Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 55 records · Page 3Linked to original sources

PubMed2001

Acute dorsal skin responses to UVB-irradiation in Wistar-derived hypotrichotic WBN/ILA-Ht rats.

Acute responses of the dorsal skin to UVB-irradiation (10 kJ/m2) were compared between Wistar-derived hypotrichotic WBN/ILA-Ht rats and Wistar rats. In the epidermis of WBN/ILA-Ht rats, intracellular edema of keratinocytes with or without nuclear shrinkage developed at 3 hours after irradiation mainly in the spinous layer. At 12 hours after irradiation, many sunburn cells characterized by eosinophilic cytoplasm and pyknotic nuclei were observed chiefly in the basal layer. Sunburn cells were mainly observed in the spinous and granular layers at 24 hours after irradiation, and they almost disappeared at 48 hours after irradiation when epidermal hyperplasia was detected. The nuclei of sunburn cells were strongly stained with TUNEL method, and they showed ultrastructural features characteristic for apoptotic nuclei. Moreover, the change in the percentage of TUNEL-positive keratinocytes corresponded well with that in the number of sunburn cells. In the dermis, inflammatory cell infiltration and edema with vascular dilatation were observed at 12 and 24 hours after irradiation. On the other hand, except for intracellular edema of keratinocytes mainly in the spinous layer, the intensity of skin lesions was greatly milder in Wistar rats. Especially, typical sunburn cells were only slightly observed in the basal layer at 24 hours after irradiation. Thus WBN/ILA-Ht rats were more sensitive to UVB-irradiation than Wistar rats, and WBN/ILA-Ht rats was considered to be a useful experimental animal in the field of photodermatology.

Acute Disease↗

PubMed2001

Carbon tetrachloride-induced acute liver injury in Mini and Wistar rats.

Acute liver injury induced by CCl4 injection (0.5 ml/kg b.w.) was compared between Mini and Wistar rats. Mini rats (Jcl:Wistar-TgN (ARGHGEN)1Nts strain) are Wistar-derived transgenic animals in which the expression of growth hormone (GH) gene is suppressed by the presence of an antisense transgene. The hepatic lesion appeared earlier and its recovery was delayed in Mini rats compared to in Wistar rats. The degree of the liver injury was more severe in Mini rats than in Wistar rats, and this corresponded well with the changes in serum AST level. Moreover, in accordance with the localization of CYP2E1-positive hepatocytes in the early stage after CCl4 treatment, the initial lesion characterized by ballooning of hepatocytes developed in the centrilobular zone in Wistar rats while it appeared in the middle zone in Mini rats. The changes in the percentage of PCNA-positive cells and the levels of HGF and TGF-beta1 mRNAs were clearly different between the two strains. These results indicate that the response of the liver to CCl4 is different between GH-suppressed Mini rats and Wistar rats.

Alkaline Phosphatase↗

PubMed2001

Histopathological and immunohistochemical studies on arteritis induced by fenoldopam, a vasodilator, in rats.

Fenoldopam, a dopaminergic (DA1) agonist, has been reported to induce medial necrosis and adventitial inflammatory response in the splanchnic arteries in rats. This study was carried out to clarify the detailed time course of the inflammatory responses, using antibodies for the inflammatory cell markers, CD3 (T cell), CD20 (B cell) and ED-1 (macrophage), and inflammatory serum factors, IgG, IgM and C3. Rats were administered fenoldopam for 24 hours by intravenous infusion. Histopathologically, medial necrosis with hemorrhage was observed at the end of infusion, but it almost disappeared on day 7 post-infusion. Adventitial inflammatory responses with ED-1-, CD3- and CD20-positive cells were very slight at the end of infusion, became prominent with marked fibrosis on days 3 and 5, decreased on day 7, and subsided on day 14. The serum factors were first present in the area of medial necrosis, then shifted to the subendothelial space or cytoplasm of smooth muscle cells, and disappeared on day 14 post-infusion. Gaps in the external elastic lamina were observed on days 3 and 5 post-infusion, and IgG and IgM were present outside the gaps in the adventitia. These results provided us with more detailed information on the inflammatory responses following medial damage induced by vasodilators.

