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Biomedical subjects

M Ebara

Publications and source records attributed to M Ebara.

At least 19 recordsLinked to original sources
PubMed2003

A promoter region of the midkine gene that is frequently expressed in human hepatocellular carcinoma can activate a suicide gene as effectively as the alpha-fetoprotein promoter.

We examined the expression of the midkine (MK) and alpha-fetoprotein (AFP) genes in 15 paired human specimens obtained from hepatocellular carcinoma (HCC) and the corresponding noncancerous regions of the same patients. A total of 14 HCC but none of the noncancerous specimens were positive for the MK mRNA. In contrast, three HCC specimens and one corresponding noncancerous sample out of the three AFP-positive HCC cases expressed the AFP gene. A 2.3-kb genomic fragment in the regulatory region of the MK gene could activate a fused reporter gene in both AFP-producing and -nonproducing HCC lines, and the MK fragment-mediated transcriptional activity was comparable to the AFP enhancer-linked AFP promoter in AFP-producing cell lines. The AFP-producing but not AFP-nonproducing HCC cell lines that were transfected with the MK promoter-linked herpes simplex virus-thymidine kinase (HSV-TK) gene became susceptible to a prodrug ganciclovir to a similar degree of the HCC transfected with the enhancer-linked AFP promoter-fused HSV-TK gene. These data suggest that the MK promoter can activate a therapeutic gene preferentially in HCC and is as useful as the AFP promoter in clinical settings.

Aged↗
PubMed2001

Irradiation with ultrasound of low output intensity increased chemosensitivity of subcutaneous solid tumors to an anti-cancer agent.

Ultrasound is a possible mechanical method to deliver small molecules into target cells. In order to evaluate the therapeutic potentials provided by ultrasound irradiation, we compared anti-tumor effects of electroporation- and ultrasound-mediated chemotherapy and efficacy of gene transfer by the two methods. Electric pulses (5 Hz, 100 V/cm, 8 square-wave/100 microsec) or ultrasound (1 MHz, 2 W/cm(2), 5 min) was delivered to subcutaneous solid tumors of murine lymphoma after the tumor-bearing mice received an intraperitoneal injection of bleomycin (BLM) (2.5 mg) or intratumoral injection of plasmid DNA containing the luciferase reporter gene. Administration of BLM alone did not affect the subsequent tumor growth but additive treatment with ultrasound irradiation suppressed the growth to the same level as electroporation. The luciferase activity of the DNA-injected tumors showed that ultrasound irradiation achieved better transfection efficiency than plasmid DNA injection alone but the efficacy was not as great as that by electroporation. The low energy level of ultrasound that is currently used for a diagnostic purpose and physical therapy in clinical fields can thereby increase the in vivo chemosensitivity of treated tumors but further modifications are necessary to achieve better efficacy of the ultrasound-mediated gene transfer.

Animals↗
PubMed2001

Overexpression of mitochondrial manganese superoxide dismutase protects against radiation-induced cell death in the human hepatocellular carcinoma cell line HLE.

We investigated the potential role of mitochondrial manganese superoxide dismutase (Mn-SOD) in protective activity against irradiation by analyzing cell viability by a colony formation assay and by detecting apoptosis in stably human Mn-SOD gene-transfected HLE, a hepatocellular carcinoma cell line. We found that overexpression of Mn-SOD reduced the levels of reactive oxygen species in the mitochondria and intracellular phospholipid peroxidation product (4-hydroxy-2-nonenal) and prevented cell death. The production of intracellular nitric oxide after irradiation was not changed by Mn-SOD overexpression. The results suggested that Mn-SOD might play an important role in protecting cells against radiation-induced cell death by controlling the generation of mitochondrial reactive oxygen species and intracellular lipid peroxidation.

Apoptosis↗
PubMed2001

Long-term evaluation of extracorporeal shock-wave lithotripsy for cholesterol gallstones.

