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Naokatsu Saeki

Publications and source records attributed to Naokatsu Saeki.

At least 19 recordsLinked to original sources
PubMed2006

A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms.

The rupture of an intracranial aneurysm (IA) results in subarachnoid hemorrhage, a catastrophic neurological condition with high morbidity and mortality. Following-up on our previous genome-wide linkage study in Japanese population, we extensively analyzed a 4.6 Mb linkage region around D7S2472 on 7q11 by genotyping 168 single nucleotide polymorphisms (SNPs). SNP association and window scan haplotype-based association studies revealed a susceptibility locus for IA on a single LD block covering the 3'-untranslated region (3'-UTR) of ELN and the entire region of LIMK1. An association study with 404 IA patients and 458 non-IA controls revealed that the ELN 3'-UTR G(+659)C SNP has the strongest association to IA (P=0.000002) and constitutes a tag-SNP for an at-risk haplotype, which contains two functional SNPs, the ELN 3'-UTR (+502) A insertion and the LIMK1 promoter C(-187)T SNP. These allelic and haplotype-based associations were confirmed in a Korean population. Ex vivo and in vitro analyses demonstrate that the functional impact of both SNPs is the decrease of transcript levels, either through accelerated ELN mRNA degradation or through decreased LIMK1 promoter activity. Elastin and LIMK1 protein are involved in the same actin depolymerization signaling pathway; therefore, these lines of evidence suggest a combined effect of the SNPs in the at-risk haplotype possibly by weakening the vascular wall and promoting the development of IA.

3' Untranslated Regions↗
PubMed2006

Ovarian hyperstimulation caused by gonadotroph cell adenoma: a case report and review of the literature.

OBJECTIVE: We present a case of spontaneous ovarian hyperstimulation caused by pituitary gonadotroph macroadenoma, and include a review of the literature. CASE REPORT: A 27-year-old woman presented with irregular menstruation and bilateral multicystic enlargement of the ovaries. Serum estradiol (E(2)) levels were marginally elevated for the follicular phase but within the physiological range. Serum luteinizing hormone (LH) was extremely low, follicle-stimulating hormone (FSH) was normal, and prolactin (PRL) was high. Magnetic resonance imaging disclosed a pituitary macroadenoma. Immunohistochemical examination of the surgically removed adenoma showed intense reactivity for FSH and LH. After the operation, E(2), LH and PRL levels were normalized, the ovaries returned to a normal morphology, and regular menstrual cycles were resumed. CONCLUSION: A review of the literature showed that ovarian hyperstimulation caused by pituitary gonadotroph adenoma is not always accompanied by elevated FSH levels. High PRL and E(2) and low LH were reported in the majority of the cases, but E(2) may stay within the range observed in normal menstrual cycles.

Adenoma↗
PubMed2005

Polyamine oxidase and acrolein as novel biochemical markers for diagnosis of cerebral stroke.

BACKGROUND AND PURPOSE: We found previously that plasma levels of acrolein (CH2=CHCHO) and spermine oxidase (SMO) were well correlated with the degree of severity of chronic renal failure. The aim of this study was to test whether the levels of these 2 markers and of acetylpolyamine oxidase (AcPAO) were increased in the plasma of stroke patients. METHODS: The activity of AcPAO and SMO and the level of protein-conjugated acrolein in plasma of the stroke patients and normal subjects were measured by high-performance liquid chromatography and ELISA, respectively. Focal infarcts were estimated by MRI or computed tomography (CT). RESULTS: The levels of AcPAO, SMO, and acrolein were significantly increased in the plasma of stroke patients. The size of stroke was nearly parallel with the multiplied value of acrolein and total polyamine oxidase (AcPAO plus SMO). After the onset of stroke, an increase in AcPAO first occurred, followed by increased levels of SMO and finally acrolein. In 1 case, an increase in AcPAO and SMO preceded focal damage as detected by MRI or CT. Furthermore, stroke was confirmed by MRI in a number of mildly symptomatic patients (11 cases) who had increased levels of total polyamine oxidase and acrolein. Among apparently normal subjects (8 cases) who had high values of acroleinxtotal polyamine oxidase, stroke was found in 4 cases by MRI. CONCLUSIONS: The results indicate that increased levels of AcPAO, SMO, and acrolein are good markers of stroke.

