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Biomedical subjects

T Takayama

Publications and source records attributed to T Takayama.

At least 55 records · Page 3Linked to original sources

Frequent beta-catenin aberration in human hepatocellular carcinoma.

Recently, mutations in the beta-catenin gene in hepatocellular carcinoma (HCC) have been reported: approximately 20% of HCCs had activating mutations at the glycogen synthase kinase 3beta phosphorylation sites within the exon 3 of the beta-catenin gene. However, changes in the level of the beta-catenin protein in HCC have not been well studied. We examined, by Western blotting, the expression level of the beta-catenin protein in cancerous tissues in comparison with that in adjacent non-cancerous tissues obtained from 32 cases of HCC with hepatitis C. An increase in the beta-catenin protein level in cancerous tissue compared to that in adjacent non-cancerous tissue was found in 15 (46.9%) of 32 cases of HCC. Mutation in exon 3 of the beta-catenin gene was found in six (18.8%) of the 32 cases, in five of which the beta-catenin protein level was increased. In total, beta-catenin aberration was found in 16 (50.0%) of 32 cases of HCC. It should be noted that beta-catenin aberration was also found in early HCC although it was observed chiefly in advanced HCCs. These results indicate that beta-catenin aberration is a frequent event in the development of HCC and may facilitate the development of HCC in the course of chronic hepatitis.

Journal Article↗

Randomized comparison of ultrasonic vs clamp transection of the liver.

HYPOTHESIS: Hepatic parenchymal transection is a technical priority in liver surgery. The use of an ultrasonic dissector for hepatectomy may result in less blood loss than conventional clamp crushing. DESIGN: Randomized controlled trial. SETTING: University teaching hospital. PATIENTS: The 132 patients scheduled to undergo partial hepatectomies were randomly assigned to receive hepatic transection by ultrasonic dissector or by clamp crushing (66 patients by each method). INTERVENTIONS: All resections were performed with inflow occlusion and were guided ultrasonographically. Hepatectomies were graded according to a predefined system based on 6 criteria (blood loss, transection time, technical error, surgical margin, landmark appearance, and postoperative morbidity), each with 3 scores (lower scores indicating higher quality). MAIN OUTCOME MEASURES: Blood loss and hepatectomy grade. RESULTS: No difference was found between the ultrasonic and clamp groups in median blood loss (515 mL [range, 15-2527 mL] vs 452 mL [range, 17-1912 mL]; P =.63), transection time (61 minutes [range, 16-177 minutes] vs 54 minutes [range, 7-205 minutes]; P =.58), or transection speed (1.1 cm(2)/min [range, 0.4-4.0 cm(2)/min] vs 1.0 cm(2)/min [range, 0.4-3.0 cm(2)/min]; P =.90). Ultrasonic dissection caused more frequent histologically proven tumor exposure at the surgical margin (9 vs 3 patients; P =.09), incomplete appearance of landmark hepatic veins on the cut surface after anatomical resection (12 vs 4 patients; P =.03), and postoperative morbidity (20 vs 14 patients; P =.32) than did clamp crushing. The hepatectomies with clamp crushing had significantly higher grades than those with ultrasonic dissection (P =.05), as indicated by the lower median sum score (4.0 [range, 0-12] vs 5.0 [range, 0-19]; 95% confidence interval for difference, -2.0 to 0; P =.03). The transection method independently influenced hepatectomy grade (adjusted odds ratio = 3.06; 95% confidence interval, 1.35-6.92; P =.01). CONCLUSIONS: Ultrasonic dissection offers no reduction in blood loss compared with clamp crushing for transection of the liver. Clamp crushing results in a higher quality of hepatectomy and is therefore the option of choice.

Adult↗

Prediction of the physiologic severity of coronary lesions using 3D IVUS: validation by direct coronary pressure measurements.

This study was performed to determine whether three-dimensional intravascular ultrasound (3D IVUS) could predict the physiologic significance of coronary lesions. Seventeen lesions were evaluated by means of 3D IVUS, pressure measurements, and quantitative coronary angiography. Physiologic parameters were calculated from the 3D IVUS measures using established equations and compared to values measured by pressure guidewire. IVUS minimum lumen area (MLA) correlated with fractional flow reserve (FFR; R2 = 0.55, P = 0.003) and pressure gradient (R2 = 0.52, P = 0.003). Lesion length (L) had a positive correlation with pressure gradient (R2 = 0.45, P = 0.007). By multivariate analysis, the only significant independent determinant of FFR was MLA/L measured by IVUS. The IVUS-predicted pressure gradient and FFR were well correlated with values measured directly (R2) = 0.88, P < 0.001; R2 = 0.90, P < 0.001, respectively). The physiologic severity of coronary lesions is primarily influenced by lumen area and lesion length and can be established by 3D IVUS.

