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Biomedical subjects

Kunio Doi

Publications and source records attributed to Kunio Doi.

At least 91 records · Page 5Linked to original sources

Development of early apoptosis and changes in T-cell subsets in mouse thymocyte primary cultures treated with nivalenol.

Nivalenol (NIV), a trichothecene mycotoxin, is a secondary fungal metabolite mainly produced by Fusarium nivale. We first reported that NIV could induce apoptosis and changes in lymphocyte subsets in lymphoid tissues of mice. In this study, to clarify the direct effects of NIV on thymocytes, mouse thymocyte primary cultures were treated with NIV at the dose levels of 0.25, 0.5 and 1.0 microg/ml and examined for up to 24 h after treatment by flow cytometry. The number of viable cells decreased significantly at and after 6 h in dose- and time-dependent manners, and FACS analysis revealed that the apoptotic cell index showed a significant increase in all treated groups at and after 3 h in a time-dependent manner. The index at 24 h was lowest in 1.0 microg/ml-group. The number of CD4(+)CD8(+) cells was prominently depleted in all groups in a time-dependent manner. On the other hand, the numbers of CD4(+)CD8(-) and CD4(-)CD8(+) cells were significantly depleted only in 1.0 microg/ml-group at 24 HAT. These results indicate that NIV directly affects thymocytes and induces apoptosis mainly in CD4(+)CD8(+)cells.

Animals↗

MHC class II-related genes expression in porcine-serum-induced rat hepatic fibrosis.

Genes, especially MHC class II-related genes, expression was examined in porcine-serum (PS)-induced hepatic fibrosis model. Brown-Norway (BN) and Wistar rats were injected intraperitoneally with 0.5 ml sterile porcine serum twice a week for 1, 2, 3, 4, and 8 weeks. Histopathologically, inflammation started at 2 weeks in BN and at 4 weeks in Wistar rats, and hepatic fibrosis developed at 4 weeks in BN rats and at 8 weeks in Wistar rats. Microarray analysis done at 2 and 4 weeks revealed that the expression of MHC class II-related genes and acute phase inflammation-related genes significantly increased at 2 weeks in BN and at 4 weeks in Wistar rats. On the other hand, the expression of some transcription-related genes was down-regulated in both strains. In BN rats, the results of semiquantitative RT-PCR analysis done on four MHC class II-related genes mRNAs corresponded well with those of microarray analysis. MHC class II is considered to be involved in the initiation of PS-induced hepatic fibrosis in rats.

Animals↗

Artificial neural networks (ANNs) for differential diagnosis of interstitial lung disease: results of a simulation test with actual clinical cases.

RATIONALE AND OBJECTIVES: To evaluate the performance of an artificial neural network (ANN) scheme with use of consecutive clinical cases and its effect on radiologists with an observer test. MATERIALS AND METHODS: Artificial neural networks were designed to distinguish among 11 interstitial lung diseases on the basis of 26 inputs (16 radiologic findings, 10 clinical parameters). Chest radiographs of 96 consecutive cases with interstitial lung disease were used. Five radiologists independently rated their radiologic findings on the 96 chest radiographs. Based on their ratings of radiologic findings and clinical parameters obtained from the hospital information system, the output values indicating the likelihood of each of the 11 interstitial lung diseases were determined. Subsequently, 30 cases were selected from these 96 cases for an observer test. Five radiologists marked their confidence levels for diagnosis of 11 possible diseases in each case without and with ANN output. The performance of ANNs and radiologists was evaluated by receiver operating characteristic analysis based on their outputs and on confidence levels, respectively. RESULTS; The average Az value (area under the receiver operating characteristic curve) indicating ANN performance for the 96 consecutive cases was 0.85 +/- 0.03. The average Az values indicating radiologists' performance without and with ANN outputs were 0.81 +/- 0.11 and 0.87 +/- 0.06, respectively. The diagnostic accuracy was improved significantly when radiologists read chest radiographs with ANN outputs (P < .05). CONCLUSION: Artificial neural networks for differential diagnosis of interstitial lung disease may be useful in clinical situations, and radiologists may be able to utilize the ANN output to their advantage in the differential diagnosis of interstitial lung disease on chest radiographs.

Adult↗

Potential usefulness of biological fingerprints in chest radiographs for automated patient recognition and identification.

