Search PubMed⌕ Search

Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 649 records · Page 36Linked to original sources
PubMed1995

Cyclosporin A and FK-506 in inhibition of rat Ito cell activation in vitro.

Ito cells are the primary matrix-producing cells in the liver. In hepatic fibrosis in vivo or culture on plastic, these cells undergo activation, a process characterized by cell proliferation, fibrogenesis, and smooth muscle alpha-actin expression. The cytosolic-binding proteins of cyclosporin A (CsA) and FK506 accelerate folding of various proteins including collagen and become inactivated by binding to those agents. CsA is shown to inhibit collagen synthesis in cultured fibroblasts. These findings prompted us to examine the effect of cyclosporin A and FK506 on Ito cell activation. CsA and FK506 reduced DNA synthesis in a dose-related manner, to 26% and 45% of controls at 5 mumol/L, respectively, without affecting total protein synthesis. CsA reduced collagen synthesis in a dose-related manner, to 70% of controls at 5 mumol/L without affecting noncollagenous protein synthesis, whereas FK506 changed neither collagen synthesis nor noncollagenous protein synthesis. Moreover, smooth muscle alpha-actin expression was reduced by 0.5 mumol/L CsA, but not by FK506. CsA merits consideration for the therapy of hepatic fibrosis. FK506 may also be a candidate for such therapy through inhibitory action on Ito cell proliferation.

Actins↗
PubMed1995

Increased proportion of plasma apoB-48 to apoB-100 in non-insulin-dependent diabetic rats: contribution of enhanced apoB mRNA editing in the liver.

To assess the alteration of apolipoprotein (apo) B mRNA editing in non-insulin-dependent diabetes mellitus (NIDDM), we measured plasma apoB-100 and apoB-48 levels and apoB mRNA editing efficiency in the liver and intestine from GK (Goto-Kakizaki) rats, a genetically NIDDM animal. Male GK rats and control littermates, aged 25 weeks, were used in this study. Ventromedial hypothalamus (VMH)-lesioned control rats were used as hyperinsulinemic models. VMH-lesioned GK rats (GK+VMH) were treated as an insulin-exhausted NIDDM model. Plasma cholesterol and triglyceride levels were increased in GK rats. Very low density lipoprotein (VLDL)-triglyceride and low density lipoprotein (LDL)-cholesterol concentrations were significantly higher in GK rats than in controls. The increase of VLDL-triglyceride was most marked in GK+VMH rats. Plasma apoB-48 levels, quantified by immunoblot, were increased in GK rats. However, apoB-100 levels were minimally elevated in GK rats. Therefore, the apoB-48/apoB-100 ratio was remarkably increased in GK rats. ApoB mRNA editing was analyzed by reverse transcriptase-polymerase chain reaction coupled with dideoxynucleotide chain termination assay. The ratio of apoB-48-type cDNA to apoB-100-type cDNA was significantly increased in the liver from GK rats compared with controls. Although the development of the VMH lesion increased plasma apoB-48 levels, it had no effect on the proportion of apoB-48-type to apoB-100-type cDNA in the liver from both GK and control littermates. ApoB mRNA in the intestine was almost totally edited (approximately 95%). Intestinal apoB-48/apoB-100 cDNA ratio showed no significant difference among the four groups. In conclusion, an enhanced apoB mRNA editing was indicated in the non-insulin-dependent diabetic rats, which might contribute to the increase of plasma apoB-48 levels.

Animals↗
PubMed1995

[Developments in brachytherapy].

Brachytherapy is one of the ideal methods of radiotherapy because of the concentration of a high dose on the target. Recent developments, including induction of afterloading method, utilization of small-sized high-activity sources such as Iridium-192, and induction of high technology and computerization, have made for shortening of irradiation time and source handling, which has led to easier management of the patient during treatment. Dose distribution at high dose rate (HDR) is at least as good as that of low dose rate (LDR), and selection of fractionation and treatment time assures even greater biological effects on hypoxic tumor cells than LDR. Experience with HDR brachytherapy in uterine cervix cancer using Cobalt-60 during the past 20 years in this country has gradually been evaluated in U.S. and Europe. The indications for HDR treatment have extended to esophagus, bronchus, bile duct, brain, intraoperative placement of source guide, and perineal region using templates, as well as the conventional use for uterus, tongue and so on.