BACKGROUND: Extracorporeal shock-wave lithotripsy (ESWL) is a treatment that preserves the gallbladder. Problems after ESWL treatment include stone recurrence and the development of biliary symptoms. METHODS: Two hundred and sixty-two patients with cholesterol-type gallstones, the best indication for ESWL treatment, and 42 control patients with cholesterol-type gallstones who received no treatment entered this study. We evaluated the factors associated with recurrence of gallstones after stone clearance and the development of biliary symptoms after ESWL treatment. RESULTS: The 3-, 5- and 7-year cumulative probabilities of gallstone recurrence were 20.6, 27.1 and 33.1%, respectively, with the recurrence probability significantly lower in patients with good gallbladder contractility. In patients with recurrence, ursodeoxycholic acid (UDCA) treatment was effective. In 69 patients with residual gallstones, the 3-, 5- and 7-year cumulative risks of biliary symptoms were 17.3, 24.9 and 30.5%, respectively. With residual gallstones, the risk of biliary symptoms developing was significantly lower in patients with a < or = 3 mm fragment size at the end of ESWL treatment and in those treated consistently with UDCA for 6 months or more after treatment with ESWL. The risk of biliary symptoms was significantly lower in ESWL-treated patients with residual stones who had a < or = 3 mm fragment size after treatment compared to those of control patients. CONCLUSIONS: Ursodeoxycholic acid was effective in clearing stones in patients with gallstone recurrence. In patients with residual stones, the fragmentation of stones to < or = 3 mm and UDCA administration effectively reduced the risk of subsequent biliary symptoms.

Case-Control Studies↗
PubMed2001

Characterization of hyperplastic foci observed in surgical specimens of hepatocellular carcinoma.

By reviewing previous surgical specimens of hepatocellular carcinoma, 17 cases with hyperplastic foci (HPF) characterized by discernible increase in nuclear densities, could be histologically selected. Nuclear densities of HPF and control hepatic parenchyma were assessed quantitatively by counting the nuclear number of hepatic cells, and proliferating cell nuclear antigen labeling index was measured. HPF occurred multifocally, confined within a lobular unit, smoothly merging into surrounding hepatic parenchyma. Nuclear densities of HPF were 1.71 times greater than those of control hepatic parenchyma. The hepatocytes of HPF also showed significantly higher proliferative activities than those of control parenchyma. In addition, noticeable structural distortions, such as focal trabecular thickening or microacinar formation of hepatocytes, were sometimes observed in HPF. However, these HPF seemed to be distinguished from minute de novo hepatocellular carcinoma (HCC) or intrahepatic HCC metastasis, because of paucity of distinctive atypical changes, and intimate correlation with neighboring hepatocytes. Several adjacent HPF were aggregated to form a much larger unit of a hyperplastic area with loss of fibrous septa of liver cirrhosis. It was suggested that grossly detectable large regenerative nodules are produced via fusion of several adjacent HPF.

Adult↗
PubMed2001

[A case of sinus pericranii manifesting as a parietal midline mass].

A case of sinus pericranii was reported. A 5-year-old boy was admitted to our hospital, complaining of scalp mass located at the midparietal region. He was noticed to have had it since 3 years before. The mass decreased in size under mild compression, and during standing position, but increased in size due to lying down. Magnetic resonance imaging (MRI) demonstrated a mass with mixed signal intensity on the T1 weighted image and high signal intensity on the T2 weighted image. Gd-DTPA study showed irregular enhancement. Cerebral angiogram showed no communication between the mass and the superior sagittal sinus. Neither did direct injection of contrast medium into the mass revealed any communication. 3D-CT demonstrated three tiny bone defects beneath the mass. Open surgery revealed that the mass existed between the galea aponeurotica and the periosteum, which had a small communication with the emissary vein. Pathological examination showed a multiple lobular cyst with endothelial wall lining. This case report highlighted the fact that sinus pericranii with minimal communication with the dural sinus can be treated by removal of the mass and closure of the cranial bone abnormalities with bone wax without craniotomy.

