Biomedical subjects

Kunio Doi

Publications and source records attributed to Kunio Doi.

At least 73 records · Page 4Linked to original sources

PubMed2005

PTHrP and PTH/PTHrP receptor 1 expression in odontogenic cells of normal and HHM model rat incisors.

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). We examined PTHrP and its receptor (PTHR1) expression patterns in odontogenic cells in normal and HHM model rat incisors. Nontreated nude rats serving as the normal control and HHM model rats produced by implantation of PTHrP-expressing tumor (LC-6) cells were prepared. HHM rats fractured its incisor, and histopathologically, restrict population of odontoblasts showed findings classified as "shortening of high columnar odontoblasts" and "dentin niche." The incisors were immunostained against PTHrP and PTHR1. In normal rats, PTHrP and PTHR1 colocalized in ameloblasts, cementoblasts, and odontoblastic cells from mesenchymal cells to columnar odontoblasts. In high columnar odontoblasts, PTHrP solely expressed. In the HHM animals, although the expression patterns were identical to those of the normal rats in normal area, the shortened high columnar odontoblasts maintained PTHR1 expression and dentin niche comprising odontoblastic cells expressed both proteins. In the HHM model, the protein expression patterns changed in the odontoblastic cells with histological anomalies, and thus direct relations between the anomalies and PTHrP/PTHR1 axis are suggested.

Animals↗

PubMed2005

Computer-aided diagnostic scheme for distinction between benign and malignant nodules in thoracic low-dose CT by use of massive training artificial neural network.

Low-dose helical computed tomography (LDCT) is being applied as a modality for lung cancer screening. It may be difficult, however, for radiologists to distinguish malignant from benign nodules in LDCT. Our purpose in this study was to develop a computer-aided diagnostic (CAD) scheme for distinction between benign and malignant nodules in LDCT scans by use of a massive training artificial neural network (MTANN). The MTANN is a trainable, highly nonlinear filter based on an artificial neural network. To distinguish malignant nodules from six different types of benign nodules, we developed multiple MTANNs (multi-MTANN) consisting of six expert MTANNs that are arranged in parallel. Each of the MTANNs was trained by use of input CT images and teaching images containing the estimate of the distribution for the "likelihood of being a malignant nodule," i.e., the teaching image for a malignant nodule contains a two-dimensional Gaussian distribution and that for a benign nodule contains zero. Each MTANN was trained independently with ten typical malignant nodules and ten benign nodules from each of the six types. The outputs of the six MTANNs were combined by use of an integration ANN such that the six types of benign nodules could be distinguished from malignant nodules. After training of the integration ANN, our scheme provided a value related to the "likelihood of malignancy" of a nodule, i.e., a higher value indicates a malignant nodule, and a lower value indicates a benign nodule. Our database consisted of 76 primary lung cancers in 73 patients and 413 benign nodules in 342 patients, which were obtained from a lung cancer screening program on 7847 screenees with LDCT for three years in Nagano, Japan. The performance of our scheme for distinction between benign and malignant nodules was evaluated by use of receiver operating characteristic (ROC) analysis. Our scheme achieved an Az (area under the ROC curve) value of 0.882 in a round-robin test. Our scheme correctly identified 100% (76/76) of malignant nodules as malignant, whereas 48% (200/413) of benign nodules were identified correctly as benign. Therefore, our scheme may be useful in assisting radiologists in the diagnosis of lung nodules in LDCT.

Algorithms↗

PubMed2005

Investigation of psychophysical measure for evaluation of similar images for mammographic masses: preliminary results.

We investigated a psychophysical similarity measure for selection of images similar to those of unknown masses on mammograms, which may assist radiologists in the distinction between benign and malignant masses. Sixty pairs of masses were selected from 1445 mass images prepared for this study, which were obtained from the Digital Database for Screening Mammography by the University of South Florida. Five radiologists provided subjective similarity ratings for these 60 pairs of masses based on the overall impression for diagnosis. Radiologists' subjective ratings were marked on a continuous rating scale and quantified between 0 and 1, which correspond to pairs not similar at all and pairs almost identical, respectively. By use of the subjective ratings as "gold standard," similarity measures based on the Euclidean distance between pairs in feature space and the psychophysical measure were determined. For determination of the psychophysical similarity measure, an artificial neural network (ANN) was employed to learn the relationship between radiologists' average subjective similarity ratings and computer-extracted image features. To evaluate the usefulness of the similarity measures, the agreement with the radiologists' subjective similarity ratings was assessed in terms of correlation coefficients between the average subjective ratings and the similarity measures. A commonly used similarity measure based on the Euclidean distance was moderately correlated (r=0.644) with the radiologists' average subjective ratings, whereas the psychophysical measure by use of the ANN was highly correlated (r=0.798). The preliminary result indicates that a psychophysical similarity measure would be useful in the selection of images similar to those of unknown masses on mammograms.

