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Y Yonekawa

Publications and source records attributed to Y Yonekawa.

At least 73 records · Page 4Linked to original sources
PubMed2000

APC mutations in sporadic medulloblastomas.

The cerebellar medulloblastoma (WHO Grade IV) is a highly malignant, invasive embryonal tumor with preferential manifestation in children. Several molecular alterations appear to be involved, including isochromosome 17q and the p53, PTCH, and beta-catenin gene mutations. In this study, 46 sporadic medulloblastomas were screened for the presence of mutations in genes of the Wnt signaling pathway (APC and beta-catenin). Single-strand conformational polymorphism (SSCP) analysis followed by direct DNA sequencing revealed 3 miscoding APC mutations in 2 (4.3%) medulloblastomas. One case contained a GCA-->GTA mutation at codon 1296 (Ala-->Val), and another case had double point mutations at codons 1472 (GTA-->ATA, Val-->Ile) and 1495 (AGT-->GGT, Ser-->Gly). Miscoding beta-catenin mutations were detected in 4 tumors (8.7%). Three of these were located at codon 33 (TCT -->TTT, Ser-->Phe) and another at codon 37 (TCT-->GCT, Ser-->Ala). Adenomatous polyposis coli (APC) gene and beta-catenin mutations were mutually exclusive and occurred in a total of 6 of 46 cases (13%). Although germline APC mutations are a well established cause of familial colon and brain tumors (Turcot syndrome), this study provides the first evidence that APC mutations are also operative in a subset of sporadic medulloblastomas.

Adenomatous Polyposis Coli Protein↗
PubMed2000

Loss of heterozygosity on chromosome 10 is more extensive in primary (de novo) than in secondary glioblastomas.

Glioblastomas develop de novo (primary glioblastomas) or through progression from low-grade or anaplastic astrocytoma (secondary glioblastomas). There is increasing evidence that these glioblastoma subtypes develop through different genetic pathways. Primary glioblastomas are characterized by EGFR and MDM2 amplification/overexpression, PTEN mutations, and p16 deletions, whereas secondary glioblastomas frequently contain p53 mutations. Loss of heterozygosity (LOH) on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas; the involvement of tumor suppressor genes, other than PTEN, has been suggested. We carried out deletion mappings on chromosome 10, using PCR-based microsatellite analysis. LOH#10 was detected at similar frequencies in primary (8/17; 47%) and secondary glioblastomas (7/13; 54%). The majority (88%) of primary glioblastomas with LOH#10 showed LOH at all informative markers, suggesting loss of the entire chromosome 10. In contrast, secondary glioblastomas with LOH#10 showed partial or complete loss of chromosome 10q but no loss of 10p. These results are in accordance with the view that LOH on 10q is a major factor in the evolution of glioblastoma multiform as the common phenotypic end point of both genetic pathways, whereas LOH on 10p is largely restricted to the primary (de novo) glioblastoma.

Adult↗
PubMed2000

Loss of heterozygosity on chromosome 19 in secondary glioblastomas.

Glioblastomas develop rapidly de novo (primary glioblastomas) or slowly through progression from low-grade or anaplastic astrocytoma (secondary glioblastomas). Recent studies have shown that these glioblastoma subtypes develop through different genetic pathways. Primary glioblastomas are characterized by EGFR amplification/overexpression, PTEN mutation, homozygous p16 deletion, and loss of heterozygosity (LOH) on entire chromosome 10, whereas secondary glioblastomas frequently contain p53 mutations and show LOH on chromosome 10q. In this study, we analyzed LOH on chromosomes 19q, 1p, and 13q, using polymorphic microsatellite markers in 17 primary glioblastomas and in 13 secondary glioblastomas that progressed from low-grade astrocytomas. LOH on chromosome 19q was frequently found in secondary glioblastomas (7 of 13, 54%) but rarely detected in primary glioblastomas (1 of 17, 6%, p = 0.0094). The common deletion was 19q13.3 (between D19S219 and D19S902). These results suggest that tumor suppressor gene(s) located on chromosome 19q are frequently involved in the progression from low-grade astrocytoma to secondary glioblastoma, but do not play a major role in the evolution of primary glioblastomas. LOH on chromosome 1p was detected in 12% of primary and 15% of secondary glioblastomas. LOH on 13q was detected in 12% of primary and in 38% of secondary glioblastomas and typically included the RB locus. Except for 1 case, LOH 13q and 19q were mutually exclusive.

