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Biomedical subjects

Hidetoshi Ikeda

Publications and source records attributed to Hidetoshi Ikeda.

At least 19 recordsLinked to original sources

Adult moyamoya disease in the asymptomatic Japanese population.

Moyamoya disease (MMD) is a spontaneous occlusive disease of the Willis circle. This study evaluated the presence of the radiological hallmarks of adult MMD on a "brain check-up" (BC) using MRI and MR angiography, in Japan. BC was offered to 11,402 healthy subjects (7570 men and 3832 women) between January 1997 and November 2003. The mean age of all subjects was 53.2 years (SD 11.1); the mean age of men was 53.2 years (SD 10.9) and women 53.2 years (SD 11.5). MMD was diagnosed according to the criteria of the Research Committee on Spontaneous Occlusion of the Circle of Willis in Japan. Eight subjects (4 men and 4 women) were diagnosed as probable MMD without neurological deficits. Thus, the percentage of subjects with asymptomatic MMD on BC was 0.07% for the total group, 0.05% in men and 0.10% in women. The female to male ratio was 3.3:1. The mean age of the MMD patients was 54.0 years (SD 12.0); men 54.8 years (SD 12.8) and women 53.3 years (SD 13.9). Estimates of the prevalence of MMD in the Japanese population were calculated as 50.7 per 100,000 people; 28.9 in men and 94.3 in women. Five patients had a family history of definite MMD and seven had a family history of subarachnoid or intracerebral hemorrhage. MRI and angiography showed stenosis of the bilateral internal carotid arteries (ICA) in five patients and a unilateral ICA in three. Moyamoya vessels were confirmed on cerebral angiography. Our standard BC protocol is limited for the detection of moyamoya vessels in the initial stages of MMD. The present study suggests that the radiological features of MMD are asymptomatic in the early stages of the disease.

Adult↗

The effects of head and body positioning on upper airway collapsibility in normal subjects who received midazolam sedation.

STUDY OBJECTIVE: To test the hypothesis that the change of body and head position affects upper airway patency during midazolam sedation. DESIGN: Clinical study using 30 healthy subjects. SETTING: Research unit for sleep study. INTERVENTIONS: We used a pressure-flow relationship to evaluate critical closing pressure (Pcrit) and upper airway resistance (Rua) in different condition of body and head position. A pressure-flow relationship was obtained in 3 body postures (supine, 15 degrees elevation, and 30 degrees elevation) and was obtained in 3 head positions (supine with the head in the neutral, supine with head extension, and supine position with head rotated). MEASUREMENTS: The pressure and inspiratory flow at subjects' nose mask were recorded. Polysomnographic parameters (electroencephalograms, electrooculograms, submental electromyograms, upper esophageal pressure, and plethysmogram) were also recorded. MAIN RESULTS: In experiment 1, 30 degrees elevation of the body significantly decreased Pcrit (P < 0.05) to -13.3 +/- 1.3 cm H(2)O compared with -8.2 +/- 1.4 cm H(2)O in supine condition without changing the slope (1/Rua). In experiment 2, head extension significantly decreased Pcrit (-12.5 +/- 1.3 cm H(2)O) (P < 0.05) compared with the value (-8.2 +/- 1.0 cm H(2)O) in supine condition without changing the slope (1/Rua). CONCLUSIONS: Our findings indicate that 30 degrees body elevation and head extension significantly decreased upper airway collapsibility during midazolam sedation and established the relative potency of maneuvers that maintain upper airway patency.

Adult↗

[Endovascular treatment for vertebral artery dissecting aneurysm: effectiveness of internal trapping with proximal flow arrest].

Ruptured vertebral artery (VA) dissecting aneurysms are associated with a higher incidence of rebleeding than saccular aneurysms, so, it is encouraged that diagnosis be followed by early treatment. The standard treatment for VA dissecting aneurysms is internal trapping using an endovascular technique. In this procedure, a proximal flow arrest is sometimes used to ensure safety. In this report, we demonstrated the usefulness of proximal flow arrest. The subjects consisted of seven patients treated with endovascular treatment for ruptured VA dissecting aneurysms from 1997 to 2005. Two of the seven patients were treated without proximal flow arrest and one of the two encountered rerupture of the aneurysm at coil embolization. Five patients were treated with proximal flow arrest. Internal trapping was safely completed in these patients. Overall outcomes measurment by Glasgow Outcome Scale were good recovery in three, moderate disability in one, vegetative state in one and dead in two. Proximal flow arrest is considered to be useful for the following four reasons: 1) for the prevention of distal embolism; 2) for the prevention of distal coil migration; and 3) to block blood flow upon rerupture; 4) for the balloon occlusion test, but the necessity of this technique is now controversial. However it is difficult to prove the necessity, we believe it is an effective optional technique for safety embolization.

