Biomedical subjects

Kunio Doi

Publications and source records attributed to Kunio Doi.

At least 145 records · Page 8Linked to original sources

PubMed2002

Regional variations in the distributions of small intestinal intraepithelial lymphocytes in germ-free and specific pathogen-free mice.

Previously, we reported the regional variations in intraepithelial lymphocytes (IELs) in the small intestine of mice. To clarify the effects of intestinal bacteria on the distribution of IELs, regional variations in IELs were examined using germ-free (GF) and specific pathogen-free (SPF) BALB/cA mice. The small intestine was taken and divided equally into three parts (the proximal, middle, and distal parts). IELs were isolated from each part of the intestine, and the total number of IELs in GF mice was about one seventh of that in SPF mice. The decreased number of IELs in GF mice suggests that intestinal bacteria may be essential for local expansion of IELs. On the other hand, similar regional variations in IEL subsets observed in both GF and SPF mice, except for some subsets. The similarity of regional variations in GF and SPF mice indicates that the regional variations in IEL subsets may not fundamentally depend on intestinal bacteria.

Animals↗

PubMed2002

Age-related changes in the regional variations in the number and subsets of intraepithelial lymphocytes in mouse small intestine.

Previously, we reported regional variations in the number and subsets of the small intestinal IELs of mice. In this study, we examined the age-related changes in the regional variations of IELs in mice from 2 to 11 weeks old. IELs were isolated from the proximal, middle and distal parts of the small intestine and analysed by flow cytometry. The total number of IELs gradually increased with age and reached a plateau at 8 weeks old. As to IEL subsets, the percentage of alpha beta T cells was higher in the distal part at and after 2 weeks of age (before weaning). The percentage of the alpha beta T cell subset of extrathymic origin was higher in the proximal part while the percentages of alpha beta T cell subsets of thymic origin were higher in the distal part at and after 3 weeks (just after weaning). It appears that regional variations in IELs may be formed before the weaning period in mice.

Age Factors↗

PubMed2002

Use of an artificial neural network to determine the diagnostic value of specific clinical and radiologic parameters in the diagnosis of interstitial lung disease on chest radiographs.

RATIONALE AND OBJECTIVES: The authors investigated the diagnostic value of each of multiple clinical parameters and radiologic findings in differentiating between various interstitial lung diseases by using an artificial neural network (ANN). MATERIALS AND METHODS: The ANN was designed to differentiate between 11 interstitial lung diseases. The authors employed 10 clinical parameters and 16 radiologic findings that were divided into three groups (location, general appearance, specific findings). The performance of the ANN was evaluated with receiver operating characteristic analysis with amodified round-robin (leave-one-out) method and 370 cases (150 actual cases, 110 published cases, and 110 hypothetical cases). The Az values of ANNs were evaluated with various combinations of 10 clinical parameters and 16 radiologic findings. RESULTS: The Az value obtained with the complete set of clinical parameters and radiologic findings was 0.947. The Az value obtained with the 10 clinical parameters alone was 0.900, which was greater than 0.843 obtained with the 16 radiologic findings alone. There were statistically significant differences among Az values for some diseases when certain clinical parameters were removed from the input. Omission of specific findings among the three groups of radiologic findings decreased the Az value significantly. CONCLUSION: These results appear to confirm that clinical parameters can be equally as or more important than radiologic findings in the diagnosis of interstitial lung diseases. Among radiologic findings, certain specific findings can be more important than the location or general appearance of abnormal findings.

Humans↗

PubMed2002

Independent versus sequential reading in ROC studies of computer-assist modalities: analysis of components of variance.

