has a strong antitumor effect in this experimental glioma model.

Animals↗

Expression of PPARgamma and its ligand-dependent growth inhibition in human brain tumor cell lines.

Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to a superfamily of thyroid / steroid hormone receptors and regulates transcription of their target genes in a ligand-dependent manner. Recently, PPARgamma was reported to be expressed in several cell lines derived from breast, colon, stomach and lung cancers. Activation of PPARgamma by its ligand inhibits the growth of these tumor cells, suggesting that PPARgamma ligand is a potential anti-cancer agent in PPARgamma-expressing tumors. However, its expression in brain tumors has not been studied. We thus studied the expression in glioma samples with different pathological stages from 20 patients. It was demonstrated that 95% of the glioma tissue expressed PPARgamma mRNA. The results prompted us to study whether PPARgamma ligand affects the growth of cell lines derived from brain tumors. The receptor expression was studied in 9 cell lines either derived from malignant glioma or neuroblastoma. The expression was detected in a glioma cell line SK-MG-1 and in a neuroblastoma cell line NB-1. Addition of one of the PPARgamma ligands, troglitazone, induced growth inhibition in both cell lines. Further analyses revealed that this growth inhibition is caused by a PPARgamma-mediated induction of apoptosis. These results suggest that PPARgamma ligands could be a potential therapeutic agent for the treatment of the brain tumors expressing this receptor.

Antineoplastic Agents↗

Changes of neural activity correlate with the severity of cortical ischemia in patients with unilateral major cerebral artery occlusion.

BACKGROUND AND PURPOSE: In major cerebral arterial steno-occlusive diseases, there can be remarkably decreased hemodynamic reserve without marked neurological impairments. In such settings, it is not known whether the neural activity is well maintained or disturbed according to the severity of cerebral ischemia. The present study was therefore undertaken to examine the neural activity under mild cerebral ischemia resulting from major cerebral arterial occlusion. METHODS: Seven patients with minor neurological impairment as well as either unilateral internal carotid artery or middle cerebral artery occlusion were studied. The severity of the cortical ischemia was assessed by measuring regional cerebral blood flow (rCBF) with positron emission tomography. The change in neural activity in the ischemic brain was then evaluated by means of somatosensory evoked magnetic field with magnetoencephalography. RESULTS: The rCBF in the primary sensory area and the strength of the initial component of somatosensory evoked magnetic field (N20 m) were significantly reduced (P<0.01) and the second component (P30 m) was significantly augmented (P<0.05) in the lesioned cerebral hemisphere as compared with the nonlesioned hemisphere. The asymmetry indexes for N20 m were positively correlated (r=0.78) and those for P30 m were inversely correlated (r=-0.92) with asymmetry indexes for rCBF. CONCLUSIONS: In patients with either unilateral internal carotid artery or middle cerebral artery occlusion and minor neural impairments, there was a reduction of afferent signal and an augmentation of the secondary response of the neurons in the primary sensory area. This showed correlation with the severity of cortical ischemia.

Adolescent↗

Evaluation of the healing process after dural reconstruction achieved using a free fascial graft.

