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Biomedical subjects

T Ashihara

Publications and source records attributed to T Ashihara.

At least 37 records · Page 2Linked to original sources
PubMed1999

Novel formula for cell kinetics in xenograft model of hepatocellular carcinoma using histologically calculable parameters.

The growth rate of tumors should be assessed in terms of both tumor cell proliferation and death. The former is considered to be determined by growth fraction and cell-cycle time, whereas the latter is mainly determined by apoptosis, especially in tumors with a low level of necrosis. While most hepatocellular carcinomas (HCCs) in a relatively early stage contain only a small amount of necrosis, the growth rate supposedly depends mainly on growth fraction, cell-cycle time, and apoptosis. However, their quantitative relationship remains unknown. We have derived a novel theoretical formula for determining this relationship in nonnecrotic HCC, using Ki-67-positive index, apoptotic score, and a correction factor, all calculable by histological assessment without injecting labeling agents. Furthermore, we confirmed the reliability of this formula, using a xenograft model of human HCC with less than 15% necrosis. In this model the values of cell-cycle time calculated from the formula were very close to those estimated by a conventional double-labeling method and showed high correlations. Since our novel formula can clarify the cell kinetics without cumbersome labeling procedures, it is expected to be clinically applicable to HCC with a small portion of necrosis, using the radiographically measured growth rate and the histologically assessed cell kinetic parameters.

Animals↗
PubMed1999

Effect of pilsicainide, a pure sodium channel blocker, on spiral waves during atrial fibrillation: theoretical analysis by numerical simulation.

This study investigated the effects of a particular type of sodium channel blocker, pilsicainide, on spiral waves, which are a possible mechanism of atrial fibrillation, by using numerical simulation. A meandering spiral wave was induced on a two-dimensional matrix corresponding to the isolated atrial myocardium. The model attempted to simulate the changes caused by pilsicainide. The conductivity was depressed and the refractory period was prolonged with little change in the action potential duration. The dynamic change in the refractory period depended on the preceding coupling interval. A blockline occurred and changed gradually because of the change in the refractory period. The spiral wave became a stable reentry rotating around the blockline, decreasing the excitation frequency in the matrix before rushing out of the matrix. The electrocardiogram showed a slow coarse wave, as well as a real electrocardiographic change by pilsicainide. This might, in part, explain how pilsicainide acts on atrial fibrillation. Key words: sodium channel blocker, pilsicainide, spiral wave, atrial fibrillation, computer simulation.

Anti-Arrhythmia Agents↗
PubMed1999

The dynamics of vortex-like reentry wave filaments in three-dimensional computer models.

Recent studies using computer simulation and biological studies in 2-dimensional excitable media have suggested that spiral wave reentrant activation and its core dynamics are important elements in the mechanism of functional reentrant tachyarrhythmias, such as atrial and ventricular fibrillation. However, vortex-like reentry has been observed in homogeneous 3-dimensional excitable media, and the dynamics of the related "filaments," which have 3-dimensionally connected "cores" in 2 dimensions, have not been clarified. In order to determine whether the filaments of vortex-like reentry waves can be observed in 3-dimensional media using a mathematical ionic current heart model and whether the abnormal ionic currents in myocardium affect the complexity of the filaments, we studied the qualitative features of vortex-like reentry dynamics using mathematical models in computer simulations. We employed the Luo-Rudy Phase I and the FitzHugh-Nagumo models for our heart media, which were cubic and ventricular shaped, and consisted of 8,000,000 and 5,636,654 myocardial units, respectively. Functional reentry, in the form of vortex waves, was induced in the media by the S1-S2 method. The vortex-like reentry waves and their filaments were displayed by computer graphics. Computations were performed on an NEC SX-4 supercomputer (NEC, Tokyo, Japan) using programs written in C language. Computer simulation studies have shown that the filament dynamics of vortex-like reentry in the original Luo-Rudy model is considerably more complex than that in the FitzHugh-Nagumo model. However, when we mathematically modified the L-type calcium current and shortened the action potential duration, just as occurs with sustained rapid ventricular pacing, the dynamics of the vortex-like reentrant wave fronts and the filaments were similar in both models. Our results suggested that the original character of myocardium causes drastic changes in filament shape and location, resulting in intricate functional reentrant waves, and that if the L-type calcium current is depressed, the complexity of the dynamics of the filaments are decreased to some degree.

Calcium↗
PubMed1999

Problems and our solutions for implementing telemedicine systems.

