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Biomedical subjects

J Kuratsu

Publications and source records attributed to J Kuratsu.

At least 19 recordsLinked to original sources

Serial changes in the regional cerebral blood flow of patients with hypertensive intracerebral hemorrhage -- long-term follow-up SPECT study.

We analyzed serial changes in the regional cerebral blood flow (rCBF) of 13 patients with intracerebral hemorrhage by single photon emission computed tomography (SPECT) during the acute- to chronic stage (2 hr to 55 weeks). The (99m)Tc-ethyl cysteinate dimmer ((99m)Tc-ECD) was used as the nuclear mediator. The SPECT timing within 48 hours after the onset was considered to be acute stage, from 48 hours to 4 weeks to be subacute stage, and after 4 weeks to be chronic stage. The region of interest was each hemisphere in the whole brain without ventricles at the thalamic level. For semi-quantitative analysis of rCBF, we used the Brain Uptake Ratio method. Of the 13 patients (mean age 65.5 years), 3 had thalamic-, 4 putaminal-, 5 subcortical-, and one a cerebellar hemorrhage; the hematoma volume varied from 4-50 ml (<20 ml, n=9; 20-30 ml, n=1; >30 ml, n=3; mean 17 ml). The rCBF changes during the long-term follow-up were classified as increase-, decrease-, and unchanged type. Of 5 patients with increased rCBF, 4 made a good recovery and one was severely disabled; of 5 patients with decreased rCBF, 1 made a good recovery, 3 were moderately-, and one was severely disabled. All 3 patients with unchanged rCBF were moderately disabled. Our findings suggest that among patients with hypertensive intracerebral hemorrhage, those with increased rCBF over time may have a favorable outcome. We further need more cases with intracerebral hemorrhage to clarify this trend.

Aged↗

Clinico-pathological study of meningiomas with haemorrhagic onset.

BACKGROUND: Haemorrhage from meningiomas is rare and the underlying pathophysiological mechanisms remain to be determined. We sought to identify these mechanisms by studying clinical and histological records of 6 meningioma patients treated at our institution. PATIENTS AND METHODS: We retrospectively studied 6 patients with meningiomas whose acute onset was due to haemorrhage. We evaluated clinical features and imaging studies. The vascularity and proliferative nature of these tumours were examined immunohistochemically and tissue factor (TF) immunoreactivity was assessed. For comparison we evaluated 25 non-haemorrhagic meningiomas. FINDINGS: At onset, the haemorrhages mimicked stroke in all 6 patients. On imaging studies, 3 of the haemorrhages were intra- and extratumoural, the other 3 were extratumoural only. Hyperintensity on T2-weighted MRI was a characteristic of these meningiomas. Histologically, they were of 3 subtypes, meningothelial (n=3), transitional (n=2), and anaplastic (n=1). The MIB-1 labelling index of the 5 WHO Grade I meningiomas was 5.8+/-2.2. The mean number of CD31-positive blood vessels did not differ in haemorrhagic and non-haemorrhagic meningiomas. The TF-positivity rate of haemorrhagic meningiomas was higher than of non-haemorrhagic meningiomas. INTERPRETATION: The proliferative nature of the meningiomas and TF expression in tumour cells may have contributed to the eventual haemorrhage of the meningiomas in our series.

Aged↗

Hippocampal transection attenuates kainic acid-induced amygdalar seizures in rats.

Since the dorsal and ventral hippocampus in the rat may act differently from one another in limbic seizures, we studied effects of orthogonal transection between the dorsal and ventral hippocampus upon kainic acid-induced amygdalar seizures. A total of 26 rats were divided into three groups. Ten rats underwent transection using a modified wire knife (transection group); 16 others were untransection group (n=10) and controls (n=6). All the rats then underwent stereotactic implantation of electrodes in the left amygdala (LA), left dorsal hippocampus (LdH), left ventral hippocampus (LvH), and the left sensorimotor cortex (LCx). A stainless steel cannula also was introduced into the LA. Rats except controls later received 1.0 microg of kainic acid (KA) via the cannula. Controls received phosphate buffer solution alone. In the untransection group, multiple spike discharges in the LA immediately propagated concurrently to the LvH and LdH. Propagation involved the LCx to become status epilepticus 1 to 2 h after KA injection. Seizures, characterized by mastication, salivation, facial twitching, forelimb clonus, and sometimes rearing and falling, lasted 1 to 2 days. Microscopic examination revealed severe neuronal cell damage in the LA, LvH, and LdH. In the transection group, multiple spike discharges initiated from the LA and were propagated to LvH, but LdH as well as LCx involvement was slight. Status epilepticus involved only the LA and LvH 1 to 2 h following KA injection. Seizures subsided within 24 h, showing no ictal manifestations except for aggressiveness. Overall, seizures were weak and transient compared with those in controls. Histologically, hippocampal neuronal damage was slight, but damage to amygdalar neurons was similar to that in untransection group. No electroclinical and histological changes were seen in controls. These results indicated that connections between the dorsal and ventral hippocampus are important for full development of KA-induced amygdalar seizures.