OBJECT: This study was undertaken to investigate the healing process and to delineate factors important for the survival of free fascial grafts used for dural repair. METHODS: A dural defect was created in guinea pigs and then reconstructed using either a free fascial graft or an expanded polytetrafluoroethylene (ePTFE) sheet. The fascial graft was covered directly by subcutaneous tissue (Group I) or by a silicone sheet to prevent tissue ingrowth from the subcutaneous tissue (Group II). The ePTFE sheet was covered with a silicone sheet (Group III). One or 2 weeks postoperatively, the strength of the dural repair was evaluated by determining the pressure at which cerebrospinal fluid (CSF) leaked through the wound margins. The dural repair was also histologically examined. In addition, using a rat model, specimens obtained from similar reconstruction sites were immunohistochemically stained with antibodies against basic fibroblast growth factor (bFGF), epidermal growth factor, or transforming growth factor-beta. The pressures at which CSF leaked after 1 and 2 weeks, respectively, were 50 +/- 14 mm Hg and 126 +/- 20 mm Hg in Group I, 70 +/- 16 mm Hg and 101 +/- 38 mm Hg in Group II, and 0 mm Hg and 8 +/- 8 mm Hg in Group III. Failure of repairs made in Group III occurred at significantly lower pressures when compared with Groups I and II. In Groups I and II, a thick fibrous tissue formed around the fascial graft. This tissue tightly adhered to adjacent dura mater. The fibrous tissue displayed a positive reaction for the presence of bFGF. In Group III, only a thin fibrous membrane surrounded the ePTFE sheet. CONCLUSIONS: Fascial grafts tolerated extraordinary intracranial pressures at 1 week postoperatively. Free fascial grafts can heal with durable fibrous tissue without the presence of a blood supply from an overlying vascularized flap.

Animals↗

Bilateral open-door cervical expansive laminoplasty with hydroxyapatite spacers and titanium screws.

OBJECT: The authors report a simple method for bilateral open-door cervical expansive laminoplasty in which hydroxyapatite (HA) spacers are secured by titanium screws. A biomechanical study was also conducted to confirm the strength of the screw fixation. METHODS: A unilateral posterior approach was used to allow preservation of the posterior supporting elements (the posterior tension band) until the laminae were cut at the base. A bilateral open-door expansive laminotomy was then performed in standard fashion. Appropriate-sized HA spacers were selected, held with a specially designed holder, and placed between the split laminae. The screw holes were made in the laminae along the direction of the screw holes in the spacer, and two screws were inserted ventrolaterally to the laminae, resulting in instantaneous fixation. This procedure was performed in 15 patients; clinical results were successful, and there were no significant intraoperative complications. Follow-up radiological studies revealed no evidence of displacement of the spacers or screw backout. The screw artifacts observed on magnetic resonance imaging were minimal, allowing evaluation of the cervical spinal cord. The sagittal alignment of the cervical spine was well preserved. In the biomechanical studies the authors found that the screw fixation was of satisfactory strength, compared with other methods of fixation. CONCLUSIONS: Bilateral open-door cervical expansive laminoplasty in which HA spacers are secured by titanium screws is a simple and quick method that yields sufficient fixation strength.

Adult↗

Experimental model of dissecting aneurysms.

BACKGROUND AND PURPOSE: The pathogenesis and optimal treatment for arterial dissection are still unclear. We devised an experimental model of arterial dissection and observed the morphologic changes with angiography. METHODS: Sixty-four experimental dissections were created in the common carotid arteries of 34 mongrel dogs. After a small incision was made in the arterial adventitia, it was dissected from the media. Elliptical defects (2, 4, 6, and 8 mm in groups I-A, I-B, I-C, and I-D, respectively; n = 47) or longitudinal incisions (4, 6, and 8 mm in groups II-A, II-B, and II-C, respectively; n = 17) were made in the intima distal to the adventitial incision to serve as an entry zone for dissection. RESULTS: Immediately after the lesions were created, the influx of blood into the dissected cavity produced massive subadventitial hematomas, resulting in stenotic changes in all of the arteries, including seven with occlusion. Follow-up (1-week) angiograms demonstrated complete healing, with normal arterial calibers in 11 (79%) of 14 I-A lesions and aneurysm formation in nine (69%) of 13 I-B lesions. All 10 I-D lesions had complete arterial occlusion. Persistent stenosis was observed in all 10 I-C lesions; six of these developed aneurysms. Pathologic examination of the freshly dissected cavities revealed a clot-filled cleft between the media and adventitia. Mature aneurysms, evaluated 3 mo later, had endothelialization within the aneurysmal dome. CONCLUSION: Morphologic changes after arterial dissection are closely related to the size of the intimal entry zone, which may determine whether a dissecting aneurysm forms.

Aortic Dissection↗