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ABSTRACT: We evaluated associations between cerebral blood flow (CBF) and histopathological features in atherosclerotic lesions of the internal carotid artery. Cerebrovascular reactivity (CVR) and CBF were measured in 72 patients with unilateral carotid artery stenosis who underwent Xe-CT before carotid endarterectomy. Collateral blood flow was estimated as stump pressure. Proportions of fibrous tissue, intraplaque hemorrhage (IPH), and calcification were pathologically compared with the entire plaque body. The Spearman's rank test and stepwise multiple linear regression analysis revealed that the IPH rate significantly and negatively correlated with CBF, whereas the calcification rate positively correlated with CVR. One-way analysis of variance showed that IPH and the absence of calcification might confer a risk for CBF and CVR reduction. Thus, not only the stenosis rate but also the degree of IPH and calcification in carotid arterial plaque are notable risk factors for ischemic stroke.
Neurosurgical Review 12/2012; · 2.04 Impact Factor
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ABSTRACT: OBJECTIVES:: Our goal was to localize lesions in poststroke depression patients using magnetic resonance imaging, based on the statistical parametric maps image analysis technique that can be used to combine image data from multiple participants and correlate these images with other data sets. METHODS:: Magnetic resonance imaging acquisitions were obtained from 149 poststroke patients, who were assessed for affective and apathetic symptoms using the Hospital Anxiety and Depression Scale and the Apathy Scale, respectively. We created a statistical parametric map that displayed an association between lesion location and affective and apathetic symptoms. RESULTS:: Among the patients with higher depressive scores, the lesion overlap centered on the brainstem, left basal ganglia, and left frontal cortex. Among the patients with higher apathy scores, the lesion overlap centered on the brainstem and bilateral striatum. The overlap lesion for both affective and apathetic depression centered mainly on the brainstem; however, the two types of depression often did not overlap. CONCLUSIONS:: Two core symptoms that can occur after stroke, affective and apathetic symptoms, appear to be associated with different monoaminergic neuroanatomic pathways (serotonergic and dopaminergic).
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 10/2012; · 3.35 Impact Factor
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ABSTRACT: Growth hormone (GH) is essential for quality of life in both children and adults, but it is also believed to enhance the growth of various neoplasms. However, the role of GH in the brain, particularly in brain tumors, has yet to be established. To clarify these problems from the perspective of receptor expression, we examined GH receptor (GHR) expression in brain tumors using immunohistochemistry and the correlation between GHR expression and clinical features. Surgical specimens obtained from patients with brain tumors (106 pituitary adenomas, 12 craniopharyngiomas, 13 germ cell tumors, 6 medulloblastomas, and 12 malignant gliomas) were examined immunohistochemically for GHR expression. The GHR positive rate was lower in malignant tumors than in benign tumors (59% in pituitary adenomas, 73% in craniopharyngiomas, 23% in germ cell tumors, and 0% in medulloblastomas and gliomas). GHR staining in pituitary adenomas was weaker than that in normal pituitary gland. Among the GH-producing pituitary adenomas, there was no difference in size between GHR-positive and -negative tumors. However, among the non-GH-producing adenomas, GHR-positive tumors were significantly smaller. Thus, immunohistochemical GHR expression may have, at least in part, a negative impact on tumor growth potential in brain tumors.
Hiroshima journal of medical sciences 03/2012; 61(1):1-6.
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Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 01/2012; 114(3):283-8.
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ABSTRACT: A 59-year-old woman presented with a rare supra-diaphragmatic pituitary adenoma manifesting as a mass lesion. Her baseline data and the response of anterior pituitary hormones to the provocation test were within the normal range. Magnetic resonance imaging showed a homogeneously enhanced tumor located on the diaphragma sellae. The tumor was totally removed by the endonasal trans-tuberculum sellae approach under combined microscopic and endoscopic observation. Her postoperative course was uneventful and the histological diagnosis was pituitary adenoma located in the suprasellar region. The trans-tuberculum sellae approach is a less invasive method to remove pituitary adenoma located in the suprasellar region.