RATIONALE AND OBJECTIVES: The authors analyzed two methods for arranging the temporal sequencing of unaided versus computer-assisted reading in multiple-reader, multiple-case receiver operating characteristic studies of detection of solitary pulmonary nodules on chest radiographs. In the "independent" mode the readings are separated by about I month; in the "sequential" mode, the computer-assisted reading immediately follows the unassisted reading. MATERIALS AND METHODS: The authors used the method of Beiden, Wagner, and Campbell (BWC) to decompose the components of variance of receiver operating characteristic accuracy measures into those that are correlated and those that are uncorrelated across reading conditions. Only the latter contribute to uncertainty in estimates of the difference in accuracy measures across reading conditions (unaided vs aided). This method was used to analyze data from two independent studies of the detection of solitary pulmonary nodules on chest radiographs. RESULTS: In the sequential reading mode the components that were correlated across reading conditions increased compared to the independent reading mode, as might be expected. What was not anticipated was the fact that the total reader variance was approximately the same for the two reading modes. The results were remarkably similar across the two independent studies analyzed. CONCLUSION: The sequential reading mode may thus be the more sensitive probe of the difference between unassisted and computer-assisted reading, if the mean effect is unperturbed (as here). It is also the least demanding on the logistics and investment of reader time.

Analysis of Variance↗

PubMed2002

Mechanisms of 5-azacytidine (5AzC)-induced toxicity in the rat foetal brain.

Mechanisms of 5-azacytidine (5AzC)-induced toxicity in the rat foetal brain were investigated. 5AzC (10 mg/kg) was injected into pregnant rats on day 13 of gestation and the protein and mRNA expressions of p53 and its transcriptional target genes, p21, bax, cyclin G1, fas, and gadd45, were examined in the foetal brain. The number of p53-positive cells peaked at 9 h after treatment (HAT) and those of apoptotic cells and p21-positive cells peaked at 12 HAT. The expressions of p21, bax, cyclin G1, and fas mRNAs were significantly elevated from 9 to 12 HAT. From the experiments using 5-bromo-2'-deoxyuridine (BrdU), as compared with controls, the migration of neuroepithelial cells significantly delayed and BrdU-positive signals were observed in many apoptotic cells from 9 to 24 HAT in the 5AzC-group. In addition, the number of S phase cells significantly decreased at 12 HAT. The present results indicate that 5AzC induced apoptosis and cell cycle arrest probably at G1 phase in the rat foetal brain and they might be mediated by p53 in response to DNA damage.

Animals↗

PubMed2002

Role of endotoxin in 6-sulfanilamidoindazole(6SAI)-induced arthritis in rats.

6-Sulfanilamidoindazole (6SAI) induces selflimiting arthritis in rats. Since close relationships exist between arthritis and endotoxin, four experiments were conducted to clarify the relationship between endotoxin and 6SAI-induced arthritis. Endotoxin levels in the plasma from the abdominal aorta and portal vein from rats that had 6SAI (500 mg/kg) administered orally for up to 7 days remained within the control values at day 1 and day 3, and were significantly elevated at day 7. Endotoxin levels in the synovial fluid from the same rats showed no significant change. Ankle swelling and redness in rats treated 11 consecutive days with 6SAI did not ameliorate when coadministered with an anti-endotoxin agent, polymyxin B sulfate. Histopathological examination on the ankles of rats treated orally with non-arthiritogenic sulfonamides including sulfonamide, sulfamethoxazole and sulfadimethoxin (250 and 500 mg/kg/day, each compound) for 2 weeks demonstrated no inflammatory changes, while hyperplasia/hypertrophy of thyroid epithelial cells were frequently observed. When histopathological changes in the ankles from rats coadministered with 6SAI and lipopolysaccharide (LPS, Escherihia coli O55:B5, 50 microg/kg, i.v.) were compared with those in rats treated with 6SAI or LPS alone, the ankles from the 6SAI+LPS treated animals had marked edematous inflammation in the synovium and surrounding connective tissues, whereas the LPS-group had only mild focal infiltration of polymorphonuclear leukocytes in the synovium and the 6SAI-group showed no apparent changes. These results suggest that endotoxin is not a direct cause but a possible acceralating factor of 6SAI-induced arthritis, and that the effects of 6SAI on gut bacteria is not related with the pathogenesis of this model.