Aged↗

Different fecal shedding patterns of two common strains of hepatitis E virus at three Japanese swine farms.

Zoonotic infections caused by eating the meat of deer, wild boar, and pig have been suggested in Japan, a country that is not epidemic for hepatitis E caused by hepatitis E virus (HEV). This virus is widely spread in domestic pigs in both epidemic and non-epidemic countries. We studied fecal HEV shedding patterns on three Japanese farms that had two common genotype III HEV strains. Two of the three farms had high shedding peaks (75% and 100%) in pigs 1-3 months of age, suggesting that these animals had the highest risk of spreading HEV through feces. Another farm had a low shedding rate in animals six months of age and a low prevalence of the IgG antibody to HEV. Fecal IgA antibody to HEV was found in sucking pigs < 13 days of age on farms that had high and low shedding patterns. A small fraction of pigs (3 of 43 [7%]) at the finishing stage (5-6 months of age) still shed HEV on the three farms.

Animals↗

[Clinicopathology, clonality, and hormone production profile of prolactinoma].

OBJECTIVE: To analyze the hormone production profiles of prolactinoma and to analyze the clonality of prolactinoma. METHODS: Clinicopathologic factors were studied in 123 patients with prolactinoma, 40 males and 83 females, aged 31.9 +/- 12.2 (16 approximately 65) who underwent resection of tumor in Japan. The specimens were fixed in either 10% neutral buffered formalin or 70% alcohol and used for light microscopy. DNA was extracted from 26 samples of alcohol-fixed tissue from female patients for human androgen receptor gene (HUMARA) assay. The data underwent Spearman rank correlation analysis and nonparametric Mann-Whitney U test. RESULTS: sixty-one cases (50%) were pure prolactinoma and 62 cases (50%) were plurihormonal prolactinoma. Spearman rank correlation analysis revealed that age was significantly positively correlated with serum prolactin (PRL) level (P = 0.0002), and tumor volume (P < 0.0001); and tumor volume was significantly positively correlated with serum PRL level (P < 0.0001). Multiple regression analysis showed a significant correlation only between tumor volume and serum PRL level (multiple correlation coefficient = 0.622, coefficient of multiple determination = 0.387, t = 7.59, P < 0.0001). Mann-Whitney U test revealed that the invasiveness of tumor was significantly positively correlated with the serum PRL level (P < 0.0001), volume of tumor (P < 0.0001), and the age of patient (P = 0.0003); that the sex of patient was significantly positively correlated with the pre-and post-operative serum PRL levels (both P < 0.0001) and the tumor volume (P < 0.0001); and that male patients had significantly higher PRL levels and larger adenomas(P < 0.0001, P < 0.0001 respectively). The HUMARA assay disclosed that 11 of the 13 plurihormonal prolactinomas (85%) were compatible with monoclonal origin. CONCLUSION: Prolactinoma secrets not only PRL but also other pituitary hormones. Most multihormone producing prolactinomas are monoclonal in origin.

Adolescent↗

Infrequent mutation of APC, AXIN1, and GSK3B in human pituitary adenomas with abnormal accumulation of CTNNB1.

We analyzed mutation of the APC, AXIN1, and GSK3genes in 14 pituitary adenomas with abnormal nuclear accumulations of CTNNB1. These tumors did not harbor mutation of the CTNNB1 gene. The genes analyzed encode proteins associated with ubiquitin-mediated degradation of CTNNB1. Although the regions encoding functional domains of these protein products were analyzed, no significant genetic alterations were found. Furthermore, the antibody for the C-terminus of APC detected normal expression of the APC protein in these pituitary adenomas. Our present results imply that an unknown mechanism(s) accelerates the accumulation of CTNNB1 that plays an important role in the pathogenesis of human pituitary adenomas. However, the possibility that mutation of regions outside of our survey or epigenetic mechanism play an important role cannot be excluded.