There are several problems on the practical use of telemedicine, for example, the difficulties involved in promoting communication between medical facilities, uncooperative clinicians, and the absence of high-speed circuits and high-resolution CRT. From the Japanese point of view, we suggest ways to resolve these problems. We will analyze and propose scenarios for realizing successful communications among medical institutions, medical communication and its characteristics, barriers to the promotion of communications among medical institutions, second-opinion centers, and separate satellites and separate circuits. We also mention the World Wide Web for teleconsultation, provision of assistance to people with data handicaps via a communications satellite, and assistance to programs designed for training telemedicine specialists. Using a communication satellite, we offer programs that explain preventive medicine, support activities for nursing at home, explain the risks of fast food, and support activities for the handicapped and women in a simple manner to computer illiterates.

Communication↗
PubMed1999

Usefulness of cytofluorometric DNA ploidy analysis in distinguishing benign cartilaginous tumors from chondrosarcomas.

In this study, we undertook to prove the usefulness of cytofluorometric DNA ploidy analysis in distinguishing benign cartilaginous tumors from chondrosarcomas. We analyzed the DNA ploidy of 47 cartilaginous tumors using DNA cytofluorometry, which is more sensitive than flow cytometry. All of these tumors were classified into six groups on the basis of clinical, radiologic, and histologic criteria. The 25 tumors in the No. 1 group showed no histologic signs of malignancy regardless of their clinical signs. The four tumors in the No. 2 group showed histologic signs of malignancy, but had benign clinical signs like small bone origin or Ollier's disease. The No. 3 group (13 tumors), No. 4 group (four tumors), and No. 5 group (three tumors) were conventional grade I, II, and III chondrosarcomas, respectively, and the No. 6 group included three dedifferentiated chondrosarcomas. Tumor cells isolated from fresh tumor materials treated with papain and collagenase were smeared on a glass slide and their nuclear DNA was stained with propidium iodide. The DNA content of each cell was measured by a cytofluorometer as fluorescence intensity. The results of this study showed that all of the tumors in the No. 1 group had a diploid pattern with a significantly lower (P<.001) cell proliferative activity than the grade I chondrosarcomas in the No. 3 group, all of which had a diploid pattern. Cytofluorometric analysis also indicated that grade II and III chondrosarcomas in the No. 4 and 5 groups had a higher frequency of hyperdiploid cells (%HDC), including aneuploid and polyploid cells than grade I chondrosarcomas. Importantly, all of the grade I chondrosarcomas showed a %HDC >8%, whereas all of the tumors in the No. 1 and 2 groups showed a %HDC <8%. Therefore, we believe that a %HDC value of 8% is borderline between biologically benign and malignant states in cartilaginous tumors. Four of five patients with aneuploid chondrosarcoma had tumor recurrence and two of these patients died of metastatic disease, although all of the patients except for one with diploid chondrosarcoma were continuously disease free after surgery. Based on these results, we concluded that the data of DNA ploidy analysis, especially cell proliferative activity expressed as %HDC, is more reliable and clinically more useful than the histologic and clinical signs of malignancy in distinguishing benign cartilaginous tumors from chondrosarcomas and even from low grade chondrosarcomas.

Adult↗
PubMed1998

Relation between cellular doxorubicin binding ability to nuclear DNA and histologic response to preoperative chemotherapy in patients with osteosarcoma.

BACKGROUND: Although chemosensitivity to antiosteosarcoma agents is the most important prognostic factor in human osteosarcoma, none of the many chemosensitivity tests reported previously are reliable and clinically useful. In this study, the authors investigated the reliability and clinical availability of doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) binding assay (ABA) as a new chemosensitivity test for osteosarcoma. METHODS: Doxorubicin (adriamycin [ADM]) binding ability (%AB) to nuclear DNA in isolated osteosarcoma cells was assessed by ABA in 14 patients with primary osteosarcoma who were treated with preoperative chemotherapy containing ADM and 6 patients with relapsed osteosarcoma after intensive chemotherapy. Histologic responses to preoperative chemotherapy were evaluated by percentage of tumor necrosis (%necrosis). RESULTS: Four of the 14 patients with primary osteosarcoma had %AB > 80% (97.3+/-3.7%) and demonstrated good histologic responses (>90% of %necrosis) to preoperative chemotherapy, whereas the remaining 10 patients had %AB < 80% (38.9+/-21.0%) and demonstrated poor responses. Patients with recurrent osteosarcoma that was clinically evaluated to be resistant to previous chemotherapy also had low %AB (34.2+/-28.3%). CONCLUSIONS: Because the results of the current study revealed that ABA is useful for predicting chemosensitivity to chemotherapy with ADM as well as chemotherapy without ADM for patients with osteosarcoma, and because ABA technically is simple and results can be assessed rapidly, the authors conclude that ABA is a clinically useful chemosensitivity test for patients with osteosarcoma.