Neurologia medico-chirurgica 01/2012; 52(2):91-5. · 0.61 Impact Factor
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ABSTRACT: Tumor-induced secondary hyperprolactinemia in patients with non-prolactin (PRL)-secreting pituitary tumors has traditionally been ascribed to pituitary stalk damage. We conducted a retrospective analysis of secondary hyperprolactinemia in 106 patients who underwent surgery for non-PRL-secreting pituitary adenoma. The incidence of hyperprolactinemia was evaluated, and pituitary-stalk damage was assessed radiographically using MRI (size of tumor and extension type) and endocrinologically by monitoring hormonal function using a provocation test. The effect of a tumor-derived intrasellar factor, leukemia inhibitory factor (LIF), on hyperprolactinemia was also investigated. Hyperprolactinemia was observed in 31 of the 106 (29.2%) patients. It was not correlated with either physical stalk compression or endocrinological dysfunction. However, LIF expression was negatively correlated with the incidence of secondary hyperprolactinemia (p<0.01). Although secondary hyperprolactinemia might be caused by pituitary stalk damage, it is possible that LIF masks the effect.
Journal of Clinical Neuroscience 12/2011; 18(12):1651-5. · 1.25 Impact Factor
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ABSTRACT: This study is a retrospective analysis of hyponatremia after transsphenoidal surgery in patients with pituitary adenoma. We evaluated (i) the incidence of post-operative hyponatremia (serum Na levels ≤ 135 mEq/L) and the emergence of hyponatremic symptoms, and assessed (ii) the risk factors under a uniform protocol of i.v. infusion with steroid and electrolyte fluid. We examined 88 consecutive operated patients (female: 60; male: 28) with pituitary adenoma. Apart from reconfirming the effects of the purported risk factors, we focused on the degree of serum Na decline on post-operative hyponatremia. Although remained stable during early post-operative period (4 days after surgery), the serum Na levels subsequently decreased after post-operative day 4 in 81 of 88 cases (92.0%). Of 88 patients, 27 (30.7%) and 9 (10.2%) cases suffered from hyponatremia, and developed hyponatremic symptoms. Interestingly, the degree of serum Na levels decline (from pre-operative levels) indicated a useful independent risk factor for monitoring hyponatremic symptoms (p = 0.006) and the degree of decline tended to be greater in elder patients (> 60 years) (p = 0.0346). Serum Na levels should be monitored from, at least, post-operative day 7 to detect early development of hyponatremia. Special attention and recovery effort should be given to elder patients with marked serum Na level decline after surgery.
Endocrine Journal 04/2011; 58(5):373-9. · 2.03 Impact Factor
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ABSTRACT: Depression and apathy are often observed after stroke and are often confused with one another. In the present review, we argue that the current concept of 'post-stroke depression' (PSD) in fact consists of two core symptoms or syndromes: (i) affective (depressive) PSD; and (ii) apathetic PSD. We argue that these two core symptoms are each associated with a different underlying neuroanatomical mechanism, a pattern that influences functional recovery. Post-stroke disabilities can provoke several distinct emotional responses, some of which are associated with severe depression. We examined one of these emotional responses previously, namely 'insistence on recovery', which was believed to be a negative indicator of functional improvement in disabled stroke patients. However, an appropriate level of insistence on recovery may, in fact, be associated with reduced depression and apathy, resulting in enhanced recovery from stroke-related disabilities. Improvements in physical disabilities (trunk stability or activities of daily living, such as walking) also reduce depression and apathy. Therefore, the experience of PSD/apathy may be intertwined with various initial emotional responses and improvements in physical functioning. Effective treatment of PSD/apathy requires a multidisciplinary approach, such that neuroanatomical/neurobiological, emotional, and physical (rehabilitation) domains are all addressed.
