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Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 433 records · Page 24Linked to original sources

Histopathology of subacute renal lesions in mice induced by streptozotocin.

Streptozotocin (SZ) was inoculated intraperitoneally to male and female mice of ICR and BALB/c strains in a different way of administration (A: single injection and B consecutive 5 days-injection) and subacute renal changes were examined light and electron microscopically 8 weeks after SZ-administration. The following changes were detected: (1) reduction in the rate of male-type Bowman's capsules in male mice, (2) karyocytomegaly of proximal tubular epithelial cells, and (3) dilation of distal tubules Tubular changes were detected with high incidence in A (males and females) and B groups (males) of ICR strain.

Animals↗

Histopathological sequence of hepatic and renal lesions in rats after cessation of the repeated administration of CCl4.

The histopathological sequence of hepatorenal lesions in rats after cessation of the repeated administration of CCl4 (0.5 ml/kg, p.o., twice a week for 12 weeks) was examined. In the liver, cirrhotic lesions reduced rapidly after cessation of the CCl4-administration and collagen bundles surrounding the pseudolobules almost disappeared 12 weeks later. In contrast, in the kidney, vacuolation of epithelial cells in the proximal tubules disappeared rapidly but glomerular lesions progressed even after cessation of the CCl4-administration, and marked glomerulosclerosis developed 12 weeks later. Electron microscopically, marked expansion of the mesangial region due to increases of mesangial cells and matrix material, irregular thickening of the capillary basement membrane with mesangial interposition, and various degenerative changes in podocytes including deposition of small-sized droplets were observed.

Animals↗

Effects of fructose-induced hypertriglyceridemia on hepatorenal toxicity of acetaminophen in rats.

The mode of hepatorenal toxicity of acetaminophen (AAP) was compared between fructose-induced hyper-triglyceridemic and normal rats. The hypertriglyceridemic and normal rats received a single dose of AAP (0, 750 and 900 mg/kg ip) at week 5 of fructose-treatment. At 24 hrs after AAP-dosing, they were sacrificed and examined blood biochemically and histopathologically. Hepatotoxicity as indicated by an increase in plasma ALT and AST activities and centrilobular necrosis of hepatocytes was more severe in the normal rats than in the hypertriglyceridemic ones. In contrast, nephrotoxicity as indicated by an increase in plasma urea nitrogen content and necrosis of epithelial cells in the proximal straight tubules was more severe in the hypertriglyceridemic rats than in normal ones. Thus, in the fructose-induced hypertriglyceridemic rats, as compared with normal ones, hepatotoxicity of AAP became apparently less severe, whereas nephrotoxicity of AAP became significantly more severe.

Acetaminophen↗

Automated segmentation of digitized mammograms.

RATIONALE AND OBJECTIVES: Fast and reliable segmentation of digital mammograms into breast and nonbreast regions is an important prerequisite for further image analysis. We are developing a segmentation algorithm that is fully automated and can operate independent of type of digitizing system, image orientation, and image projection. METHODS: The algorithm identifies unexposed and direct-exposure image regions and generates a border surrounding the valid breast region, which can then be used as input for further image analysis. The program was tested on 740 digitized mammograms; the segmentation results were evaluated by two expert mammographers and two medical physicists. RESULTS: In 97% of the mammograms, the segmentation results were rated as acceptable for use in computer-aided diagnostic schemes. Segmentation problems encountered in the remaining 22 images (2.9%) were most often caused by digitization artifacts or poor mammographic technique. CONCLUSION: The developed algorithm can serve as a component of an "intelligent" workstation for computer-aided diagnosis in mammography.

Algorithms↗

Computerized analysis of interstitial infiltrates on chest radiographs: a new scheme based on geometric pattern features and Fourier analysis.

RATIONALE AND OBJECTIVES: Detection of interstitial infiltrates on chest radiographs is difficult and subjective. Therefore, we developed a computerized method to provide quantitative analysis of lung texture to increase diagnostic accuracy. METHODS: Two hundred chest radiographs--100 healthy and 100 abnormal with interstitial infiltrates--were digitized using a laser scanner. They were analyzed by an automated computerized scheme that uses a combination of two methods for detection of interstitial infiltrates: a lung texture analysis based on the Fourier transform and a geometric pattern feature analysis based on filtering techniques. RESULTS: The overall sensitivity and specificity of the computerized scheme were 92% and 90%, respectively. The scheme achieved a sensitivity of 80% in subtle cases (n = 15) and 88% in cases with localized interstitial disease (n = 26), whereas the specificity remained unchanged. There was good correlation between the computer output and the radiologists' severity rating. CONCLUSION: This enhanced computerized scheme exhibits high sensitivity and specificity with a large database.

Adolescent↗

[Familial clustering case of hepatitis delta].

We report a familial clustering case of hepatitis delta. All of the members of this family had evidence of past infection of hepatitis B. We investigated the hepatitis delta, three of the members had positive serological hepatitis delta markers. We assayed by polymerase chain reaction the primers corresponding to hepatitis delta antigen. The results of polymerase chain reaction was three positive. The 2nd polymerase chain reaction was used, two geno-type specific primers one was for Japanese S type the other was for Japanese M type7). Three were positive the 2nd polymerase chain reaction for Japanese M, one was negative for all of hepatitis delta polymerase chain reaction.

Child↗

Computer-aided diagnosis for interstitial infiltrates in chest radiographs: optical-density dependence of texture measures.

