Biomedical subjects

Kunio Doi

Publications and source records attributed to Kunio Doi.

At least 109 records · Page 6Linked to original sources

PubMed2004

The susceptibility of pregnant mice to encephalomyocarditis (EMC) virus infection on different days of gestation.

Pregnant mice of the BALB/c CrSlc strain were experimentally infected with the D variant of encephalomyocarditis virus (EMC-D, 5 x 10(2) PFU/head) on three different gestational days (GD). Mice were intraperitoneally inoculated with EMC-D on 11, 13 and 15 GD and sacrificed 3 days post inoculation. There was no significant difference in the fetal mortality among all inoculation groups. Placenta showed higher virus titer than fetus and dam's serum in all inoculation groups, and the virus titer of the fetus was lowest in the 15GD group. Histopathological changes and signals of viral RNAs detected by in situ hybridization were observed almost restricted to the spongiotrophoblast layer of the placenta in all inoculation groups, and the signals were strongest in the 11GD group. In the fetus of the11GD group, signals of viral RNAs were also seen in myocardium and hepatocytes. Ultrastructurally, intracytoplasmic aggregations of virus-like particles in crystalline array were observed in trophoblast cells and giant cells in the spongiotrophoblast layer in all inoculation groups.

Animals↗

PubMed2004

The role of CD4(+) T cells in biphasic hind limb paralysis induced by the D variant of encephalomyocarditis virus (EMC-D) in DBA/2 mice.

DBA/2 CrSlc mice infected with the D variant of encephalomyocarditis virus (EMC-D) (10 PFU/head) developed biphasic hind limb paralysis due to spinal cord lesion. The early phase lesion was characterized by demyelination with infiltration of macrophages in the funiculus lateraris and the late phase lesion by degeneration of motor neurons with infiltration of CD4(+) T cells in the cornu ventrale. In the present study, treatment with anti-Mac1 monoclonal antibody (MAb) or anti-CD4 MAb prior to virus infection (-3 to -1 days) reduced the early phase lesion and the incidence of the first paralysis. Signals of viral RNAs were observed only in a few oligodendrocytes in the funiculus lateraris. Treatment with anti-CD4 MAb from 31 to 33 days post infection when mice showed recovery from the first paralysis reduced the late phase lesion and prevented the second paralysis. Signals of viral RNAs were still detected in a few degenerated neurons in the cornu ventrale. These results indicate that while macrophages and CD4(+) T cells participate in the early phase lesion and paralysis and only CD4(+) T cells in the late phase lesion and paralysis.

Animals↗

PubMed2004

Comparative study on picryl chloride (PCL)-induced contact dermatitis in female IQI/Jic and BALB/c mice.

Ear skin responses to picryl chloride (PCL)-induced contact dermatitis were compared in detail between IQI/Jic mice developed in Japan and BALB/c mice often used for the investigation of contact dermatitis. PCL was applied to the left ear of each mouse 4 (1st), 11 (2nd), 18 (3rd) and 25 days (4th) after sensitization of the abdominal skin with PCL. Time course examinations were carried out on the ear swelling responses, total IgE levels, skin histology and immunohistochemistry for infiltrated cells after the 1st and 4th application. In IQI mice, the peak time of the ear swelling responses tended to shift from 24 h to 9 h with marked elevation of total IgE levels and marked increase of mast cells showing degranulation after the 4th application when CD8(+) cells as well as CD4(+) cells also prominently increased. In BALB/c mice, except for the total IgE levels and the number of mast cells, the degrees of ear swelling responses, histological changes and increase of CD4(+) and CD8(+) cells were much less severe. Female IQI mice are considered to be a useful mouse strain for further investigations on the role of CD4(+) and CD8(+) T cells in the pathogenesis of contact dermatitis.

Animals↗

PubMed2004

Improved detection of lung nodules on chest radiographs using a commercial computer-aided diagnosis system.

