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Biomedical subjects

H Yokote

Publications and source records attributed to H Yokote.

At least 19 recordsLinked to original sources

[MR hydrography of the abdomen: technical consideration of data acquisition and future prospects for clinical applications].

Recent advances in MR hydrography have enabled various clinical applications in the areas of abdominal and pelvic disorders, for example, MR cholangiopancreatography (MRCP), MR urography(MRU), and MR hydrography of the fetus. Although the two-dimensional(2D) single-slice method provides excellent information as to the global relationship between lesions and various anatomical structures, small lesions or detailed anatomical characteristics may not be visualized owing to the partial volume effect. Source images of the 2D multislice method are most suitable for the detection of small lesions and detailed evaluation of anatomical structures as "tomographic imaging", while the three-dimensional(3D) method is useful in obtaining data sets for 3D imaging. MR hydrography is a promising method for the noninvasive evaluation of various abdominal disorders, and it has the potential to play new roles in various anatomical regions. However, knowledge of the proper indications is essential for successful clinical application.

Abdomen↗

Dephosphorylation-induced decrease of anti-apoptotic function of Bcl-2 in neuronally differentiated P19 cells following ischemic insults.

It is known that Bcl-2 has a protective effect against neuronal ischemia. Some reports speculate anti-apoptotic function of Bcl-2 depends not on the expression level but on the phosphorylation state. We found induction of apoptosis and CPP32 activation by energy impairment (3-nitropropionic acid (3-NP)-treatment or glucose-deprivation) in the neuronally differentiated P19 cells. Time course study of cell viability following ischemic insults showed that the number of viable cells decreased along with the increase in the amount of dephosphorylated Bcl-2 without obvious quantitative alteration of the protein. Then, we generated differentiated P19 cells overexpressing wild-type Bcl-2 (P19/wt. Bcl-2) or phosphorylation-negative Bcl-2 mutant (P19/mut.Bcl-2), in which alanine was substituted for serine 70. When the cell viability was examined within 24 h, P19/mut.Bcl-2 was more vulnerable to energy impairment as compared with P19/wt.Bcl-2. In addition, overexpression of wild-type Bcl-2 inhibited DNA laddering and CPP32 activation induced by the insults, while that of mutant Bcl-2 did not. These findings suggest that the phosphorylation state, as well as the expression level, of Bcl-2 plays an important role to modulate its protective effect against ischemic insults.

Animals↗

Treatment of restenosis after percutaneous transluminal angioplasty for internal carotid artery stenosis.

The efficacy of repeated percutaneous transluminal angioplasty (PTA) and carotid endarterectomy (CEA) was examined in patients with restenosis after PTA for carotid stenosis. After percutaneous transluminal angioplasty (PTA) for 63 cases of internal carotid stenoses 13 cases of restenosis appeared. They were treated by PTA or carotid endarterectomy. The treatment was chosen by the patient after explanation of each treatment. We initially treated seven patients by repeat PTA and six by carotid endarterectomy. The degree of stenosis improved from 82% to 30% on average after repeated PTA. However, one patient in the PTA group had restenosis, and carotid endarterectomy was then performed. The other cases also had restenosis and were treated by PTA. The six cases treated by carotid endarterectomy were successfully treated without difficulty. The success rate of PTA was 5/7 (71%) in the restenosis cases. Patients with a greater residual stenosis after initial PTA had significantly more frequent restenosis. Repeat PTA and CEA both appeared effective treatment for restenosis after initial PTA, although PTA had a restenosis rate similar to that of initial PTA.

Aged↗

Promotion of survival and regeneration of nigral dopamine neurons in a rat model of Parkinson's disease after implantation of embryonal carcinoma-derived neurons genetically engineered to produce glial cell line-derived neurotrophic factor.