Algorithms↗

PubMed2005

Computer-aided detection of peripheral lung cancers missed at CT: ROC analyses without and with localization.

PURPOSE: To retrospectively evaluate whether a difference-image computer-aided detection (CAD) scheme can help radiologists detect peripheral lung cancers missed at low-dose computed tomography (CT). MATERIALS AND METHODS: Institutional review board approval and informed patient and observer consent were obtained. Seventeen patients (eight men and nine women; mean age, 60 years) with a missed peripheral lung cancer and 10 control subjects (five men and five women; mean age, 63 years) without cancer at low-dose CT were included in an observer study. Fourteen radiologists were divided into two groups on the basis of different image display formats: Six radiologists (group 1) reviewed CT scans with a multiformat display, and eight radiologists (group 2) reviewed images with a "stacked" cine-mode display. The radiologists, first without and then with the CAD scheme, indicated their confidence level regarding the presence (or absence) of cancer and the most likely position of a lesion on each CT scan. Receiver operating characteristic (ROC) curves were calculated without and with localization to evaluate the observers' performance. RESULTS: With the CAD scheme, the average area under the ROC curve improved from 0.763 to 0.854 for all radiologists (P = .002), from 0.757 to 0.862 for group 1 (P = .04), and from 0.768 to 0.848 for group 2 (P = .01). The average sensitivity in the detection of 17 cancers improved from 52% (124 of 238 observations) to 68% (163 of 238 observations) for all radiologists (P < .001), from 49% (50 of 102 observations) to 71% (72 of 102 observations) for group 1 (P = .02), and from 54% (74 of 136 observations) to 67% (91 of 136 observations) for group 2 (P = .006). The localization ROC curve also improved. CONCLUSION: Lung cancers missed at low-dose CT were very difficult to detect, even in an observer study. The use of CAD, however, can improve radiologists' performance in the detection of these subtle cancers.

Aged↗

PubMed2005

Malignant NK/T-cell lymphoma associated with simian Epstein-Barr virus infection in a Japanese macaque (Macaca fuscata).

A case of spontaneous malignant lymphoma in a Japanese macaque (Macaca fuscata) was pathologically, etiologically and virologically studied. Nasal cavity was involved in the neoplastic lesions in addition to lymphoid and visceral tissues. Histopathological analyses revealed the presence of neoplastic cells classified into histiocytic Hodgkin-like cells and Reed-Sternberg-like cells. Histiocytic Hodgkin-like cells were CD16+ and CD20+, and the CD16+ cells were also positive for simian Epstein-Barr virus (sEBV)-encoded early RNA transcripts. RS-like cells were negative for CD3, CD16 and CD20. Antibodies to early antigen of sEBV were detected, while antibodies to simian T-cell leukemia virus-1 were negative. The case may correspond to EBV-associated nasal type NK/T-cell lymphoma in humans rather than Hodgkin lymphoma.

Animals↗

PubMed2005

Electron microscopic study of subcapsular cell hyperplasia in the adrenal glands of IQI/Jic mice.

Hyperplastic cells in subcapsular cell hyperplasia (SCH) lesion in adrenal glands of female IQI/Jic mice were examined by electron microscopy. These cells were small and polygonal, and had irregular nuclei, elongated mitochondria with lamellar cristae and dense lipid droplets. While these cells showed different features, some of them had desmosomes and basement membranes, and a few round mitochondria with tubular cristae as endocrine cells. These findings suggest that hyperplastic cells in SCH lesions might originate from endocrine blastemic cells.

Adrenal Glands↗

PubMed2004

Malignant versus benign nodules at CT screening for lung cancer: comparison of thin-section CT findings.