Amygdala↗

Trends in the incidence of primary intracranial tumors in Kumamoto, Japan.

BACKGROUND: The introduction of modern neuro-imaging techniques, as well as various environmental factors, have been changing the incidence and the proportions of the types of clinically diagnosed intracranial tumors. The aim of this study was to determine recent trends in the occurrence of primary intracranial tumors in the residents of Kumamoto Prefecture, Japan. METHODS: We surveyed 2129 patients who were diagnosed with primary intracranial tumors between 1989 and 1998, with histological diagnosis being obtained in 71% of the patients. RESULTS: Of the 2129 patients, 710 (33.3%) had meningiomas, 390 (18.3%) had pituitary adenomas, 315 (14.8%) had malignant gliomas, and 208 (9.8%) had schwannomas. The overall age-adjusted incidence rates were 10.97/100,000/year (males, 9.70; females, 11.86). One hundred and nine patients (5.1%) were younger than 15 years, and 480 patients (22.5%) were older than 70 years. The most common tumors in children were astrocytomas (37.6%), followed by germ-cell tumors (16.5%) and craniopharyngiomas (11.9%), medulloblastomas (11.0%), and ependymomas (4.6%). Meanwhile, the most common tumors in elderly residents were meningioma (51.7%), followed by malignant glioma (13.7%), pituitary adenoma (11.4%), schwannoma (7.7%), malignant lymphoma (4.6%), and astrocytoma (2.7%). The proportion of asymptomatic tumors increased, from 24.6% in 1989-1994 to 33.0% in 1995-1998; 169 (62.8%) were meningiomas, followed by pituitary adenomas (14.1%).

Adenoma↗

Dural congestion accompanying meningioma invasion into vessels: the dural tail sign.

Our purpose was to verify the histological appearance of the dural tail accompanying meningiomas on MRI. We studied seven patients such a dural tale. We examined the point of attachment of the tumour and the adjacent dura mater histologically. In all patients, rich vascularity and dilated vessels were observed in the dura mater at the point of attachment of the tumour; tumour cells invaded the dura mater and vessels, packing the latter. In the adjacent dura mater, showing as a dural tail on MRI, there was tumour-cell invasion in only one patient. Vascular congestion around the vessels compacted by the tumour cells in the dura mater and dilated vessels were seen in all patients. We therefore suggest that the mechanism of the dural tail sign is as follows. First, tumour cells invade vessels and pack them at the point of tumour attachment. Then, vessel congestion is induced in the adjacent dura mater, as a result of which it enhances markedly, giving rise to the dural tail sign.

Adult↗

Metastatic brain tumours from oesophageal carcinoma: neuro-imaging and clinicopathological characteristics in Japanese patients.

BACKGROUND: Since metastatic brain tumours from esophageal carcinoma are essentially rare, previous reports have not determined the common neuro-radiological findings and its clinical aspects. FINDINGS: We report the neuro-imaging and clinicopathological features of our 8 metastatic brain tumours from an esophageal site. Histologically, 6 of our 8 patients had squamous cell carcinoma and 2 had small cell carcinoma, a rare variant form. Both histological types mainly exhibited cystic lesions with a thin enhanced rim on magnetic resonance images (MRI, 4 of 6 squamous cell carcinomas and 1 of 2 small cell carcinomas). Combination therapy (irradiation and chemotherapy) after surgical treatment, the number of metastatic brain tumours, and the interval between their appearance and the diagnosis of the primary lesion could be prognostic factors in our series. INTERPRETATION: Among Japanese, the vast majority of primary esophageal cancers are squamous cell carcinomas. Therefore, MRI findings of a cystic tumour with a thin enhanced rim may alert one to the possibility of a metastatic brain tumour from the esophagus.

Aged↗

Suprasellar hemangioblastoma in a patient with von Hippel-Lindau disease confirmed by germline mutation study: case report and review of the literature.

BACKGROUND: Hemangioblastoma (HBL) in the suprasellar region is extremely rare. CASE DESCRIPTION: A suprasellar mass was found in a 33-year-old woman with retinal HBL and bilateral adrenal pheochromocytomas. The diagnosis of von Hippel-Lindau (VHL) disease was confirmed preoperatively not only by these clinical manifestations but also by germline mutation study. The existence of VHL disease indicated a diagnosis of HBL for the suprasellar mass. The results of our mutation study indicated that this patient had type II VHL disease, suggesting that careful follow-up is essential for the early detection of renal cell carcinoma, which is often associated with type II VHL disease. Here, we summarize the previously reported features of sellar and suprasellar HBLs. CONCLUSIONS: HBLs in this region may be one manifestation of VHL disease. Genetic testing of the VHL gene of our patient could provide useful information to determine appropriate medical care and management.