OBJECT: The P19 embryonal carcinoma-derived cell line consists of undifferentiated multipotential cells, which irreversibly differentiate into mature neurons after exposure to retinoic acid (RA). In the present study, the authors genetically engineered P19 cells to produce glial cell line-derived neurotrophic factor (GDNF), and grafted the cells in a rat model that had been rendered parkinsonian. METHODS: Undifferentiated P19 cells were grown in vitro and transduced with GDNF complementary DNA. The level of GDNF released from the transduced cells was measured using an enzyme-linked immunosorbent assay, and its neurotrophic activities were assessed by testing the effects on rat embryonic dopamine (DA) neurons in culture. After having been exposed to RA for 48 hours and allowed to differentiate into postmitotic neurons, the GDNF gene-transduced cells were implanted into the midbrain of immunosuppressed rats. A unilateral nigrostriatal lesion was then induced by intrastriatal infusions of 6-hydroxydopamine. Immunohistochemical analyses performed 4 weeks postgrafting revealed that the GDNF-producing cells expressed several neuronal markers without evidence of overgrowth. The grafts expressed GDNF protein and prevented the death of nigral DA neurons. Furthermore, the GDNF-producing cells implanted 4 weeks after nigrostriatal lesions restored the expression of tyrosine hydroxylase in injured DA neurons and induced their dendritic sprouting. CONCLUSIONS: The results indicate that the P19 cell line transduced with the GDNF gene can stably secrete functional levels of GDNF, even after being converted to postmitotic neurons. Because it is has been established that GDNF exerts trophic effects on DA neurons, the means currently used to deliver GDNF into the brain could be a viable strategy to prevent the death of nigral DA neurons in cases of Parkinson's disease.

Analysis of Variance↗

Presumed intraventricular meningioma treated by embolisation and the gamma knife.

A 58-year-old woman with a presumed incidentally discovered meningioma in the left lateral ventricle was treated by superselective embolisation and gamma knife therapy. The diameter of the tumour was 40 mm, and its main feeding artery was the left lateral posterior choroidal artery. This vessel was embolised with microcoils. At 8 months following embolisation, the diameter of the tumour had decreased and was stable. The gamma knife was chosen as an adjuvant therapy for the further control 13 months after embolisation. Embolisation and gamma knife therapy may be an alternative treatment for meningiomas where surgical resection appears difficult.

Cerebral Ventricle Neoplasms↗

Enhancement of cisplatin sensitivity in high mobility group 2 cDNA-transfected human lung cancer cells.

To elucidate the role of high mobility group 2 protein (HMG2) in cis-diamminedichloroplatinum (II) (cisplatin, CDDP) sensitivity, we constructed a human HMG2-transfected human non-small cell lung cancer cell line, PC-14/HMG2. The HMG2 mRNA expression level was approximately twice those of parental PC-14 and mock-transfected PC-14/CMV. Gel mobility shift assay revealed a CDDP-treated DNA-protein complex in the nuclear extract of PC-14/HMG2, which was not found in the extracts of PC-14 and PC-14/CMV. This complex formation was subject to competition by CDDP-treated non-specific salmon sperm DNA, indicating that ectopic HMG2 recognizes CDDP-damaged DNA. PC-14/HMG2 showed more than 3-fold higher sensitivity to CDDP than PC-14 and PC-14/CMV. The intracellular platinum content of PC-14/HMG2 after exposure to 300 microM CDDP was 1.1 and 1.5 times that of PC-14 and PC-14/CMV, respectively. Cellular glutathione levels were not different in these cell lines. Repair of DNA interstrand cross-links determined by alkaline elution assay was decreased in PC-14/HMG2. These results suggest that HMG2 may enhance the CDDP sensitivity of cells by inhibiting repair of the DNA lesion induced by CDDP.

Carboplatin↗

The C-terminal domain of p53 catalyzes DNA-renaturation and strand exchange toward annealing between intact ssDNAs and toward eliminating damaged ssDNA from duplex formation through preferential recognition of damaged DNA by a duocarmycin.

The C-terminal domain of p53 may bind single-stranded (ss) DNA ends and catalyze renaturation of ss complementary DNA molecules, suggesting a possible direct role for p53 in DNA repair (Proc. Natl. Acad. Sci. USA, 92, 9455-9459, 1995). We found that DU-86, a duocarmycin derivative which alkylates DNA, bound ssDNA and enhanced the DNA binding activity of the p53 C-terminus. DU-86 weakened p53-mediated catalysis of complementary ssDNA renaturation. p53 C-terminus catalyzed DNA strand transfer toward annealing between intact ssDNAs and toward eliminating DU-86-damaged ssDNA from duplex formation. These results suggest that p53, via the C-terminal domain, may play a direct role in DNA repair by preferential recognization and elimination of damaged DNA.