Psychogeriatrics 03/2011; 11(1):68-76. · 1.21 Impact Factor
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ABSTRACT: Mobile plaque is associated with increased risk of ischemic stroke, but definitions have remained unclear. We have previously reported that carotid ultrasonography can detect the mobile component of the carotid plaque surface, which rises and falls in a manner inconsistent with arterial pulsatile wall motion (Jellyfish sign). However, clinical and pathological features of Jellyfish sign remain unclear. The subjects comprised of 165 patients with carotid plaque and degree of area stenosis ≥50% on ultrasonography. Using magnetic resonance imaging, we quantified intraplaque hemorrhage (IPH) and defined ischemic stroke in each patient. Fifteen surgical specimens were obtained by carotid endarterectomy, and pathological features (area of fibrous cap and intraplaque atheromatous lesion) were compared with ultrasonographic plaque surface movement rate. Carotid plaques with IPH were seen in 78 cases, with Jellyfish sign in 31 cases. Jellyfish sign was not detected in patients without IPH. In these 15 patients, the fibrous cap covered the atheromatous lesion, and cap thickness correlated negatively with Jellyfish-positive plaque surface movement rate. Kaplan-Meier and Cox multiple regression analysis demonstrated that the most important predictor of ischemic stroke during follow-up is Jellyfish sign, not IPH. Stroke events in patients with Jellyfish sign repeated within a short interval after diagnosis. Jellyfish sign on ultrasonography is a sign of high-risk plaque vulnerability, suggesting rupture of the fibrous cap associated with the release of thrombogenic factors into the arterial lumen, and resulting in repeated ischemic stroke during a short interval after diagnosis.
Neurosurgical Review 10/2010; 33(4):419-30. · 2.04 Impact Factor
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ABSTRACT: The function of the cyclin-dependent kinase (cdk) inhibitor p27 is regulated by translocation between the nucleus (activate) and the cytosol (inactivate). No previous reports have examined the subcellular localization of p27 in glioma which was evaluated here regarding the prognosis in high-grade astrocytomas.
The pattern of subcellular localization of p27 expression was examined immunohistochemically in 49 patients with high-grade astrocytoma who were over 20 years of age. The relationship between p27 localization and the prognosis was statistically examined.
Kaplan-Meier survival analysis showed that cytoplasmic p27 expression was statistically associated with a worse prognosis (p = 0.0203), while nuclear p27 expression showed some tendency towards a better prognosis (p = 0.1180). Cox multiple regression analysis showed the combination of high nuclear and low cytoplasmic p27 expression associated with a significantly better prognosis in high-grade astrocytoma.
A combination of low cytoplasmic and high nuclear expression of p27 predicts a better prognosis in high-grade astrocytomas and thus the subcellular localization of p27 expression is useful for predicting the prognosis for these patients.
Anticancer research 03/2009; 29(2):597-603. · 1.73 Impact Factor
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ABSTRACT: The present study used two-step analyses to examine the effect of acceptance of disability or 'insistence on recovery' in Japanese stroke patients: first on their functional improvement and second, on their psychological symptoms.
Disability was assessed using functional independence measurements (FIM), examining the stage of acceptance of disability by observation using Fink's theory (from shock to defensive retreat, acknowledgement, and acceptance/change stage), and estimation of insistence on recovery (on a scale of 1-4) by observation. The differences over time and the effects on the improvement in their FIM were then assessed. Depression was measured using the Zung Self-rating Depression Scale (SDS); apathy was measured using the Apathy Scale (AS), and the correlation with the acceptance stage or insistence on recovery was analyzed.
The acceptance stage and functional improvement progressed significantly, but insistence on recovery did not change significantly during hospitalization. Multiple regression indicated that the insistence on recovery score (but not the acceptance stage) was a good predictor of the degree of improvement in FIM (FIM gain per week) in the elderly group. Post-hoc testing showed that the SDS or AS score decreased from the first stage to the fourth stage (but increased at the third stage) of acceptance; whereas for insistence on recovery score, the SDS and AS scores decreased as insistence on recovery score changed from 1 to 3, and then increased as insistence on recovery score changed from 3 to 4.
The appropriate level of insistence on recovery reduced depression and apathy, resulting in enhanced improvement of disability after a stroke in elderly stroke patients.
Psychiatry and Clinical Neurosciences 09/2008; 62(4):386-95. · 2.13 Impact Factor
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ABSTRACT: While depression and apathy are common after stroke, past studies have done little to examine the influence of these two symptoms on functional outcome respectively. This study was designed to examine the effect of depression or apathy on functional recovery after stroke in 237 Japanese stroke patients.
