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Biomedical subjects

T Ohmoto

Publications and source records attributed to T Ohmoto.

At least 199 records · Page 11Linked to original sources

Experimental analysis of brain surface elastance in cats.

Brain surface elastance, defined as the pressure needed to compress the cortex 3 mm, was measured using the ophthalmodynamometer in six cats using three burr holes (frontal, parietal, and occipital) on each side. An intracranial mass was then used to compress the right side for 3 hours, and cardiac arrest was induced after the mass was removed. Elastance was measured four times: before insertion of the mass, 10 and 70 minutes after removal of the mass, and 60 minutes after cardiac arrest. The results showed that: brain surface elastance does not change between sides, but varies among regions with the parietal region having the highest elastance; elastance increases after compression by an intracranial mass, but not after cardiac arrest; and stiff brain tends to restore poorly. Elastance is apparently increased by the formation of edema. Measuring brain elastance may be useful in predicting brain restoration subsequent to removal of mass lesions.

Animals↗

Factors influencing the recurrence rate of intracranial meningiomas after surgery.

The postoperative recurrence rate was examined in 242 patients with intracranial meningiomas to identify correlations with age, location, histology, or extent of surgery (Simpson's grade). There was no significant difference in the recurrence rate among the histological subtypes, but malignant meningiomas and hemangiopericytomas tended to recur earlier. Anterior basal meningiomas demonstrated a higher recurrence rate, but this depended on the feasibility of complete surgical removal. The recurrence rates significantly decreased in the order Simpson's grade I surgery, grade II or III surgery, and grade IV surgery (p < 0.001). These results indicate that the most important factor to influence recurrence is the extent of surgical removal.

Adolescent↗

[Synergistic effect of carboplatin and hyperthermia in rat and human glioma cell lines].

To assess the interaction of carboplatin and hyperthermia in vitro, the thermochemosensitivities of three glioma cell lines, C6 rat glioma cell line, human glioma cell lines T98G and KMG4, were examined by 3-(4,5-dimethylthiazol-2-yl) -2,5 diphenyltetrazolium bromide (MTT) assay. The cell survival of each cell line decreased according to increasing CBDCA concentration and temperature. With a certain CBDCA concentration, the cell survival at following temperature was significantly decreased from that at 37 degrees: 43 degrees C and 44 degrees C for C6 cells (2.5 micrograms/ml); 41 degrees C, 42 degrees C, 43 degrees C and 44 degrees C for C6 cells (128 micrograms/ml); 42 degrees C, 43 degrees C and 44 degrees C for KMG4 cells (8 micrograms/ml) (CBDCA concentration within parentheses). It is generally considered that the highest tolerable temperature of normal brain is 42 degrees C for 60 minutes, while under 43 degrees C, there is a possibility that a sufficient tumoricidal effect might not be obtained. This study revealed enhanced cytotoxicity of CBDCA with hyperthermia at the temperature lower than 42 degrees C and suggests the possibility to gain increased tumoricidal effect without injuring normal brain by hyperthermia at the normal-tissue-tolerant temperature with systemic administration of relatively lower dose of CBDCA.

Animals↗

[Collateral venous channels in occlusion of deep cerebral veins and sinuses].

The authors report on the relationship between occlusion or stenosis of the deep cerebral veins and sinuses and the development of collateral venous channels in pineal region tumors. Five cases of meningioma arising from the falcotentorial junction were the subject of this study. There were two males and three females with an average age of 51.2 years (range: 26-67). The straight sinus (SS) and posterior part of the great vein of Galen (GVG) were included in the occlusion or stenosis of the deep cerebral veins and sinuses in 3 cases, the GVG, SS and posterior part of the internal cerebral vein in 1, and the SS alone in 1. The various types of collateral venous channels following the occlusion could be classified a type 1, from the basal vein of Rosenthal (BVR) to the petrosal vein via the lateral mesencephalic and/or anterior pontomesencephalic veins; type 2, via the veins on the medial surface of the parietal and/or occipital lobe to the superior sagittal sinus (SSS); type 3, dilated superficial anastomotic veins; type 4, via the posterior fossa venous circulation to the transverse sinus or the SS; and type 5, via the falcian veins to the SSS. The first three types of collateral venous channels seem to be important following occlusion or stenosis of deep cerebral veins and sinuses. Stereoscopic angiograms are essential to analyze deep venous channels around deep-seated tumors. Clear identification of occlusion or stenosis and the development of venous system collaterals on angiograms is important to the surgical treatment of pineal region tumors.