Antineoplastic Agents, Alkylating↗

Carotid endarterectomy and simultaneous percutaneous transluminal angioplasty for tandem internal carotid stenoses.

We treated three patients with tandem internal carotid stenoses in single procedures including carotid endarterectomy (CEA) for the proximal stenosis and percutaneous transluminal angioplasty (PTA) for the distal stenosis. We devised a Y-shaped shunt tube for the CEA, through which a balloon catheter was introduced to perform PTA guided by mobile digital subtraction angiography. No cerebrovascular events occurred during follow-up. Our approach avoids the risk of a second procedure while effectively treating tandem stenoses.

Aged↗

Percutaneous transluminal angioplasty for intracranial arteriosclerotic lesions.

We report 17 cases of intracranial arterial stenosis treated by percutaneous transluminal angioplasty (PTA), including 9 on the intracranial internal carotid (ICA), 4 on the middle cerebral (MCA), and 4 on vertebrobasilar artery (VBA) system. All patients had ischaemic brain symptoms and stenoses of more than 60% (calculated angiographically). We treated four patients by PTA for residual stenoses after thrombolysis for acute occlusion. We used PTA balloon catheters 2.0-3.5 mm in diameter for all procedures. As a rule, the balloon was inflated for 1 min at 6 atm. All arteries were successfully dilated (stenosis less than 50%) except for one treated by PTA for residual MCA stenosis after thrombolysis. The patient died of a massive infarct due to MCA reocclusion caused by arterial dissection. Stenosis recurred in 4 of 16 patients. Repeat PTA was successfully carried out in these cases. However, stenosis recurred in one of these patients 3 months after PTA, but the patient is being followed because he is asymptomatic. PTA of intracranial arteries is effective, but its indications should be based strictly on potential risks, such as acute occlusion derived from arterial dissection.

Aged↗

Circumvention of glutathione-mediated mitomycin C resistance by a novel mitomycin C analogue, KW-2149.

A novel antitumor antibiotic 7-N-[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl] mitomycin C (KW-2149), an analogue of mitomycin C (MMC), is activated by thiol molecules, such as glutathione (GSH). To clarify the relationship between cellular GSH levels and the cytotoxicity of KW-2149, a murine fibroblast cell line (NIH/3T3) was transfected with human gamma-glutamylcysteine synthetase (gamma-GCS) cDNA, which codes a rate-limiting enzyme of GSH synthesis. Transfected cells (3T3/GCS) displayed increased gamma-GCS mRNA levels, gamma-GCS activity and GSH content, compared with NIH/3T3 cells. 3T3/GCS cells exhibited a 4.4-fold resistance to MMC, but not to KW-2149 (x 0.69), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, suggesting that the increased cellular GSH levels did not affect the growth-inhibitory effect of KW-2149. KW-2149 exerted a greater growth-inhibitory effect than MMC on cisplatin- and doxorubicin-resistant cells with cross-resistance to MMC. KW-2149 exhibited a greater growth inhibitory effect than MMC not only on cells with GSH-mediated MMC resistance but also on cells with acquired resistance. We thus conclude that KW-2149 might be a clinically useful drug.

3T3 Cells↗

The effect of endovascular therapy for cerebral arterial spasm, its limitation and pitfalls.

PURPOSE: The effect of endovascular treatment for vasospasm was investigated by analysing the results of patients treated in Wakayama City in 1994. MATERIALS AND METHODS: Ninety nine patients with ruptured cerebral aneurysms, who survived more than one week and were treated in Wakayama City in 1994, were studied. Twenty five patients caused symptomatic vasospasm and 25 were treated by endovascular therapy, percutaneous transluminal angioplasty (PTA) and/or intra-arterial papaverine infusion (IAP). PTA was performed for proximal vasospasm which located in the main arterial trunk, such as ICA, M1, BA (n = 3). IAP was chosen for distal vasospasm which located mainly in the M2, A1, A2 (n = 12). PTA and/or IAP was performed for diffuse vasospasm which located in proximal and distal arteries (n = 10). RESULTS: In the proximal vasospasm group, all patients were good to moderately disabled on the Glasgow outcome scale (GOS). In the distal vasospasm group, 8 patients were good to moderately disabled, and 4 patients were severely disabled. The overall results were as follows: 17 (68%), good to moderately disabled, 4 (16%), severely disabled, 4 (16%), dead. The morbidity and mortality rate was 8/25 (32%) in symptomatic spasm group. CONCLUSION: PTA was very effective especially for proximal vasospasm, but IAP was not always effective for distal or diffuse vasospasm. Diffuse vasospasm revealed a high mortality rate in spite of the endovascular therapy.