RATIONALE AND OBJECTIVES: The purpose of this study was to demonstrate the potential usefulness of "biological fingerprints" in chest radiographs for automated patient recognition and identification. MATERIALS AND METHODS: Thoracic fields, cardiac shadows, the superior mediastinum, lung apices, a part of the right lung, and the right lower lung that includes the costophrenic angle were used as biological fingerprints in chest radiographs. Each of the biological fingerprints in a current chest radiograph was used as a template for determination of the correlation value with the corresponding biological fingerprint in a previous chest radiograph for patient recognition and identification. The overall performance of the method developed was examined in terms of receiver operating characteristic curves. RESULTS: Receiver operating characteristic curves obtained with different biological fingerprints, except for the part of the right lung, indicated a high performance in identifying patients. These results showed that a new concept of biological fingerprints in radiologic images would be useful in patient recognition and identification. The low performance with the part of the right lung seems to be related to a general observation that this region does not usually include features unique to a specific patient. The performance of the artificial neural networks by use of a combination of five biological fingerprints was higher than results obtained with each biological fingerprint. CONCLUSION: The use of automated patient identification based on biological fingerprints in chest radiographs is promising for helping to discover misfiled patient images, especially in a picture archiving and communication system environment.

Dermatoglyphics↗

Improved detection of lung cancer arising in diffuse lung diseases on chest radiographs using temporal subtraction.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the usefulness of temporal subtraction for the detection of lung cancer arising in pneumoconiosis, idiopathic pulmonary fibrosis, and pulmonary emphysema. MATERIALS AND METHODS: Fifteen cases of lung cancer arising in diffuse lung diseases, including three cases of pneumoconiosis, six of idiopathic pulmonary fibrosis, and six of pulmonary emphysema, were evaluated. Pathologic proof was obtained by surgery or transbronchial lung biopsy. The average interval between previous and current radiographs was 356 days (range, 31-947 days). All chest radiographs were obtained with a computed radiography system, and temporal subtraction images were produced by subtracting of a previous image from a current one with a nonlinear image-warping technique. The effect of the temporal subtraction image was evaluated by observer performance study with receiver operating characteristic analysis. RESULTS: The average observer performance with temporal subtraction was significantly improved (Az = 0.935) compared with that without temporal subtraction (Az = 0.857, P < .0001). CONCLUSION: The temporal subtraction technique is useful for the detection of lung cancer arising in pneumoconiosis, idiopathic pulmonary fibrosis, and pulmonary emphysema.

Adenocarcinoma↗

Computer-aided diagnosis in chest radiology.

Chest radiography is still a useful examination in various situations, although CT has become a modality of choice as a diagnostic examination in many cases. Current computer-aided diagnosis (CAD) schemes for chest radiographs include nodule detection, interstitial disease detection, temporal subtraction, differential diagnosis of interstitial disease, and distinction between benign and malignant pulmonary nodules. All of these schemes are demonstrated as providing potentially useful tools for radiologists when the output of these schemes is used as a "second opinion." There are some commercially available products for these schemes and more are expected to be available in the near future. The current status of CAD for CT is also discussed briefly in this article.

Diagnosis, Computer-Assisted↗

Overview on research and development of computer-aided diagnostic schemes.

Computer-aided diagnosis (CAD) has become a practical clinical approach in diagnostic radiology, although at present only in the area of detection of breast cancer in mammograms. Current research efforts have been focused on detection and classification of images of many different types of lesions in a number of organs, obtained with various imaging modalities. It is likely that the present results of CAD are only at the tip of the iceberg. Although automated computer diagnosis is a concept based on computer algorithms only, CAD is a concept established by taking into account equally the roles of physicians and computers. The effect of CAD on differential diagnosis has already indicated that the performance level is high, and that CAD would be ready for clinical trials and commercialization efforts. The presentation of images similar to those of an unknown case may be useful as a supplemental tool for CAD in the differential diagnosis.

Database Management Systems↗

Gene expression profiles in pregnant rats treated with T-2 toxin.