PURPOSE: To evaluate thin-section computed tomographic (CT) characteristics of malignant nodules on the basis of overall appearance (pure ground-glass opacity [GGO], mixed GGO, or solid opacity) in comparison with the appearance of benign nodules. MATERIALS AND METHODS: Institutional review board approval and patient consent were obtained. Follow-up diagnostic CT was performed in 747 suspicious pulmonary nodules detected at low-dose CT screening (17 892 examinations). Of 747 nodules, 222 were evaluated at thin-section CT (1-mm collimation), which included 59 cancers and 163 benign nodules (3-20 mm). Thin-section CT findings of malignant versus benign nodules with pure GGO (17 vs 12 lesions), mixed GGO (27 vs 29 lesions), or solid opacity (15 vs 122 lesions) were analyzed. Fisher exact test for independence was used to compare differences in shape, margin, and internal features between benign and malignant nodules. Positive predictive value (PPV) was analyzed when a category was significantly different from the others. RESULTS: Among nodules with pure GGO, a round shape was found more frequently in malignant lesions (11 of 17, 65%) than in benign lesions (two of 12, 17%; P = .02; PPV, 85%); mixed GGO, a subtype with GGO in the periphery and a high-attenuation zone in the center, was seen much more often in malignant lesions (11 of 27, 41%) than in benign lesions (two of 29, 7%; P = .004; PPV, 85%). Among solid nodules, a polygonal shape or a smooth or somewhat smooth margin was present less frequently in malignant than in benign lesions (polygonal shape: 7% vs 38%, P = .02; smooth or somewhat smooth margin: 0% vs 63%, P < .001), and 98% (46 of 47) of polygonal nodules and 100% (77 of 77) of nodules with a smooth or somewhat smooth margin were benign. CONCLUSION: Recognition of certain characteristics at thin-section CT can be helpful in differentiating small malignant nodules from benign nodules.

Adenocarcinoma↗

PubMed2004

Expression of Btcl2, a novel member of Btcl gene family, during development of the central nervous system.

Cell-cell interactions are primarily mediated by secreted and transmembrane proteins which play essential roles in the neuronal circuit formation. However, molecular mechanisms underlying neuronal circuit formation, which is mediated by the cell-cell interactions, remain largely elusive. We isolated and characterized a novel gene, Btcl2 (brain-specific transmembrane protein containing CUB [complement subcomponent C1r/C1s, sea urchin protein Uegf, and BMP-1] and LDLa [low-density lipoprotein receptor domain class A] domains 2), using the signal sequence trap (SST) method. The extracellular domain of BTCL2 contains two CUB domains and an LDLa domain. BTCL2 and BTCL1 have similar domain structures, sharing 51% overall identity. The CUB1, CUB2, and LDLa domains of these two proteins share 63%, 72%, and 84% identity, respectively. The CUB domains of BTCL1 and BTCL2 share significant identity with those of neuropilins. Btcl2 mRNA was detected as a single 6-kb transcript in Northern blot analysis. In situ hybridization (ISH) analysis revealed that both Btcl1 and Btcl2 mRNAs were observed restrictively in brain throughout embryonic and postnatal stages. Btcl1 and Btcl2 mRNAs were expressed uniquely in the pontine nucleus and subplate, which are required for establishing the neuronal circuit formation. These results will aid in resolving the mechanisms underlying neuronal circuit formations (e.g., pontocerebellar and thalamocortical axon guidance) and permit more precise studies aimed at understanding the role of BTCL1 and BTCL2 in the central nervous system.

Amino Acid Sequence↗

PubMed2004

Involvement of p53 in 1-beta-D-arabinofuranosylcytosine-induced trophoblastic cell apoptosis and impaired proliferation in rat placenta.