Cerebral Angiography↗
PubMed2000

Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma.

BACKGROUND/AIM: Accumulation of copper (Cu) in hepatocellular carcinoma (HCC), especially in small tumors, is greater than that in the surrounding liver parenchyma. Metallothionein (MT) is considered to be present as Cu-MT, Zn,Cu-MT or Zn-MT. The aim of this study was to determine the presence and localization of Cu-MT and Zn-MT in HCC and surrounding liver parenchyma. METHODS: In 16 HCC patients, surgically resected specimens including HCC and surrounding liver parenchyma were evaluated. RESULTS: The level of Cu present in small HCC (<4 cm in diameter) was significantly greater than that in the surrounding liver parenchyma (p<0.05). However, the level of Cu in large HCC (>4 cm in diameter) was similar to that in the surrounding liver parenchyma. Analysis by Sephadex G-75 gel filtration revealed that the peak fraction due to Cu was identical to that due to MT in 14 (87.5%) of 16 HCC, the peak fraction due to Cu and Zn was identical to that due to MT in 2 (12.5%) HCC, and the peak fraction due to Zn was identical to that of MT in none of 16 HCC. CONCLUSIONS: Accumulation of Cu in small HCC, in which Cu was present as Cu-MT or Zn, Cu-MT, was greater than that in the surrounding liver parenchyma. Cu accumulation and the presence of MT in the liver may be related to carcinogenesis of HCC, because of the similarity of these findings in the experimental data of Long-Evans rats with a cinnamon-like coat color who develop HCC spontaneously.

Adult↗
PubMed2000

Clinical evaluation of sonoelasticity measurement in liver using ultrasonic imaging of internal forced low-frequency vibration.

The aim of this study is to evaluate liver elasticity noninvasively. We have already proposed an ultrasonic imaging system that can reconstruct vibration maps inside tissue under forced mechanical vibration. With this system, shear elastic properties of soft tissue can be evaluated as vibration velocities. Theoretically, these velocities increase with the increase of tissue elasticity. Sonoelasticity imaging was performed on 236 patients with chronic hepatitis and liver cirrhosis, and 50 healthy volunteers. The average of the velocities was 598.8 +/- 151.7 cm/s in healthy volunteers, 984.4 +/- 362.5 cm/s in chronic hepatitis and 1189.0 +/- 411.7 cm/s in liver cirrhosis. The average velocity of Child C group was statistically faster than those of Child A and B groups. Fibrotic rate from biopsy specimens statistically had the strongest positive correlation with velocities. With our system, the degree of liver fibrosis and function can be estimated objectively and noninvasively.

Adult↗
PubMed2000

Accumulation of copper in the liver and hepatic injury in chronic hepatitis C.

BACKGROUND AND AIMS: Relationships between chronic liver disease and trace metals have not been clearly understood. To examine connections between severity of hepatic fibrosis in chronic hepatitis C and copper, iron and zinc we measured the contents of these metals in liver tissue and serum in the patients. METHODS: Forty-one patients (26-62 years), 13 with fibrosis representing grade F1, 16 with F2, seven with F3, and five with F4, entered this study. Metals were quantified in needle liver-biopsy specimens by particle-induced X-ray emission. In serum, metals were measured by flameless atomic absorption spectrometry. RESULTS: Hepatic copper content increased with progression of hepatic fibrosis (P < 0.05). The copper content correlated positively with bilirubin (r = 0.466, P = 0.0023), and with type IV collagen (r = 0.402, P = 0.0086) and correlated negatively with albumin (r = -0.404, P = 0.080). However, hepatic iron and zinc contents did not show a significant differences between grades of fibrosis. CONCLUSIONS: Copper accumulation in fibrotic livers caused by chronic hepatitis C may contribute to hepatic injury. The real mechanism is not known at present, but excess copper may damage the liver by oxidative stress.

