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Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 91 records · Page 5Linked to original sources
PubMed2000

High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma.

Survivin (SVV) is a family member of inhibitor of apoptosis proteins (IAPs) and its expression is cell cycle regulated. The gene is mapped to chromosome 17q25, the region of which is frequently gained in advanced stages of neuroblastoma (NBL). However, the role of SVV in NBL is poorly understood. Here we studied the clinical and biological role of SVV in NBL. A 1.9 kb SVV transcript was expressed in all of 9 NBL cell lines at higher levels than those in adult cancer cell lines. In 34 primary NBLs, high levels of SVV expression was significantly associated with age greater than 12 months (two sample t-test: P= 0.0003), advanced stages (P = 0.0136), sporadic tumors (P= 0.0027) and low levels of TrkA expression (P = 0.0030). In NBL cell lines, SVV mRNA expression was dramatically down-regulated in CHP134 and IMR32 cells undergoing apoptosis after treatment with all-trans retinoic acid (RA) or serum deprivation. It was only moderately decreased in cells (SH-SY5Y and CHP901) undergoing RA-induced differentiation. On the other hand, in proliferating NBL cells or RA-treated SK-N-AS line which is refractory to RA, the SVV mRNA remained at steady state levels or rather up-regulated. Furthermore, transfection of SVV into CHP134 cells induced remarkable inhibition of the RA-induced apoptosis. Collectively, our results suggest that high expression of SVV is a strong prognostic indicator for the advanced stage neuroblastomas, and that it could be one of the candidate genes for the 17q gain.

Apoptosis↗
PubMed2000

Role of survivin, whose gene is mapped to 17q25, in human neuroblastoma and identification of a novel dominant-negative isoform, survivin-beta/2B.

PROCEDURE: We investigated the expression of survivin (SVV) and its isoform (SVV-beta/2B) during different biological properties in neuroblastoma (NBL). RESULTS: High levels of SVV mRNA expression were significantly associated with advanced stages of NBL, diagnosis at over 1 year of age, low levels of TrkA expression, and sporadic tumors. Expression of a novel isoform, SVV-beta/2B, which had an insertion of 23 amino acids within the unique BIR domain was predominant in some favorable NBLs, while it was low and ubiquitous in most normal and malignant tissues. The SVV expression wasdown-regulated during apoptosis induced by retinoic acid (RA) in CHP134 NBL cells, which was inhibited by forced expression of SVV. In contrast, SVV-beta was constantly expressed during apoptosis. Like SVV,SVV-beta was also highly expressed during G(2)/M in a cell cycle-dependent manner, and was associated with but competed against SVV for binding with polymerized tubulin. CONCLUSION: These data suggest that expression of SVV is a poor prognostic indicator in human NBL, and it promotes growth and survival by regulating the levels of both isoforms.

Chromosome Mapping↗
PubMed2000

Vascular abnormalities in surgical specimens obtained from the resected focus of intractable epilepsy.

The histopathological features, particularly hypervascularity, were examined in specimens resected from 21 patients, 15 with intractable epilepsy accompanying cortical dysplasia or dysembryoplastic neuroepithelial tumor (DNT), and 6 with benign brain tumors, such as ganglioglioma and low-grade glioma. Hypervascularity was found in resected specimens from 15 of the 21 patients (71.4%) and in 10 of the 12 patients (83.3%) who had double pathology. Counting of numbers of vessels by CD31 immunohistochemistry revealed that hypervascularity was prominent, especially in cases of vascular malformation or cortical dysplasia. However, almost all cases were negative for vascular endothelial growth factor (VEGF) staining, except for some cases of benign brain tumors. Moreover, all cases showed low or no proliferative potential in MIB-1 immunohistochemistry. These results suggest that the etiology of hypervascularity in the dysplastic lesions is one of a variety of cerebral malformations, as is the case with abnormal maturation and differentiation in neuroglial elements.

Adolescent↗
PubMed2000

Correlation of EEG, neuroimaging and histopathology in an epilepsy patient with diffuse cortical dysplasia.

The correlation between scalp EEG, intraoperative electrocorticogram, neuroimaging and histopathology was examined in an epileptic child with diffuse cortical dysplasia. The 6-year-old girl with moderate mental retardation had suffered from intractable complex partial and generalized epilepsies since the age of 2 years. MR images demonstrated unilateral large macrogyria/polymicrogyria and schizencephaly in the right occipital lobe. The epileptic focus was detected on the macrogyria by EEG and single photon emission tomography. However, the intraoperative electrocorticogram showed frequent spikes from the polymicrogyria and no paroxysmal activity in the macrogyria. The polymicrogyria and the macrogyric lesion were resected, using an image-guided system. The histological findings revealed that the macrogyria was covered with and separated by glial bundles. It has been reported that epileptogenicity is produced from abnormal neurons and their arrangement in cortical dysplasia; in this case, however, the major dysplastic lesion had no epileptogenicity; rather the focus might be in the polymicrogyria around the lesion.

Cerebral Cortex↗
PubMed2000

Cerebral complications associated with selective perfusion of the arch vessels.

BACKGROUND: Few studies have determined risk factors for postoperative cerebral complications associated with surgery of the aortic arch using selective cerebral perfusion. METHODS: Between November 1992 and December 1998, 113 patients underwent aortic arch repair combined with selective cerebral perfusion. For each patient, three arch vessels were perfused using a single roller pump at a rectal temperature of 23 degrees C. RESULTS: Among the 108 patients who underwent postoperative neurologic assessment, 25 patients (23%) suffered from cerebral complications. Five patients (5%) suffered from transient neurologic disturbance and 17 patients (16%) suffered from stroke, and 7 patients (7%) of the preceding 17 patients had residual neurologic disturbance upon discharge. Three patients (3%) with either preoperative coma (n = 1) or post bypass cardiac arrest (n = 2) sustained severe global cerebral dysfunction. The occurrence of cerebral complications was not related to cerebral perfusion time. Independent risk factors for cerebral complications included a history of cerebrovascular disease, perioperative shock, distal anastomosis below the left pulmonary artery, malperfusion of extremities, and older age (> 60 years). CONCLUSIONS: Although high-level brain function was well preserved in most patients, the incidence of stroke when using current selective cerebral perfusion techniques is still high.