Adenoma↗

Delayed lymphocytic infundibuloneurohypophysitis following successful transsphenoidal treatment of Cushing's disease.

Lymphocytic infundibuloneurohypophysitis is a rare disorder in which neurohypophyseal function is impaired by an autoimmune process. Although several etiologies for this rare entity have been suggested, its occurrence following transsphenoidal adenomectomy has not been reported. A 20-year-old man presented with diabetes insipidus - seven years after successful transsphenoidal microadenomectomy for Cushing's disease, first diagnosed at the age of 13. Seven years later, he developed fairly rapid onset of polydipsia and polyuria. Magnetic resonance imaging demonstrated swelling of the posterior pituitary gland with thickening of the pituitary stalk. Endocrinological evaluation revealed neurohypophyseal dysfunction without the adenohypophysis being affected. On the basis of these findings, a diagnosis of lymphocytic infundibuloneurohypophysitis was made. The mass lesion of the posterior pituitary resolved after the administration of corticosteroids for two months and no operation was required. Lymphocytic infundibuloneurohypophysitis should be considered in the differential diagnosis of pituitary mass lesions following transsphenoidal surgery, especially when the mass is confined to the posterior pituitary gland with neurohypophyseal function being compromised.

Adenoma↗

Resistance against Friend leukemia virus-induced leukemogenesis in DNA-dependent protein kinase (DNA-PK)-deficient scid mice associated with defective viral integration at the Spi-1 and Fli-1 site.

Retroviral DNA integration is mediated by the viral protein integrase. However, elements of the host DNA repair machinery such as the phosphatidylinositol 3-kinase (PI-3K)-related protein kinase family system would play a role in the integration of viral DNA into the host DNA. Here, we show that a host PI-3K-related protein kinase, DNA-dependent protein kinase (DNA-PK), plays a role in the specific integration of retroviral DNA and induction of retroviral diseases in vivo. DNA-PK-deficient scid mice inoculated with Friend leukemia virus (FLV) exhibited a random integration into their genomic DNA and expressed the viral envelope protein gp70. However, the specific integration of FLV at Spi-1 or Fli-1 sites did not occur in association with the significant resistance of scid mice to FLV-induced leukemogenesis. In contrast, the knockout of another member of the PI-3K-related protein kinase family, encoded by the ataxia telangiectasia mutated (ATM) gene, resulted in mice as sensitive to FLV-induced leukemogenesis as the wild type mice. FLV was specifically integrated into the DNA at Spi-1 and Fli-1 sites with significant expression of these transcription factors. These findings indicated that DNA-PK would be essential for controlling the in vivo integration of FLV at specific sites as well as the susceptibility to FLV-induced leukemogenesis.

Animals↗

Diagnostic value of super-selective bilateral cavernous sinus sampling with hypothalamic stimulating hormone loading in patients with ACTH-producing pituitary adenoma.

AIMS: Early diagnosis and early treatment by transsphenoidal surgery is desirable for ACTH-producing pituitary microadenoma, but accurate localization of the functional lesion is not always possible before surgery because magnetic resonance (MR) imaging may provide false negative and/or positive findings. The diagnostic value of super-selective bilateral cavernous sinus sampling with the administration of corticotropin-releasing hormone (CRH) was assessed in patients with functioning ACTH-producing pituitary adenoma. METHODS: Fifteen patients with pituitary adenoma (14 with microadenoma) aged from 23 to 74 years (mean 46.7 years) underwent cavernous sinus sampling with or without the CRH loading test and subsequent transsphenoidal surgery in our institute from October 1997 through to November 2002. MR imaging including dynamic scan failed to detect the adenomatous lesion in all patients. To eliminate the bias due to uneven blood flow in the cavernous sinuses and the multi-hormonal response to CRH administration, the ACTH/FSH ratios were evaluated. The inter-cavernous gradient (ICG) was calculated as the higher/lower ACTH venous blood levels in the right and left cavernous sinuses with or without CRH loading. The adjusted ICG was calculated using the ACTH/FSH ratios. The results were compared with the surgical findings. An ICG of 1.4 or greater was considered to indicate the localization of the responsible lesion. RESULTS: Transsphenoidal surgery revealed the functioning lesion on the right in five cases, the left in six, the midline in three and the bilateral lateral wings (double adenoma) in one. Adjusted ICG with CRH loading had a localization accuracy of 93.3% (14/15), which was significantly higher than that of 73.3% (11/15) using ICG without hypothalamic stimulating hormone loading (p = 0.0402). CONCLUSIONS: Super-selective cavernous sinus sampling with hypothalamic stimulating hormone administration can provide accurate localization of the responsible lesion in patients with ACTH-producing pituitary adenoma.