Astrocytoma↗
PubMed2000

Near-real-time guidance using intraoperative magnetic resonance imaging for radical evacuation of hypertensive hematomas in the basal ganglia.

OBJECTIVE: To report our preliminary clinical experience in treating patients with hypertensive hemorrhage in the basal ganglia using a minimally invasive approach facilitated by intraoperative real-time imaging of an open magnetic resonance imaging (MRI) system and a newly designed cutting suction device. METHODS: We developed an artifact-free device for use during intraoperative MRI consisting of a guiding base that locks into a burr hole, a side-cutting composite-based cannula connected to a standard aspirator, and a handpiece that allows aspiration strength to be regulated by the surgeon. Thirteen patients with hypertensive bleeding in the basal ganglia were included in the study. Outcome was evaluated by mortality, Glasgow Outcome Scale score, activities of daily living score, and Rankin score at 2 weeks and at a median of 4.2 months after the hemorrhage. RESULTS: In this group of 13 patients, complete evacuation was achieved in 8 patients (62%) and subtotal evacuation of 75 to 90% of the initial volume in 4 patients (31%); the evacuation was partial in 1 patient (8%). Vascular malformations were preoperatively excluded angiographically. There was no rebleeding during surgery or postoperatively, as demonstrated by immediate postoperative MRI and computed tomography on the 1st postoperative day. Hematomas were evacuated on median Day 4 after the hemorrhage, varying between Day 1 and Day 8; evacuation was performed on Day 21 after the hemorrhage in one patient. Twelve of the 13 patients survived during a median follow-up time of 4.2 months. Neurological function improved in 11 of the 12 patients eligible for assessment. One patient with an additional head injury died 15 days after surgery from pulmonary embolism. CONCLUSION: This study shows an excellent outcome with regard to mortality and a positive trend regarding neurological outcome for the specific group of patients with hypertensive hematomas in the basal ganglia. This minimally invasive approach is feasible in the open intraoperative MRI in combination with the cutting suction device developed in our institution. Online imaging is extremely helpful for planning, guiding, and real-time monitoring of the procedure.

Adult↗
PubMed2000

A new artifact-free device for frameless, magnetic resonance imaging-guided stereotactic procedures.

OBJECTIVE: A new, artifact-free, nonobstructive device was required for planning, guiding, and performing stereotactic procedures in an open magnetic resonance imaging (MRI) system (Signa SP; General Electric, Milwaukee, WI). DESCRIPTION OF INSTRUMENTATION: We devised an MRI-compatible instrument set that was adapted to an optical triangulation system (FlashPoint System; Image Guided Technologies, Boulder, CO) and consisted of a Pathfinder for planning burr holes and trajectories and a Snapper-Stereoguide for guiding minimally invasive instruments such as biopsy cannulae, endoscopes, and laser fibers. The instruments were composed of biocompatible plastic (polyacetal). During evaluation, special attention was paid to safety, accuracy, operation times, and susceptibility artifacts of the system. RESULTS: The first 20 stereotactic procedures performed in the open MRI scanner included 15 biopsies, 1 cyst and 3 abscess evacuations, and 1 endoscopic procedure for treatment of multiseptate hydrocephalus. There were no adverse outcomes, and all biopsies were diagnostic. The frameless stereotactic system in combination with the FlashPoint System proved to be accurate, with a mean error of 1.5 mm. The biopsy devices did not cause any susceptibility artifacts. Highly vascularized structures were clearly visible and were included in the trajectory planning. With experience, the procedure time was reduced to less than 1 hour. CONCLUSION: This device was found to be quite helpful for planning and guiding stereotactic procedures in the open MRI scanner. Nearly real-time planning and monitoring of stereotactic procedures and the positional accuracy of the system make the open MRI system a definite improvement, compared with conventional stereotactic systems.