1-beta-D-Arabinofuranosylcytosine (Ara-C), a DNA-damaging agent, severely inhibits fetal growth and has teratogenicity. Recently, we reported that Ara-C also causes placental growth retardation and increases placental apoptosis. The aim of the present study is to elucidate the mechanisms of placental injury induced by genotoxic stress and involvement of p53, which mediates apoptosis and cell-cycle arrest after DNA damage. We injected Ara-C into pregnant rats on Day 13 of gestation and examined the placentas from 1 to 48 h after the administration. Terminal deoxynucleotidyltransferase-mediated dUTP end-labeling (TUNEL) revealed that the apoptosis of trophoblastic cells in the placental labyrinth zone increased from 3 h after the treatment and peaked at 6 h before returning to control levels at 48 h. An increase in cleaved caspase-3 immunoreactivity was also detected at 6 h. Proliferative activity as measured by immunohistochemistry for topoisomerase II alpha and by mitotic index significantly decreased after the treatment in the labyrinth zone. Immunoreactivity for p53 protein in the placental labyrinth zone was remarkably enhanced and peaked at 3 h after treatment, although no increase in p53 mRNA expression was detected with a reverse transcription- polymerase chain reaction. Regarding p53 target genes, p21, cyclinG1, and fas mRNA levels increased significantly and peaked at around 9 h after the treatment. These results indicate that Ara-C would induce apoptosis and impair cell proliferation in the placental labyrinth zone, and p53 and its transcriptional target genes may play an important role in the pathogenesis of the Ara-C-induced placental toxicity.

Animals↗

PubMed2004

Computerized scheme for automated detection of lung nodules in low-dose computed tomography images for lung cancer screening.

RATIONALE AND OBJECTIVES: A computerized scheme for automated detection of lung nodules in low-dose computed tomography images for lung cancer screening was developed. MATERIALS AND METHODS: Our scheme is based on a difference-image technique for enhancing the lung nodules and suppressing the majority of background normal structures. The difference image for each computed tomography image was obtained by subtracting the nodule-suppressed image processed with a ring average filter from the nodule-enhanced image with a matched filter. The initial nodule candidates were identified by applying a multiple-gray level thresholding technique to the difference image, where most nodules were well enhanced. A number of false-positives were removed first in entire lung regions and second in divided lung regions by use of the two rule-based schemes on the localized image features related to morphology and gray levels. Some of the remaining false-positives were eliminated by use of a multiple massive training artificial neural network trained for reduction of various types of false-positives. This computerized scheme was applied to a confirmed cancer database of 106 low-dose computed tomography scans with 109 cancer lesions for 73 patients obtained from a lung cancer screening program in Nagano, Japan. RESULTS: This computed-aided diagnosis scheme provided a sensitivity of 83% (91/109) for all cancers with 5.8 false-positives per scan, which included 84% (32/38) for missed cancers with 5.9 false-positives per scan. CONCLUSION: This computerized scheme may be useful for assisting radiologists in detecting lung cancers on low-dose computed tomography images for lung cancer screening.

False Positive Reactions↗

PubMed2004

Automated computerized scheme for detection of unruptured intracranial aneurysms in three-dimensional magnetic resonance angiography.

RATIONALE AND OBJECTIVES: A computerized scheme for automated detection of unruptured intracranial aneurysms in magnetic resonance angiography was developed based on the use of a three-dimensional selective enhancement filter for dots (aneurysms). MATERIALS AND METHODS: Twenty-nine cases with 36 unruptured aneurysms (diameter, 3 to 26 mm; mean, 6.6 mm) and 31 non-aneurysm cases were used in this study. The isotropic 3-dimensional magnetic resonance angiography images with 400 x 400 x 128 voxels (voxel size, 0.5 mm) were processed by use of the selective enhancement filter. The initial candidates were identified by use of a multiple gray-level thresholding technique on the dot-enhanced images and a region-growing technique with monitoring some image features. All candidates were classified into four types of candidates according to the size and local structures based on the effective diameter and skeleton image of each candidate (ie, large candidates and three types of small candidates including short-branch type, single-vessel type, and bifurcation type). In each group, a number of false-positives were removed by use of different rules on localized image features related to gray levels and morphology. Linear discriminant analysis was used for further removal of false-positives. RESULTS: With this computer-aided diagnostic scheme, all of 36 aneurysms were correctly detected with 2.4 false-positives per patient based on a leave-one-out-by-patient test method. CONCLUSION: This computer-aided diagnostic system would be useful in assisting radiologists for the detection of intracranial aneurysms in magnetic resonance angiography.

False Positive Reactions↗

PubMed2004

Effect of temporal subtraction images on radiologists' detection of lung cancer on CT: results of the observer performance study with use of film computed tomography images.

