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Biomedical subjects

T Furuta

Publications and source records attributed to T Furuta.

At least 217 records · Page 12Linked to original sources

Acute effects of interstitial hyperthermia on normal monkey brain--magnetic resonance imaging appearance and effects on blood-brain barrier.

The magnitude and time course of histological and neuroradiological changes due to interstitial hyperthermia in normal cerebral white matter were investigated in eight adult Japanese monkeys. A cooling system enveloping a 2450-MHz microwave antenna was inserted stereotactically into the brain under general anesthesia. A point located 5 mm away from the surface of the cooling system was used as the reference point (RP). Hyperthermia was given to maintain the RP at 43 degrees C for 60 minutes. Two animals were sacrificed under general anesthesia following the intravenous administration of Evans blue, immediately and 1, 3, and 7 days after treatment. After removing the brain, histological changes were investigated. Magnetic resonance (MR) imaging was performed at 1, 3, and 7 days after treatment. Evans blue extravasation was most prominent in the region heated to 43 degrees C or above immediately after treatment. MR imaging showed obvious enhancement in the region heated to 43 degrees C or above 1 day after treatment, related to the disruption of the blood-brain barrier (BBB) by hyperthermia. Three days after treatment, ring-like enhancement with a central low-intensity area was seen in the region heated to about 43 degrees C, caused by BBB disruption and slight neovascularization. One week after treatment, an enhanced ring was observed in the region heated to less then 43 degrees C which surrounded a low-intensity area. The enhancement seen 1 week after treatment was caused by prominent neovascularization. T2-weighted imaging showed a high-intensity area, caused by edema, most prominent 3 days after treatment. Thus chemotherapeutic agents should be given just before the end of hyperthermia.

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↗

[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↗

Early stage hepatocellular carcinoma detected during intraoperative ultrasonography.

OBJECTIVES: Recently, it has been recognized that there are increasing incidences of hepatocellular carcinoma (HCC) multicentricity. Thus, intraoperatively detected hepatic lesions that were once thought to be metastatic lesions now need to be carefully reexamined to determine whether they are true metastatic lesions or the multicentric development of HCC. METHODS: We investigated the histological characteristics of small nodular lesions detected during intraoperative ultrasonography in 33 consecutive patients with small HCC who underwent laparotomy at our institution. RESULTS: Fourteen nodular lesions were found incidentally in 10 of 33 patients (30.3%), and were classified into the following three groups: 11 nodules in nine patients (27.3%) were HCC, two nodules in two patients (6.1%) were hemangioma, and one nodule in one patient (3.0%) was a large regenerative nodule. HCC therefore comprised 78.6% of the intraoperatively detected nodular lesions. Of the 11 HCCs, six were hyperechoic, four were hypoechoic, and one was isoechoic. Five (83.3%) of six small hyperechoic HCCs and two (50.0%) of four hypoechoic HCCs were well differentiated and retained their preexisting liver structure. These findings closely coincide with the characteristics of early stage HCC. Thus, early stage HCC comprised 63.6% of the intraoperatively detected HCC cases. CONCLUSIONS: A certain proportion of small satellite HCCs detected during intraoperative ultrasonography in patients with small HCC, which were previously thought to be metastatic lesions from the main HCC, may instead be early stage HCCs. Such findings would also support the concept of the multicentric development of HCC. Approximately 60% of all small HCC cases detected intraoperatively may be early stage HCC. As a result, it is predicted that the emergence of HCC is either multicentric or unicentric, with early intrahepatic spread, although the former seems to be more common.

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↗

Participation of macrophages in segmental endocapillary proliferation preceding focal glomerular sclerosis.