Adenoma↗

A novel susceptibility locus for moyamoya disease on chromosome 8q23.

Moyamoya disease (MIM 252350) is characterized by stenosis or occlusion of the terminal portions of the bilateral internal carotid arteries and by abnormal vascular networks at the base of the brain. There is a high incidence of moyamoya disease in Asia, especially in Japan. Multifactorial inheritance is estimated with lambda(s)>40. Previous linkage studies have indicated that susceptibility loci for the disease are located on chromosomes 3p, 6q, and 17q. In the present study, we searched for loci linked to the disease in 12 Japanese families using 428 microsatellite markers and found significant evidence for linkage to 8q23 [maximum LOD score (MLS) of 3.6] and suggestive evidence for linkage to 12p12 (MLS=2.3). The present study revealed a novel locus for moyamoya disease.

Chromosome Mapping↗

Polymerase chain reaction-based genetic typing of Japanese porcine reproductive and respiratory syndrome viruses.

Porcine reproductive and respiratory syndrome viruses (PRRSVs) are classified into 2 distinct genotypes: the North American type and the European type. The Japanese PRRSVs were genotyped by reverse transcriptase-polymerase chain reaction using the reported primer pairs that were either reactive to both types, specific to the North American type or specific to the European type. All the PRRSV genomes from 66 tissue homogenates or sera and 55 infectious viruses were of the North American type, whereas no European-type viral genome was detected. Two PCR primers specific to the North American type showed different detection efficiency. Half of the tissue samples and 15% of the infectious viruses were not detected with one primer pair, although all of them were detected with the other primer pair. Nucleotide sequencing analysis of the forward-and reverse primer-binding sites of the nonreactive viruses indicated that all these viruses had nucleotide mismatches within the 4 bases corresponding to the 3' end of the reverse primer. These mismatches appeared to be responsible for the nonreactivity of the former primers to these viruses.

Animals↗

Salmon roe-like amyloid deposition in a prolactinoma: a case report.

An unusual case of prolactin-producing adenoma with extensive amyloid deposition is reported to clarify its radiological, intraoperative, and light- and electron-microscopic findings. A 41-year-old female patient complained of amenorrhea persisting for 20 years. Magnetic resonance imaging (MRI) revealed a pituitary adenoma, which included low-intensity spots on T1- and T2-weighted images. Intraoperative examination found multiple small, yellowish, spherical masses resembling salmon roe within the adenoma. Light and electron microscopy revealed the presence of immunoreactive cells for prolactin intermingled with concentric lamellar bodies of radially arranged amyloid fibrils originating from the endoplasmic reticulum in prolactinoma cells. The extracellular lamellar amyloid deposits were apparently due to degradation of prolactin-producing cells, but the reason for the production and radially arranged accumulation of amyloid remains to be identified.

Adult↗

Familial moyamoya disease in a Greek family.

Moyamoya disease (M-M) is characterized by progressive obstruction of the supraclinoid portion of internal carotid arteries and the proximal middle, anterior and posterior cerebral arteries, associated with the formation of a characteristic net of collateral vessels in the basal ganglia region. Clinical manifestations in childhood include transient ischaemic attacks, seizures and multiple infarcts. Approximately 7% of M-M cases are familial. We report two affected Greek siblings with typical clinical and neuroradiological findings of M-M. Linkage analysis of the whole family was consistent with linkage to the region 3p24-26, as previously reported in other familial Japanese M-M cases.

Alleles↗

Immunohistochemical study of anaplastic meningioma with special reference to the phenotypic change of intermediate filament protein.