We assessed the psychological status using self-rating scales [the Zung Self-Rating Depression Scale (SDS) for depression and the Apathy Scale (AS) for apathy] and an observer-rating scale [the Neuropsychiatric Inventory (NPI)]. We assessed physical disability using the Functional Independence Measurement (FIM). Post-hoc test and multiple regression analysis were used to determine the independent effects of post-stroke depression and apathy on functional outcome.
Depression was observed in 75 (31.6%) using SDS and 88 (40.2%) using NPI, and apathy in 95 (40.1%) using AS and 42 (19.2%) using NPI, respectively. Post-hoc test and multiple regression analysis indicated that the cognitive variable (Mini-Mental State Examination: MMSE score) and AS score, but not SDS score, correlated negatively with improvement in FIM.
Apathy might be more frequently associated with functional abilities and likely interact with the recovery process as compared with depression after stroke.
International Journal of Geriatric Psychiatry 11/2007; 22(10):1046-51. · 2.42 Impact Factor
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ABSTRACT: The aim of the present study was to assess the relationship between sitting balance at an early stage and activities of daily living (ADL) function in 452 stroke patients. The effect of sitting balance on the two core elements of depression (apathy and depressive mood) was also examined. The ability to maintain a sitting position for 10 min (10-min sitting balance) was assessed, along with ADL using the Functional Independence Measurement, and psychological status using the Zung Self-rating Depression Scale (depressive mood), Apathy Scale (apathy) and Neuropsychiatric Inventory. Proportional-hazards analysis was used to determine the independent effect of post-stroke depression on functional outcome. Comparisons between sitting balance and psychological status were performed using logistic multiple regression analysis. Cox multiple regression analysis showed that significant differences were obtained for the sitting balance (P < 0.0002) and Mini-Mental State Examination scores (P < 0.02) in all six ADL subscales, and for age in four of the six ADL subscales (Dressing-Upper Body and Dressing-Lower Body, Toileting, Walking). Kaplan-Meier survival curves for reaching independence in ADL subscales showed highly significantly differences in achievement rate and time to reach goal for each subgroup on 10-min sitting balance (with or without assistance) and on age (young, <65; elderly, >/=65 years). Ten-minute sitting balance correlated with depressive mood and apathy. A rapid and simple screening method, 10-min sitting balance was related to scores for two core depressive symptoms, lowered mood and apathy, and was predictive of post-stroke ADL outcomes in the rehabilitation unit along with age.
Psychiatry and Clinical Neurosciences 10/2007; 61(5):543-51. · 2.13 Impact Factor
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ABSTRACT: This study was designed to examine the correlation between damage to the basal ganglia or frontal lobe and depression status (both affective and apathetic dimensions) in 243 stroke patients. We assessed the affective dimension in post-stroke depression (PSD) using the Zung Self-rating Depression Scale (SDS) and the apathetic dimension in PSD using the apathy scale (AS). We classified basal ganglia or frontal lobe damage into four groups: no damage, damage to the left side only, damage to the right side only, and damage to both sides. Affective and/or apathetic PSD was found in 126 patients (51.9%). The severity of affective depression (SDS score) was associated with left frontal lobe (but not basal ganglia) damage, and that of apathetic depression (AS score) was related to damage to the bilateral basal ganglia (but not to the frontal lobe). The anatomical correlates of PSD differ depending on the PSD dimension (affective or apathetic) and may explain interstudy differences regarding the association between lesion location and type of PSD.
European Archives of Psychiatry and Clinical Neuroscience 05/2007; 257(3):149-52. · 3.49 Impact Factor
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ABSTRACT: Subcellularly localized (nuclear and/or cytoplasmic) survivin has various functions, and correlates with prognosis of malignant tumors. However, there have been no reports about the significance of subcellularly localized survivin in high-grade astrocytomas. The aim of the present study was to examine the relationship between prognosis and subcellular localization of survivin in high-grade astrocytoma.
We immunohistochemically examined the pattern of subcellular localization of survivin expression (nuclear, cytoplasmic, or both) in 51 patients with high-grade astrocytoma (19 anaplastic astrocytomas; 32 glioblastomas). We statistically examined the relationship between survivin localization and prognosis, using multivariate analysis including other clinicopathological factors (age, sex, WHO grade, extent of resection, MIB-1 labeling index, and expression of p53 and epidermal growth factor receptor).