Brachytherapy↗
PubMed1995

[Assessment of bone mineralization of hemodialyzed patients with SPA and DPA--different effect of PTX with the site].

We analyzed the bone changes at each site of secondary hyperparathyroidism (2 degrees HPT) on hemodialyzed patients using both single photon absorptiometry (SPA) and dual photon absorptiometry (DPA). The subjects were 35 hemodialysis patients (12 male, 24 female) with 2 degrees HPT. The bone mineral densities (BMD) of 1/3 radius, head, total body and 3rd lumbar spine were measured before and after parathyroidectomy (PTX). Before PTX, the BMD of 2 degrees HPT patients were lower than the normal range of all sites, especially at the radius which mainly consisted of cortical bone. After PTX, the BMD at all sites increased especially in the head. The BMD of the radius also continued to increased up two years after PTX, but it was not as increased as the BMD of head. The BMD of the lumbar spine which consisted of cancellous bone mainly increased after PTX for one year and decreased thereafter. This decrease was influenced by age. There was a difference with the site of BMD after PTX. The determination of changes of BMD of head and radius was considered useful for the judgment of treatment.

Absorptiometry, Photon↗
PubMed1995

Diagnosis of chronic liver disease from liver scintiscans by fuzzy reasoning.

UNLABELLED: We investigated the possibility that fuzzy reasoning might be used to standardize diagnosis of liver disease based on scintigraphic results and compared the results with those obtained when scintiscans were scored conventionally. METHODS: Seventy-five patients with chronic liver disease (11 patients had chronic persistent hepatitis, 26 had chronic aggressive hepatitis and 38 had cirrhosis) and 25 controls were studied. Another 75 patients with hepatitis or cirrhosis were examined to test the effectiveness of the membership functions. Liver scintiscans were taken 20 min after the intravenous injection of 111 MBq of 99mTc-phytate. Fuzzy reasoning was used to evaluate the following five items: the ratio of the sizes of the left and right lobes, splenomegaly, radioactivity in the bone marrow, deformity of the liver and distribution of radioactivity in the liver. The degree of conformity to each of the three liver diseases being investigated was substituted into the membership function for the conclusion. The center of gravity for each patient's results was calculated. Conventional scoring was made with three levels for each of the five items examined by fuzzy reasoning. RESULTS: Distinctions between chronic persistent hepatitis and chronic aggressive hepatitis were difficult to assess with fuzzy reasoning and conventional scoring. The diagnostic accuracy was 95% for patients with cirrhosis and 88% for patients with chronic hepatitis with fuzzy reasoning. With conventional scoring the accuracy was 86% for patients with cirrhosis and 75% for patients with chronic hepatitis. When fuzzy reasoning was used to examine the other 75 patients with chronic liver diseases, the accuracy was 93% for patients with cirrhosis and 86% for patients with chronic hepatitis. CONCLUSION: The method is simple and can be used routinely in clinical settings.

Adult↗
PubMed1995

Radiographic changes following radiotherapy in the patients with lung cancer. Is the irradiated area of the mediastinum in the simulation film a significant factor?

BACKGROUND: Radiation induced lung injury is an ominous adverse reaction in the management of thoracic disease by radiation therapy. Although the importance of the area of irradiated lung is well known, the irradiated area of mediastinum is little to be considered in the routine treatment. PURPOSE: To evaluate the significance of the irradiated area of the mediastinum in the simulation film for radiation induced lung injury. PATIENTS AND METHODS: A total of 208 patients with primary lung cancer treated with radiation therapy were analyzed for incidence of radiation induced lung injury. Lung injury was defined as the appearance of an abnormal shadow on the chest radiograph. CT images were used to differentiate recurrence or other conditions. Age, sex, irradiation dose, irradiated lung area, T and N factors of the tumor, irradiated mediastinum area, performance status of patients, location of irradiated fields and use of chemotherapy were analyzed with Cox's multivariate regression model. RESULTS: The cumulative rate of radiation induced lung injury at 12 months was 85%. Significant factor of radiation induced lung injury was irradiated area of the mediastinum (p = 0.03). Irradiated area of the lung (p = 0.18, n.s.), total tumor dose (p = 0.1, n.s.), use of chemotherapy (p = 0.08, n.s.) and location of irradiated field (p = 0.08, n.s.) may also have an effect on radiation induced lung injury. CONCLUSION: The irradiated area of the mediastinum is one of the significant factors in radiation induced lung injury.