Adult↗

[Clinical pharmacokinetics of carboplatin and MCNU in malignant brain tumor and normal brain tissues].

We measured the concentrations of MCNU and CBDCA in the serum, brain tumor and normal brain tissue. Six patients with malignant glioma were treated with intravenous chemotherapy using 80mg/m2 MCNU and 300mg/m2 CBDCA during surgery. After drug administration, specimens of serum, tumor and normal brain tissue were collected every 30 min and then the drug concentration in each sample was measured. The highest MCNU levels in all samples were obtained immediately after administration which followed by gradual decrease. On the contrary, the mean CBDCA levels in the tumor and normal tissue remained almost at a constant level, although serum CBDCA level declined rapidly as MCNU. As expected, MCNU seemed to have advantages in the treatment of brain tumors as it distributed with higher concentration in the tumor tissue than in the serum and normal brain tissue. On the contrary, CBDCA in the tumor tissue did not exceed the concentration in the serum. Nevertheless, it remained longer in the tumor tissue with a constant level, suggesting that CBDCA can achieve an effective area under the concentration versus time curve (AUC) in the brain tumor tissue to kill tumor cells.

Aged↗

[A case of pineal region germinoma treated by interstitial brachytherapy].

Although radiation therapy has been universally accepted as treatment for primary intracranial germinomas, the optimal technique for both diagnosis and treatment continues to be a matter of controversy. We report a case of germinoma in the pineal region treated by interstitial brachytherapy. A 23-year-old female was admitted with diplopia and consciousness disturbance. Magnetic resonance imagings (MRI) revealed an enhanced tumor of the pineal region and hydrocephalus. No serum and CSF tumor markers such as alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) or placental alkaline phosphatase (PLAP) were detectable. Stereotactic needle biopsy was performed using BRW MRI-guided stereotactic apparatus. After the histological diagnosis confirmed the presence of germinoma, three catheters for interstitial brachytherapy were implanted into the tumor through the biopsy tract, and iridium-192 seeds were inserted into the catheters and kept there for 5 days to give 35 Gy of irradiation at the tumor periphery. Subsequent MRI showed marked tumor regression and the clinical symptoms were gradually improved, and Gd-enhanced tumor on MRI completely disappeared 2 months after brachytherapy. Histological diagnosis is essential before initiation of treatment because a germinoma is commonly thought to be radiosensitive. However, pineal region tumor is dangerous to remove surgically because of high morbidity and mortality rates. Image-guided stereotactic technique provides a safe method to obtain an accurate diagnosis, and subsequent interstitial brachytherapy enables selective irradiation of the tumor, and does not give rise to complications caused by external irradiation such as mental disturbance, hypopituitarism, visual disturbance and brain necrosis. Interstitial brachytherapy following image-guided biopsy can be a useful tool for patients with germinoma.

Adult↗

[Patterns of recurrence in malignant gliomas after brachytherapy].