Pregnant rats on day 13 of gestation were treated orally with T-2 toxin at a single dose of 2 mg/kg and sacrificed at 24 hours after treatment. Histopathologically, apoptosis was increased in the liver, placenta and fetal liver. Microarray analysis was performed to examine the gene expression in the liver, placenta, and fetal liver. The results of microarray analysis showed that the changes in the expression of apoptosis genes, metabolic enzymes and oxidative stress-related genes were detected in these tissues. Suppression of phase I and II enzymes-related genes expression in the liver, and suppression of phase II enzymes-related genes expression in the placenta and fetal liver were observed. Semiquantitive RT-PCR analysis also showed the same results as those of microarray analysis. From the results of microarray analysis and histopathological examination, T-2 toxin seems to induce oxidative stress in these tissues, following the changes in metabolism-related genes expression. These changes may alter the intracellular environments resulting in the induction of apoptosis. Further studies on the gene expression profiles at the earlier time point are necessary to clarify the detailed mechanisms of T-2 toxin-induced toxicity in pregnant rats.

Administration, Oral↗

Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice.

We have reported the streptozotocin (SZ)-induced hepatic lesions in the subacute phase (4 to 12 weeks after the treatment), which are characterized by appearance of oncocytic hepatocytes, cytomegalic hepatocytes and bile duct hyperplasia. In this study, we focused on the acute phase (6 to 48 hours after the treatment) of the SZ-induced hepatic lesions of mice to clarify the onset of the hepatic alterations, especially before the induction of hyperglycemia. Livers were taken from 8-week-old Crj:CD-1 (ICR) male mice at 6, 12, 24, 36 and 48 hours after the 200 mg/kg b.w. of SZ-injection. SZ-induced hyperglycemia was noted at 36 and 48 hours after the treatment, but the hepatic changes including lipid peroxidation, mitochondrial swelling, peroxisome proliferation and inhibition of hepatocyte proliferation occurred before the elevation of the serum glucose levels. The present findings indicate the direct effects of SZ on hepatocytes rather than the secondary effects of diabetes, and certain correlations between the hepatocytic changes in the acute phase and those in the subacute one. In addition, ulcer and submucosal edema of the gallbladder were observed at 36 or 48 hours after the SZ-treatment, which can be a novel finding in SZ-treated animal.

Acute Disease↗

Immunohistochemical detection of beta-amyloid and beta-amyloid precursor protein in the canine brain and non-neuronal epithelial tissues.

We examined the immunohistochemical localization of beta-amyloid (Abeta) and beta-amyloid precursor protein (AFPP) in the neuronal and non-neuronal tissues of 14 aged (over 10 years old) and 4 young (0-4 years old) dogs. Abeta was detected only in the senile plaque in the cerebrum of aged dogs. AbetaPP was expressed in the neuronal cell body, neuronal fiber, senile plaque and perimalacic tissue independent of age. In addition, epithelial cells in the bronchus, bronchial glands, gastric and intestinal mucosa, intrahepatic bile ducts, and pancreatic ducts and exocrine glands were immunopositive for AbetaPP. Thus, it is suggested that AbetaPP may be expressed in the non-neuronal epithelial tissues independent of age and of the presence of senile plaques, and the expression may depend on individual differences or physiological conditions.

Aging↗

Q-switched ruby laser irradiation on spotty pigmentation in the skin of the hairless dog.

OBJECTIVE: To investigate macroscopically and histopathologically the dermatological changes after Q-switched ruby laser (QRL) irradiation with different exposure doses in UVB-induced pigmentation in hairless dogs. METHODS: QRL irradiation with 3.0, 5.0 and 7.0 J/cm(2) was carried out on the UVB-induced spotty pigmentation in the skin of the hairless dog. Gross appearance was observed daily throughout this study. Histopathological examination was performed 1 day before QRL irradiation and 1 and 3 days and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 and 16 weeks after QRL irradiation. RESULTS: Immediately after QRL irradiation, spotty pigmentation was removed. One week after QRL irradiation, re-epithelialization started from the margin of the irradiated sites. between 5 and 10 weeks after QRL irradiation, the skin color returned to normal and some portions showed recurrence of hyperpigmentation. Histopathologically, spotty pigmentation had a heavy deposition of melanin granules in the stratum basale, spinosum and corneum. One day after QRL irradiation, the skin showed destruction of melanin granules. Seven days after QRL irradiation, re-epithelialization began from the surroundings of the QRL-irradiated sites and the pilosebaceous units. The delayed process of re-epithelialization was dependent on the incident exposure dose with QRL. The repaired epidermis was devoid of melanin granules. By 5 weeks after QRL irradiation with 3.0 and 5.0 J/cm(2), the stratum basale and spinosum revealed a redistribution of melanin granules. In the sites of recurrent hyperpigmentation, the bases of the remaining hair follicles showed a notable increase in the reproduction of melanin granules. Melanin granules abundantly aggregated in the bottom portion of the nucleus in each epidermal cell. CONCLUSION: These results revealed that hairless dogs were invaluable laboratory animals, which developed spotty pigmentation after successive UVB irradiation. In addition, UVB-induced spotty pigmentation in hairless dogs is useful for investigating the process of depigmentory treatment with QRL irradiation and recurrence of this lesion.