RATIONALE AND OBJECTIVES: To evaluate the effect of temporal subtraction images on the radiologists' detection of early primary lung cancer in computed tomography (CT) scans. MATERIALS AND METHODS: Fourteen cases with primary lung cancer and 16 normal cases were used for this study from a database of low-dose CT images, which were obtained from a lung cancer screening program in Nagano, Japan. Images were obtained with a single-detector helical CT scanner using 10 mm collimation and 2:1 pitch. Each case had both previous and current CT scans. Temporal subtraction images were obtained by subtracting the warped previous images from the current images. Seven radiologists, including four attendings and three residents, provided their confidence levels for the presence or absence of lung cancers with use of film CT images without and with temporal subtraction images. Receiver operating characteristic analysis was used to compare their performance without and with temporal subtraction images. RESULTS: The mean Az values (area under the receiver operating characteristic curve) of seven observers without and with temporal subtraction images were 0.868 and 0.930, respectively. Diagnostic accuracy was significantly improved by using temporal subtraction images (P = .007). Temporal subtraction images were especially useful when a nodule was present near the pulmonary hilum, where radiologists tended to overlook it. CONCLUSION: The temporal subtraction technique can significantly improve the sensitivity and specificity for detection of lung cancer on CT scans.

Adult↗

PubMed2004

Effects of prenatal hydroxyurea-treatment on mouse offspring.

Hydroxyurea (HU), a ribonucleotide reductase inhibitor, induces morphological anomalies in the central nervous system, craniofacial tissues and limb buds in animals, and neonatal respiratory distress in humans. The neonates and offspring of pregnant mice treated with 400 or 800 mg/kg of HU on day 13 of gestation were examined at 0 day and 10 weeks after birth to find a clue for clarifying the relationship between HU-induced apoptosis in the fetal tissues and teratogenicity. The offspring from dams treated with HU were retarded in growth compared with controls. But there was no significant difference in the body weight gain between the 400 and 800mg/kg groups. In the teratologic changes, microencephaly, hydrocephalus and curved coccygeal vertebrae were observed in the offspring, and the incidence of these teratologic changes was similar but their degree was more severe in the 800 mg/kg group than in the 400 mg/kg group. Based on the above-mentioned previous and present studies of ours, we suggest that HU-induced apoptosis in fetal tissues may play an important role in the development of anomalies in the corresponding tissues of offspring.

Abnormalities, Drug-Induced↗

PubMed2004

Morphological and microarray analysis of T-2 toxin-induced rat fetal brain lesion.

To examine morphological and gene expression changes induced by T-2 toxin in the fetal brain in detail, pregnant rats on day 13 of gestation were treated orally with a single dose of T-2 toxin (2 mg/kg) and sacrificed at 1, 3, 6, 9, 12 and 24 h after treatment (HAT). Histopathologically, the number of apoptotic neuroepithelial cells in the telencephalon increased from 1 HAT and peaked at 12 HAT. Based on the histopathological examinations, microarray analysis was performed at 6, 12 and 24 HAT. Microarray analysis showed that the expression of oxidative stress-related genes (heat shock protein 70 (HSP70) and heme oxygenase (HO)) was strongly induced by T-2 toxin at 12 HAT, the peak time point of apoptosis induction. The expression of mitogen-activated protein kinase (MAPK)-related genes (MEKK1 and c-jun) and other apoptosis-related genes (caspase-2 and insulin-like growth factor-binding protein-3 (IGF-BP3)) was also induced by the T-2 toxin treatment. The changes observed by microarray analysis were confirmed for four up-regulated genes (HSP70, HO, IGF-BP3 and VEGF-A) using real-time RT-PCR. Our results suggest that the T-2 toxin-induced apoptosis in the fetal brain is due to oxidative stress, and that the MAPK pathway may be involved in T-2 toxin-induced toxicity.

Administration, Oral↗

PubMed2004

A comparative study of age-related brain pathology--are neurodegenerative diseases present in nonhuman animals ?

Although some aged dogs definitely have dementia-like conditions, they have rather different brain histopathology from that seen in Alzheimer's disease including the shape of senile plaques, severity of neuron loss and absence of neurofibrillary tangles. Aged wild-type mice never show such brain lesions at all. In addition, no cases of Parkinson's disease have been reported in nonhuman animals yet. The reason for this might be non-parallel aging of the whole body and brain. If such nonhuman animals had a longer life span, like humans, typical Alzheimer's and Parkinson's lesions would be formed in the brain. As the rate of deposition of the misfolded proteins causing the lesions might be slow, nonhuman animals normally die before the lesions appear.