More than 80% of malignant gliomas have been reported to recur locally after conventional chemoradiation therapy. This regional pattern of recurrence has encouraged the introduction of new treatments for local tumors. Since 1987 interstitial brachytherapy using Iridium-192 seeds has been carried out in our department for malignant brain tumors. The present study was designed to evaluate the patterns of recurrence following interstitial brachytherapy and to assess how this recurrence differs from that observed in patients treated by conventional means. Ten patients who satisfied the following criteria were selected among 41 patients treated with brachytherapy. The criteria were; 1) histologically diagnosed to be malignant glioma (astrocytoma grade III or glioblastoma), 2) followed up with MRI every month after the brachytherapy, 3) follow-up period was more than 6 months, and 4) the time of recurrence was confirmed. The patients were classified into 3 groups according to the patterns of tumor recurrence as follows; 1. Local recurrence group: The tumor recurred near the pretreatment tumor site. 2. Necrotomy group: Reoperation was performed because of neurological deterioration and radiographic evidence of increasing mass effect with surrounding edema. Neurological symptoms were unchanged or improving during the 6 months after the reoperation. 3. CSF seeding group: Primary tumor was well controlled, but seeding via cerebrospinal fluid was recognized on MRI. Local recurrence occurred in three patients, necrotomy was carried out in three patients, and CSF metastases were defined by both MRI and clinical symptoms in four patients. Median radiation does was 33 Gy in the local recurrence group, 57.6 Gy in the necrotomy group, and 43.2Gy in the CSF seeding group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Xenogeneic dopaminergic grafts reverse behavioral deficits induced by 6-OHDA in rodents: effect of 15-deoxyspergualin treatment.

Foetal rat mesencephalic dopamine-containing tissue was transplanted into the lateral ventricle of mice previously subjected to a 6-OHDA lesion of dopaminergic nerve terminals in the corpus striatum. The graft recipients were immunosuppressed by subcutaneous injections of 15-deoxyspergualin (DSG). Four weeks postgrafting, all DSG-treated mice showed partial or complete functional compensation in amphetamine-induced motor asymmetry. The immunohistochemical staining of tyrosine hydroxylase (TH) revealed large numbers of surviving dopamine neurons and abundant fibers in the grafted animals. In contrast, all grafts in non-DSG-treated animals were rejected and functional compensation was lacking. It is concluded that DSG treatment promotes xenogeneic intracerebral graft survival, recovery of function and reduce the histological sign of rejection.

Amphetamine↗

The influence of donor age on cografting of adrenal medulla with pretransected peripheral nerve.

Pretransected peripheral nerve has been demonstrated to enhance the survival of cografted adrenal medullary chromaffin cells and the recovery of host dopaminergic (DA) systems in animal models of Parkinson's disease. In the present study, we examined the effect of donor age on survival of cografted chromaffin cells. Adrenal medulla and pretransected peripheral nerve from young (1-month-old) or aging (12-month-old) donors were cografted into the striatum of MPTP-treated young (2-month-old) C57/BL mice. Although chromaffin cell survivability was increased by cografting with pretransected peripheral nerve despite donor age, survivability of chromaffin cells from aging donors was less than that using young donors. Image analysis of striatal DA fibers and chemical analysis of striatal DA showed that cografting with pretransected peripheral nerve enhanced the recovery of striatal DA systems more prominently than adrenal grafting alone. However, this effect was less in mice receiving aging donor tissues compared with mice receiving young donor tissues.

Adrenal Medulla↗

Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging.

Studies have suggested that the restorative effects of adrenal medullary chromaffin cell grafts in animal models of Parkinson's disease may be related to trophic factors contained within the chromaffin cells. Basic fibroblast growth factor (bFGF) is present in chromaffin cells and has been shown to exert trophic effects on dopaminergic neurons in vitro. Basic FGF was stereotaxically injected into the striatum of young (2-month-old) and aging (12-month-old) C57BL/6 mice which had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1 week earlier. MPTP treatment reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and striatal dopamine (DA) concentration in both the young and older mice 5 weeks later. Computerized image analysis of striatal DA fibers in young mice treated with bFGF showed significant recovery of DA fibers up to 600 microns from the injection site 5 weeks after MPTP administration. Striatal DA fibers in older mice treated with bFGF showed significant recovery only up to 300 microns from the injection site, and the degree of recovery was very limited compared with young mice. HPLC analysis of DA concentration revealed that striatal DA in young mice recovered significantly when treated with bFGF, but no significant recovery was observed in older mice. It is concluded that bFGF enhances the recovery of striatal DA systems from MPTP toxicity both in young and in older mice, but that such benefits are very limited in older mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Suppression of immunorejection against rat fetal dopaminergic neurons in a mouse brain by 15-deoxyspergualin.