Adolescent↗
PubMed1998

Actin organization associated with the expression of multidrug resistant phenotype in osteosarcoma cells and the effect of actin depolymerization on drug resistance.

We have previously reported that P-glycoprotein (Pgp)-overexpressing multidrug resistant (MDR) osteosarcoma cells were functionally more differentiated than their parent cells. The present study showed that in the parent cells, the actin filaments were sparsely distributed or were diffusely spread throughout the cytoplasm, whereas the MDR osteosarcoma cells exhibited a remarkable increase in well-organized actin stress fibers. Furthermore, dihydrocytochalasin B, a specific inhibitor of actin polymerization, dramatically disrupted this network of stress fibers, increased the intracellular accumulation of doxorubicin (DOX) and modified the resistance against DOX. These results indicate that the organization of actin filaments associated with cellular differentiation may be involved in the expression of Pgp function in the MDR osteosarcoma cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Aberrations of chromosomes 1 and 17 in six human osteosarcoma cell lines using double-target fluorescence in situ hybridization.

Analysis of six human osteosarcoma cell lines was performed by using double-target fluorescence in situ hybridization (FISH). FISH was applied to interphase nuclei, not to metaphase chromosomes. In this study, numerical aberrations of chromosomes 1 and 17 or structural chromosomal aberrations of chromosome arm 1p or 17p, in which it has been suggested that there are one or more tumor suppressor genes in various malignant tumors, were examined with this technique. All six of the human osteosarcoma cell lines studied had extra copies of chromosomes 1 and 17. A high frequency of deletions (> 60%) in chromosome 1 was found in two cell lines and deletions of chromosome 17 were found in one cell line.

Bone Neoplasms↗
PubMed1998

Angiogenesis in hepatocellular carcinoma as evaluated by CD34 immunohistochemistry.

To clarify the relationship between angiogenesis and hepatocarcinogenesis on progression of hepatocellular carcinoma (HCC), we quantitatively evaluated angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67 immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated using monoclonal antibody MIB-1. We used an image analysis system to assess the microvessel density as the area percentage of the endothelial area. Angiogenesis was generally observed in HCC and there was no significant difference among all clinical stages and histological grades of HCC. On the other hand, the staining of CD34 was partly observed in sinusoids of AH, although no positive staining was seen in any sinusoids of LC. The proliferative activity was significantly correlated with the clinical stage and histological grade of HCC. Our results indicate that the quantitation of angiogenesis does not provide significant prognostic information in HCC, but that it may have diagnostic value in distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically diagnosed as cancer, shows positive staining for CD34, suggesting that some portion of AH contains cancerous characteristics.

Adenoma↗
PubMed1998

Expression of inducible nitric oxide synthase and inflammatory cytokines in alveolar macrophages of ARDS following sepsis.

STUDY OBJECTIVE: The objective of this study was to evaluate the role of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines in alveolar macrophages (AMs) in the pathogenesis of ARDS following sepsis. SETTING: ICU in a university hospital. DESIGN: Prospective exploratory, open-labeled study was carried out. PATIENTS: A total of 24 patients were investigated: 8 patients diagnosed as having ARDS following sepsis (ARDS group); 8 patients under general anesthesia in the operating room whose lung functions were normal (control group); and 8 patients who were intubated and artificially ventilated for 1 week in the ICU whose lung functions were not deteriorated without fulfilling the ARDS criteria and whose general state fulfilled the sepsis criteria (long-term ventilation group, or LTV group). MEASUREMENTS AND RESULTS: The expression of iNOS, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) in AMs obtained from BAL fluid (BALF) was determined by the immunofluorescent technique. We observed the significant expression of iNOS, IL-6, and IL-8 only in the ARDS group. Meanwhile, NOx (the sum of NO2- + NO3-) was elevated in the BALF supernatant, and IL-6 and IL-8 levels in both the BALF supernatant and the serum were also elevated in the ARDS group. No significant expressions were detected in the control and the LTV group. CONCLUSIONS: The result that iNOS was detected only in ARDS patients following sepsis suggests that iNOS together with proinflammatory cytokines produced by AMs might play a pivotal role in the pathogenesis of acute lung injury and be useful for monitoring disorders in the lung in such conditions.