Coronary Disease↗

Bcl-X expression in esophageal squamous cell carcinoma: association with tumor progression and prognosis.

BACKGROUND AND OBJECTIVES: Bcl-2 family proteins are regulators of programmed cell death and important in the development and progression of human various tumors. The role of these proteins in the development, progression and differentiation of esophageal squamous cell carcinoma (ESCC) is unclear. METHODS: We investigated the expression of Bcl-2, Bcl-X, and Bax using immunohistochemistry in 86 ESCCs, and scored the expression by the weighted score. RESULTS: Bcl-2 expression related to pT category (P=0.043) and histological grade (P = 0.001). Bcl-X expression related to pT category (P = 0.003), pN category (P = 0.041) and the number of positive nodes (P = 0.036), and had a tendency to relate to histological grade (P = 0.086). Bax expression had a tendency to relate to pN category (P = 0.081). The inverse relationship between Bcl-2 and Bcl-X expression was detected (P = 0.001), while the positive one between Bcl-X and Bax expression was detected (P = 0.014). Patients with low Bcl-X weighted score had a significantly longer survival compared with those with high Bcl-X weighted score. Multivariate analysis revealed Bcl-X expression as the independent prognostic factors (P = 0.022). CONCLUSION: These results imply that Bcl-2 family proteins, especially Bcl-X, may contribute to the progression in ESCC.

Adult↗

Increase in the concentration of carbon 18 monounsaturated fatty acids in the liver with hepatitis C: analysis in transgenic mice and humans.

Steatosis is one of the histologic characteristics of chronic hepatitis C and is well reproduced in a transgenic mouse model for hepatocellular carcinoma (HCC) in which the core protein of hepatitis C virus (HCV) plays a pivotal role in inducing steatosis and HCC. In the present study, the lipid composition in the liver of the HCV core gene transgenic mice as well as in those of chronic hepatitis C patients was determined. The concentration of carbon 18 monounsaturated (C18:1) fatty acids, such as oleic and vaccenic acids, which are known to increase membrane fluidity leading to higher cell division rates, significantly increased in the livers of transgenic mice compared to nontransgenic control mice. The concentration of C18:1 fatty acids also significantly increased in the livers of chronic hepatitis C patients compared to subjects without HCV infection. These results suggest that HCV may affect a specific pathway in the lipid metabolism and cause steatosis in the liver.

Animals↗

Clinical approach to renal study incidental to 99mTc-MDP bone scintigraphy.

In order to investigate the feasibility of the assessment of renal function with 99mTc-MDP, we compared renographical images, renogram patterns and the glomerular filtration rate (GFR) obtained by means of a modified Gates' method and 200 MBq of 99mTc-MDP with those obtained by means of 99mTc-DTPA. Because 19 of 20 patients had malignant tumors in the genitourinary tract, there was no difference between the two tracers in identifying a parenchymal defect corresponding to renal cancer. Of eight patients with hydronephrosis, four had a defect or decreased uptake with a dilated pelvis, whereas the other four had marked radioisotope retention in the renal pelvis or the whole kidney on serial images. There was also no difference between the two tracers in identifying hydronephrosis. Of 38 paired renograms 35 showed the same renogram patterns with both tracers. Of three patients with different renogram patterns, two had hydronephrosis. In 20 patients including three patients with bone metastasis, total GFR and split GFR obtained with both tracers correlated with a correlation coefficient of r = 0.920 (p < 0.001) and r = 0.944 (p < 0.001), respectively. Excluding bone metastasis from the analysis, a linear-regression analysis showed excellent agreement between the two measurements with a correlation coefficient of r = 0.960 (p < 0.001) and r = 0.963 (p < 0.001), respectively. The linear regression equations were Y = 1.009X - 0.111 and Y = 1.034X - 0.714, respectively. In conclusion, 99mTc-MDP can be used as a supplement to evaluate renal function incidental to the survey of bone metastases in patients with malignant tumor.

Aged↗

The CdTe detector module and its imaging performance.