OBJECTIVE: The aim of this study was to evaluate the usefulness of a new commercially available computer-aided diagnosis (CAD) system with an automated method of detecting nodules due to lung cancers on chest radiograph. MATERIALS AND METHODS: For patients with cancer, 45 cases with solitary lung nodules up to 25 mm in diameter (nodule size range, 8-25 mm in diameter; mean, 18 mm; median, 20 mm) were used. For healthy patients, 45 cases were selected on the basis of confirmation on chest CT. All chest radiographs were obtained with a computed radiography system. The CAD output images were produced with a newly developed CAD system, which consisted of an image server including CAD software called EpiSight/XR. Eight radiologists (four board-certified radiologists and four radiology residents) participated in observer performance studies and interpreted both the original radiographs and CAD output images using a sequential testing method. The observers' performance was evaluated with receiver operating characteristic analysis. RESULTS: The average area under the curve value increased significantly from 0.924 without to 0.986 with CAD output images. Individually, the use of CAD output images was more beneficial to radiology residents than to board-certified radiologists. CONCLUSION: This CAD system for digital chest radiographs can assist radiologists and has the potential to improve the detection of lung nodules due to lung cancer.

Adult↗

PubMed2004

Application of an artificial neural network to high-resolution CT: usefulness in differential diagnosis of diffuse lung disease.

OBJECTIVE: The purpose of our study was to evaluate the diagnostic performance of an artificial neural network (ANN) in differentiating among certain diffuse lung diseases using high-resolution CT (HRCT) and the effect of ANN output on radiologists' diagnostic performance. MATERIALS AND METHODS: We selected 130 clinical cases of diffuse lung disease. We used a single three-layer, feed-forward ANN with a back-propagation algorithm. The ANN was designed to differentiate among 11 diffuse lung diseases by using 10 clinical parameters and 23 HRCT features. Therefore, the ANN consisted of 33 input units and 11 output units. Subjective ratings for 23 HRCT features were provided independently by eight radiologists. All clinical cases were used for training and testing of the ANN by implementing a round-robin technique. In the observer test, a subset of 45 cases was selected from the database of 130 cases. HRCT images were viewed by eight radiologists first without and then with ANN output. The radiologists' performance was evaluated with receiver operating characteristic (ROC) analysis with a continuous rating scale. RESULTS: The average area under the ROC curve for ANN performance obtained with all clinical parameters and HRCT features was 0.956. The diagnostic performance of four chest radiologists and four general radiologists was increased from 0.986 to 0.992 (p = 0.071) and 0.958 and 0.971 (p < 0.001), respectively, when they used the ANN output based on their own feature ratings. CONCLUSION: The ANN can provide a useful output as a second opinion to improve general radiologists' diagnostic performance in the differential diagnosis of certain diffuse lung diseases using HRCT.

Adolescent↗

PubMed2004

Radiologists' performance for differentiating benign from malignant lung nodules on high-resolution CT using computer-estimated likelihood of malignancy.

OBJECTIVE: The purpose of our study was to evaluate whether a computer-aided diagnosis (CAD) scheme can assist radiologists in distinguishing small benign from malignant lung nodules on high-resolution CT (HRCT). MATERIALS AND METHODS: We developed an automated computerized scheme for determining the likelihood of malignancy of lung nodules on multiple HRCT slices; the likelihood estimate was obtained from various objective features of the nodules using linear discriminant analysis. The data set used in this observer study consisted of 28 primary lung cancers (6-20 mm) and 28 benign nodules. Cancer cases included nodules with pure ground-glass opacity, mixed ground-glass opacity, and solid opacity. Benign nodules were selected by matching their size and pattern to the malignant nodules. Consecutive region-of-interest images for each nodule on HRCT were displayed for interpretation in stacked mode on a cathode ray tube monitor. The images were presented to 16 radiologists-first without and then with the computer output-who were asked to indicate their confidence level regarding the malignancy of a nodule. Performance was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: The area under the ROC curve (Az value) of the CAD scheme alone was 0.831 for distinguishing benign from malignant nodules. The average Az value for radiologists was improved with the aid of the CAD scheme from 0.785 to 0.853 by a statistically significant level (p = 0.016). The radiologists' diagnostic performance with the CAD scheme was more accurate than that of the CAD scheme alone (p < 0.05) and also that of radiologists alone. CONCLUSION: CAD has the potential to improve radiologists' diagnostic accuracy in distinguishing small benign nodules from malignant ones on HRCT.

Diagnosis, Differential↗

PubMed2004

[ROC analysis of detection of interval changes in interstitial lung diseases on digital chest radiographs using the temporal subtraction technique].