Adult↗
PubMed2000

Importance of hypercoagulability over hyperglycemia for vascular complication in type 2 diabetes.

To critically evaluate the relative importance of coagulation abnormalities over other clinical variables for micro- and macrovascular diabetic complications, prothrombin fragment (F1+2), thrombin-antithrombin III complex (TAT), fibrin degradation product d-dimer, and alpha2 plasmin inhibitor complex were determined in 101 stable, relatively well controlled patients with Type 2 diabetes (the mean HbA1c, age and duration of diabetes, 7.1%, 61 and 7.5 years, respectively). First, incidence and severity of diabetic micro- and macroangiopathies were progressively increased with the severity of coagulation abnormalities. Next, correlation of the four values with the presence of micro- and macrovascular complications, respectively, was analyzed by the multiple logistic regression analysis, with the inclusion of other variables such as age, duration of diabetes, HbA1c, blood pressure, and urinary albumin excretion. With the presence of microangiopathies, F1+2 and systolic blood pressure were significantly related, with the relationship being very strong for the former (P=0.003) and weak for the latter (P=0.035). On the other hand, with the presence of macroangiopathies, F1+2 (P=0.003), TAT (P=0.002), duration of diabetes (P=0.015), and age (P=0.013) were related. Other clinical variables were not significantly related with the presence of complications. Coagulation and fibrinolytic abnormalities are stronger determinants of the presence of diabetic vascular complications than other clinical variables including the degree of glycemia, in stable, relatively well controlled patients with Type 2 diabetes.

Adult↗
PubMed2000

Enhanced sensitivity to alkylating agent in lymphocytes from patients with multiple endocrine neoplasia type 1.

Chromosome instability is known to be associated with certain autosomal recessive cancer-prone disorders such as Fanconi's anemia. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disorder characterized by development of tumors in two or more endocrine organs, and chromosome instability in patients with MEN 1 has been described. The clinical features of MEN 1 are, however, distinct from other DNA instability syndromes except predisposition to tumors. Therefore, we reevaluated chromosome instability in patients with familial MEN 1. An increase in the frequency of chromosome aberrations was observed in MEN 1 patients but not in control subjects when peripheral mononuclear cells were exposed to an alkylating agent, diepoxybutane (DEB). DEB reduced survival of mononuclear cells in a dose-dependent manner in both MEN 1 patients and control subjects, but this effect was more prominent in MEN I patients. There was no apparent correlation between certain MEN1 gene mutations and sensitivity to DEB. From these results, we conclude that hypersensitivity to alkylating agents exists in patients with MEN 1. Molecular mechanisms of this phenomenon and relationship to tumorigenesis in endocrine organs should be elucidated.

Antineoplastic Agents, Alkylating↗
PubMed2000

Antiepileptic effect of nefiracetam on kainic acid-induced limbic seizure in rats.

Nefiracetam is being studied as a novel cognition-enhancing agent; however, it has been suggested from studying its chemical structure that it has a potential anticonvulsive effect. We examined the antiepileptic effect of nefiracetam on kainic acid (KA)-induced seizures. KA was infused into the left basolateral amygdaloid nucleus and focal limbic seizures were induced in 43 male Wistar rats. During status epilepticus, 10, 50, 100 or 200 mg/kg of nefiracetam was intravenously injected. Nefiracetam inhibited KA-induced limbic seizures at doses over 100 mg/kg while it had a sedative effect on the animals. In (14C) deoxyglucose autoradiographic studies, the propagation of seizure-induced hypermetabolic areas was also suppressed dose-dependently. From the results, it was indicated that nefiracetam has an antiepileptic effect and that its application may suppress seizure propagation. Further study is required, whether this agent is available as a novel anticonvulsant.

Animals↗
PubMed2000

Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation of TGF-beta1 and MMPs.

Transforming growth factor beta1 (TGF-beta1) and matrix metalloproteinases (MMPs) produced by tumor cells play important roles in tumor invasion. PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response modifier for cancer patients. In this study, we focused on the effects of PSK on invasiveness, TGF-beta1 production, and MMPs expression in two human tumor cell lines, pancreatic cancer cell line (NOR-P1) and gastric cancer cell line (MK-1P3). PSK significantly decreased the invasiveness of both cell lines through Matrigel-coated filters but did not affect cell viability, proliferation, or adhesion. Decreased invasion was associated with the inhibition of TGF-beta1, MMP-2, and MMP-9 at both mRNA and protein levels as assessed by reverse transcriptase-polymerase chain reaction, gelatin zymography, and enzyme-linked immunosorbent assay. Antibody against TGF-beta1 neutralized the MMP activities of both cell lines. PSK also suppressed the expression of urokinase plasminogen activator (uPA) and uPA receptor but did not change plasminogen activator inhibitor-1 (PAI-1) expression. Western blot analysis showed that PSK reduced uPA protein expression but not PAI-1 expression in the both cell lines. These results indicate that PSK suppresses tumor cell invasiveness through down-regulation of several invasion-related factors including TGF-beta1, uPA, MMP-2, and MMP-9.

Adjuvants, Immunologic↗