Animals↗

PubMed2001

Effects of double UVB-irradiations with different intervals on the dorsal skin of wistar-derived hypotrichotic WBN/ILA-Ht rats.

The effects of double irradiations of UVB (10 kJ/m2) with different intervals (12, 24 and 48 hr) were examined on the dorsal skin of Wistar-derived hypotrichotic WBN/ILA-Ht rats as the first step for long-term repeated irradiation study. The dorsal skin responses to a single UVB-irradiation were similar to those previously reported by our research group (Exp Toxicol Pathol, in press). In the groups which were given the 2nd irradiation at 12 and 24 hr after the 1st one, erythema, epidermal damage and subsequent hyperplasia, intradermal inflammatory cell infiltration and edema developed earlier and were more prominent especially in 12 hr-group compared with a single irradiation. However, the sequence of sunburn cells, the most characteristic epidermal change, was not different from that after a single irradiation. On the other hand, the dorsal skin responses to the 2nd irradiation at 48 hr after the 1st one were almost similar to those observed in the single irradiation-group except for epidermal hyperplasia being more prominent in 48 hr-group. This suggests that the responsibility of the dorsal skin almost recovered at 48 hr after the 1st irradiation.

Animals↗

PubMed2001

Kinetics of cytokines mRnas expression in the dorsal skin of WBN/ILA-Ht rats following topical application of T-2 toxin.

The kinetics of cytokines mRNAs expression was examined in the dorsal skin of Wistar-derived hypotrichotic WBN/ILA-Ht rats topically applied with T-2 toxin. After the application of 10 microl (0.5 microg/microl) of T-2 toxin solution, the total mRNA was obtained from skin biopsies at 3, 6, 12 and 24 hours after treatment (HAT). Reverse transcription-polymerase chain reaction (RT-PCR) was carried out with pairs of oligonucleotide primers corresponding to the cDNA sequences of rat TNF-alpha, IL-1 alpha, IL-1beta, IL-6 and IL-10 cytokines. The level of TNF-alpha mRNA showed marked elevation at 3HAT and decreased toward 24HAT, but it remained significantly higher level even at 24HAT. In addition, the level of IL- 1beta mRNA expression showed a sligth but significant elevation at 3 and 24HAT. On the other hand, no significant differences were observed in other cytokines mRNAs expression between T-2 toxin-treated and control groups througth the observation period. Together with our previous report describing the sequence of epidermal cell apoptosis (Albarenque et al. 1999), the present results suggest that the elevation of TNF-alpha mRNA expression may play an important role in T-2 toxin-induced epidermal cell apoptosis.

Administration, Topical↗

PubMed2001

Development of apoptosis and changes in lymphocyte subsets in thymus, mesenteric lymph nodes and Peyer's patches of mice orally inoculated with T-2 toxin.

Development of apoptosis and changes in lymphocyte subsets were examined mainly by flow cytometer in thymus, mesenteric lymph nodes and Peyer's patches of mice up to 24 hours after oral inoculation with T-2 toxin (10 mg/kg). T-2 toxin attacked Peyer's patches first, then mesenteric lymph nodes, and finally thymus in relation to the course of enteric absorption of orally inoculated T-2 toxin. The degree of lymphocyte apoptosis was prominent in the thymus, moderate in the Peyer's patches, and somewhat mild in the mesenteric lymph nodes, suggesting the difference in lymphocyte population susceptible to T-2 toxin. As to the changes in lymphocyte subsets, CD4+ CD8+ T cells were most sensitive to T-2 toxin, and CD4+ CD8- T cells were more severely depressed than CD4- CD8+ T cells in the thymus. In the mesenteric lymph nodes, CD3+ cells was more clearly affected than CD19+ cells, and the numbers of CD4+ and CD8+ cells were similarly decreased. In the Peyer's patches, the numbers of CD3+, CD 19+, CD4+ and CD8+ cells were unexceptionally decreased. In addition, among IgM+, IgG+ and IgA+ B cells, the number of IA+ B cells which are more important in the mucosal immunity was most severely affected.