PURPOSE: To demonstrate the clinical usefulness of a temporal subtraction technique for the detection of interval changes in various interstitial lung diseases on digital chest radiographs. MATERIALS AND METHODS: One hundred pairs of chest radiographs in 34 patients (63 with and 37 without interval changes) with various interstitial lung diseases were selected. All cases were confirmed by serial chest computed tomography (CT) and ascertained by radiologists. All chest radiographs were obtained with a computed radiography (CR) system, and temporal subtraction images were produced with an iterative image-warping technique. Four radiologists and two thoracic physicians provided confidence levels for interval changes in interstitial lung diseases with and without temporal subtraction. Their performances with and without temporal subtraction were evaluated by means of receiver operating characteristic (ROC) analysis using a sequential test. RESULTS: The area under the ROC curve (Az) values of six observers obtained with and without temporal subtraction were 0.90 and 0.78, respectively. Results showed that the detection of interval changes in interstitial lung diseases was significantly improved by the use of temporal subtraction images compared with CR images alone(P = 0.002). Furthermore, the high detection rate was achieved with temporal subtraction images regardless of the subtlety and location of interval changes. CONCLUSION: Temporal subtraction improved the diagnostic accuracy of radiologists in detecting interval changes in interstitial lung diseases on chest radiographs. It was also useful for cases of multiple interval changes.

Adult↗

PubMed2003

A novel gene, Btcl1, encoding CUB and LDLa domains is expressed in restricted areas of mouse brain.

A variety of secreted and membrane proteins play key roles in the formation of neuronal circuits in the central nervous system. Using the signal sequence trap method, we isolated and characterized a novel gene, Btcl1 (brain-specific transmembrane protein containing two CUB and an LDLa domains). BTCL1 has significant homology with neuropilin-1 and -2 in their CUB domains. Domain structure of BTCL1 indicates that BTCL1 belongs to a new class of brain-specific CUB domain-containing protein. On Northern blot analysis, Btcl1 mRNA was observed as a single transcript of 3.7 kb specifically in the brain. In situ hybridization analysis revealed that Btcl1 mRNA was highly expressed in the hippocampal CA3 region, olfactory bulb, and neocortex in the adult brain. Expression pattern of mRNA and structural similarity with neuropilin suggest that BTCL1 plays a role in the development and/or maintenance of neuronal circuitry.

Amino Acid Sequence↗

PubMed2003

Development of early apopotosis and changes in lymphocyte subsets in lymphoid organs of mice orally inoculated with nivalenol.

Development of early apoptosis and changes in lymphocyte subsets were examined in lymphoid organs of female BALB/c mice after oral administration of 15 mg/kg b.w. of nivalenol (NIV), the major type B trichothecene mycotoxin, by FACS analysis. Judging from the results of viable cell count and apoptotic cell index, NIV attacked Peyer's patches first and thymus most severely. In thymus, selective damage in CD4(+)CD8(+) cells was observed at 12 and 24 h after inoculation (HAI), following the peak of apoptosis at 9 HAI. CD4(+) cells were clearly suppressed at 3 HAI in Peyer's patches, at and after 9 HAI in mesenteric lymph nodes, and 3 to 12 HAI in spleen, respectively. CD8(+) cells were also suppressed at 24 HAI in mesenteric lymph nodes and at 12 HAI in spleen, respectively. As to changes in B cell subsets, IgG(+) cells significantly decreased from 3 to 12 HAI and all B cell subsets at 24 HAI in mesenteric lymph nodes. In spleen, IgM(+) cells were suppressed at 9 HAI. On the other hand, in Peyer's patches, following clear decrease in the numbers of pan-T and pan-B cells and viable cells at 3 HAI, all B cell subsets, especially IgA(+) cells, showed a significant increase in their numbers at 9 HAI, and the numbers of IgA(+) and IgM(+) cells remained higher values than controls thereafter. Taken together, in the course of recovery from NIV-induced prominent damage in Peyer's patches at 3 HAI, interaction of NIV with Peyer's patches might result in in vivo stimulation of interleukin production at this site and result in increased proliferation and differentiation of IgA-secreting B cells at and after 9 HAI.

Administration, Oral↗

PubMed2003

Kinetics of chemokines and their receptors in mercuric chloride-induced tubulointerstitial lesions in brown Norway rats.