Adult↗
PubMed1998

[Predictability of Gleason score and reduction time (tau) of prostatic volume after castration for the prognosis of prostatic cancer].

PURPOSE: The efficacy of the reduction time (tau) after castration as a prognostic factor was examined by comparing to Gleason score. MATERIALS AND METHODS: The change of prostatic volume after castration was observed from the castration to 3 months after in 24 cases of prostatic cancer. Prostatic volume was examined by transrectal ultrasonography of the prostate. Survival curves was calculated by Kaplan-Meier method. Differences among survival curves were analyzed using Cox-Mantel test. RESULTS: tau had a close relationship to the prognosis of each case (Wilcoxon test: p < 0.05, Cox-Mantel test: p < 0.05). Gleason score had a weak relationship to prognosis (Wilcoxon test: N. S., Cox-Mantel test: p < 0.05). CONCLUSIONS: tau was efficient as prognostic factor compared to Gleason score.

Aged↗
PubMed1998

[The usefulness of MRCP in the initial diagnosis of the biliary and pancreatic diseases compared with ERCP].

The purpose of this study was to determine the effectiveness and the limitation of the MR cholangiopancreatography (MRCP) in the initial diagnosis for the biliary and pancreatic diseases compared with the image of Endoscopic retrograde cholangiopancreatography (ERCP). MRCP showed higher performance toward the discovery of the choledocholithiasis of a diameter 4 mm and more. Furthermore, MRCP reflected a malignant tumor at the constrictive part and the dilated proximal part of the biliary and pancreatic duct in 23 example all. An advantage of ERCP was the ability to carry out biopsies and therapeutic procedures, such as biliary drainage and sphincterotomy, while MRCP was an important diagnostic modality in the work-up of the biliary and pancreatic diseases and could help in planning treatment. MRCP would become the examination method first used, and it would be popularized all the more from now on.

Bile Duct Neoplasms↗
PubMed1997

Ploidy analysis in paraffin-embedded malignant fibrous histiocytoma by DNA cytofluorometry and flourescence in situ hybridization.

To prove the relationship between chromosomal aberration and DNA ploidy in human malignant fibrous histiocytoma (MFH), fluorescence in situ hybridization (FISH) and DNA cytofluorometry were performed in this study. For FISH study, the nucleus of each tumor cell was isolated from paraffin-embedded tissue of nine MFHs. Five chromosome-specific DNA probes (1p36, 1q12, 8q21.3, 11 centromere, and 17 centromere) were hybridized on cell nuclei. Cells with more than three probe signals were regarded as chromosome polysomy. All of the tumors analyzed by FISH had extra copies. The average percentage of polysomy in all tumors was high, ranging from 10.2% to 49.2%. The DNA ploidy patterns, and the percentage of hyperdiploid cells showing a greater DNA content than diploid cells, were obtained from DNA cytofluorometry. Three of nine were diploid patterns and six were non-diploid patterns, and the percentage of hyperdiploid cells in all tumors was high, ranging from 9.1% to 61.9%. The percentage of polysomy could be correlated with the percentage of hyperdiploid cells in each cell. In this study, we found that the DNA ploidy change was closely correlated with aberrations of chromosome copy number in MFH. In addition, the alterations of specific chromosome copy number could be detected in MFH showing diploid cells. Thus, these data indicate that FISH and DNA cytofluorometry are available as a cytogenetic tool for the analysis of interphase nuclei of bone and soft tissue tumors including MFH.

Biopsy↗
PubMed1997

Signal analysis and compression performance evaluation of pathological microscopic images.

Digitizing high-quality microscopic images and developing input/output technology for displaying those results is critical to telepathology in which pathological microscopic images are transferred to remote locations where they are diagnosed by specialists. This paper will discuss the results achieved by directly digitizing (nonfilm process) pathological microscopic images at a 2k x 2k resolution, and then using a super-high-definition imaging system to analyze their signals and evaluate compression performance. We will start off by digitizing samples that a pathologist will actually use in making a diagnosis, and then analyze their color distribution and spatial frequencies characteristics by comparing them to general images. This will make it apparent that such pathological images characteristically contain high spatial frequency in their chrominance components. We will also discuss the evaluation results of color differences for L*a*b* space and compression ratios achieved when using JPEG to encode pathological images. We will also present a subjective evaluation of the influence subsampling of chrominance components has on image quality.

Computer Systems↗
PubMed1996

Cytogenetic analyses of hepatocellular carcinoma by in situ hybridization with a chromosome-specific DNA probe.