Adult↗
PubMed2000

Novel bifunctional polymer with reactivity and temperature sensitivity.

To introduce reactive groups into temperature-responsive polymeric chains of poly(N-isopropylacrylamide) (PIPAAm), IPAAm is copolymerized with other monomer such as acrylic acid (AAc). IPAAm homopolymer exhibited temperature-responsive properties and phase transition at 32 degrees C, however, the lower critical solution temperature (LCST) of the IPAAm-AAc copolymer shifts to a higher temperature and the phase transition becomes insensitive with increasing AAc content. To achieve a useful bifunctional copolymer containing both reactivity and temperature-sensitivity, we assumed that the homopolymer-like structure in the polymer chain would be required to maintain a sensitive temperature response with functional groups. Therefore, we designed a reactive monomer, 2-carboxyisopropylacrylamide (CIPAAm), and investigated its copolymerization with IPAAm. The important characteristic of the poly(IPAAm-co-CIPAAm) structure is that it was composed of the same polymer backbone and isopropylamide groups and some additional carboxyl groups. The transmittance measurement of the polymer aqueous solution revealed that phase transition of IPAAm-co-CIPAAm random copolymer occurred within a very narrow temperature range in pH 6.4, 7.4, and also even 9.0 phosphate buffered solution. These profiles were almost same as that of IPAAm homopolymer. While, under the same conditions, phase transition properties of poly(IPAAm-co-AAc)s solution were considerably influenced by small AAc content. We succeeded with the preparation of bifunctional polymer that possessed reactive functional groups and very sensitive response to temperature change.

Acrylamides↗
PubMed1999

Early detection of radiation-induced liver injury in rat by superparamagnetic iron oxide-enhanced MR imaging.

The detectability of early liver injury induced by irradiation was studied using magnetic resonance (MR) imaging enhanced with superparamagnetic iron oxide (SPIO), a tissue-specific contrast agent against the reticuloendothelial system (RES). In rat, 3 days after focal irradiation (0-10 Gy), MR imaging was performed and specimens were obtained to observe the phagocytic function of RES. The irradiated portion of the liver was visualized with a clear demarcation from the nonirradiated part by SPIO-enhanced MR images as a decrease in negative enhancement reflecting the function of RES (P < 0.05), whereas this was impossible with nonenhanced MR images. Significant regression was observed as a dose-related change of the signal intensity in the irradiated portion on SPIO-enhanced MR images (R = 0.867, P < 0.0001). SPIO-enhanced MR imaging was reliable for detecting the range and extent of liver injury a few days after low-dose irradiation, and it may be a useful procedure for verifying the target area in clinical cases of radiation therapy.

Animals↗
PubMed1999

Parenchymal echo patterns of cirrhotic liver analysed with a neural network for risk of hepatocellular carcinoma.

BACKGROUND: To objectively evaluate the parenchymal echo patterns of the liver in cirrhosis, an image analysing system in which a neural network is used has been found capable of numerically calculating coarse score (CS). Using this system, we analysed whether or not CS can serve as a predictive factor for the development of hepatocellular carcinoma (HCC). METHODS: The risk factors for HCC were evaluated in 95 patients with liver cirrhosis with an average follow-up period of 2041 +/- 823 days. We used a three-layer feed-forward neural network and a back-propagation algorithm to calculate CS. RESULTS: There were strong correlations between CS, alanine aminotransferase (ALT) and alpha-fetoprotein (AFP) and the average cumulative incidence rate of HCC evaluated by the Cox's proportional hazards model. The adjusted rate ratios were estimated to be 3.00, 2.80 and 2.01, respectively. The cumulative risks of HCC were significantly higher with an initial CS > or = 1.5 than with an initial CS < 1.5, with ALT > or = 80 IU/L than with initial ALT < 80 IU/L and with AFP > or = 20 ng/mL than with initial AFP < 20 ng/mL, all analysed by the log-rank test. CONCLUSIONS: Coarse score is a useful predictor for development of HCC.