Animals↗

Depigmentation and rejuvenation effects of kinetin on the aged skin of hairless descendants of Mexican hairless dogs.

The depigmenting and anti-aging effects of kinetin (KN) solutions on the aged skin of hairless dogs were clinically and histologically investigated. Grossly, all KN-treated sites became mildly depigmented. At 50 days of topical treatment with KN solutions, apparent improvement was observed in the skin texture, wrinkling, and pigmentation. At 100 days of KN treatment, both the skin rejuvenation and depigmentation effects became more prominent. Throughout the experimental period of KN treatment, no adverse effects were found in any sites treated with KN solutions. In the colorimetric system, at 100 days of topical treatment with KN solutions, the L* and b* values in the sites treated with KN solutions significantly increased. Histologically, at 50 days of topical treatment with KN solutions, the KN-treated sites showed a decrease in the thickness of the corneal layers. Melanin granules decreased throughout all epidermal layers. In the dermis, the large number of fine collagen and elastic fibers were densely aligned. At the end of the treatment, this agent was equally effective against pigmented lesions irrespective of the concentration of KN solution. The distribution of melanin granules returned to normal in the skin of adult hairless dogs. Throughout the present study, there were no histologic abnormalities in the epidermis and the dermis. These results revealed that topical treatment with lower concentrations of KN solutions normalized hyperpigmentation and improved the aged skin structure of hairless dogs. In addition, it was clarified that KN solutions had no adverse effects on the skin of hairless dogs and that this agent was a safe chemical for long-term application.

Adenine↗

Effects of tacrolimus (FK506) on encephalomyocarditic virus-induced diabetes in mice.

The effects of tacrolimus on insulin-dependent diabetes mellitus (IDDM) induced by the D-variant of encephalomyocarditis virus (D-EMCV) have been investigated. Male BALB/c mice were treated with tacrolimus before viral inoculation, and then were inoculated with 10 plaque forming units (PFU) of DEMCV. The mice continued to be treated with tacrolimus until the animals were sacrificed. D-EMCV-infected mice, which were treated with saline as controls, showed abnormal glucose tolerance test (GTT) values, whereas all infected mice with tacrolimus pretreatment were normal on 7 days-post inoculation (DPI). Histological observations revealed that non-treated tacrolimus D-EMCV-infected mice and which developed diabetes showed severe insulitis in their islets of Langerhans. On the other hand, D-EMCV-infected mice treated with tacrolimus were normal. In D-EMCV-infected mice, viruses in the pancreata were detected at the same level regardless of treatment with tacrolimus or saline. Expressions of TNF-alpha and IFN-gamma mRNA in spleens of tacrolimus-treated D-EMCV-infected mice were lower than that of non-treated tacrolimus DEMCV-infected mice on 7 DPI. The results suggest that tacrolimus suppresses expressions of TNF-alpha and IFN-gamma mRNAs to prevent the onset of D-EMCV-induced IDDM.

Animals↗

Computer-aided diagnosis scheme for histological classification of clustered microcalcifications on magnification mammograms.

The histological classification of clustered microcalcifications on mammograms can be difficult, and thus often require biopsy or follow-up. Our purpose in this study was to develop a computer-aided diagnosis scheme for identifying the histological classification of clustered microcalcifications on magnification mammograms in order to assist the radiologists' interpretation as a "second opinion." Our database consisted of 58 magnification mammograms, which included 35 malignant clustered microcalcifications (9 invasive carcinomas, 12 noninvasive carcinomas of the comedo type, and 14 noninvasive carcinomas of the noncomedo type) and 23 benign clustered microcalcifications (17 mastopathies and 6 fibroadenomas). The histological classifications of all clustered microcalcifications were proved by pathologic diagnosis. The clustered microcalcifications were first segmented by use of a novel filter bank and a thresholding technique. Five objective features on clustered microcalcifications were determined by taking into account subjective features that experienced the radiologists commonly use to identify possible histological classifications. The Bayes decision rule with five objective features was employed for distinguishing between five histological classifications. The classification accuracies for distinguishing between three malignant histological classifications were 77.8% (7/9) for invasive carcinoma, 75.0% (9/12) for noninvasive carcinoma of the comedo type, and 92.9% (13/14) for noninvasive carcinoma of the noncomedo type. The classification accuracies for distinguishing between two benign histological classifications were 94.1% (16/17) for mastopathy, and 100.0% (6/6) for fibroadenoma. This computerized method would be useful in assisting radiologists in their assessments of clustered microcalcifications.