Adolescent↗
PubMed2000

[The HSV-TK/GCV gene therapy in five cases of recurrent glioblastoma multiforme].

Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy was performed in five cases of recurrent glioblastoma multiforme. The mean age of cases, three males and two females, was 60 +/- 5 years old. All of the tumors were confirmed pathologically as glioblastoma multiforme and recurred after the initial treatments (surgery and irradiation). A total number of 1 x 10(9) vector producer cells (VPCs), which produce retroviral vectors containing the HSV-TK gene, was inoculated into the tumor-bed spaces after removal of the recurrent tumors. From the following 14th day to the 27th day, GCV was transfused 5 mg/kg i.v. twice a day. The effect of the HSV-TK/GCV gene therapy was evaluated by the Karnofsky performance scale and MRI findings sequentially, before the therapy and in the 1st, 2nd, 4th and 6th month after the VPCs inoculation. During the follow-up period of 12 months, two cases died (survival period; 8.4 and 9.9 months), whereas the other three are still alive for over 12 months (1-year survival; 60%). Karnofsky performance scale showed the maximum at the 2nd and 4th month in all cases; the mean performance rating of living cases was 80% and that of dead cases was 70%. MRI revealed progression in none of the cases until the 2nd month. These results obtained in five cases suggest that the HSV-TK/GCV gene therapy may promise a feasible approach against glioblastoma multiforme.

Adult↗
PubMed2000

[The biosafety of the HSV-TK/GCV gene therapy in five cases of recurrent glioblastoma multiforme].

Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) therapy was performed in five cases of recurrent glioblastoma multiforme. In the last study, the authors demonstrated response of the HSV-TK/GCV therapy against tumor progression (Adachi N, et al.: No Shinkei Geka). The aim of this study is to estimate the biosafety of in vivo HSV-TK gene transfer and GCV administration in five cases. Six parameters were analyzed sequentially up to the 6th month after the vector producer cells (VPCs) inoculation as follows; i) clinical symptom, ii) vital sign, iii) peripheral blood cell count, iv) blood biochemical analysis, v) serological test, vi) molecular biological test in peripheral leukocytes. In addition, ten systemic organs extracted from the two subjects in whom death occurred were also analyzed biologically. One case suffered from transient deterioration of left hemiparesis on the 34th day, which could be considered a probably-related but not adverse event. Serological tests detected anti-VPC antibody at the 1st month in one case and anti-vector antibody at the 1st and 4th month in another. The other examinations revealed no abnormal findings at all. These data indicate that the HSV-TK/GCV therapy might be a satisfactorily safe approach against glioblastoma multiforme.

Adult↗
PubMed1999

Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis.

KIF3A is a classical member of the kinesin superfamily proteins (KIFs), ubiquitously expressed although predominantly in neural tissues, and which forms a heterotrimeric KIF3 complex with KIF3B or KIF3C and an associated protein, KAP3. To elucidate the function of the kif3A gene in vivo, we made kif3A knockout mice. kif3A-/- embryos displayed severe developmental abnormalities characterized by neural tube degeneration and mesodermal and caudal dysgenesis and died during the midgestational period at approximately 10.5 dpc (days post coitum), possibly resulting from cardiovascular insufficiency. Whole mount in situ hybridization of Pax6 revealed a normal pattern while staining by sonic hedgehog (shh) and Brachyury (T) exhibited abnormal patterns in the anterior-posterior (A-P) direction at both mesencephalic and thoracic levels. These results suggest that KIF3A might be involved in mesodermal patterning and in turn neurogenesis.

Animals↗
PubMed1999

Endovascular treatment of cerebral vasospasm: assessment of treatment effect by cerebral angiography and transcranial colour Doppler sonography.