Administration, Oral↗

PubMed2002

Nitrofurazone induces non-regenerative hepatocyte proliferation in rats.

The antibiotic nitrofurazone (NF) has been known for its testicular toxicity; in contrast, much less is known about its effect on the liver. NF was given to male rats for up to 7 consecutive days to evaluate NF-induced effects on the liver. NF increased hepatocyte DNA synthesis and liver weight in a dose-dependent manner, with no apparent histological or biochemical evidence of cell damage or loss. The hepatocyte proliferation ceased after a few days despite the continuation of treatment. The absence of cell damage indicates that NF-induced hepatocyte proliferation is different from regenerative proliferation that is seen after partial hepatectomy or cell necrosis.

Administration, Oral↗

PubMed2002

Nivalenol--induced apoptosis in thymus, spleen and Peyer's patches of mice.

ICR:CD-1 male mice were orally administered with Nivalenol(NIV) at the dose levels of 5, 10 and 15 mg/kg body weight, and examined at 12, 24 and 48 hours after inoculation (HAI), respectively, to elucidate the process of development of apoptosis in the thymus, spleen and Peyer's patch. There were no signs of clinical disorders and no changes in body and organ weights until 48 HAI except for that the thymus weight significantly decreased at 48 HAI. Immunohistochemically, the number of apoptotic lymphocytes evaluated by in situ detection for fragmented DNA showed a dose-dependent increase at 12 HAI in both the thymus and the Peyer's patch, while it became to increase at 24 HAI in the spleen. Dead lymphocytes in the thymus, spleen and Peyer's patch showed ultrastructural characteristics of apoptosis. Moreover, the DNA ladder was first detected by agarose gel electrophoresis at 12 HAI in the thymus of 15 mg/kg-group. The results clearly indicate that NIV is able to induce apoptosis in the lymphoid tissues of mice.

Administration, Oral↗

PubMed2002

Granulocyte colony-stimulating factor exacerbates the acute lung injury and pulmonary fibrosis induced by intratracheal administration of bleomycin in rats.

We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on lung injury induced by intratracheal administration of bleomycin (BLM, 2 mg/200 micro1) in rats. In experiment 1, G-CSF (10, 30 and 100 microg/kg/day, s.c.) was administered to rats treated with BLM or saline for 7 days starting immediately after BLM administration. In rats receiving G-CSF alone, a large number of neutrophils were noted in the pulmonary capillaries, although there were no lung lesions. In rats receiving BLM alone, diffuse alveolar damage was observed. The administration of G-CSF to BLM-treated rats increased the total lung lesion per unit of pulmonary parenchyma (total lung lesion %) along with increases in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion in a dose-dependent fashion. In experiment 2, 100 microg/kg/day of G-CSF was administered to rats treated with BLM or saline for up to 28 days starting immediately after BLM administration. The administration of 100 microg/kg/day of G-CSF to BLM-treated rats showed no effects at 14 days but it increased the lung lesion % and the score of lung fibrosis along with the increase in the number of neutrophils infiltrating in the pulmonary lesion at 28 days. These findings suggest that G-CSF administration to BLM-treated rats influenced and exacerbated the BLM-induced acute lung injury, and also exacerbated pulmonary fibrosis in a dose-dependent fashion. The exacerbation of lung injury coincided with the marked increase in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion.

Acute Disease↗

PubMed2002

Ultrastructural changes in the dorsal skin of Wistar-derived hypotrichotic WBN/ILA-Ht rats exposed to subchronic ultraviolet B (UVB)-irradiation.