Acrolein↗
PubMed2005

Lack of benefit of spinal irradiation in the primary treatment of intracranial germinoma: a multiinstitutional, retrospective review of 180 patients.

BACKGROUND: The current study assessed the contribution of spinal irradiation to the treatment outcome of patients with intracranial germinoma. METHODS: Clinical data from 180 patients with intracranial germinoma, who were treated with radiotherapy and/or chemotherapy from 1980 to 2001, were collected from 6 institutions. The patients' median age was 16 years (range, 1-47 yrs), and the male-to-female ratio was 133:47. Pathologic verification was obtained in 88 patients. A solitary tumor was seen in 129 patients, and multifocal or disseminated tumors were detected in 51 patients. The median tumor size was 2.5 cm (range, 0.6-7.0 cm). Local field and/or whole brain irradiation was performed in 114 patients, and craniospinal irradiation was performed in 66 patients. Fifty-five patients were treated with chemotherapy. The median follow-up time was 89 months (range, 3-297 mos). RESULTS: Eight-year overall and event-free survival rates were 91% and 89%, respectively. The 8-year recurrence rates at the primary site, intracranial space, and the spinal space were 1%, 6%, and 6%, respectively. Cox regression analysis showed that spinal irradiation (hazard ratio, 1.050; 95% confidence interval [CI], 0.355-3.170) did not contribute to a favorable event-free survival. CONCLUSIONS: Spinal irradiation did not contribute to favorable event-free survival in patients with intracranial germinoma.

Adolescent↗
PubMed2005

Successful pregnancy and delivery after removal of gonadotrope adenoma secreting follicle-stimulating hormone in a 29-year-old amenorrheic woman.

We report a case of ovarian hyperstimulation related to a gonadotroph adenoma in a 29-year-old woman. The patient presented with amenorrhea and large cystic ovaries. Her serum estradiol was markedly elevated (up to 31,100 pmol/l). Serum LH was low, but serum FSH and PRL were normal. Cranial magnetic resonance imaging study revealed a pituitary macroadenoma. After successful removal of the pituitary tumor, FSH, LH and estradiol normalized and fluctuated within normal ranges thereafter. The patient resumed regular cycles of menstruation and conceived spontaneously. During pregnancy, estradiol increased and FSH and LH decreased. The finding confirms restoration of negative feedback of estradiol on FSH and LH secretion. The pregnancy course was uneventful and enlargement of ovaries did not occur.

Adenoma↗
PubMed2005

Diagnostic value of thallium-201 chloride single-photon emission computerized tomography in differentiating tumor recurrence from radiation injury after gamma knife surgery for metastatic brain tumors.

OBJECT: The authors assessed the diagnostic value of 201Tl Cl single-photon emission computerized tomography (SPECT), performed after gamma knife surgery (GKS) for metastatic brain tumors in differentiating tumor recurrence from radiation injury. METHODS: Of 6503 metastatic brain tumors treated with GKS, 201Tl SPECT was required in 72 to differentiate between tumor recurrence and radiation injury. When the Tl index was greater than 5, the lesion was diagnosed as a tumor recurrence. When the index was < 3.0 it was called radiation injury. In cases with a Tl index between 3 and 5, 201Tl SPECT was repeated once per month until the Tl index was greater than 5 or less than 3. If the Tl index fluctuated between 3 and 5 for 2 months, the lesion was diagnosed as radiation injury. The final diagnosis was based on histological examination or clinical course. The sensitivity of the method was 91%; thus 201Tl SPECT is effective for differentiating between tumor recurrence and radiation injury in metastatic brain tumors treated with GKS. Caution is necessary, however, for the following reasons: 1) simple interinstitutional comparisons of Tl indices are not possible because measurement methods are institute specific; 2) steroid administration decreases the Tl index to a variable degree; and 3) a severe radiation injury lesion, as is often seen after repeated GKS or very high dose GKS, may have a Tl index greater than 5. CONCLUSIONS: Used with critical insight 201Tl Cl SPECT can be useful in distinguishing between tumor regrowth and radiation necrosis in patients with cerebral metastases.