UNLABELLED: In recent years investigations into the application of semiconductor detector technology in gamma cameras have become active world-wide. The reason for this burst of activity is the expectation that the semiconductor-based gamma camera would outperform the conventional Anger-type gamma camera with a large scintillator and photomultipliers. Nevertheless, to date, it cannot be said that this expectation has been met. METHODS: While most of the studies have used CZT (Cadmium Zinc Telluride) as the semiconductor material, we designed and fabricated an experimental detector module of CdTe (Cadmium Telluride). The module consists of 512 elements and its pixel pitch is 1.6 mm. We have evaluated its energy resolution, planar image performance, single photon emission computed tomography (SPECT) image performance and time resolution for coincidence detection. RESULTS: The average energy resolution was 5.5% FWHM at 140 keV. The intrinsic spatial resolution was 1.6 mm. The quality of the phantom images, both planar and SPECT, was visually superior to that of the Anger-type gamma camera. The quantitative assessment of SPECT images showed accuracy far better than that of the Anger-type camera. The coincidence time resolution was 8.6 ns. All measurements were done at room temperature, and the polarization effect that had been the biggest concern for CdTe was not significant. CONCLUSION: The results indicated that the semiconductor-based gamma camera is superior in performance to the Anger-type and has the possibility of being used as a positron emission computed tomography (PET) scanner.

Brain↗

Comparison of 99mTc-tetrofosmin uptakes on planar images with those in excised rats organs.

UNLABELLED: The radioactivity in the organs adjacent to the heart causes interference with the quantitative assessment of myocardial uptake of tracer on scintigraphy. In order to investigate how much the functions of these organs affect myocardial uptake seen in imaging, we compared the myocardial uptake measured by means of a gamma camera with the actual activity in the excised organs. METHODS: Thirty-three rats were imaged at 5, 10, 15, 30, 45, 60, 90 and 120 min after the administration of 99mTc-tetrofosmin, and % injected dose per pixel (%ID/pixel) for each organ was assessed on planar images (PI measurement). Percent injected dose per gram of tissue (%ID/g) in the heart as well as lungs, liver, gastrointestines and blood was measured by means of a well scintillation counter (WC measurement). Comparison between PI and WC measurements was performed with % uptake, the PI-to-WC ratio and heart-to-organ ratios. RESULTS: Our WC measurement showed an increase in cardiac uptake until 30 min (1.67 +/- 0.31%) postinjection and subsequent gradual decrease, whereas PI measurement showed maximum activity of 1.81 +/- 0.52% at 15 min postinjection. There was a prominent difference between the two measurements, particularly at 10 min, with a PI/WC ratio of about 1.6 times. Our WC measurement showed maximum pulmonary uptake at 15 min (0.87 +/- 0.31%) and a gradual decrease over 15 min, whereas PI measurement showed maximum uptake at 10 min (1.14 +/- 0.38%). There was hardly any variation in activity observed later than at 10 min. Our WC measurement showed hardly any variance in hepatic activity from 5 min (0.77 +/- 0.19%) to 30 min (0.69 +/- 0.27%) with a subsequent gradual decrease. The percent uptake in PI measurement was generally greater than that in WC measurement, and high values were found at 10 min and 15 min with PI/WC ratios of about 3.3 times and 2.3 times, respectively. CONCLUSION: Percent uptakes in PI measurement were greater than those in WC measurement. The difference between the two measurements was prominent in the early phases. The cardiac uptake in PI measurement was significantly greater than that in WC measurement at 10 min. It was considered that this discrepancy between the two measurements was caused by the Compton scatter from the organs adjacent to the heart.

Animals↗

Reversible hepatofugal portal flow after liver transplantation using a small-for-size graft from a living donor.

We describe a case of reversible hepatofugal portal flow 1 week after transplantation of a small-for-size liver graft from a living donor. A transient increase in intrahepatic portal vascular resistance was the suspected cause. The portal venous flow normalized after residual collateral channels had been interrupted surgically. The patient was discharged on the 90th postoperative day. Liver transplant clinicians should be aware that hepatofugal flow can occur with small-for-size liver grafts, despite sufficient portal venous flow immediately after transplantation.

Female↗

Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment.

A methylxanthine, pentoxifylline (PTX), has the potential to improve tumour microcirculation and oxygenation in vivo. We aimed to determine whether this agent would enhance the response of tumours to experimental radioimmunotherapy (RIT). Balb/c nu/nu mice with xenografts of LS180 human colon cancer were treated with 4.63 MBq of 131I-A7 anti-colorectal monoclonal antibody. A dose of 50 mg/kg of PTX was administered i.p. immediately after the 131I-A7 injection and daily thereafter for 7 days. The effect of PTX administration on 131I-A7 targeting in tumours was assessed with biodistribution and radioluminography on day 2. Intratumoural pO2 was measured with microelectrodes. The administration of PTX alone did not suppress tumour growth, but the efficacy of RIT with 131I-A7 was significantly improved by PTX: tumour volumes on day 15, relative to the initial volume, were 16.8+/-3.60 in the nontreated controls, 13.9+/-2.17 with PTX, 3.43+/-0.44 with RIT, and 1.86+/-0.59 with RIT+PTX (P<0.05). PTX administration did not alter the biodistribution or intratumoural distribution of 131I-A7. However, intratumoural pO2 was significantly improved by PTX administration: 16.9+/-9.75 mmHg in control tumours versus 25.6+/-11.3 mmHg in PTX-treated tumours (P<0.01). These results indicate that PTX-induced radiosensitisation of tumour cells due to better oxygenation is responsible for the better RIT outcomes, because the net radiation absorbed dose to the tumours did not appear to be changed.