Ultrastructural changes in the dorsal skin were examined in Wistar-derived hypotrichotic WBN/ILA-Ht rats exposed to subchronic UVB-irradiation (10 kJ/m2 per rat per day for up to 3 months). Epidermal hyperplasia developed at I month of UVB-irradiation and progressed thereafter, resulting in epidermal thickening and formation of epidermal ingrowths projecting into the dermis. In some portions of the epidermal ingrowths at 2 and 3 months, keratinocytes were somewhat pleomorphic. In addition, some of the keratinocytes showing cytoplasmic projections migrated into the dermis. The basement membrane and hemidesmosomes at the epidermal-dermal junction became to disappear along with the development of edema spreading from the upper dermis to the epidermis. However, Langerhans cells were still detected in the hyperplastic epidermis even at 3 months. In the dermis, in addition to edema, fibroblast proliferation and mast cell infiltration progressed with time, and degranulation of mast cells was obvious at 2 and 3 months. Only a few basophils as well as eosinophils were also found. In the upper dermis, especially beneath the epidermis, decrease in diameter and disintegration of collagen fibrils were observed. Ultrastructural characteristics of the dorsal skin responses to subchronic UVB-irradiation were clarified in the present study.

Animals↗

PubMed2002

Immunohistochemical study on inducible type of nitric oxide (iNOS), basic fibroblast growth factor (bFGF) and tumor growth factor-beta1 (TGF-beta1) in arteritis induced in rats by fenoldopam and theophylline, vasodilators.

Arteritis induced in rats by vasodilators, fenoldopam and theophylline, was examined immunohistochemically for expressions of inducible type of nitric oxide synthase (iNOS), basic fibroblast growth factor (bFGF) and tumor growth factor-beta1 (TGF-beta1). Rats were administered fenoldopam for 24 hours by intravenous infusion with or without following repeated daily oral administrations of theophylline. Irrespective of theophylline administration, iNOS antigens were remarkably abundant in ED-1-positive cells on day 5 and 8 post-fenoldopam-infusion (DPI); bFGF antigens were remarkably abundant in ED-1-positive cells on 1 and 3 DPI; TGF-beta1 antigens were observed in ED-1-positive cells on and after 5 DPI. These results suggest that the peak expression of iNOS antigen was followed by that of bFGF antigen, and bFGF may have a suppressive effect on iNOS expression in these rat arteritis models. On the other hand, TGF-beta1 was not considered to have a suppressive effect on iNOS expression in these models.

Administration, Oral↗

PubMed2002

5-Azacytidine (5AzC)-induced histopathological changes in the central nervous system of rat fetuses.

5-Azacytidine (5AzC) is a cytidine analogue which possesses nitrogen atom instead of carbon atom at the position 5 of the pyrimidine ring. In this study, detailed histopathological changes were sequentially examined in the rat fetal brain obtained from dams treated with 5AzC (10 mg/kg) on day 13 of gestation (GD13). At 6 hours after treatment (HAT), a prominent accumulation of neuroepithelial cells showing pleomorphic mitotic figures were observed in the telencephalic wall. The mitosis-index peaked at 6 HAT, and decreased thereafter. Neuroepithelial cells positive for nick end labeling (TUNEL) method, which is widely used for the detection of apoptotic cells, prominently increased at 9 HAT, and the TUNEL-index peaked at 12 HAT. TUNEL-positive cells showed ultrastructural characteristics of apoptosis. At 24 HAT, the formation of rosette-like structures was observed in the fetal brain. From the results of the present study, it was evident that abnormal mitosis and neuronal apoptosis were induced in the rat fetal brain following 5AzC-administration to dams on GD13. In addition, it is suggested that 5AzC-induced apoptosis might occur mainly in the post mitotic phase of cell cycle.

Animals↗

PubMed2002

Ethylnitrosourea-induced apoptosis in primordial germ cells of the rat fetus.