BACKGROUND: Numerical chromosome analysis has been established in solid tumors by using in situ hybridization (ISH) with a chromosome-specific probe. We analyzed human hepatocellular carcinoma (HCC) by ISH for chromosome 17 and investigated the correlation of its copy number with histologic malignancy, proliferative activity, p53 mutation, and DNA ploidy. METHODS: Chromosome 17 was hybridized with a pericentromere-specific DNA probe directly on the tumor cells isolated from paraffin blocks of 25 surgically resected HCCs. Proliferative activity was measured by Ki-67 immunohistochemistry, p53 mutation was analyzed by p53 immunohistochemistry, and DNA ploidy was estimated by cytofluorometry. RESULTS: Forty-four percent of the 25 HCCs showed numerical abnormality of chromosome 17. Many disomic cases had a less malignant histology, whereas many polysomic cases had a more malignant histology. The Ki-67 positive index of polysomic cases was higher than that of disomic cases. In 22 cases (88.0%), the copy number of chromosome 17 was well matched with DNA ploidy. However, the numerical abnormality of chromosome 17 did not show a significant correlation with p53 mutation. Two of four HCCs that showed histologic heterogeneity were also heterogenous on ploidy pattern and the copy number of chromosome 17. Conversely, there was one case in which only ISH could demonstrate heterogeneity, although the other features exhibited homogeneity. CONCLUSIONS: Numerical chromosome abnormalities correlated with the increase of histologic malignancy proliferative activity, and DNA ploidy. Moreover, ISH analysis was useful in assessing the intratumoral heterogeneity in HCC, especially when current methods failed to detect it. Thus, ISH provides information on important biologic features, such as malignant potential and intratumoral heterogeneity, in HCC.

Adult↗
PubMed1996

Myocardial adrenergic nervous activity is intensified in patients with heart failure without left ventricular volume or pressure overload.

OBJECTIVES: To clarify whether myocardial adrenergic activity is different in patients with heart failure without left ventricular volume or pressure overload, we used iodine-123 metaiodobenzylguanidine (MIBG) imaging to study patients with mitral stenosis. BACKGROUND: In patients with heart failure due to cardiomyopathy or to valve diseases with volume or pressure overload, or both, myocardial adrenergic nerve activity is accelerated independent of underlying cause. However, it is not clear whether this change in myocardial adrenergic nerve activity is present in patients without left ventricular volume or pressure overload. METHODS: The study patients were 20 men and women with normal left ventricular function and heart failure due to mitral stenosis. Planar MIBG images obtained from these patients were compared with images from nine age-matched healthy subjects (control group). Myocardial uptake of MIBG was calculated as the heart/mediastinal activity ratio. Storage and release of MIBG were calculated as percent myocardial MIBG washout from 15 min to 4 h after isotope injection. All 20 study patients underwent echocardiography, and 16 underwent right heart catheterization. RESULTS: The heart/mediastinal activity ratio in the immediate images (15 min) did not show any significant difference between the patient and control groups. Myocardial washout was increased in patients with severe heart failure. The level of myocardial washout correlated with left atrial diameter (r = 0.51, p = 0.02) and mitral valve area calculated with Doppler echocardiography (r = -0.61, p < 0.01) and mitral valve area calculated with cardiac catheterization (r = -0.62, p = 0.02). The closest correlation existed between myocardial washout and cardiac output (r = -0.80, p < 0.01). CONCLUSIONS: In heart failure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. A decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification.

3-Iodobenzylguanidine↗
PubMed1996

[Occurrence of numerical aberrations of chromosomes in metachronous liver metastases of colorectal cancers].

To investigate the change of numerical aberrations of chromosome 17 or 18 during progression of Colorectal carcinoma, we applied FISH, using chromosome specific probes, to 3 colorectal primary carcinomas and a total of 4 metachronous metastatic lesions in the liver. We also investigated the relationship between the DNA content of whole nucleus and the number of chromosome 17 by multiparametric analysis using autostage cytofluorometry. When compared with the results for primary lesions, in 4 metastatic lesions, the population of tetrasomy 17 cells increased in 2 lesions, and that of monosomy 18 cells increased in 1 lesion. The nuclear DNA contents histograms for disomy 17 and aneusomy 17 cells analyzed individually for 3 primary and 4 metastatic lesions, showed almost no appreciable difference of peak DNA values. These results indicate that the numerical aberrations of chromosome 17 and 18 accumulate during the progression of colorectal carcinomas, and that the subpopulation of aneusomy 17 consist mainly of those cells that involve the numerical aberrations in a few chromosomes.

Chromosome Aberrations↗