In a retrospective study of 30 consecutive patients with symptomatic vasospasm the mean degree of narrowing as compared to the initial angiogram was 35% (+/- 24%) in 12 intradural internal carotid arteries (ICA), 42% (+/- 17%) in 42 proximal middle cerebral (MCA) and 38% (+/- 19%) in 27 anterior cerebral arteries (ACA). The corresponding increase in mean flow velocities from baseline values obtained by transcranial colour Doppler sonography (TCD) within 12 h of the first angiogram to the time of clinical vasospasm was considerably higher, with 49% (+/- 34%) in the ICA 119% (+/- 92%) in the MCA and 147% (+/- 170%) in the ACA. Following superselective intra-arterial papaverine application in 66 arteries and balloon angioplasty of 15 arteries, 78 (96.3%) of 81 dilated. Sustained clinical improvement was achieved in 22 patients (73.3%). The mean reversal of angiographic vasospasm was 71% for the ICA (range 10-100%), 81% for the MCA (range 9-100%) and 82% (range 0-100%) for the A1 segment. The mean reduction of flow velocities after treatment was much less with 23% (+/- 21%) in the ICA, 32% (+/- 24%) in the MCA and 25% (+/- 22%) in the A1 segment.

Adult↗
PubMed1999

Colour-coded Doppler sonographic study of the haemodynamics in the parent artery of intracranial aneurysms.

We investigated the haemodynamics in the parent artery of 17 small (< 9 mm) and 17 large (L 9.5 mm) saccular aneurysms by transcranial colour-coded Doppler sonography (TCCD) and related the findings to digital subtraction angiography (DSA). We measured flow velocity within the parent artery and, by positioning the Doppler gate within the colour flow image close to the ostium of the aneurysm, obtained a superselective Doppler spectral waveform. The parameters measured included the time-averaged maximal velocity (TAMX), peak systolic, and end-diastolic velocity and pulsatility index (PI). The values were compared to the contralateral side and between small and large aneurysms. DSA was analysed for parent artery stenosis. Mean systolic velocities in the parent arteries of large aneurysms were significantly higher than in the contralateral normal artery (1.08 +/- 0.23 vs 0.80 +/- 0.23 m/s; P = 0.0003) and higher than in the parent artery of small aneurysms (0.89 +/- 0.18 m/s; P = 0.01). Increased systolic velocity accounted for a higher PI in the parent artery of large aneurysms (mean 1.48 +/- 0.42) than on the other side (0.87 +/- 0.12; P = 0.0001) and in the parent artery of small aneurysms (0.85 +/- 0.14; P = 0.0001). PI proximal to seven thrombosed large aneurysms was higher (mean 1.85 +/- 0.38) than close to unthrombosed large aneurysms (1.23 +/- 0.22; P = 0.0005). Increased PI and systolic velocities could not be shown within branches of 5 large aneurysms and were reversible in the parent artery of four patients examined again after occlusion of the aneurysm. Systolic velocities and PI did not differ significantly (P = 0.41 and P = 0.25, respectively) in ruptured and unruptured aneurysms. Stenosis of the parent artery was not shown by DSA in any case.

Adult↗
PubMed1999

A case history of glioma progression.

Low-grade diffuse astrocytomas have an intrinsic tendency for malignant progression but the factors determining the kinetics of this process are still poorly understood. We report here the case of a male patient who developed a fibrillary astrocytoma at the age of 33 years and who underwent six surgical interventions over a period of 17 years without radiotherapy or chemotherapy. The first three biopsies spanned a period of 11 years and led to the diagnosis of low-grade, diffuse astrocytoma (WHO grade II), with a growth fraction (MIB-1 labeling index) of 2.3-3.7%. The fourth to sixth biopsies showed histological features of anaplastic astrocytoma (WHO grade III), with growth fractions between 5.0 and 10.5%. The fraction of gemistocytic neoplastic astrocytes also increased, from 0.3% in the first biopsy to 17.5% in the last biopsy and preceded the increase in proliferative activity and transition to anaplastic astrocytoma. The fraction of tumor cells immunoreactive to BCL-2 increased from 0.3% to 8.2%. A p53 mutation in codon 273 (CGT-->TGT, Arg-->Cys) was identified in the first biopsy and persisted throughout the course of the disease. However, the fraction of cells with p53 protein accumulation increased significantly during progression, from 3.2% in the first biopsy to 13.7% in the last. The absence of additional genetic alterations (PTEN mutations, loss of chromosome 10 and 19q) may be responsible for the slow progression and lack of glioblastoma features even after a 17-year disease duration.