In this study, the immunosuppressive effect of 15-deoxyspergualin (DSG) on the survivability of rat embryonic dopaminergic neurons grafted into the lateral ventricle of adult mice was investigated. DSG was administered daily in dose of 5 mg/kg for 2 weeks postgrafting, commencing on the day of transplantation, in the immunosuppressant-treated groups. Animals were then allowed to survive for 2 to 4 weeks after transplantation. Histological analysis revealed that most of transplanted rat fetal neural tissue was destroyed and scavenged in 2 weeks after transplantation in the non-immunosuppressed group. However, a large number of tyrosine hydroxylase (TH)-positive grafted neurons survived and grew postgrafting in the brain of the host administered with DSG even if they suffered from T lymphocyte infiltrations visualized by cytotoxic T cell immunohistochemistry. The results thus indicated that DSG is an potent immunosuppressant in neural transplantation as well as in transplantation of other organs in animals. It seems to be able to block, at least in part, the ability of mature specific cytotoxic T cells to lyse their targets.

Animals↗

Analysis of the transformation products of dehydro-L-ascorbic acid by ion-pairing high-performance liquid chromatography.

Dehydro-L-ascorbic acid, the oxidation form of L-ascorbic acid, converts nonenzymatically to a variety of transformation products depending upon the incubating conditions. These products, called the ascorbate cascade, possess different absorption spectra and reducing activities. Ion-pairing high-performance liquid chromatography with multiwavelength uv absorption and amperometric electrochemical detection has proven to be a useful technique for the analysis of these products. Separation and characterization in the present investigations reveal three kinds of transformation products: the polymerized intermediates of browning reaction, the reductant possessing an absorption maximum at 345 nm as the six-carbon compound, and erythro-L-ascorbic acid, 2-furoic acid, 3-hydroxy-2-pyrone, 5-methyl-3,4-dihydroxytetrone, reductic acid, and furfural as the five-carbon compound. These products possess an absorption maximum above 240 nm, and most of them are electrochemically active reducing compounds which are derived from nonreducing dehydro-L-ascorbic acid through the processes of delactonization, decarboxylation, and intramolecular rearrangement.

Chromatography, High Pressure Liquid↗

CT and MRI of haemorrhage into intracranial neuromas.

Six patients with haemorrhage into intracranial neuromas were studied by computed tomography (CT) and magnetic resonance imaging (MRI) at 0.5 T with spin-echo pulse sequences. The nature of the tumour and the presence of a haematoma were confirmed by surgery and microscopic examination in all cases. Four neuromas arose from the acoustic nerves and two from the trigeminal. Four of the six patients suffered from sudden onset or rapid worsening of symptoms including headache, vertigo and/or hemifacial motor and sensory disturbances. CT in the acute stage revealed a hyperdense area or a fluid-fluid level (FFL). The hyperdense area disappeared on CT repeated in the chronic stage. On MRI in subacute and chronic stages the haemorrhage showed hyperintensity on both T1 and T2 weighting in five cases examined between 16 and 46 days after the onset, and isointensity on T1 weighting and an FFL on T2 weighting in one case examined 12 days after the onset of symptoms. A well-defined low intensity rim indicating prior haemorrhage was observed on T2-weighted images in three cases. MRI was more effective than CT in detecting haemorrhage into the tumours and in staging it.

Adult↗

Experimental study of venous circulatory disturbance by dural sinus occlusion.