We investigated the kinetics of chemokines and their receptors in mercuric chloride-treated brown Norway (BN) rats from the viewpoint of its relation to the development of tubulointerstitial fibrosis with mononuclear cell infiltration. BN rats were injected subcutaneously with 1 mg/kg b.w. of mercuric chloride one or three times. The kidney was examined histopathologically and the kinetics of chemokines and their receptors in the kidney were also examined using immunohistochemistry and RT-PCR. As a result, mercuric chloride induced tubular injury and subsequent tubulointerstitial fibrosis accompanied with mononuclear cell infiltration. Macrophages were the most predominant population of infiltrating cells and lymphocytes were the next. In the lesions, the expression of MCP-1 mRNA was most prominently elevated, and those of RANTES and IP-10 mRNAs also increased, and their proteins were localized in tubular epithelium. As to their receptors, the levels of CCR1, CCR2, and CXCR3 mRNAs showed significant and prominent elevations, CCR5 mRNA also increased moderately, and their receptor protein-expressing cells also increased. The present findings suggest that MCP-1, RANTES, and IP-10 may participate in the pathogenesis of mercuric chloride-induced tubulointerstitial fibrosis with mononuclear cell infiltration, via CCR2, CCR1 or CCR5, and CXCR3, respectively.

Animals↗

PubMed2003

Distribution of N-methyl-D-aspartate receptors (NMDARs) in the developing rat brain.

The N-methyl-D-aspartate receptor (NMDAR), which is one of the glutamate receptors, is considered to have a close relationship to synaptic plasticity in the developing brain. In addition, it is known that the excessive stimulation of NMDARs can trigger neuronal apoptosis. In this study, we examined the distribution of NMDAR subunits [anti-NR1, NR2(A-C)] in the developing rat brain immunohistochemically. As a result, NR1, an essential subunit for the formation of a functional NMDAR complex, was mildly expressed in the restricted areas such as the temporal region of the cerebral cortex and the hippocampus in the fetal brain at Embryonal Days 18 and 20. On the other hand, in neonates, NR1 was expressed widely throughout the whole brain. The distributions of NR2A and NR2C showed temporal and spatial similarities to that of NR1, while the expression of NR2B showed differences in the intensity and distribution. A progressive change in subunit expression seen prenatally and postnatally could contribute to variation of NMDARs and synaptic plasticity during the developing period.

Animals↗

PubMed2003

Susceptibility of primary culture neurons from rats of different ages to encephalomyocarditis (EMC) virus infection.

The changes in susceptibility of neurons to the D variant of EMC virus (EMC-D) (10(6) PFU/well) were investigated in developing hippocampal primary cultures from postnatal days of 1, 7, and 56 Fischer 344 rats (P1, P7, and P56) for up to 12 h after infection (12 HAI). The virus titer of primary culture neurons increased at 1 HAI, decreased at 2 HAI, increased at 3 HAI, peaked at 8 HAI, and decreased at 12 HAI in all age groups. The titers at 1 and 8 HAI were lowest in P56 cultures. The virus titer of neurons was always higher than that of culture media, especially at 1 HAI, in P1 cultures, whereas the former was lower than the latter from 2 to 3 HAI in P7 cultures and from 2 to 4 HAI in P56 cultures, respectively. Signals of viral RNA detected by in situ hybridization were first observed in the peripheral cytoplasm of neurons at 1 HAI in P1 and P7 cultures and at 4 HAI in P56 cultures, respectively. The signals spread to a large or whole area of cytoplasm and also to processes thereafter. The number of viral RNA-positive neurons and the amount of signals decreased with age. The present results indicated that the susceptibility of primary culture neurons to EMC-D decreased with age but viral replication still occurred in P56 cultures.

Aging↗

PubMed2003

The fates of trichothecene mycotoxins, nivalenol and fusarenon-X, in mice.