Adult↗
PubMed1999

Clinical, angiographic, and sonographic findings after structured treatment of cerebral vasospasm and their relation to final outcomes.

OBJECTIVE: To report the early clinical results, quantitative angiographic and sonographic findings, and final outcome in patients with symptomatic vasospasm who had undergone surgical occlusion of the aneurysm and a structured protocol including aggressive intensive care management, endovascular procedures (EP), and barbiturate coma (BC). RESULTS: Thirty consecutive patients (19 women, 11 men, age: 51 +/- 8 years) underwent 38 EP for the treatment of 81 vascular territories (15 balloon dilatations and 66 papaverine infusions). Overall angiographic vasospasm in the intradural ICA improved significantly from 44.7 +/- 19.8% to 16.5 +/- 16%, in the MCA from 44.2 +/- 14.7% to 14.4 +/- 14%, and in the ACA from 38.7 +/- 18.6% to 13.3 +/- 12%. Mean flow velocities (Vm) in the MCA and ACA decreased significantly from 135 +/- 48 cm/sec to 87 +/- 32 cm/sec and from 110 +/- 36 cm/sec to 84 +/- 30 cm/sec, respectively. No significant Vm improvement in the ICA could be demonstrated. Six patients (20%) developed intractable vasospasm after repeated EP and five patients underwent BC. The correlation coefficient between percentage of angiographic vasospasm and Vm increase was -0.19 (p = NS) for the ICA, 0.2 (p < 0.001) for the MCA, and 0.3 (p < 0.05) for the ACA. Correlation coefficient between percentages of angiographic and sonographic improvement was -0.12 (p = NS) for the ICA, 0.42 (p < 0.001), and 0.1 (p < 0.05) for the ACA. Early clinical improvement after EP was observed in 73% of patients and was significantly associated with favourable outcome (GOS 4-5). Sixteen patients (53%) had a GOS 5, six patients (20%) a GOS 4, six patients (20%) a GOS 3, and two patients (6.6%) died as consequence of devastating vasospasm. CONCLUSIONS: Changes in vessel diameter and increases of Vm during vasospasm correlate weakly. In spite of the fact that significant differences in vessel diameter and Vm were demonstrated after treatment, a moderately good correlation between percentages of angiographic and Vm improvement was observed only in the M1 segments. In our experience, a reduction of mortality and disabilities can be achieved with a maximal structured treatment of vasospasm. Early clinical improvement after endovascular treatment is strongly associated with favourable outcome, nevertheless, cost-benefit and controlled trials are necessary to evaluate these techniques.

Adult↗
PubMed1999

Acquisition of the glioblastoma phenotype during astrocytoma progression is associated with loss of heterozygosity on 10q25-qter.

Loss of heterozygosity on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas and occurs in more than 80% of cases. We recently reported that PTEN (MMAC1) on 10q23.3 is mutated in approximately 30% of primary (de novo) glioblastomas but rarely in secondary glioblastomas that progressed from low-grade or anaplastic astrocytomas. Because secondary glioblastomas also show LOH#10, tumor suppressor genes other than PTEN are likely to be involved. We analyzed LOH on chromosomes 10 and 19, using polymorphic microsatellite markers in microdissected foci showing histologically an abrupt transition from low-grade or anaplastic astrocytoma to glioblastoma, suggestive of the emergence of a new tumor clone. When compared to the respective low-grade or anaplastic astrocytoma of the same biopsy, deletions were detected in 7 of 8 glioblastoma foci on 10q25-qter distal to D10S597, covering the DMBT1 and FGFR2 loci. Six of 8 foci showed LOH at one or two flanking markers of PTEN but did not contain PTEN mutations. LOH on 10p and 19q was found in only one case each. These data indicate that acquisition of a highly anaplastic glioblastoma phenotype with marked proliferative activity and lack of glial fibrillary acidic protein expression is associated with loss of a putative tumor suppressor gene on 10q25-qter.