Using a newly devised model of dural sinus occlusion, we investigated the pathophysiology of venous haemorrhage as well as venous circulatory disturbance. The superior sagittal sinus (SSS) and diploic veins (DV) were occluded in 16 cats. Intracranial pressure (ICP), cerebral blood volume (CBV) and regional cerebral blood flow (rCBF) were measured for 12 hours after the occlusion. At the end of the experiment, cerebral water content was estimated. In another 8 cats additional occlusions of cortical veins were carried out. In both groups, the blood-brain barrier permeability was evaluated with Evans blue or horseradish peroxidase. The SSS and DV occlusion produced a significant increase in ICP and CBV concomitant with a significant decrease in rCBF. Cerebral water content also increased significantly. However, there was no transition of Evans blue and horseradish peroxidase through the cerebral vessels, and no haemorrhages could be observed. In contrast, the additional occlusion of cortical veins produced haemorrhagic infarctions with Evans blue extravasation in 6 out of the 8 cats. These data suggest that dural sinus occlusion may lead to an increase in CBV and cerebral water content resulting in intracranial hypertension and decreased rCBF. The brain oedema in this model seemed to be mainly hydrostatic oedema, and might also be contributed by cytotoxic oedema. The additional occlusion of cortical veins might be essential in the development of haemorrhage in this model, and the blood-brain barrier was also disrupted in these areas.

Animals↗

Evaluation of MRI score in the differentiation between glioblastoma multiforme and metastatic adenocarcinoma of the brain.

The authors statistically analyzed the MR configurations of 14 glioblastoma multiformes (GBMs) and 15 metastatic adenocarcinomas (MACs) of the brain in order to distinguish these two histological types on MR images. MR configurations were classified and scored upon the 9 criteria of heterogeneity, cyst or necrosis, haemorrhage, crossing of the midline by the tumour, oedema or mass effect, border definition, flow void sign, degree and heterogeneity after contrast enhancement. The mean value of GBMs was 1.47 +/- 0.22, and that of MACs was 0.91 +/- 0.37 (P < 0.001). GBMs had significantly higher values in five out of the nine criteria: border definition, heterogeneity, crossing of the midline of the tumour, flow void sign, and degree of the contrast enhancement (P < 0.001-0.05). Border definition was the best criterion for distinguishing two histological types. Six cases of MACs displayed hypo-intense lesions on T2 weighted images in contrast to GBMs which showed hyperintense lesions in all cases. In 4 out of the 6 MACs which were shown as hyperintensities on T2 weighted images, a hypo-intense peritumoural rim was noticed between the tumour parenchyma and the surrounding oedema. These data strongly suggest that GBMs and MACs can be distinguished on MR image by using MRI score.

Adenocarcinoma↗

Expression of a putative catalytic domain of the human APEX nuclease (a major apurinic/apyrimidinic endonuclease) in Escherichia coli.

1. Sequence analyses of APEX nuclease, a mammalian major apurinic/apyrimidinic (AP) endonuclease homologous to Escherichia coli exonuclease III, suggested that APEX nuclease is organized into two domains, a Mr 6000 N-terminal domain containing nuclear location signals and a Mr 29,000 C-terminal catalytic domain. 2. In order to study the enzyme structure further, vectors expressing APEX nuclease (pTAPXH1) and the Mr 29,000 C-terminal region (pTAPXH61) were constructed using cDNA (APX cDNA) for the human APEX nuclease and pTrc99A plasmid. The constructs were introduced into BW2001 strain (xth-11, nfo-2) cells of E. coli to produce transformants designated as BW2001/pTAPXH1 and BW2001/pTAPXH61, respectively. Both the APEX nuclease expressed in BW2001/pTAPXH1 and the Mr 29,000 C-terminal peptide expressed in BW2001/pTAPXH61 were partially purified by column chromatography and highly purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 3. The purified APEX nuclease and the Mr 29,000 C-terminal peptide both showed equally high AP endonuclease activity which indicates that the Mr 29,000 C-terminal region of the APEX nuclease is (or contains) the AP endonuclease domain.

Amino Acid Sequence↗

Lanosterol and 27-norlanosterol oligosaccharides from the bulbs of Chionodoxa gigantea.

New lanosterol and 27-norlanosterol oligosaccharides were found in the bulbs of Chionodoxa gigantea. Their structures were established mainly by extensive 2D NMR analysis as well as by comparison with spectral data of known compounds. The inhibition of cyclic AMP phosphodiesterase by the lanosterol derivatives was assayed as the primary screening test to find new medicinal materials.

3',5'-Cyclic-AMP Phosphodiesterases↗