Administration, Oral↗

PubMed2001

Kinetics of matrix metalloproteinases and their regulatory factors in mercuric chloride-induced tubulointerstitial fibrosis in Brown Norway rats.

We investigated the kinetics of matrix metalloproteinases (MMPs) and their regulatory factors mRNAs in the kidneys of mercuric chloride-treated Brown Norway rats. The expression of MMP-1 mRNA remained at lower levels than control, while other MMPs mRNAs were upregulated. The expression of tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA showed significant upregulation. On the other hand, the expressions of TIMP-2 and TIMP-3 mRNAs were not significantly changed. In the plasmin-dependent pathway, the expression of plasminogen activator inhibitor (PAI-1) mRNA was continuously increased, while the expression of urokinase-type plasminogen activator (uPA) mRNA was not increased. The signals of TIMP-1 and PAI-1 mRNAs examined by in situ hybridization, were localized in the regenerative epithelial cells of the proximal tubules. In conclusion, these findings suggest that the activity of MMPs may bealtered by MMP-1 downregulation and inhibition of MMP activity by PAl-1 and TIMP-1 generated from tubular epithelial cells.

Animals↗

PubMed2001

Expression of cytochrome P450 (CYP) isozymes in rat placenta through pregnancy.

The placenta plays a vital role in maintenance of pregnancy and is able to metabolize many foreign chemical compounds by cytochrome P450 (CYP) system. It is very important to clarify the expression of CYPs in the rat placenta, because rats are frequently and widely used in the embryo- and feto-toxicity studies on foreign chemical compounds. In this study, we investigated the changes in the expression and localization of CYPs protein in the placenta of F344 rats at 9, 11, 13, 16 and 19 days of gestation by Western blot analysis and immunohistochemical staining. Among nine isozymes examined (CYP1A1, 2B1, 2C6, 2C12, 2D1, 2D4, 2E1, 3A1 and 4A1), only CYP3A1 was clearly detected by Western blot analysis at all days of gestation examined. Immunohistochemically, the cytoplasm of giant cells in the trophoblastic region was positively stained by anti-CYP3A1 antibodies. These results suggest that CYP3A1 may be a major component of CYP system in the rat placenta.

Animals↗

PubMed2001

Significance of auditory evoked responses (EABR and P300) in cochlear implant subjects.

An electrically derived auditory brainstem response (EABR) was recorded intra-operatively, and the event-related potential (P300) postoperatively in post-lingually deaf adult cochlear implantees. EABR and P300 were recorded from two groups of 25 subjects each. All subjects had a cochlear mini-22 system implanted at our center between 1994 and 1998. Two parameters of EABR, threshold (T) and the gradient of the amplitude-growth (AG) curve, were used for correlation with postoperative speech reception scores. The consonant recognition score (CRS) measured 1 month postoperatively showed a significant correlation with the AG curve of EABR (Spearman rank order test, p = 0.004), but not at later points in time. No correlation was found between the T and CRS at any time postoperatively. As the AG curve reflects the number of remaining spiral ganglion cells in the inner ear, a large number of surviving neurons is thought to be advantageous only for initial speech learning. The latency of P300 was measured for correlation with the speech reception score. The division of the cochlear implant subjects into a fair and a good hearing group according to their CRS showed that the average latency of P300 was significantly longer for the fair hearing group than for the good hearing group. A follow-up study showed that P300 latency significantly correlated with CRS measured at 6 months, 1 year and at a later time. As the latency of P300 is thought to reflect the time for sound processing in the central auditory system, our results indicate that plasticity of the central auditory system is more important than that of the peripheral auditory system for speech learning in cochlear implant subjects.

Adult↗

PubMed2001

Alteration of antioxidants during the progression of heart disease in streptozotocin-induced diabetic rats.