Adult↗

Subdural and meaningful involvement related to Wegener's granulomatosis: case report.

OBJECTIVE AND IMPORTANCE: The first case of Wegener's granulomatosis associated with subdural empyema is presented. CLINICAL PRESENTATION: A 37-year-old man was admitted to our hospital for treatment of bilateral subdural masses. Magnetic resonance imaging demonstrated strong bilateral subdural and meningeal enhancement. The patient was treated with subdural drainage, based on the diagnosis of bilateral subdural hematoma or empyema as revealed by magnetic resonance imaging. Even after surgery, he developed systemic symptoms that are typical for Wegener's granulomatosis, including hemosputum, papules, peripheral nervous disorders, hematuria, myalgia, and joint pain. A diagnosis of Wegener's granulomatosis was confirmed by positive circulating antineutrophil cytoplasmic antibodies and histological findings from the skin and nasal mucosa. We diagnosed the subdural masses as Wegener's granulomatosis from the laboratory and neuroimaging studies, retrospectively. INTERVENTION: Pus-like fluid containing hematoma with negative micro-organism was evacuated by surgery. CONCLUSION: Wegener's granulomatosis should be suspected in young patients with pulmonary symptoms and subdural hematoma without head injury. This is the first case of Wegener's granulomatosis associated with subdural masses.

Adult↗

p16INK4 expression is associated with the increased sensitivity of human non-small cell lung cancer cells to DNA topoisomerase I inhibitors.

Inactivation of p16INK4, an inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6), may be essential for oncogenesis in non-small cell lung cancer (NSCLC). We examined the sensitivity of two clones of p16INK4-transfected NSCLC cell line with homozygous deletion of p16INK4, A549/p16-1 and 2, to DNA topoisomerase I (topo I) inhibitors. A549/p16-1 and -2 showed 7.7- and 9.1-fold increases in sensitivity to CPT-11 (11,7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin ), respectively, compared with A549 cells. Ectopic p16INK4-expressing cells also showed approximately 4.0-fold increase in sensitivity to SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of CPT-11, compared to the parent cells. The topo I-mediated DNA relaxation activities of ectopic p16INK4-expressing cells were approximately 5 times higher than those of the parent cells. Northern and western blot analyses indicate that these increased topo I activities of ectopic p16INK4-expressing cells were due to an elevated topo I mRNA level and an increase in topo I protein. The chemosensitivity to topo I inhibitors, topo I mRNA level, protein content and activity of a p16INK4 revertant, lacking functional p16INK4, tended to be restored toward those of the parental phenotype to some extent. These results suggest that p16INK4 expression is closely associated with the increased sensitivity of ectopic p16INK4-expressing NSCLC cells to topo I inhibitors. The up-regulation of topo I mRNA level, protein content and activity may be responsible for this hypersensitivity.

Antineoplastic Agents, Phytogenic↗

Effect of glutathione depletion on cisplatin resistance in cancer cells transfected with the gamma-glutamylcysteine synthetase gene.

Overexpression of the human gamma-glutamylcysteine (gamma-GCS) gene resulted in cisplatin resistance with an increased glutathione (GSH) content, increased ATP-dependent glutathione S-conjugate export pump (GS-X pump) activity and decreased platinum accumulation in human lung cancer cells transfected with a gamma-GCS cDNA expression vector, as we previously reported. In this study, we examined the effects of buthionine sulfoximine (BSO), a specific inhibitor of gamma-GCS, to determine whether GSH depletion alters cisplatin resistance in a gamma-GCS-transfected cell line, SBC-3/GCS. In the presence of 10 microM BSO for 4 days, SBC-3/GCS still showed resistance to cisplatin, although it was partially reversed. Under these conditions, GS-X pump activity remained up-regulated in spite of low GSH content, and the platinum content was decreased. These data suggest that the GS-X pump itself influences cisplatin resistance, as well as cellular GSH content.