Ethylnitrosourea (ENU) is a simple alkylating agent. It induces gene mutations in fetal primordial germ cells (PGCs), and a high incidence of congenital malformations is also found in the offspring of male mice treated with ENU at the embryonic stage. It is also reported that decreases in the fertility rate and weights of the testis and ovary were found in the offspring from dams treated with ENU. In this study, we analyzed the occurrence of apoptotic cell death and the expression of p53 protein which is thought to play an important role in the DNA damage-induced apoptosis after administration of ENU to pregnant rats on day 13 of gestation to obtain a clue for clarifying the toxic effect of ENU on PGCs. Apoptotic cells increased in PGCs in fetal gonads from 3 h after treatment. The number of apoptotic PGCs peaked at 6 h and gradually decreased towards 24 h after treatment. On the other hand, p53-positive PGCs increased from I h after treatment, prior to the induction of apoptosis. The number of p53-positive PGCs peaked at 3 h and returned to the control level at 24 h after treatment. These results suggest that ENU induces apoptosis in rat fetal PGCs immediately after its administration to dams and excess cell death by apoptosis may have a close relation to the later occurrence of decreases in the fertility rate and gonadal weight. Moreover, a possible involvement of p53 is suggested in the ENU-induced apoptosis in PGCs.

Alkylating Agents↗

PubMed2002

Dorsal skin responses to topical application with hydrogen peroxide in Mini and Wistar rats.

Mini rats (Jcl: WistarTGN(ARGHGEN) 1Nts) (MRs) are Wistar rat (WR)-derived transgenic rats in which the expression of growth hormone (GH) gene is suppressed under the presence of antisense RNA transgene. In order to evaluate the effects of GH-deficiency on the acute injury by external stimuli, the dorsal skin responses to a single topical application with 20% hydrogen peroxide (HPO), one of the environmental oxidative stressors, were histologically compared between male MRs and WRs of 8 weeks old, whose hair cycle was under the telogen phase. As a result, formation of granulation tissues, reepithelialization and regrowth of hair follicles were delayed in MRs compared with WRs. While hair follicles of MRs of this age are under a long-lasting telogen phase after their 2nd cycle, a new hair cycle started not only in the HPO-applied area but also in the solvent-applied area with a little time lag. These findings suggest that GH-deficiency may influence the skin responses to the external chemical stimuli.

Administration, Topical↗

PubMed2002

Ethylnitrosourea induces apoptosis and growth arrest in the trophoblastic cells of rat placenta.

Ethylnitrosourea (ENU), a well known alkylating agent, induces congenital anomalies in fetuses when it is administered to pregnant animals. In previous studies, we reported that ENU induced apoptosis and growth arrest in fetal tissues and organs immediately after its administration to pregnant rats. In the present study, we investigated the histopathological changes of the placenta after ENU administration to pregnant rats on Day 13 of gestation (GD13) to obtain a clue for clarifying the role of the placenta in the process of fetal developmental disability induced by genotoxic stress. Apoptotic cells increased and DNA-replicating cells decreased in the trophoblastic cells in the placental labyrinth zone of the ENU-treated group by 3 h after treatment. The number of apoptotic cells peaked at 6 h after treatment and returned to control levels at 48 h after treatment. The number of DNA-replicating cells reached minimum levels at 6 h after treatment and returned to control levels at 48 h after treatment. By immunohistochemistry, p53-positive signals were observed in trophoblastic cells in the labyrinth zone of the ENU-treated group from 3 to 6 h after treatment. Significant decreases in fetal and placental weights were observed in the ENU-treated group at 2 days (GD15) and 8 days (GD21) after treatment. A reduction in the thickness of the labyrinth zone was histopathologically significant in the ENU-treated group. These results indicate that ENU induces apoptosis and growth arrest not only in fetal tissues, but also in trophoblastic cells in the rat placental labyrinth zone, and these placental changes may have roles in the induction of fetotoxicity and teratogenicity of ENU. Moreover, a possible involvement of p53 in the induction of apoptosis and growth arrest is suggested.