Involvement of oxidative stress is implicated in the progression of complication of diabetes mellitus. With respect to heart diseases, we have studied role of oxidative stress/antioxidants using rats treated with streptozotocin to induce diabetes (DM). Hemodynamic and echocardiographic measurements showed thickening of the wall and an increase in the internal dimension of the left ventricle (LV) in DM rats at 8th week. Decrease in diastolic posterior wall velocity and rate of LV pressure change, and increase in LV end diastolic pressures also proved cardiac dysfunction. These changes were further developed in DM rats after 12 weeks. Utilizing rat hearts at 8th and 12th weeks, the following estimations were performed. There was a decrease in the activity of Mn-superoxide dismutase (SOD), suggesting abnormal mitochondrial metabolism of reactive oxygen species. The level of glutathione (GSH) decreased concomitant with a decrease in the expression of gamma-glutamylcysteine synthetase (gamma-GCS). The expression of transforming growth factor-beta1 (TGF-beta1), known as a growth factor and a suppressor of GSH synthesis, elevated in DM rat hearts. Immunohistochemical estimation showed an increase in type IV collagen in DM hearts. Collectively, it was suggested a linkage between mitochondrial damage to generate reactive oxygen species and inactivation of Mn-SOD and elevation of the expression of TGF-beta1 to lead suppression of GSH synthesis and induction of fibrous change for the consequent cardiac dysfunction in DM.

Animals↗

PubMed2001

Regional variations in the distribution of small intestinal intraepithelial lymphocytes in alymphoplasia (aly/aly) mice and heterozygous (aly/+) mice.

Regional variations in intraepithelial lymphocytes (IELs) in the small intestine were examined in alymphoplasia mutant (aly/aly) mice, which are characterized by the systemic absence of lymph nodes and Peyer's patches, and heterozygous (aly/+) mice. The small intestines were taken from 10 to 12-week-old mice and divided equally into 3 parts (the proximal, middle and distal parts). IELs were isolated from each part of the intestine and analyzed with a flow cytometer. The number of IELs in the distal part was significantly fewer in aly/aly mice compared with aly/+ mice, although the total number of small intestinal IELs were comparable between them. As to the IELs subsets, regional variations in alphabeta T cells and gammadelta T cells were observed in aly/+ mice, but they disappeared in aly/aly mice. However, regional variations in composition of alphabeta T cell subsets were similarly observed in both aly/aly mice and aly/+ mice. This indicates that, although not essential, mesenteric lymph nodes (MLN) and/or Peyer's patches may modify the regional variations in IELs.

Animals↗

PubMed2001

Utility of Tc-99m GSA whole-body scintigraphy in detecting bone metastases from hepatocellular carcinoma.

Recent advances in the treatment of hepatocellular carcinoma (HCC) have prolonged patient survival. However, the number of patients with bone metastases identified during follow-up examinations has increased. Tc-99m Sn-N-pyridoxy-5-methyltryptophan (Tc-99m PMT) has been reported to accumulate at a high rate in HCC lesions and bone metastases. In the patient described here, whole-body scintigraphy showed accumulation of DTPA galactosyl human serum albumin (Tc-99m GSA) and Tc-99m PMT in bone metastases from HCC. The authors suggest that asialoglycoprotein receptors may be present in bone metastases from well-differentiated HCC. Tc-99m GSA whole-body imaging can be used to detect bone metastases from HCC and to evaluate hepatic reserve.

Albumins↗

PubMed2001

An automated patient recognition method based on an image-matching technique using previous chest radiographs in the picture archiving and communication system environment.

An automated patient recognition method for correcting "wrong" chest radiographs being stored in a picture archiving and communication system (PACS) environment has been developed. The method is based on an image-matching technique that uses previous chest radiographs. For identification of a "wrong" patient, the correlation value was determined for a previous image of a patient and a new, current image of the presumed corresponding patient. The current image was shifted horizontally and vertically and rotated, so that we could determine the best match between the two images. The results indicated that the correlation values between the current and previous images for the same, "correct" patients were generally greater than those for different, "wrong" patients. Although the two histograms for the same patient and for different patients overlapped at correlation values greater than 0.80, most parts of the histograms were separated. The correlation value was compared with a threshold value that was determined based on an analysis of the histograms of correlation values obtained for the same patient and for different patients. If the current image is considered potentially to belong to a "wrong" patient, then a warning sign with the probability for a "wrong" patient is provided to alert radiology personnel. Our results indicate that at least half of the "wrong" images in our database can be identified correctly with the method described in this study. The overall performance in terms of a receiver operating characteristic curve showed a high performance of the system. The results also indicate that some readings of "wrong" images for a given patient in the PACS environment can be prevented by use of the method we developed. Therefore an automated warning system for patient recognition would be useful in correcting "wrong" images being stored in the PACS environment.