Age Factors↗

PubMed2004

Placental and milk transmission of trichothecene mycotoxins, nivalenol and fusarenon-X, in mice.

In order to investigate the transfer of nivalenol (NIV) and fusarenon-X (FX) from pregnant to fetal mice and from lactating to suckling mice, (3)H-NIV or (3)H-FX was given p.o. to pregnant or lactating mice. Radioactivity was detected in the whole fetal tissues as well as the fetal liver and kidney, the levels being comparable to those of the maternal tissues. Radioactivity was also detected in the milk, and liver and kidney tissues taken from suckling mice of both (3)H-NIV or (3)H-FX administered dams. HPLC analysis of fetal tissue homogenates from non-labeled FX- or NIV-administered pregnant mice revealed transmission of NIV to fetuses after administration of either toxin. In mice given the non-labeled FX, major and minor peaks of NIV and FX on HPLC were noted in suckling pup tissue homogenates. The results demonstrate that NIV transfers in unchanged form to fetal or suckling mice via placenta or milk, respectively, and that FX does so mainly after being metabolized to NIV in maternal body.

Animals↗

PubMed2004

Characteristics of testicular lesions in mice infected with a low dose of encephalomyocarditis (EMC) virus.

We investigated the characteristics of testicular lesions induced in mice with a low dose (10 plaque forming units/mouse) of the D variant of encephalomyocarditis (EMC-D) virus. The virus titers of blood and testis peaked at 5 days post-inoculation (5 DPI) and were no longer detected at 14 DPI. The IFN-gamma and iNOS mRNAs expression in the testis and spleen detected by RT-PCR was prominently elevated at 7 DPI, although the expression level of TNF-alpha mRNA was not affected. Signals of viral RNA were clearly detected in degenerative germinal epithelia (in situ hybridization) at 7 DPI, which were surrounded by a small number of macrophages and a few CD4 + T cells and CD8 + T cells (immunohistochemistry). Signals were no longer detected at 21 DPI when seminiferous tubules were highly degenerative and accompanied with infiltration of many macrophages and a small numbers of CD4 + T cells and CD8 + T cells. At 35 DPI, marked atrophy of germinal epithelia composed of Sertoli cells alone was observed, and there were almost no infiltrating cells detected. The present results suggest that macrophages may play an important role in the development of testicular lesions induced in mice with a low dose of EMC-D.

Animals↗

PubMed2004

Experimental encephalomyocarditis virus infection in pregnant mice.

The present study was carried out to clarify the mode of encephalomyocarditis (EMC) virus infection in pregnant mice. Pregnant BALB/c mice were intraperitoneally inoculated with the D variant of EMC virus (EMC-D) (5 x 10(2) PFU/mouse) on 11 days of gestation and killed at 1, 3, and 5 days post-inoculation (DPI). The virus titer (dam's serum, placenta, and fetus), histopathology (fetus, placenta, and uterus), distribution of viral RNA (fetus, placenta and uterus), and ultrastructure (fetal heart and placenta) were examined. No deaths occurred to fetuses at 1 DPI but almost all fetuses died at 5 DPI. The virus titers of dam's serum and placenta were elevated at 1 DPI, peaked at 3 DPI, and the former was not detected at 5 DPI. The virus titer of fetus was first elevated at 3 DPI and the level was lower than those of others. Histopathological changes and signals of viral RNAs detected by in situ hybridization (ISH) were observed in the spongiotrophoblast layer of placenta and in the fetal myocardium and liver at 3 DPI. The uterus was free from lesions and signals of viral RNA. Ultrastructural changes developed in trophoblast cells and giant cells in the spongiotrophoblast layer at and after 1 DPI and in fetal myocardial cells at 3 DPI. In the cytoplasm of trophoblast cells and giant cells, aggregations of virus-like particles 20-30 nm in diameter were observed in crystalline array. These results suggest that trophoblast cells and giant cells in the spongiotrophoblast layer are the main target of EMC virus in the placenta and that placental damage as well as the direct effect of virus to fetuses may be a cause of fetal death.

Animals↗