In order to investigate the comparative fates of nivalenol (NIV) and 4-acetyl derivative of NIV (fusarenon-X, FX) in mice, 3H-FX or 3H-NIV was given p.o. to mice. Radioactivity was excreted mainly via the urine in mice given 3H-FX, but mainly via the feces in mice given 3H-NIV. The plasma radioactivity reached a peak at 30 or 60 min after the administration of 3H-FX or 3H-NIV, respectively. The plasma peak level was 5 times higher, and the area under curve (AUC) was 10 times higher, in 3H-FX-administered than 3H-NIV-administered mice. These findings clearly demonstrate that FX is absorbed from the gastrointestinal tract more rapidly and efficiently than NIV. The HPLC profile of radioactivity of acetonitrile extracts of urine and feces indicated that FX is rapidly metabolized to NIV after being absorbed from the gastrointestinal tract. In vitro incubation of tissue homogenates with 3H-FX demonstrated that the liver and kidney are the organs responsible for the FX-to-NIV conversion. Thus this study demonstrated that the higher oral toxicity of FX than NIV that has been observed in mice and rats is due to the efficient absorption of FX than NIV from the gastrointestinal tract, followed by its rapid conversion to NIV by the liver and kidney.

Animals↗

PubMed2003

Low-dose computed tomography screening for lung cancer in a general population: characteristics of cancer in non-smokers versus smokers.

RATIONALE AND OBJECTIVES: To report the detection rate for lung cancers in computed tomography (CT) screening in Japanese adults, and to analyze differences in the appearance of the cancers in non-smokers versus smokers. MATERIALS AND METHODS: Subjects consisted of 7,847 Japanese adults who received low-dose CT screening at least once in a 3-year period. The detection rate of lung cancers and the correlation of imaging, clinical, and pathologic findings of cancers in non-smokers versus smokers were examined. RESULTS: The detection rate for lung cancer was 1.1% for both non-smokers (45 of 4,251) and smokers (39 of 3,596). The prevalence of well-differentiated adenocarcinomas was greater in non-smokers (88%; 22 of 25) than in smokers (29%; 4 of 14) (P < .001). The prevalence and incidence of pathologic stage IA disease were greater in non-smokers than in smokers (92%; [22 of 24] vs 58% [7 of 12], and 100% [19 of 19] vs 70% [14 of 20]) (both P < .05). The mean size of the tumors in the non-smokers (12.4 mm) was smaller than that in smokers (18.2 mm) (P < .001). The percentage of cancers categorized as pure or mixed ground-glass opacity (86%; 38 of 44) on CT was greater in non-smokers than in smokers (46%; 16 of 35) (P < .001). CONCLUSION: Most of the lung cancers in non-smokers were slow-growing adenocarcinomas appearing as faint ground-glass opacities on CT, whereas rapidly growing cancers appearing as solid nodules were more commonly seen in smokers.

Adenocarcinoma↗

PubMed2003

Effect of high sensitivity in a computerized scheme for detecting extremely subtle solitary pulmonary nodules in chest radiographs: observer performance study.

RATIONALES AND OBJECTIVES: This study investigated the effect of a high sensitivity in computer-aided diagnosis (CAD) for detecting lung nodules in chest radiographs when extremely subtle cases were presented to radiologists. MATERIAL AND METHODS: The chest radiographs used in this study consisted of 36 normal images and 54 abnormals containing solitary lung nodules, of which 25 were extremely subtle and 29 were very subtle. Receiver operating characteristic analysis for detecting lung nodules was performed without and with CAD. The levels of CAD output were simulated with a hypothetical ideal performance of 100% sensitivity, but with three or four false positives per image. Six radiologists participated in an observer study in which cases were interpreted first without and then with the use of CAD. RESULTS: The average A(z) values for radiologists without and with CAD were 0.682 and 0.808, respectively. The performance of radiologists was improved significantly when high sensitivity was used (P = .0003). However, the radiologists were not able to recognize some extremely subtle nodules (5 of 54 nodules by all radiologists), even with the correct CAD output; these nodules were then considered as non-actionable. None of 306 computer-false positives was incorrectly regarded as a nodule by all radiologists, but 63 false positives were incorrectly identified by one or more radiologists. CONCLUSION: The accuracy of radiologists in the detection of some extremely subtle solitary pulmonary nodules can be improved significantly when the sensitivity of a CAD scheme can be made to be at an extremely high level. However, all of the six radiologists failed to identify some nodules (about 10%), even with the correct output of the CAD.

Humans↗

PubMed2003

Ultrastructural features of mast cells in picryl chloride (PCL)-induced contact dermatitis in IQI/Jic mice.