Biophysical Phenomena↗

PubMed2001

Computer-aided diagnostic scheme for lung nodule detection in digital chest radiographs by use of a multiple-template matching technique.

We have been developing a computer-aided diagnostic (CAD) scheme to assist radiologists in improving the detection of pulmonary nodules in chest radiographs, because radiologists can miss as many as 30% of pulmonary nodules in routine clinical practice. A key to the successful clinical application of a CAD scheme is to ensure that there are only a small number of false positives that are incorrectly reported as nodules by the scheme. In order to significantly reduce the number of false positives in our CAD scheme, we developed, in this study, a multiple-template matching technique, in which a test candidate can be identified as a false positive and thus eliminated, if its largest cross-correlation value with non-nodule templates is larger than that with nodule templates. We describe the technique for determination of cross-correlation values for test candidates with nodule templates and non-nodule templates, the technique for creation of a large number of nodule templates and non-nodule templates, and the technique for removal of nodulelike non-nodule templates and non-nodulelike nodule templates, in order to achieve a good performance. In our study, a large number of false positives (44.3%) were removed with reduction of a very small number of true positives (2.3%) by use of the multiple-template matching technique. We believe that this technique can be used to significantly improve the performance of CAD schemes for lung nodule detection in chest radiographs.

Algorithms↗

PubMed2001

Potential of computer-aided diagnosis to reduce variability in radiologists' interpretations of mammograms depicting microcalcifications.

PURPOSE: To evaluate whether computer-aided diagnosis can reduce interobserver variability in the interpretation of mammograms. MATERIALS AND METHODS: Ten radiologists interpreted mammograms showing clustered microcalcifications in 104 patients. Decisions for biopsy or follow-up were made with and without a computer aid, and these decisions were compared. The computer was used to estimate the likelihood that a microcalcification cluster was due to a malignancy. Variability in the radiologists' recommendations for biopsy versus follow-up was then analyzed. RESULTS: Variation in the radiologists' accuracy, as measured with the SD of the area under the receiver operating characteristic curve, was reduced by 46% with computer aid. Access to the computer aid increased the agreement among all observers from 13% to 32% of the total cases (P <.001), while the kappa value increased from 0.19 to 0.41 (P <.05). Use of computer aid eliminated two-thirds of the substantial disagreements in which two radiologists recommended biopsy and routine screening in the same patient (P <.05). CONCLUSION: In addition to its demonstrated potential to improve diagnostic accuracy, computer-aided diagnosis has the potential to reduce the variability among radiologists in the interpretation of mammograms.

Biopsy↗

PubMed2001

An inwardly rectifying K(+) channel, Kir4.1, expressed in astrocytes surrounds synapses and blood vessels in brain.

Glial cells express inwardly rectifying K(+) (Kir) channels, which play a critical role in the buffering of extracellular K(+). Kir4.1 is the only Kir channel so far shown to be expressed in brain glial cells. We examined the distribution of Kir4.1 in rat brain with a specific antibody. The Kir4.1 immunostaining distributed broadly but not diffusely in the brain. It was strong in some regions such as the glomerular layer of the olfactory bulb, the Bergmann glia in the cerebellum, the ependyma, and pia mater, while little activity was detected in white matter of the corpus callosum or cerebellar peduncle. In the olfactory bulb, Kir4.1 immunoreactivity was detected in a scattered manner in about one-half of the glial fibrillary acidic protein-positive astrocytes. Immunoelectron microscopic examination revealed that Kir4.1 channels were enriched on the processes of astrocytes wrapping synapses and blood vessels. These data suggest that Kir4.1 is expressed in a limited population of brain astrocytes and may play a specific role in the glial K(+)-buffering action.

Animals↗

PubMed2001

Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells.