The phenotypic changes in the transformation of classic or atypical meningioma to anaplastic meningioma were investigated. Among nine patients with anaplastic meningioma, four men and five women ranging in age from 32 to 75 years, four cases were identified as anaplastic meningioma at the first operation (de novo type), while five cases were identified as classic or atypical meningioma at the first operation but at recurrence had transformed to anaplastic meningioma (secondary type). Immunohistochemical analysis was performed with the avidin-biotin complex method using monoclonal antibodies for glial fibrillary acidic protein, cytokeratin, alpha-internexin, neurofilament proteins (70 kd, 168 kd, and 200 kd), desmin, vimentin, CD34, Ki-67, epithelial membrane antigen, and S-100 protein. Immunohistochemical analysis showed positive immunoreactivity for cytokeratin, alpha-internexin, neurofilament proteins, vimentin, and glial fibrillary acidic protein during the course of progression. Expression of epithelial membrane antigen decreased with malignant progression. Marked expression of cytokeratin was observed in anaplastic meningioma. Ki-67 labeling index increased at every recurrence of both the de novo and secondary types. The major phenotypic changes in the transformation of meningioma from the classic to the anaplastic type are loss of meningioma architecture, decreased expression of epithelial membrane antigen, increased expression of vimentin, and metaplastic expression of alpha-internexin and neurofilament triplet proteins.

Adult↗

Evaluation of the delta subunit of bovine adaptor protein complex 3 as a receptor for bovine leukaemia virus.

A candidate gene of the bovine leukaemia virus (BLV) receptor (BLVR) was cloned previously and predicted to encode a transmembrane protein. Subsequent cloning of related genes from other organisms indicated that the candidate gene is related, but unique, to a gene family of the delta subunit of the adaptor protein (AP) complex 3, AP-3. Therefore, bovine cDNAs (boAP3delta) that are highly homologous to the candidate gene were cloned and sequenced. The nucleotide sequences suggested that the boAP3delta cDNA encodes the delta subunit of boAP3 without transmembrane domains. Part of the AP3delta cDNA isolated from the lymph node, spleen and MDBK cells, from which the BLVR candidate cDNA was derived, has almost the same nucleotide sequences as the boAP3delta cDNA. A boAP3delta protein tagged with green fluorescent protein was localized in the cytoplasm and incorporated into AP-3 in bovine cells. Unlike the previous report about the candidate gene, the boAP3delta gene introduced into murine NIH 3T3 cells did not increase the susceptibility of the cells to BLV infection. Many small insertions and deletions of nucleotides could generate the predicted transmembrane and cytoplasmic regions of the BLVR protein from the prototypic boAP3delta gene.

3T3 Cells↗

A plurihormonal TSH-producing pituitary tumor of monoclonal origin in a patient with hypothyroidism.

OBJECTIVE: A clinicopathological and clonal study of a pituitary tumor was made in a 26-year-old woman with chronic thyroiditis to differentiate TSH-producing adenoma from TSH hyperplasia. METHODS: Tumor specimens were subjected to histopathological study and clonal analysis (HUMARA). RESULTS: Immunohistochemical examination disclosed TSH-beta, PRL, GH, ACTH, FSH-beta, LH-beta, and alpha-subunit production in the adenoma cells. These heterogeneous phenotypes are characteristic of both thyrotroph hyperplasia and plurihormonal TSH-producing adenoma. However, the HUMARA method demonstrated monoclonality of the tumor cells. CONCLUSION: Monoclonality of the tumor cells proved that the pituitary tumor was plurihormonal TSH-producing adenoma, not TSH hyperplasia.

Adenoma↗

Demonstration of monoclonality in coexisting GH-producing adenoma and neuronal tissue.

BACKGROUND: Pituitary adenoma and neuronal components may coexist in the sellar region, but discussion of the histogenesis of the neuronal component has been mainly based on the morphological similarity with the adenomatous component using immunohistochemical and ultrastructural methods. Neuronal differentiation within pituitary adenoma may be a metaplastic process, but no clear supporting evidence has been obtained. To investigate the monoclonality or polyclonality of the mixed lesion by the X-chromosome inactivation method. CASE REPORT: Tumor specimens from a 55-year-old acromegalic woman were subjected to histopathological study and clonal analysis. Histological examination found varying proportions of adenoma cells and neuronal component in the specimens. Light and electron microscopy revealed cells with transitional morphology between adenoma cells and neurons. However, the X-chromosome inactivation method demonstrated monoclonality of both adenoma and neuron-like cells. CONCLUSIONS: Clonal analysis of the mixed lesion demonstrated that all tumor cells originated from a single cell.

Adenoma↗