All specimens stained positive for survivin: localized in nucleus only (nuclear-positive group), 10 cases (20%); localized in cytoplasm only (cytoplasmic-positive group), 23 cases (45%); simultaneous expression in nucleus and cytoplasm (nuclear-cytoplasmic group), 19 cases (35%). There was no significant difference in prognosis between the nuclear-positive group and cytoplasmic-positive group (P=0.796). However, the nuclear-cytoplasmic group had significantly shorter overall survival than the nuclear-positive group and the cytoplasmic-positive group (P<0.0001).
We found that simultaneous expression of survivin in both the nucleus and cytoplasm is an important prognostic factor for high-grade astrocytoma. The present findings indicate that subcellular localization of survivin expression is a reliable prognostic factor for patients with this tumor.
Journal of Neuro-Oncology 04/2007; 82(2):193-8. · 3.21 Impact Factor
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ABSTRACT: Geminin is a nuclear protein that belongs to the DNA replication inhibitor group. It inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance protein onto chromatin, as is required for DNA replication. For this study, the authors investigated geminin expression in high-grade astrocytic tumors, including anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), with a view to predicting clinical outcomes on this basis in patients with these malignant brain tumors.
Immunohistochemistry was used to detect geminin expression in 51 patients with high-grade astrocytic tumors (19 AA and 32 GBM). Samples were categorized by taking the median value as the cut-off point for constructing Kaplan-Meier curves. The relation of geminin expression to clinical outcome in these malignant brain tumors was analyzed by using the Kaplan-Meier method and a Cox proportional hazards regression model.
Geminin was expressed in all high-grade astrocytomas (mean geminin labeling index [LI], 24.90%). Kaplan-Meier curves showed that the group with higher geminin LI (>or=22.50%) had a better prognosis than the group with lower LI (<22.50%; P = .0296). Similarly, the Cox regression analysis showed that geminin expression has a significant correlation with survival in patients with high-grade astrocytoma (P = .0278), especially in an early stage.
Although it is an inhibitor of DNA proliferation and, thus, is a cell cycle inhibitor, geminin expression was found in all malignant astrocytic tumors. The geminin LI was a significant predictive factor of outcomes in patients with high-grade astrocytoma, with higher expression indicating a good prognosis.
Cancer 03/2007; 109(5):949-56. · 4.77 Impact Factor
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ABSTRACT: To investigate the mechanism of staurosporine-induced glioma cell death and cell cycle arrest using adenovirus-mediated gene transfection, as well as the function of retinoblastoma (Rb) and genetic instability induced by staurosporine.
Cell cycle regulation, cell death and nuclear abnormalities induced by staurosporine were examined using an adenovirus vector expressing Rb, p16 or p21 genes in human glioma cell lines.
The Rb-defective SF-539 cell line was resistant to staurosporine compared with cell lines expressing intact Rb. SF-539 glioma cells exposed to staurosporine became multinucleated and then died. Multinucleation was prevented in SF-539 cells transfected with the Rb gene, thus decreasing the death rate of these cells.
These results imply that enforced Rb expression protects cells from genomic instability induced by staurosporine regardless of its upstream molecular effects.
Pathobiology 02/2007; 74(1):22-31. · 1.18 Impact Factor
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ABSTRACT: The negative consequences of the cytoplasmic localization of p16 in patients with high-grade astrocytomas, on their prognosis, was investigated.
p16 Expression was examined in 20 anaplastic astrocytoma and 42 glioblastoma patients by immunohistochemical analysis, and the relationship between both cytoplasmic and nuclear p16 expression and prognosis analyzed.
The cytoplasmic expression of p16 statistically correlated with poor prognosis. On the other hand, no correlation was observed between p16 nuclear expression and patient survival.
The cytoplasmic immunoreactivity of p16 appears to be an unfavorable prognostic indicator in high-grade astrocytoma patients. The localization of p16 expression should be determined when evaluating the prognosis of these patients.