Aged↗
PubMed2005

Analysis of genes dominantly expressed in rat cerebral endothelial cells using suppression subtractive hybridization.

In mammals, a fully developed, highly branched vascular system specialized for each particular organ or tissue is essential for obtaining metabolic nutrients supply. The formation of a blood-brain barrier that protects against environmental insults is a distinguishing feature of the brain's vascular system. Since this is accomplished by cerebral endothelial cells (CECs), we analyzed the genes specifically and/or dominantly expressed in rat CECs using Suppression Subtractive Hybridization (SSH). We found 39 genes specifically and/or dominantly expressed in CECs. 24 genes of known function (thrombospondin-2, vimentin, etc.), 13 genes of known sequence but unknown function including 7 of ESTs (SNERG1, rat GPCR, etc.), and 2 novel genes. The physiological significance of these genes in CECs has been under investigation. SSH is useful for identifying genes regulated in an organ-specific manner in cells such as CECs to obtain clarification of their physiological roles.

Animals↗
PubMed2005

MR imaging of normal perivascular space expansion at midbrain.

BACKGROUND AND PURPOSE: A previous investigation of the MR imaging findings in the midbrain reported expanded perivascular (PV) spaces in only the ponto-mesencepalic junction (PMJ) in 20% of healthy subjects, whereas pathologically expanding PV spaces have been reported at the mesencephalo-diencephalic junction (MDJ) as multi-lobulated, cystic lesions with signal intensity compatible with that of CSF that cause aqueductal stenosis. To clarify the anatomical distinctions between normally expanded and pathologically expanding PV spaces, we defined their distribution in the normal midbrain by using high-spatial-resolution MR imaging. METHODS: Heavily T2-weighted MR imaging was performed in 115 adult subjects with neurologic complaints without cerebral disease. Histologic studies were performed from two normal midbrain blocks. RESULTS: Expanded PV spaces were visible at the PMJ in 87% of subjects and at the MDJ in 63% of subjects. On axial images, ovoid or linear lesions with signal intensity compatible to CSF were present behind the cerebral peduncle at both the PMJ and MDJ. These areas varied from less than 1 mm to 5 mm (maximum diameter on coronal sections). Histologic studies confirmed the distribution of expanded PV spaces, as noted on MR images. CONCLUSION: This study, by using high-spatial-resolution MR imaging, revealed that expanded PV spaces were visible at the PMJ and MDJ. Our finding of expanded PV spaces normally present at the MDJ may be related to pathologically expanding PV spaces, which should be kept in mind as a differential diagnosis for intraparenchymal cystic lesions in the midbrain with signal intensity compatible to CSF.

Adolescent↗
PubMed2005

Pituitary cysts in childhood evaluated by MR imaging.

BACKGROUND AND PURPOSE: Pituitary cysts are common findings on pathologic examination and imaging studies. They are generally considered to be rarer in children than in adults; however, no good data exist to substantiate this opinion. We reviewed MR imaging studies to evaluate the frequency and imaging features of pituitary cysts in children. METHODS: We retrospectively reviewed T1-weighted sagittal images in 341 patients <15 years of age to evaluate for pituitary cysts. Paramagnetic contrast was administered in 86 of the 341 patients. Sagittal or coronal fast spin-echo T2-weighted images were performed in 166 patients. For patients having pituitary cysts, pituitary function was examined by assessing blood levels of pituitary hormones. RESULTS: A cystic pituitary lesion was recognized in 4 patients (1.2%) aged 1-4 years. None of the 4 manifested endocrinologic signs or symptoms or were the results of their laboratory studies abnormal. All the lesions were sharply demarcated and situated just posterior to the anterior pituitary lobe. All were iso- or hypointense compared with the pons on T1-weighted images without contrast enhancement, suggesting a Rathke cleft cyst. MR imaging of a patient with probable low-grade gliomas in the left hypothalamic region and optic chiasma showed complete resolution of a pituitary cyst at a 1-year follow-up study. CONCLUSION: The frequency of pituitary cysts on MR imaging in childhood is almost equal to that of Rathke cleft cysts, as assessed in autopsy studies of subjects aged 10 to 29 years. These cysts are common in children and should be considered, in the absence of signs or symptoms of pituitary dysfunction, as incidental findings.