Alkylating Agents↗

PubMed2002

Automatic detection of abnormalities in chest radiographs using local texture analysis.

A fully automatic method is presented to detect abnormalities in frontal chest radiographs which are aggregated into an overall abnormality score. The method is aimed at finding abnormal signs of a diffuse textural nature, such as they are encountered in mass chest screening against tuberculosis (TB). The scheme starts with automatic segmentation of the lung fields, using active shape models. The segmentation is used to subdivide the lung fields into overlapping regions of various sizes. Texture features are extracted from each region, using the moments of responses to a multiscale filter bank. Additional "difference features" are obtained by subtracting feature vectors from corresponding regions in the left and right lung fields. A separate training set is constructed for each region. All regions are classified by voting among the k nearest neighbors, with leave-one-out. Next, the classification results of each region are combined, using a weighted multiplier in which regions with higher classification reliability weigh more heavily. This produces an abnormality score for each image. The method is evaluated on two databases. The first database was collected from a TB mass chest screening program, from which 147 images with textural abnormalities and 241 normal images were selected. Although this database contains many subtle abnormalities, the classification has a sensitivity of 0.86 at a specificity of 0.50 and an area under the receiver operating characteristic (ROC) curve of 0.820. The second database consist of 100 normal images and 100 abnormal images with interstitial disease. For this database, the results were a sensitivity of 0.97 at a specificity of 0.90 and an area under the ROC curve of 0.986.

Algorithms↗

PubMed2002

Computerized detection of pulmonary embolism in spiral CT angiography based on volumetric image analysis.

A fully automated method for computerized detection of pulmonary embolism in spiral computed tomography angiography was developed based on volumetric image analysis. The detection method is based on segmentation of pulmonary vessels to limit the search space, and analysis of several three-dimensional features inside segmented vessel volume. The features utilized are vascular size, local contrast based on mathematical morphology, degree of curvilinearity based on second derivatives, and geometric features such as volume and length. Detection results were obtained for 19 clinical data sets and the performance of the method was evaluated. Using the number and locations of thrombi diagnosed by radiologists as the gold standard, 100% sensitivity was achieved with 7.7 false positives per case, and 85% sensitivity was obtained with 2.6 false positives. For identification of all the positive cases as positive, i.e., detection of at least one thrombus per positive case, 1.9 false positives per case were obtained. These preliminary results suggest that the method has potential for fully automated detection of pulmonary embolism.

Algorithms↗

PubMed2002

Automated computerized scheme for distinction between benign and malignant solitary pulmonary nodules on chest images.

A novel automated computerized scheme has been developed to assist radiologists for their distinction between benign and malignant solitary pulmonary nodules on chest images. Our database consisted of 55 chest radiographs (33 primary lung cancers and 22 benign nodules). In this method, the location of a nodule was indicated first by a radiologist. The difference image with a nodule was produced by use of filters and then represented in a polar coordinate system. The nodule was segmented automatically by analysis of contour lines of the gray-level distribution based on the polar-coordinate representation. Two clinical parameters (age and sex) and 75 image features were determined from the outline, the image, and histogram analysis for inside and outside regions of the segmented nodule. Linear discriminant analysis (LDA) and knowledge about benign and malignant nodules were used to select initial feature combinations. Many combinations for subgroups of 77 features were evaluated as input to artificial neural networks (ANNs). The performance of ANNs with the selected 7 features by use of the round-robin test showed Az = 0.872, which was greater than Az = 0.854 obtained previously with the manual method (P= 0.53). The performance of LDA (Az = 0.886) was slightly improved compared to that of ANNs (P = 0.59) and was greater than that of the manual method (Az = 0.854) reported previously (P = 0.40). The high level of its performance indicates the potential usefulness of this automated computerized scheme in assisting radiologists as a second opinion for distinction between benign and malignant solitary pulmonary nodules on chest images.

Adult↗