Adult↗
PubMed1999

Small hepatocellular carcinoma: relationship of signal intensity to histopathologic findings and metal content of the tumor and surrounding hepatic parenchyma.

PURPOSE: To investigate the relationship between the metal content of hepatocellular carcinoma (HCC) and the signal intensity pattern on magnetic resonance images. MATERIALS AND METHODS: The signal intensity patterns of 59 HCCs 3 cm in diameter or smaller were correlated with histologic findings and metal content. RESULTS: HCCs with high signal intensity on T1-weighted images demonstrated more steatosis (P = .035) and higher copper content (P = .008) than did surrounding hepatic parenchyma. HCCs with high signal intensity on T2-weighted images demonstrated more clear cells (P = .001) than did surrounding hepatic parenchyma. The higher signal intensities on T1-weighted and T2-weighted images were related to a higher and a lower degree of histologic differentiation, respectively. Multivariate analysis showed that the contrast-to-noise ratio between the HCC and surrounding hepatic parenchyma was affected by intratumoral copper content (P = .0338), zinc content of surrounding hepatic parenchyma (P = .0379), and the degree of histologic differentiation on T1-weighted (P = .0031) and T2-weighted (P = .0062) images. CONCLUSION: The signal intensity of HCC on T1-weighted images is related to the degree of histologic differentiation, intratumoral copper content, and zinc content of surrounding hepatic parenchyma, whereas the signal intensity on T2-weighted images is related to the degree of histologic differentiation.

Adult↗
PubMed1999

Radiotherapy for large hepatocellular carcinoma combined with transcatheter arterial embolization and percutaneous ethanol injection therapy.

This study was performed to determine the effect of radiotherapy (RT) combined with transcatheter arterial embolization (TAE) and percutaneous ethanol injection (PEI) on large HCC. Between 1988 and 1996, 102 patients with unresectable, biopsy proven HCC underwent uniform pretreatment assessment followed by TAE and PEI. Of the 102 patients, 68 (67%) had more than 2 lesions in the liver, and the largest tumor sizes in each patient ranged from 3 to 8 cm in diameter. Immediately after TAE and PEI, external beam RT (36 to 70 Gy) was administered to the largest tumors only in 44 patients. The cause-specific 5-year survival rate for all patients was 39.9%. The 3-year survival rate of the RT group was better than that of the no RT group (81.1% vs. 54.6%). The cumulative local control rates of the largest treated tumors were 53.2% in the RT group and 32.7% in the no RT, respectively (p=0.006). When the survival rate was compared between patients with and without local control in the RT group, that of patients with local control was significantly better than that with local recurrences (p=0.048). No deaths or major treatment related complications occurred. RT combined with TAE and PEI did not clearly show improvement of the survival, however, it effectively controlled large HCC, and demonstrated minimal toxicity. This treatment may represent therapeutic option for some patients with unresectable large HCC.

Aged↗
PubMed1999

[A ruptured aneurysm of the anterior and posterior inferior cerebellar artery: a case report].

We report a case of an anterior and posterior-inferior cerebellar artery (AICA-PICA) aneurysm. The patient was a 62-year-old woman who suffered from sudden onset of severe headache and nuchalgia. Computed tomography (CT) scan revealed subarachnoid hemorrhage in the ambient cistern and blood clots in the 3rd and 4th ventricles. Vertebral angiography demonstrated an aneurysm located at the distal segment of the left AICA-PICA. Three demensional CT scan was very useful for the decision concerning surgical strategy. The patient underwent bilateral occipital craniectomy and the aneurysm was clipped successfully via the midline suboccipital approach. Her postoperative course was uneventful. Postoperative angiography showed successful clipping of the aneurysm. Distal AICA-PICA aneurysm is a very rare disease and only one case has been reported in the literature. The clinical features, CT findings, and surgical approach of distal AICA-PICA aneurysms are briefly discussed while reviewing the literature.

Aneurysm, Ruptured↗