Brain Neoplasms↗
PubMed2004

Roles of cyclin-dependent kinase 4 and p53 in neuronal cell death induced by doxorubicin on cerebellar granule neurons in mouse.

Cell cycle regulators such as cyclin-dependent kinases (Cdks) and their inhibitors (Ckis) have been reported to be involved in neuronal cell death (NCD) induced by a variety of insults such as ischemia, UV-irradiation, nerve growth factor (NGF)-withdrawal, and anticancer therapeutics. But their precise interactive regulation has still to be unveiled. In the present study, we focused on cell cycle regulators such as Cdk4, p21(WAF1) and p53 to clarify their regulatory mechanisms, using NCD induced by doxorubicin (D-NCD) in mouse cerebellar granule neurons as a model. Doxorubicin induced NCD in a dose-dependent manner, a typical feature of apoptosis as determined by TUNEL assay. Doxorubicin increased the protein expression of p53 in time- and dose-dependent manners. The protein expression of p21(WAF1), a Cki of Cdk4, was stimulated by doxorubicin at low concentrations, but it disappeared at high concentrations. Doxorubicin activated the kinase activity of Cdk4 without the enhancement of Cdk4 protein. 3-Amino-9-thio(10H)-acridone (3-ATA), the specific inhibitor of Cdk4, prevented D-NCD in a dose-dependent manner. Wortmannin, an inhibitor of ATM (ataxia telangiectasia, mutated) that has high homology with the phosphatidyl-inositol-3-kinase (PI3K) family and has protein kinase activity for the induction of p53 with specificity for serine and threonine residues, inhibited the activation of Cdk4 without the induction of p53 in D-NCD. These data suggest that (1) Cdk4 is one of the essential components for inducing NCD, that (2) p53 may prevent D-NCD through the induction of p21(WAF1) at low concentrations of doxorubicin, and that (3) Cdk4 might be activated by the same signal-molecules, like ATM, that are necessary for the activation of p53 in D-NCD.

Animals↗
PubMed2004

A rare case of metastatic renal cell carcinoma resembling a nerve sheath tumor of the cauda equina.

We present a rare case of solitary metastasis to the cauda equina from the kidney. The patient was a 68-year-old man with a two-year history of low back pain. His past medical history revealed a renal cell carcinoma diagnosed seven years earlier. His lumbosacral MR imaging showed a well-demarcated, intradural extramedullary mass at the L3 level. He underwent an L2-4 laminectomy. The operative findings of the tumor quite resembled that of a nerve sheath tumor. It did not infiltrate into the subarachnoid space and involved only one spinal nerve. Pathology of the tumor was a metastasis of the renal cell carcinoma. Only 10 cases with such a metastasis to the cauda equina have been reported in the English literature. We added the 11th and reviewed the literature with reference to tumor pathologies, clinical findings and route of metastasis to the cauda equina.

Aged↗
PubMed2004

Histologic characteristics of normal perivascular spaces along the optic tract: new pathogenetic mechanism for edema in tumors in the pituitary region.