Adult↗
PubMed1995

DNA fragmentation of human infarcted myocardial cells demonstrated by the nick end labeling method and DNA agarose gel electrophoresis.

Myocardial tissue taken from 19 autopsy cases of myocardial infarction were examined both by the nick and labeling method (NELM) and by DNA agarose gel electrophoresis in order to demonstrate the localization of cells with fragmented DNA and to confirm the internucleosomal cleavage of DNA biochemically. The nuclei corresponding to those with the histological features of acute myocardial infarction in hematoxylin and eosin (H&E)-stained sections were stained strongly positive with the nick end labeling method. Myocardial cells corresponding to those with nick end labeling method-stained nuclei, on the other hand, had mostly pyknotic and karyolytic nuclei and some unremarkable nuclei, even nuclear ghosts, and showed degenerated cytoplasm, including contraction band necrosis in H&E-stained preparations. The agarose gel electrophoresis of DNA extracted from the corresponding areas mentioned above showed the ladder pattern of internucleosomal cleavage characteristic of apoptosis. The present study revealed that infarcted myocardial cells with nuclear outlines, even nuclear ghosts, showed a distinct DNA fragmentation with the ladder pattern of internucleosomal cleavage. It is concluded from this study that the damaged myocardial cells of acute myocardial infarction represent a coagulation necrosis having the biochemical nature of apoptosis.

Aged↗
PubMed1995

Application of 198Au grains for carcinoma of oral cavity.

PURPOSE: The purpose of this study is to analyze the results of the treatment using gold grain implants over the past 9 years and to evaluate the usefulness of this treatment method. PATIENTS AND METHODS: From January 1985 through April 1993, a total of 45 patients with squamous cell carcinomas of the oral cavity and the oropharynx were treated with 198Au grain (gold grain) at the Department of Radiology, Osaka University Medical School. The initial activity of the grains supplied weekly by the Japan Radioisotope Association was usually 5 mCi (185 MBq), and single implants were usual. In case of combined external irradiation, telecobalt gamma-rays or 4 MV X-rays were used for treatment before implant. RESULTS: The local control rate for patients with T1 stages was 80% (20/25) and with T2 stages, 59% (10/17). The local control rate was 71% (10/14) for gold grain alone and 72% (13/18) for external irradiation combined with gold grain implants (combined therapy). In combined therapy, the median of the interval between external irradiation and gold grain implants was 21 days. The treatment interval for patients with recurrent diseases was 22 days, 22, 27, 39 and 46, respectively. The progression rate showed a tendency to increase in the patients with longer interval (more than 21 days), and with partial regression after external irradiation (p = 0.0085). CONCLUSION: Our findings show that the time interval between external irradiation and gold grain implantation is an important factor in combined therapy. Therefore, we emphasize that the time interval should be shorter than 3 weeks.

Adult↗
PubMed1995

Radiotherapy for laryngeal cancer in patients under 50 years old.

Fifty-nine cases of laryngeal cancer treated by radiotherapy at the National Cancer Center Hospital between 1962 and 1990 were analyzed retrospectively. All the patients were less than 50 years old. The median total dose of the radiation delivered to the primary tumor site was 70 Gy. The overall 5-yr survival rate and 5-yr local control rate were 88% and 72%, respectively. Five (8.5%) of the 59 patients developed late recurrence more than five yr after initial treatment, but subsequent salvage operations were successful for disease control; three patients had T1 glottic cancer, one had T2-3 glottic cancer and one had T3N1 supraglottic cancer. Since the local control rate and the 5-yr survival rate after radiotherapy are satisfactory, radiotherapy, which allows both functional and esthetic conservation, has an important role in the treatment of laryngeal cancer in adults under 50 yr of age.