To elucidate the significance of oxidative stress in the modulation of endothelial functions, we examined the effects of H(2)O(2) on the expression of two endothelium-derived vasoactive peptides, endothelin (ET) and adrenomedullin (Am), and their interaction. H(2)O(2) dose dependently suppressed ET secretion and ET-1 mRNA expression in bovine carotid endothelial cells (ECs). Menadion sodium bisulfate, a redox cycling drug, also decreased ET secretion in a dose-dependent manner. Catalase, a H(2)O(2) reductase, and dl-alpha-tocopherol (vitamin E) significantly inhibited H(2)O(2)-induced suppression of ET secretion. Downregulation of ET-1 mRNA under oxidative stress was regulated at the transcriptional level. In contrast, H(2)O(2) increased Am secretion (and its mRNA expression) accompanied by the augmentation of cAMP production. Am, as well as 8-bromo-cAMP and forskolin decreased ET secretion in a dose-dependent fashion. Furthermore, an anti-Am monoclonal antibody that we developed abolished H(2)O(2)-induced suppression of ET secretion at 6-24 h after the addition of H(2)O(2). H(2)O(2) increased the intracellular Ca(2+) concentration ([Ca(2+)](i)). Moreover, treatment with ionomycin, a Ca(2+) ionophore, and thapsigargin, an inhibitor of endoplasmic reticulum ATPase, decreased ET secretion dose dependently for 3 h. These results suggest that the production of ET was decreased via activation of the Am-cAMP pathway and by the elevation of [Ca(2+)](i) under oxidative stress. These findings elucidate the coordinate expression of two local vascular hormones, ET and Am, under oxidative stress, which may protect against vascular diseases.

Adrenomedullin↗

PubMed2001

Oxidized LDL regulates vascular endothelial growth factor expression in human macrophages and endothelial cells through activation of peroxisome proliferator-activated receptor-gamma.

Vascular endothelial growth factor (VEGF) has been recognized as an angiogenic factor that induces endothelial proliferation and vascular permeability. Recent studies have also suggested that VEGF can promote macrophage migration, which is critical for atherosclerosis. We have reported that VEGF is remarkably expressed in activated macrophages, endothelial cells, and smooth muscle cells within human coronary atherosclerotic lesions, and we have proposed the significance of VEGF in the progression of atherosclerosis. To clarify the mechanism of VEGF expression in atherosclerotic lesions, we examined the regulation of VEGF expression by oxidized low density lipoprotein (Ox-LDL), which is abundant in atherosclerotic arterial walls. A recent report has revealed that peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed not only in adipocytes but also in monocytes/macrophages and has suggested that PPARgamma may have a role in the differentiation of monocytes/macrophages. Furthermore, 9- and 13-hydroxy-(S)-10,12-octadecadienoic acid (9- and 13-HODE, respectively), the components of Ox-LDL, may be PPARgamma ligands. Therefore, we investigated the involvement of PPARgamma in the regulation of VEGF by Ox-LDL. PPARgamma expression was detected in human monocyte/macrophage cell lines, human acute monocytic leukemia (THP-1) cells, and human coronary artery endothelial cells (HCAECs). Ox-LDL (10 to 50 microg/mL) upregulated VEGF secretion from THP-1 dose-dependently. VEGF mRNA expression in HCAECs was also upregulated by Ox-LDL. The mRNA expression of VEGF in THP-1 cells and HCAECs was also augmented by PPARgamma activators, troglitazone (TRO), and 15-deoxy-(12,14)-prostaglandin J(2) (PGJ2). In contrast, VEGF expression in another monocyte/macrophage cell line, human histiocytic lymphoma cells (U937), which lacks PPARgamma expression, was not augmented by TRO or PGJ2. We established the U937 cell line, which permanently expresses PPARgamma (U937T). TRO and Ox-LDL augmented VEGF expression in U937T. In addition, VEGF production by THP-1 cells was significantly increased by exposure to 9-HODE and 13-HODE. In conclusion, Ox-LDL upregulates VEGF expression in macrophages and endothelial cells, at least in part, through the activation of PPARgamma.

Arteriosclerosis↗