Animals↗

The STR locus D11S554: allele frequencies and sequence data in a Japanese population.

A population study on the short tandem repeat (STR) locus D11S554 was carried out in a sample of 362 unrelated Japanese individuals living in the Gifu Prefecture. A total of 46 different alleles ranging from 180 bp to 340 bp and 135 genotypes were revealed. Sequence analysis of alleles was carried out for 185 samples. The sequence structures of the repeat regions of the alleles were found to be complex and the alleles were classified into nine sequence types, including four new sequence types. According to the system of Adams et al. (1993), we designated the new sequence types IA3, IA4, IA5 and IB3, respectively. Out of the 46 different alleles, 11 showed sequence heterogeneity. The results of this study demonstrated that the D11S554 locus is a powerful and useful genetic marker for forensic practice in the Japanese population.

Alleles↗

Morphology of the mitochondria and endoplasmic reticula of chorion laeve cytotrophoblasts: their resemblance to villous syncytiotrophoblasts rather than villous cytotrophoblasts.

We examined the morphological features of the mitochondria and endoplasmic reticula of chorion laeve cytotrophoblasts from term human fetal membranes, and compared them with those of syncytiotrophoblasts and cytotrophoblasts from human placental villi. Ultrastructural enzyme histochemistry of cytochrome c oxidase and glucose-6-phosphatase were used as cytochemical markers for these intracellular organelles. Chorion laeve cytotrophoblasts possessed abundant endoplasmic reticula, and small mitochondria with a few cristae, which were characteristic of villous syncytiotrophoblasts rather than villous cytotrophoblasts. As for these organellar structures, statistical analysis confirmed similarities between chorion laeve cytotrophoblasts and villous syncytiotrophoblasts, but significant differences between laeve cytotrophoblasts and villous cytotrophoblasts. Though these two cytotrophoblasts originated from one common cell in early placental development, they exhibited quite different organellar morphology during placental/chorioamniotic differentiation. Considering previous data, we concluded that chorion laeve cytotrophoblasts were metabolically active cells, similar to villous syncytiotrophoblasts, performing many functions in fetal membrane physiology.

Biomarkers↗

Seroepidemiological study of hepatitis E virus infection in Japan using a newly developed antibody assay.

PURPOSE: A seroepidemiological study of hepatitis E virus (HEV) infection was conducted in Japan, where HEV infection is not considered endemic. METHODS: IgG and IgM class antibodies to HEV were measured with a newly developed enzyme-linked immunosorbent assay in which recombinant virus-like particles were used as an antigen. A total of 1253 individuals (401 males and 852 females; age range, 6-89 years) were enrolled from two different areas: area 1 (n = 478), in which hepatitis C was endemic; and area 2 (n = 775), in which it was not endemic. RESULTS: The HEV antibody (IgG class) positive rate was 6.7% in area 1 and 4.6% in area 2. Similarly, the HAV antibody (IgG class) positive rates were 65.3% and 72.3%. The age- and sex-specific prevalence of both HAV and HEV antibodies was quite similar in the two areas, and the HAV antibody positive rate clearly increased with age in both males and females. On the other hand, the HEV antibody positive rate showed a slight tendency to increase with age in males, but not in females. None of the 32 individuals with the HEV antibody who were interviewed had a history of visiting countries in which hepatitis E was endemic. In both areas, the mean age, percentage of males, and HAV antibody positive rate were significantly higher in the group of individuals with the HEV antibody than in the group of those without it, according to conventional statistical analyses. Of the three factors age, male sex, presence of HAV antibody, and the area factor, only male sex was statistically significant (P < 0.001) on multivariate logistic regression analysis. Two (0.2%) of the total of 1253 individuals were positive for the IgM class antibody to HEV. CONCLUSIONS: Our results suggest the possibility that HEV infection is circulating in Japan at a low level. HEV infection was associated with male sex, but not with HAV infection.

Adolescent↗

Primary intestinal lymphangiectasia successfully treated with octreotide.