Aminoacyltransferases↗

Preoperative embolization of meningiomas fed by ophthalmic branch arteries.

BACKGROUND: The efficacy of preoperative embolization for hypervascular meningiomas mainly fed by the branches of the ophthalmic arteries was examined. CASES AND METHODS: Five hypervascular meningiomas mainly fed by the branches of the ophthalmic arteries, four posterior ethmoidal arteries, one anterior falx artery, and one recurrent middle meningeal artery were embolized with Gel-foam powder, polyvinyl alcohol (PVA) particles, and/or microcoils as a preoperative treatment using a microcatheter. RESULTS: Catheterization of the ophthalmic and tumor feeding artery was possible and feeding arteries and lesion embolization were effective to reduce the bleeding during surgery in all cases. In three cases, visual acuity and visual field were preserved. However, in one case, visual acuity and visual field defect appeared due to the migration of Gelfoam powder (Upjohn, Kalamazoo, MI) into the retinal artery. In another case, the retinal artery was embolized with the feeding arteries since the patient was already blind. CONCLUSION: Embolization of hypervascular meningioma feeding vessels arising from the ophthalmic artery is possible and effective with preservation of vision, if embolic agents are injected gently enough not to reflux into the central retinal artery.

Adult↗

Transluminal angioplasty for arteriosclerotic disease of the distal vertebral and basilar arteries.

OBJECTIVE: Percutaneous transluminal angioplasty (PTA) for the distal vertebral and basilar artery is now being performed in selected patients with haemodynamically significant lesions of the posterior cerebral circulation. Its effect and overall results were examined. PATIENTS AND METHODS: A balloon dilatation catheter specifically developed for these procedures, with a 2.0-3.5 mm balloon diameter, at 6 atmospheres of pressure, was used. Angioplasty was performed in 12 patients (including six whose initial results have been reported) with angiographically documented stenotic lesions involving either the intracranial vertebral artery (C1-C2 portion) or the basilar artery, and satisfying the following criteria: (1) clinical symptoms suggestive or consistent with a transient ischaemic attack refractory to medical treatment, or small infarction of the posterior circulation; and (2) angiographically documented stenosis greater than 70%. Two of 12 patients had complete thrombosis of the distal vertebral and basilar artery and PTA was performed after successful intra-arterial thrombolysis. RESULTS: Successful results, without complications, were obtained in eight patients, with complete resolution of vertebrobasilar ischaemic symptoms. Immediate complications occurred in four patients including two with vessel dissection, and two with thromboembolism. The two patients with acute arterial dissection were reoperated but developed small infarctions with permanent neurological deficits. The two patients with thromboembolic complication showed transient neurological deficit. The overall stenosis ratio decreased from a mean of 84% pretreatment to 44% after the angioplasty procedure. Restenosis occurred in two patients. Long term clinical follow up in 11 patients who survived more than six months showed resolution of ischaemic symptoms after PTA in all except for one with a restenosis who had recurrent transient ischaemic attacks. CONCLUSION: Transluminal angioplasty may be an effective procedure to treat vertebrobasilar ischaemia secondary to high grade arteriosclerotic disease affecting either the distal vertebral or basilar artery regions that do not respond to medical treatment.

Acute Disease↗

Clinical use of mechanical detachable coils for dural arteriovenous fistula.

Seven dural arteriovenous fistulas were successfully embolized with mechanical detachable coils. Two lesions were located in the transverse-sigmoid sinus, four in the cavernous sinus, and one in the marginal sinus. All lesions were completely occluded on postembolization angiography. No recurrent symptoms appeared during a mean follow-up period of 11 months. Owing to the length and retrievability of the mechanical detachable coils, embolization was quicker and safer, and coils were packed more densely, than is possible with conventional coils. Coil migration was avoided because coils of the appropriate size were chosen before they were placed.

Aged↗