Adult↗

A device for stereotactic transection of fiber bundles in rats.

We have designed a device for stereotactic transection of fiber bundles in experiments using rats. Here, we present our assessment of its features relative to those of conventional methods. The instrument consists of a stainless steel cannula and a thin inner wire with a hook at one end and a hilt at the other. The hook can be extended or withdrawn freely by pushing or pulling the hilt. Lesions were evaluated in 12 male Wistar rats, after two targets, the anterior commissure (n=6) and the caudate-putamen (n=6), were transected. After the cannula was introduced into the target, the inner hook was extended in an anterior direction orthogonally to the transverse plane. Next, the entire device was pulled back along the insertion path to transect the neuronal fibers. Then the inner hook was withdrawn into the cannula and the entire device was removed. Seven days later, brains were removed for histologic processing. Microscopic examination demonstrated a slit like gap produced by transection at the target; the lesions were infiltrated by microglia and surrounded by gliosis. Adjacent regions were minimally damaged. The path of the cannula demonstrated only minimal gliosis. Unlike conventional methods, this device permits precise transection of deep fiber bundles with minimal damage to surrounding brain tissue.

Animals↗

Identification of the cis-acting region in the NF2 gene promoter as a potential target for mutation and methylation-dependent silencing in schwannoma.

BACKGROUND: Although mutational inactivation and allelic loss in the NF2 gene appear to be causal events in the majority of vestibular schwannomas, involvement of another potentially important mechanism, transcriptional inactivation, has not been investigated. RESULTS: We cloned and functionally characterized the 5'-flanking region of the human NF2 gene and identified the molecular mechanisms that regulate NF2 expression. Luciferase assay and site-directed mutagenesis demonstrated that a 70-base pair (bp) region (-591 to -522 bp from the translation start site) was essential for the basic expression of the NF2 gene. A gel mobility shift assay indicated recognition by nuclear protein of the unusually long ( approximately 66 bp) sequences in this region. Recognition was inhibited by either mutation of the binding core sequence or by methylation of three CpG sites. Point mutations at these CpG sites significantly decreased promoter activity, suggesting the importance of these sites. In 14 of 23 vestibular schwannomas, these three CpG sites were methylated in a site-specific manner and the methylation status was consistent with the expression of NF2 mRNA. CONCLUSIONS: Suppressed expression by aberrant methylation or mutation of the promoter elements could be an alternative mechanism for inactivation of the NF2 gene.

Animals↗

A case of non-functioning pituitary adenoma with Cushing's syndrome upon recurrence.

A 49-year-old woman presented with left visual disturbance. No signs of Cushing's disease were evident. Basal levels of serum cortisol and plasma adrenocorticotropic hormone (ACTH) were 16.8 microg/dL and 66.0 pg/mL, respectively. MRI demonstrated an irregularly shaped large pituitary tumor, and the patient then underwent transsphenoidal surgery. By light microscopy the tumor represented a chromophobic adenoma with a few of the adenoma cells showing immunoreactivity for ACTH. On the basis of clinical and light microscopic examinations, the diagnosis of silent corticotroph adenoma was made. Electron microscopy, however, demonstrated the honeycomb Golgi complex that has been reported as a typical finding of gonadotroph adenomas. MRI taken 7 months after the first operation revealed adenoma regrowth. Transcranial surgery was performed, and histology demonstrated a chromophobic pituitary adenoma with most cells immunopositive for ACTH. She was treated with gamma knife postoperatively. Three months later, MRI revealed remarkable shrinkage of the adenoma, but she developed typical signs and symptoms of Cushing's disease. Thus, the hormone immunostaining and biological activity of pituitary adenomas may change with time.

Adrenocorticotropic Hormone↗

Inhibitory effect of epigallocatechin-gallate on brain tumor cell lines in vitro.