Adult↗
PubMed1995

[Pulmonary tuberculosis with systemic lymph node swelling].

A 31-year-old woman was admitted to our hospital because of cervical and axillar lymph node swelling. A chest X-ray film showed many nodular shadows and a cavity in the left upper lung field. The tuberculin test was positive. Transbronchial lung biopsy and cervical lymph node biopsy were done. Examination of the biopsy specimens revealed epithelial granulomas with caseous necrosis. Thus, pulmonary tuberculosis with systemic lymph node swelling was diagnosed. Examinations during the patient's hospital stay showed that she was not an immunocompromised host. Pulmonary tuberculosis with systemic lymph node swelling occurs only rarely in a non-immunocompromised host.

Adult↗
PubMed1995

Structure and stability of DNA containing alpha-deoxyadenosine.

The alpha-anomer of 2'-deoxyadenosine (alpha) is a major adenine lesion produced by hydroxyl radicals. This lesion was specifically incorporated in duplexes d(TGAGXGTAC).d(GTACNCTCA), where X = alpha and N = A, G, C, or T. The thermodynamic and structural perturbations introduced into DNA by alpha were assessed by UV-melting measurements and molecular mechanics calculations.

DNA↗
PubMed1994

Mutant isolation of mouse DNA topoisomerase II alpha in yeast.

For characterizing in vivo functions of a mammalian protein, it is informative to obtain conditional mutations and apply them to the mouse genetic system. However, the isolation of conditional mutations has been quite difficult in cultured cells. We report here that functional expression of a heterologous mammalian gene in the yeast Saccharomyces cerevisiae provides a system for isolating mutated genes. We found that the cloned mouse TOP2 alpha cDNA, which encodes mouse DNA topoisomerase II (topo II) alpha, could rescue the lethal phenotype caused by yeast top2 null mutation. In order to generate and select temperature-sensitive mouse topo II alpha, an expression plasmid was mutagenized in vitro and was transformed, using the plasmid shuffling method, into the yeast strain, in which the endogenous TOP2 gene had been disrupted. We observed that one of such clone of yeast cells harboring a mutagenized mouse TOP2 alpha showed temperature-sensitive growth. Enzymatic assays and sequencing analysis revealed that this phenotype was caused by the thermosensitive nature of the mutant mouse protein, which has isoleucine at amino acid 961 instead of threonine. Therefore we have isolated the first conditional mutation in the mouse TOP2 alpha.

Amino Acid Sequence↗
PubMed1994

Structural analyses of DNA fragments integrated by illegitimate recombination in Schizosaccharomyces pombe.

In order to elucidate the mechanisms of illegitimate recombination in eukaryotes, we have studied the structure of DNA fragments integrated by illegitimate recombination into the genome of fission yeast. Nonhomologous recombination was rarely identified when a long region of homology with the chromosomal leu1+ gene was present in the introduced leu1::ura4+ DNA fragment; but a decrease in length of homology leads to an increase in the ratio of non-homologous to homologous recombination events. The introduced DNA fragments were integrated into different sites in the chromosomes by nonhomologous recombination. The results suggested that there are multiple modes of integration; most events simply involve both ends of the fragments, while in other cases, fragments were integrated in a more complicated manner, probably via circularization or multimerization. To analyze the mechanism of the major type of integration, DNA fragments containing the recombination junctions of three recombinants were amplified by inverted polymerase chain reaction (IPCR) and their nucleotide sequences were determined. There was no obvious homology between introduced DNA and chromosomal DNA at these recombination sites. Furthermore it was found that each terminal region of the introduced DNA was deleted, but that there were no or very small deletions in the target sites of chromosomal DNA. Two models are proposed to explain the mechanism of nonhomologous integration.

Base Sequence↗