A 21-year-old man with diarrhea and edema was admitted to our hospital and diagnosed with protein-losing enteropathy caused by primary intestinal lymphangiectasia. He was placed, in turn, on a low-fat diet, an elemental diet, and, subsequently, fasting therapy with total parenteral nutrition (TPN) support. However, his symptoms were not relieved, but, rather were exacerbated. On the 45th day of hospitalization, octreotide therapy was initiated. After 2 weeks of treatment, his clinical symptoms, as well as hypoproteinemia and hypoalbuminemia, gradually became alleviated. The improvement was confirmed in terms of scintigraphy, endoscopy, and histology of the duodenum. The patient remained healthy until 6 months after the commencement of octreotide treatment, when he discontinued octreotide at his own discretion, at which point the symptoms recurred. Resumption of the drug, however, again brought about remission, which has continued until the present, March 2000. Thus, octreotide therapy is one modality which may be useful for refractory primary intestinal lymphangiectasia.

Adult↗

An obstructed venous aneurysm presenting as an abdominal mass: report of a case.

We report herein the case of a 32-year-old woman found to have a venous aneurysm originating from the ovarian vein. The patient presented with a 9-cm abdominal tumor, and surgery was performed under the preoperative diagnosis of a mesenteric cyst. The tumor was easily ablated from the mesentery and resected with the right ovarian artery and vein. Histologically, the wall of the cyst showed the structure of a vein, and the diagnosis of a venous aneurysm was made. This disease is difficult to diagnose preoperatively when a patient presents with no symptoms other than a palpable mass, or when the lumen is obstructed by thrombus. This report serves to demonstrate that a venous aneurysm should be considered in the differential diagnosis of an asymptomatic abdominal mass.

Adult↗

Telomerase activity as a predictive marker for recurrence of hepatocellular carcinoma after hepatectomy.

BACKGROUND: Expression of telomerase activity and stabilization of telomeres are concomitant with attainment of immortality in tumor cells. Telomerase activity levels in hepatocellular carcinoma (HCC) may serve as a predictive marker for recurrence after surgery. METHODS: Telomerase activity levels in HCC were measured in 37 patients undergoing hepatectomy by the telomeric repeat amplification protocol. The clinicopathologic factors and telomerase activity were analyzed to identify factors that were important in affecting recurrence of HCC and recurrence-free survival. RESULTS: Telomerase activity was detected in 23 patients (62.2%), and was not significantly associated with seven other HCC-related factors. After a median follow-up of 34 months, 24 patients (64.9%) had recurrence of HCC. In univariate analyses, telomerase activity of more than 20 total product generated (TPG) and portal vein invasion were found to be significantly related to a shorter time to recurrence. Multivariate analysis demonstrated that telomerase activity (>20 TPG) was significantly related to an increased risk of recurrence (relative risk 2.36, 95% confidence interval 1.03 to 5.43, P = 0.04). CONCLUSIONS: Telomerase activity can be identified as an independent predictor for recurrence after resection of HCC.

Adult↗

Intracoronary electrocardiogram for early detection of myocardial viability during coronary angioplasty in acute myocardial infarction.

PURPOSE: The clinical value of the intracoronary electrocardiogram (ECG) for detecting myocardial viability in acute myocardial infarction was evaluated by thallium-201 scintigraphy and left ventriculogram at the chronic stage. METHODS: Intracoronary ECGs, recorded from the tip of a guidewire during emergency coronary angioplasty, were obtained in 65 patients with reperfused anterior myocardial infarction. Further ST segment elevation of greater than 0.2 mV detected during the balloon inflation was taken as significant. The left ventricular segmental shortening was measured from left ventriculograms recorded at acute and chronic stages. The infarct area was defined as viable when a thallium uptake of more than 50% was detected on thallium-201 myocardial scintigraphy at the chronic stage. RESULTS: During emergency coronary angioplasty, significant ST segment elevation was noted in 45 patients (Group A); however, the ST segment was not significantly elevated in the other 20 patients (Group B). The infarct area of 42 patients in Group A and three patients in Group B was viable on scintigraphy. Improvement left ventricular wall motion of the infarct area was observed in 39 of the 42 patients in Group A and the three patients in Group B. Therefore, intracoronary ECG can predict reversible dysfunction with excellent sensitivity (92.9%) and specificity (73.9%). CONCLUSIONS: The myocardium within an infarct area can be regarded as viable when a further ST segment elevation occurs on intracoronary ECG during emergency coronary angioplasty. It is useful, therefore, to monitor the intracoronary ECG during coronary angioplasty balloon inflation to assess the myocardial viability of the infarct area.

Angioplasty, Balloon, Coronary↗