Journal of Neuro-Oncology 06/2006; 77(3):273-7. · 3.21 Impact Factor
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Shinya Matsuura,
Yoshiyuki Matsumoto,
Ken-ichi Morishima,
Hideki Izumi,
Hiroshi Matsumoto,
Emi Ito,
Keisuke Tsutsui,
Junya Kobayashi,
Hiroshi Tauchi,
Yoshinori Kajiwara, Seiji Hama,
Kaoru Kurisu,
Hidetoshi Tahara,
Mitsuo Oshimura,
Kenshi Komatsu,
Tatsuro Ikeuchi,
Tadashi Kajii
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ABSTRACT: Cancer-prone syndrome of premature chromatid separation (PCS syndrome) with mosaic variegated aneuploidy (MVA) is a rare autosomal recessive disorder characterized by growth retardation, microcephaly, childhood cancer, premature chromatid separation of all chromosomes, and mosaicism for various trisomies and monosomies. Biallelic BUB1B mutations were recently reported in five of eight families with MVA syndrome (probably identical to the PCS syndrome). We here describe molecular analysis of BUB1B (encoding BubR1) in seven Japanese families with the PCS syndrome. Monoallelic BUB1B mutations were found in all seven families studied: a single-base deletion (1833delT) in four families; and a splice site mutation, a nonsense mutation, and a missense mutation in one family each. Transcripts derived from the patients with the 1833delT mutation and the splice site mutation were significantly reduced, probably due to nonsense-mediated mRNA decay. No mutation was found in the second alleles in the seven families studied, but RT-PCR of BUB1B and Western blot analysis of BubR1 indicated a modest decrease of their transcripts. BubR1 in the cells from two patients showed both reduced protein expression and diminished kinetochore localization. Their expression level of p55cdc, a specific activator of anaphase-promoting complex, was normal but its kinetochore association was abolished. Microcell-mediated transfer of chromosome 15 (containing BUB1B) into the cells restored normal BubR1 levels, kinetochore localization of p55cdc, and the normal responses to colcemid treatment. These findings indicate the involvement of BubR1 in p55cdc-mediated mitotic checkpoint signaling, and suggest that >50% decrease in expression (or activity) of BubR1 is involved in the PCS syndrome.
American Journal of Medical Genetics Part A 03/2006; 140(4):358-67. · 2.39 Impact Factor
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Fumiyuki Yamasaki,
Junko Takaba,
Megu Ohtaki,
Nobukazu Abe,
Yoshinori Kajiwara,
Taiichi Saito,
Hiroyuki Yoshioka, Seiji Hama,
Tomohide Akimitsu,
Kazuhiko Sugiyama,
Kazunori Arita,
Kaoru Kurisu
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ABSTRACT: The signals of lactate and lipids partially overlap in single-voxel proton MR spectroscopy (1HMRS), sometimes making them difficult to differentiate in clinical settings. Our aim in this study was to identify lactate and lipids by varying the echo time (TE). We expect that the accurate detection of lactate and lipids will have high diagnostic value in the diagnosis of brain tumors. Following our protocol, we obtained meaningful 1HMRS spectra from 213 patients, including 163 patients with brain tumors, between August 1999 and February 2004. 1HMRS was performed with a TE of 144 ms followed by a TE of 30 ms and/or a TE of 288 ms, if necessary. For the 213 patients, lactate level was "negative" in 47 patients, "positive" in 131 patients, and "strongly positive" in 35 patients. The lipid level was "negative" in 90 patients, "positive" in 56 patients, and "strongly positive" in 67 patients. Based on logistic discriminant analyses of neuro-epithelial tumor WHO grade and lactate and lipid levels, lactate and lipid levels were significant between WHO grades 2 and 3 (P=0.0239) and between grades 3 and 4 (P=0.0347). Lipids are a more significant factor for the discrimination between WHO grades 2 and 3 (P=0.0073) and between grades 3 and 4 (P=0.0048). With our method of varying the TE, it is possible accurately and efficiently to detect lactate and lipids in the brain. We found a significant correlation between lactate and lipid expression and WHO grade of neuro-epithelial tumors.
Neurosurgical Review 11/2005; 28(4):267-77. · 2.04 Impact Factor