Mast cells are one of the major effector cells in the pathogenesis of allergic diseases such as contact dermatitis. In the present study, ultrastructural features of mast cells in contact dermatitis were examined. Namely, the ear of IQI/Jic mice was topically applied with picryl chloride (PCL) at 4 (1st), 11 (2nd), 18 (3rd) and 25 days (4th) after the sensitization with PCL to the abdominal skin. The changes in the ear swelling responses, total serum IgE levels and histology including mast cell numbers were similar to those of previous reports by our research group (Ikeda et al. 2000; Jung et al. 2001). Ultrastructurally, after the 1st application, a close spacial relationship between mast cells and neutrophils and phagocytosis of mast cell granules by neutrophils were observed. Mast cells generally contained non-fused swollen granules filled with altered contents with low electron density and showed an extrusion of membrane-free granules through membrane pores. In addition, interestingly, a few mast cells secreted membrane-bound granules into the dermis without leaving cell membrane damage. After the 4th application when the number of mast cells prominently increased and the total serum IgE level was greatly elevated, in addition to mast cells showing typical anaphylactic degranulation, many mast cells probably in the recovery process from degranulation and several immature mast cells characterized by well-developed Golgi apparatus, many ribosomes and a few electron-dense secretory granules in the peripheral cytoplasm were also observed at the same time. The present results clarified the ultrastructural features of mast cells in the course of PCL-induced contact dermatitis in IQI/Jic mice.

Anaphylaxis↗

PubMed2003

Induction of CYP3A1 by dexamethasone and pregnenolone-16alpha-carbonitrile in pregnant rat and fetal livers and placenta.

Cytochrome P450 (CYP) 3A1 was detected in the cytoplasm of giant cells in the trophoblastic region of rat placenta through pregnancy (Ejiri et al. 2001). In the present study, changes in the expression of CYP3A1 protein as well as in the histology of pregnant rat and fetal livers and placenta after treatment with dexamethasone (DEX) or pregnenolone-16alpha-carbonitrile (PCN), well-known CYP3A1 inducers, at 16 day of gestation (DG) (DEX1 and PCN1 groups: 100 mg/kg) or from 13 to 16 DG (DEX4 group: 25 mg/kg/day; PCN4 group: 50 mg/kg/day). All animals were killed at 17 DG, and Western blot and immunohistochemical analyses on CYP3A1 expression and histological examination were done. Western blot analysis revealed that PCN induced CYP3A1 more clearly than DEX and that the induction was most prominent in the fetal liver and lowest in the placenta. Except for the placenta, changes in the immunohistochemical stainability for CYP3A1 almost corresponded to those in the expression of CYP3A1 by Western blot analysis. In addition, swelling and and/or vacuolization of hepatocytes were generally observed in the mother and fetal livers showing increased expression of CYP3A1. These results suggest that DEX and PCN might pass through the placenta with no prominent induction of CYP3A1 at the placenta and be distributed to the fetal liver rapidly, resulting in high induction of CYP3A1 in the fetal liver.

Animals↗

PubMed2003

Impaired liver regeneration after partial hepatectomy in db/db mice.

Fatty liver is the most common hepatic disorder in humans and supposed to be a cause of poor prognosis after liver transplantation and hepatic resection which could be resulted from impaired liver regeneration. This study was carried out to analyze the process of liver regeneration in db/db mice which show severe steatosis because of abnormal leptin receptor. We performed 70% partial hepatectomy (PH) on db/db mice and normal +m/+m mice, and then sacrificed the animals 1, 2, 3, 5, 7 and 10 days later. The liver samples were weighed and examined histologically or immunohistochemically. As a result, the liver mass restitution was significantly inhibited in db/db mice compared with +m/+m mice. The BrdU labelling index peaked at 2 days after PH in both strains, although the value was lower in db/db mice. After that, interestingly, it decreased to the control level at 5 days in +m/+m mice while the recovery was delayed in db/db mice. Similar sequence was also observed in the PCNA labelling index. In addition, the peak time of the mitosis index was 2 days and 5 days after PH in +m/+m mice and in db/db mice, respectively. Thus, although not significant, the proliferative response of hepatocytes to PH occurred somewhat more transient and sharply in +m/+m mice while it lasted somewhat longer in db/db mice. This suggests that db/db mice may be valuable as one of the animal models for the investigation of the effects of steatosis on the liver regeneration.

Animals↗