Adult↗
PubMed1999

Solitary thoracic intradural extramedullary ependymoma.

Intradural extramedullary ependymomas of the cervical or thoracic spine are extremely rare. We present a 62-year-old woman with progressive thoracic back pain over 9 months. Magnetic resonance imaging rerevealed a thoracic intradural extamedullary tumour which was surgically removed in total. Histologic examination identified the tumour as ependymoma, WHO Grade II. Our radiological and surgical findings are consistent with the hypothesis that these tumours develop from heterotopic glial tissue pinched off from the neural tube during its closure. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMed1999

Transcollicular approach to intrinsic tectal lesions.

OBJECTIVE: We used a paramedian, infratentorial-supracerebellar, transcollicular approach to resect 11 intrinsic tectal lesions, including 8 tumors and 3 hematomas, in 11 patients. The route of access to the lesions was designed to minimize the anatomic and functional damage to the surrounding structures. METHODS: Access was through one superior colliculus in each of seven patients, through one inferior colliculus in each of two patients, and through the superior and inferior colliculi of one side in each of two patients. RESULTS: Of the eight tumors, three were totally resected, four were nearly totally resected, and one was partially resected. The preoperative ocular symptoms did not change in six of these eight patients and worsened in two, and the neurological deficits, except ocular symptoms, improved in two. All three hematomas were completely removed, along with abnormal blood vessels in the wall of the hematoma cavity; all three of these patients experienced neurological improvement. CONCLUSION: We conclude that the paramedian, infratentorial-supracerebellar, transcollicular approach permits safe removal of intrinsic tectal lesions. Resection of the superior or inferior colliculus or both on one side seems to be neurologically well tolerated.

Adult↗
PubMed1999

Identification in human brain tumors of DNA sequences specific for SV40 large T antigen.

Simian virus 40 (SV40) sequences have recently been identified in a variety of human neoplasms, including mesothelioma, osteosarcoma, and brain tumors, but significant discrepancies exist regarding the frequency at which this occurs. The SV40 genome is 70% homologous to JC and BK, two related polyomaviruses that are highly prevalent in humans and which may cause in immune-compromised patients progressive multifocal leukoencephalopathy (PML) and cystitis, respectively. We have established a specific and sensitive method to identify SV40 sequence in DNA extracted from histological sections, using PCR followed by Southern hybridization to probes specific to the large T region. We found SV40 large T antigen sequences in all brain tumor types investigated. High frequencies were found in low-grade astrocytomas, anaplastic astrocytomas and secondary glioblastomas derived thereof (13/22, 59%) while somewhat lower frequencies were found in gemistocytic astrocytomas (9/28, 32%) and oligodendrogliomas (3/12, 25%). Primary glioblastomas, giant cell glioblastomas, and gliosarcomas, which clinically develop de novo, contained SV40 sequences in 11-25% of cases. Presence of viral DNA was also observed in pediatric brain tumors, including ependymomas (9/16, 56%), choroid plexus papillomas (6/16, 38%), and medulloblastomas (5/17, 29%). In 8 tumor biopsies with SV40 sequences, the adjacent normal brain tissue was also analyzed but was devoid of viral DNA in all but one case. BK and JC virus sequences were rarely detected, the overall frequencies being 3% and 2%, respectively. It remains to be shown whether the presence of SV40 contributes significantly to malignant transformation or whether certain human neoplasms provide a microenvironment that favors viral replication in humans with latent SV40 infection.

Adolescent↗
PubMed1999

Activation of the left motor cortex during left leg movements after right central resection.

A patient with Rasmussen's encephalitis underwent a right central resection at the age of 6 as a treatment for status epilepticus. She became seizure free, but suffered a left hemiplegia which improved so that she could walk. Because of the recurrence of seizures an enlargement of the resection to a hemispherectomy was carried out 17 years after the first operation. Various examinations, including H(2)(15)O PET and amytal testing, performed before this second operation indicated that a compensatory reinforcement of the ipsilateral uncrossed corticospinal and spinocortical pathways had taken place. This was confirmed postoperatively. The patient had no new sensorimotor deficits.

Adult↗