We studied infiltrating cells in the glomeruli of eight cases with focal segmental endocapillary proliferation (FSEP) using monoclonal antibodies to leukocyte common antigen, T cells, B cells, and monocytes/macrophages (Mo/M psi). It was demonstrated by sequential biopsies performed in five cases that FSEP preceded focal glomerular sclerosis (FGS). Cell types in FSEP were compared with those in FGS from 17 patients with persistent nephrotic syndrome, ten non-nephrotic patients, and eight patients with nephrotic syndrome which was initially responsive to steroid therapy but relapsed, as well as minimal change specimens from nine nephrotic patients. In the glomeruli, the mean total leukocyte counts increased significantly in the FSEP group (P < 0.01). The serial sections in FSEP revealed that Mo/M psi were the predominant cells and were localized in areas of endocapillary proliferation. T-cell or B-cell infiltration was less marked. The extensive intracapillary distribution of p150,95 antigen belonging to the integrin family and acting as a C3bi receptor suggested that FSEP may be mediated by adhesion molecules expressed on Mo/M psi. These findings indicate that Mo/M psi may play a key role in FGS which shows endocapillary proliferation in the initial stage.

Adolescent↗

Severe pulmonary pneumocystosis in simian acquired immunodeficiency syndrome induced by simian immunodeficiency virus: its characterization by the polymerase-chain-reaction method and failure of experimental transmission to immunodeficient animals.

Pneumocystis carinii (Pc) infection was observed in three of five rhesus monkeys infected with simian immunodeficiency virus (SIVmac251). They showed severe symptoms similar to those associated with human acquired immunodeficiency syndrome (AIDS). Histopathology revealed severe pulmonary pneumocystosis in one of three Pc-positive monkeys, and anti-Pc antibodies were detected in sera from two of the three monkeys. Localization of Pc organisms in various organs of the monkeys was examined by the polymerase-chain-reaction (PCR) method, and Pc-specific bands of DNA amplification were detected in the liver, kidney, spleen, adrenal gland, testis, brain, and other organs examined, but no Pc organism was found in these organs by histopathologic examination. These results suggest that the activation of a latent infection of Pc occurs in SIV-infected rhesus monkeys as well as in human AIDS. Experimental transmission of Pc derived from a simian was attempted in severe combined immunodeficiency (SCID) mice and athymic nude (rnu/rnu, F344) rats. These animals were inoculated intranasally with 10(4) Pc cysts, but neither histopathologic changes nor Pc organisms were detected in SCID mice at 4 months after inoculation or in nude rats at 2 months postinoculation, suggesting that simian Pc is species-specific.

Animals↗

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↗

Comparative study of QRST values from body surface potential mapping, 12-lead ECGs, VCGs in detecting inferior myocardial infarction, and evaluating the severity of left ventricular wall motion abnormalities in simulated left bundle branch block.

The authors compared the ability of QRST time-integral values (QRST values) from body surface potential maps (BSPM), 12-lead electrocardiograms (ECGs), and Frank lead vectorcardiograms (VCGs) in diagnosing a prior inferior myocardial infarction (MI) in simulated left bundle branch block (LBBB). The study included 32 patients whose digitized ECGs were recorded simultaneously for BSPM, ECGs, and VCGs during normal sinus rhythm and during right ventricular pacing simulating LBBB (18 with and 14 without an inferior MI). QRST values were calculated in each lead point of ECGs. Data on 608 normal subjects were used as controls; mean +/- 2 SD was regarded as the normal range. The following parameters were derived: sigma DM, sigma DE, sigma DV, the sum of the differences between the normal mean QRST value, and the QRST value of a given patient in leads where the QRST value was less than the normal range ("-2 SD area") in BSPM, ECGs, and VCGs (Y lead). The correlation coefficients for sigma DM, sigma DE, and sigma DV between the two activation sequences were highly significant. Sensitivity and specificity were as follows: 89% and 93% for sigma DM > 100 mV.ms, 89% and 93% for sigma DE > 50 mV.ms, and 56% and 100% for sigma DV > 10 mV.ms, respectively. Although sigma DM, sigma DE, and sigma DV were significantly (P < .01) correlated with the asynergy index calculated from left ventriculograms, sigma DM showed the best correlation. QRST values from BSPM, ECGs, and VCGs provide information that is useful in detecting an inferior MI and in estimating the severity of left ventricular wall motion abnormalities in the setting of LBBB. Of the three parameters, BSPM showed the best correlation with the severity of left ventricular wall motion abnormalities.

Aged↗