Algorithms↗

Clinical and histopathological findings in pustular psoriaform dermatitis (pityriasis rosea) in pigs.

Three cases of pustular psoriaform dermatitis (pityriasis rosea) in pigs were clinically and histopathologically examined. Grossly, the affected skin was characterized by multiple, circumscribed lesions. Three pigs were the descendants derived from the same Landrace boar. Skin lesions expanded centrifugally to became ring-shaped plaques. There were no abnormal values in hematological and serum biochemical profiles. Histopathologically, the epidermis showed remarkable thickening. The dermal lesions were characterized by a prominent component of superficial and deep perivascular infiltration of eosinophils. Dilatation of microvasculature was accompanied with congested vessels. These results revealed that the etiology of pustular psoriaform dermatitis in pigs was associated with a hereditary predisposition derived from the specific boars. This dermatosis is histopathologically characterized by microcirculatory disturbances with infiltration of abundant eosinophils.

Animals↗

Secondary erythrocytosis associated with schwannoma in a dog.

An 11-year-old, spayed female mixed-breed dog showed clinical signs of right forelimb lameness and pain by palpation around the neck. Radiography and computed tomography (CT) revealed an extradural mass at the 6th and 7th cervical vertebrae, which compressed the spinal cord. The mass was surgically removed and histopathologically diagnosed as schwannoma. The dog recovered her normal gait after hemilaminectomy and removal of the mass. Ten months after the surgery, the tumor recurred with absolute erythrocytosis and was surgically removed again. This removal temporarily resolved the erythrocytosis with a decrease in plasma erythropoietin (EPO) concentration. EPO protein was detected immunohistochemically in the tumor cells. Erythrocytosis in this dog may be caused by ectopic EPO produced in the schwannoma tissues.

Animals↗

Prevalence of autoantibody in cerebrospinal fluids from dogs with various CNS diseases.

To examine the prevalence of autoantibody in canine cerebrospinal fluids (CSFs), CSFs were collected from 14 healthy controls and 88 clinical cases with various diseases in the central nervous system (CNS), and were analyzed by an indirect fluorescence antibody test on frozen sections of the cerebrum from normal Beagle dogs. An anti-astrocyte autoantibody was detected in 31 clinical cases with titers ranging from 1:1 to >/=1:100. All tested cases with necrotizing meningoencephalitis (NME: n=22) and granulomatous meningoencephalitis (GME: n=3) possessed the anti-astrocyte autoantibody, while the autoantibody was negative in most cases with other inflammatory CNS diseases. The autoantibody was also detected in 4 of 12 cases with brain tumors. Hence, examination of the autoantibody in the canine CFS would be significant for diagnosing NME and/or GME, as well as for understanding peritumoral events in cases with brain tumors.

Animals↗

Thymoma in a dog with a part of granular cell proliferation and concurrent lymphoma cells.

A 12-year-old male Shiba dog showed anemia and the swelling of systemic lymph nodes. X-ray and post mortal examinations revealed a anterior mediastinal mass. Histologically, the tumor mass consisted of four different elements; cord-like proliferation of cuboidal epithelial cells, tubular or cystic structures lined with ciliated epithelial cells, proliferation of large round-shaped epithelial cells with PAS-slightly positive granular cytoplasm, and diffuse proliferation of neoplastic lymphocytes. Epithelial cells in cord-like or cystic structures were strongly positive for cytokeratin. Granular or foamy cells were negative for all markers examined and had myelin-like bodies in the cytoplasm by electron microscopy. The neoplastic lymphocytes in the tumor mass were considered being derived from concurrent multicentric lymphoma. Based on these findings, the present case was diagnosed as thymoma with a part of granular cell proliferation and concurrent lymphoma cells.

Animals↗