We investigated the effect of epigallocatechin-gallate (EGCG), the main constituent of green tea polyphenols, on human glioblastoma cell lines U-373 MG and U-87 MG, rat glioma cell line C6, and rat nonfunctioning pituitary adenoma cell line MtT/E. Cell viability was determined by assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and the extent of apoptosis was studied by flow cytometric analysis. Apoptosis was also characterized by morphology using fluorescent microscopy. The role of insulin-like growth factor-I (IGF-I) was studied by assay with MTT, immunohistochemistry, and immunoradiometric assay. After 72-h exposure, a statistically significant loss of viability (P = < 0.0001) was observed at concentrations of 12.5, 25, 50, and 100 microg/ml in U-373 MG cells and U-87 MG cells. EGCG at concentrations of 50 microg/ml and higher significantly reduced the viability of C6 cells. EGCG inhibited viability of MtT/E cells only at a concentration of 100 microg/ml. Quantitative study by flow cytometry demonstrated that lower doses of EGCG (12.5, 25, 50 microg/ml) induced apoptosis in U-373 MG, U-87 MG, and C6 cells; however, only the highest dose (100 microg/ml) induced apoptosis in MtT/E cells. Compared with other cell lines, MtT/E cells showed stronger IGF-I immunoreactivity. Neutralization of IGF-I with an antihuman IGF-I antibody reduced viability of the cell lines. It can be concluded that EGCG has an inhibitory effect on malignant brain tumors, and IGF-I may be involved in the effects of EGCG.

Adenoma↗

Angiogenic effect of thymidine phosphorylase on macrophages in glioblastoma multiforme.

OBJECT: Thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF) are known angiogenic factors; however, there are few reports in which the relationship between these two factors is addressed. The authors compared expression patterns of TP and VEGF and investigated their role in the angiogenesis of glioblastoma multiforme (GBM). METHODS: Surgical specimens from 41 cases of GBM were immunohistochemically stained for TP, VEGF, CD68 (a macrophage marker), and CD31 (an endothelial cell marker). Both TP labeling indices and VEGF immunoreactivity displayed significant correlations with vascular density. Although VEGF was diffusely distributed in the tumor, TP was strongly expressed around blood vessels and in vascular proliferation. Double labeling for TP and CD68 in 10 cases indicated that cells that reacted strongly positive for TP were almost always macrophages, and only small numbers of CD68-negative cells weakly expressed TP. The TP messenger (m)RNA expression was investigated using reverse transcription-polymerase chain reaction in six GBMs. All six specimens expressed TP mRNA. In addition, TP mRNA was detected in two of three groups of cultured GBM cells derived from surgical specimens. Macrophages, the production of which was induced from two volunteers' peripheral blood monocytes by applying macrophage colony-stimulating factor, also expressed TP mRNA. The glioma cell lines U251MG and U87MG, which barely express TP mRNA under normal conditions, expressed TP mRNA in response to interferon-beta stimulation or while in an anoxic condition. CONCLUSIONS: Although it is feasible that GBM cells can express TP depending on their growing conditions, the majority of TP-expressing cells present in GBMs appear to be infiltrating macrophages. Coexistence of VEGF and TP may indicate a synergistic upregulation for angiogenesis because VEGF exerts a chemotactic activity on macrophages that express TP.

Brain Neoplasms↗

Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors: correlation with patient age and survival.

OBJECT: The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. METHODS: The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMs. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. CONCLUSIONS: In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.

Adult↗

Highly efficient electro-gene therapy of solid tumor by using an expression plasmid for the herpes simplex virus thymidine kinase gene.

We report successful electro-gene therapy (EGT) by using plasmid DNA for tumor-bearing mice. Subcutaneously inoculated CT26 tumor was subjected to EGT, which consists of intratumoral injection of a naked plasmid encoding a marker gene or a therapeutic gene, followed by in vivo electroporation (EP). When this treatment modality is carried out with the plasmid DNA for the green fluorescent protein gene, followed by in vivo EP with the optimized pulse parameters, numerous intensely bright green fluorescent signals appeared within the tumor. EGT, by using the "A" fragment of the diphtheria toxin gene significantly inhibited the growth of tumors, by about 30%, on the flank of mice. With the herpes simplex virus thymidine kinase gene, followed by systemic injection of ganciclovir, EGT was far more effective in retarding tumor growth, varying between 50% and 90%, compared with the other controls. Based on these results, it appears that EGT can be used successfully for treating murine solid tumors.

Animals↗

MRI of a cerebral cryptococcal granuloma.

We report a patient with a cerebral cryptococcal granuloma who presented with recent memory disturbance and deteriorating mental status followed by temporary loss of consciousness. To our knowledge, this is the first report of a cerebral cryptococcal granuloma examined by a combination of conventional MRI, fluid-attenuated inversion recovery and diffusion-weighted imaging and in which the surgical specimen was analysed histochemically.

Diagnosis, Differential↗

Bilateral thalamic glioma: case report.

We report a 63-year-old man who had a rare bilateral thalamic glioma. He complained of difficulty with calculations and had mental deterioration. T1-weighted images revealed bilateral thalamic swelling with homogeneous low signal and no contrast enhancement. The tumour, showing decrease of N-acetylaspartate and the presence of lactate on magnetic resonance spectroscopy, was diagnosed as an astrocytoma by stereotactic biopsy.

Astrocytoma↗