BACKGROUND AND PURPOSE: Perivascular (PV) spaces are known to distend and cause edema along the optic tract (OT) in pituitary-region tumors. Interstitial fluid may be retained in PV spaces when tumors block their drainage outlets to subarachnoid spaces. However, these spaces and their outlets have not been anatomically elucidated. Our purpose was to evaluate how often large PV spaces are present along the OT and demonstrate their superficial communication points to adjacent subarachnoid spaces. METHODS: We examined serial histologic sections of 10 hemispheric blocks obtained from cadavers without cerebral abnormality. RESULTS: Large PV spaces, 0.5-1.5 mm in maximum height, were always present along the middle portion of the OT. Perforation points of the largest spaces were noted at the medial sulcus of the OT in seven hemispheres and through the OT in three. CONCLUSION: Large PV spaces are present along the middle portion of the OT. Their communication point to adjacent subarachnoid spaces was histologically demonstrated. The locations and variations of the outlet of large PV spaces explain the clinical features of edemas; these findings anatomically support the hypothesis that blockage of the outlets to subarachnoid spaces may play a role in distending the PV spaces and in causing edema in pituitary-region tumors. Only MR imaging has revealed this change; further pathologic investigations are awaited.

Aged↗
PubMed2004

Increase in metalloproteinase activity in the plasma of smoke-extract-injected rats.

Cigarette smoking is known to be one of the risk factors of subarachnoid hemorrhage (SAH), yet the precise mechanism remains to be proved. Based on the hypothesis that smoke components might enhance protease activity in the arterial wall, we examined the proteinase activities of plasma from smoke-extract-injected rats. Rats were injected intraperitoneally with smoke extract and the protease activity in the plasma was examined by zymography in the presence or the absence of proteinase inhibitors. Metalloproteinase activity was measured using a synthetic substrate. Proteolytic activities of 80- and 100-kDa against gelatin and collagen type I-V were induced 6 h after the injection. Inhibition of the activity by a metalloproteinase inhibitor but not by serine, cysteine or aspartic protease inhibitors suggested that the proteinases can be attributed to metalloproteinases. Cleavage activity in plasma toward a synthetic metalloproteinase substrate also increased within 24 h after the injection of the smoke extract. The results indicate that the induction of plasma metalloproteinase activity by smoke extract might account for the causal role of smoking in the development of SAH.

Animals↗
PubMed2003

Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients.

BACKGROUND: The relative roles of surgical resection, radiotherapy, and chemotherapy in the management of patients with intracranial nongerminomatous malignant germ cell tumors have been controversial. The authors retrospectively investigated the results of different treatment regimens in patients with these tumors. METHODS: The records of 41 patients who were treated between 1981 and 2001 were reviewed. They were grouped into patients with a good prognosis (n=3), an intermediate prognosis (n=24), and a poor prognosis (n=14) based on the histology of their tumors. Fifteen patients (37%) underwent surgical resection and received radiotherapy, and 26 patients (63%) also received chemotherapy. The median follow-up of 18 patients who remained alive was 61 months (range, 14-194 months). RESULTS: The 5-year actuarial overall survival rates for patients in the good prognosis, intermediate prognosis, and poor prognosis groups were 100%, 68%, and 8%, respectively. In the analysis, histology alone had a statistically significant impact on overall survival (P<0.0001). All 3 patients in the good prognosis group were treated successfully with surgical resection and radiotherapy. In the intermediate prognosis group, the 5-year actuarial overall survival rate was 44% for patients who underwent surgical resection and received radiotherapy (n=9) and 84% for patients who also received chemotherapy (n=15; P=0.01). Patients in the poor prognosis group who underwent surgical resection and received radiotherapy (n=3) or who underwent incomplete resection and received both radiotherapy and chemotherapy (n=8) all died of disease, whereas 2 of 3 patients who underwent macroscopic total resection and received both radiotherapy and chemotherapy survived free of disease. CONCLUSIONS: The treatment of patients with intracranial nongerminomatous malignant germ cell tumors should be based on tumor histology. For patients who had a good prognosis (mature teratoma with germinoma), surgical resection and radiotherapy were sufficient; however, for patients in the intermediate prognosis group, multimodal treatment, including surgical resection, radiotherapy, and chemotherapy, was effective. Conversely, for patients in the poor prognosis group, more intensive multimodal treatment, including macroscopic total resection, may improve the survival rate.

Actuarial Analysis↗
PubMed2003

MR demonstration of partial lesions of the lateral geniculate body and its functional intra-nuclear topography.

Two rare cases with a partial lesion of the lateral geniculate body (LGB) presumably due to ischemia are demonstrated on high resolution MR imaging. A 62-year-old woman (case 1) presented with left homonymous superior quadrantanopia on Goldmann perimetry. Heavily T2 weighted MR images showed a localized lesion at the lateral portion of the LGB. The visual field defect was macular and horizontal meridian sparing and persisted for 9 years. A 49-year-old woman (case 2) presented with a sudden onset of left homonymous horizontal sectoranopia on Humphrey automated perimetry and heavily T2 weighted images demonstrated a lesion localized at the more medial part of the right LGB. Axons originating from inferior, central and superior retina are essentially located laterally, centrally and medially, respectively, in the LGB, based on the electrophysiological studies of animal experiments and this observation has been applied to humans. This study radiologically shows that a discrete lateral lesion of the LGB produced homonymous upper quadrantanopia in case 1, whereas a more medially located lesion produced homonymous sectoranopia in case 2, and reveals that the axons originating from inferior retina are located more laterally than those from central retina in the human LGB.

Axons↗
PubMed2003

Posterior pituitary bright spot in large adenomas: MR assessment of its disappearance or relocation along the stalk.

PURPOSE: To evaluate the disappearance or relocation patterns of posterior pituitary bright spot (PPBS) in the infundibuloneurohypophyseal (INH) system and endocrinologic implications in large pituitary adenomas. MATERIALS AND METHODS: Sixty-nine patients with adenoma and supradiaphragmatic extension were classified into PPBS-visible and PPBS-nonvisible groups on the basis of findings at preoperative T1-weighted magnetic resonance (MR) imaging. The adenoma shapes were classified into hourglass type with indentation and barrel type without indentation at the diaphragmatic level. RESULTS: The PPBS-visible group included 55 (80%) patients. PPBS most commonly occurred at the distal pituitary stalk immediately above the diaphragm in 48 patients with hourglass-type adenoma. In the remaining seven patients with barrel-type adenoma, PPBS occurred in the sella or in varying sites along the pituitary stalk. Postoperatively, two patients, whose PPBS became nonvisible, developed persistent diabetes insipidus. The PPBS-nonvisible group included 14 (20%) patients. Five had hourglass-type and nine had barrel-type adenoma. Occurrence of the barrel type was marked. In these patients, four developed postoperative permanent diabetes insipidus. CONCLUSION: The diaphragm, a probable major anatomic determinant of indentation, may serve as a transportation blockade and facilitate proximal accumulation of PPBS material, as evidenced in the hourglass-type adenoma. PPBS was more commonly nonnvisible in the barrel-type adenoma. The presence of PPBS in the INH system indicates its functional maintenance in large adenomas.

Adenoma↗
PubMed2003

Congenital spondylolysis of the axis with associated myelopathy. Case report.

Cervical spondylolysis is a rare clinical entity and occurs predominantly at the C-6 level. The authors describe a patient with congenital spondylolysis of the axis that caused myelopathy. The patient was a 57-year-old woman with long-standing gait disturbance. Plain cervical radiography revealed a radiolucent defect across the pedicle of the axis. Magnetic resonance imaging of the cervical spine in the neutral, flexion, and extension neck positions as well as a computerized tomography myelography in the neutral neck position failed to demonstrate any spinal cord compression. When she rotated her neck, however, the spinal cord was caught between the hypertrophic anterior arch of the atlas and posterior part of the slipped pedicle of the axis on the contralateral side. The spinal cord was transformed into a pear shape. Mechanical injury to the spinal cord seemed to explain her neurological presentation. This is, to the authors' knowledge, the 15th case of axial spondylolysis and the sixth case of spinal cord involvement of the cervical spondylolysis. No cases involving myelopathy secondary to such a unique mechanism have been reported previously in the literature.

Axis, Cervical Vertebra↗