We have been developing a computerized scheme for automated detection and characterization of interstitial infiltrates based on the Fourier transform of lung texture. To improve the performance of the scheme, which was developed using digitized screen-film radiographs, optical-density dependence of both the gradient of the film used and the system noise associated with the laser scanner were investigated. Two hundred chest radiographs, including 100 abnormal cases with interstitial infiltrates, were digitized using a laser scanner. The root-mean-square (RMS) variations and the first moments of the power spectra, which correspond to the magnitude and coarseness of lung texture, were determined by Fourier transform of lung textures in numerous regions of interest (ROIs). The RMS variation was dependent upon the average optical density in the ROI, though no obvious trend existed for the first moment of the power spectrum. Dependence of the RMS variations on optical density was corrected for using the gradient curve of the film. Also, system noise associated with the laser scanner was corrected. Results indicated that the specificity was improved from 81% (without correction) to 89% (with corrections), without any loss of sensitivity (90%). Thus, the correspondence between the computer output and consensus interpretation of radiologists was improved with the new scheme compared to the previous one. This improved computerized scheme may be useful to radiologists in detecting interstitial infiltrates in chest radiographs.

Automation↗

Comparison of two methods for accurate measurement of modulation transfer functions of screen-film systems.

The modulation transfer function (MTF) of a screen-film system can be measured by two methods, i.e., a slit method with Fourier transform on the line spread function and a square-wave response function (SWRF) method. However, it is still uncertain whether MTFs obtained by the two methods are identical. In this study, MTFs of relatively sharp and unsharp screen-film systems were measured by using the two methods. The slit method provided slightly greater MTF for the relatively sharp system than the SWRF method. However, MTFs of the unsharp system obtained with the two methods were comparable. Generally, the slit method tends to provide reliable results for unsharp systems, whereas the SWRF method is favorable for sharp systems. Accuracy and consistency of these measurements were examined by comparison of experimental and theoretical edge responses derived from the measured MTFs. However, the difference in edge responses obtained by the two methods was relatively small compared with the variation of the measured edge responses, and thus results were considered inconclusive as to whether either of the methods can provide more accurate MTFs. International interlaboratory comparison indicated that the variation in the measured MTFs at six different institutions was relatively large for both methods. However, the MTFs of two screen-film systems measured by the slit method appear to agree with those by the SWRF method within the variation expected from the interlaboratory comparison.

Fourier Analysis↗

Image feature analysis and computer-aided diagnosis in mammography: reduction of false-positive clustered microcalcifications using local edge-gradient analysis.

To improve the performance of a computerized scheme for detection of clustered microcalcifications in digitized mammograms, causes of detected false-positive microcalcification signals were analyzed. The false positives were grouped into four categories, namely, microcalcification like noise patterns, artifacts, linear patterns, and others. In an edge-gradient analysis, local edge-gradient values at signal-perimeter pixels of detected microcalcification signals were determined to eliminate false positives that look like subtle microcalcifications or are due to artifacts. In a linear-pattern analysis, the degree of linearity for linear patterns was determined from local gradient values from a set of linear templates oriented in 16 different directions. Threshold values for the edge-gradient analysis and the linear-pattern analysis were determined using a training database of 39 mammograms. It was possible to eliminate 59% and 25%, respectively, of 91 detected false-positive clusters with loss of only 3% of true-positive clusters. The combination of the two methods further improved the scheme in eliminating a total of 73% of the false-positive clusters with loss of 3% of true-positive clusters. Using these thresholds, the two methods were evaluated on another database of 50 mammograms. 62%, 31%, and 80% of the false-positive clusters were eliminated with loss of 3% of true-positive clusters or less, in the edge-gradient analysis, the linear-pattern analysis, and the combination of the two methods, respectively. The edge-gradient analysis and the linear-pattern analysis can reduce the false-positive detection rate, while maintaining a high level of the sensitivity.

Artifacts↗

Toward consensus on quantitative assessment of medical imaging systems.

Consensus has been developing over the past few decades on a number of measurements required for the laboratory assessment of medical imaging modalities. Nevertheless, understanding of the connection between these measurements and human observer performance in a broad range of tasks remains far from complete. Focusing primarily on projection radiography to provide concrete examples, this overview indicates areas in which consensus on methodology for physical image-quality measurement has been established. Concepts such as "noise equivalent quanta" (NEQ) and "detective quantum efficiency" (DQE) have been found useful for normalizing physical measurements on an absolute scale and for relating those measurements to the decision performance of a hypothetical "ideal observer" that effectively performs decision tasks from the image data. The connection between ideal observer performance and human performance, as determined by receiver operating characteristic (ROC) analysis, remains to be understood for many clinically relevant tasks.

Biophysical Phenomena↗

Image feature analysis for computer-aided diagnosis: accurate determination of ribcage boundary in chest radiographs.

A computerized method for accurate determination of the ribcage boundary in chest images has been developed for use in computer-aided diagnosis (CAD) schemes for automated detection of abnormalities such as the pulmonary lung nodules, pneumothorax, interstitial disease, cardiomegaly, and interval changes in clinical chest images. With our method, the average position of the top of the lung in the chest image is determined first. Top lung edges and ribcage edges are determined within search ROIs, which are selected over top lung cages and ribcages. Three polynomial functions are applied separately to yield smooth curves for top lung edges and right and left ribcage edges. The complete ribcage boundary is then obtained by smoothly connecting three curves. A total of 1000 radiographs were digitized to 1k x 1k matrix size and a 10-bit gray scale with a laser scanner and analyzed by our method. The subjective evaluation indicated that our method produced moderately to highly accurate results in approximately 96% of the 1000 cases examined.

Humans↗

Computerized detection of clustered microcalcifications: evaluation of performance on mammograms from multiple centers.

To investigate the performance of a computerized method for the automated detection of clustered microcalcifications in digitized mammograms from a variety of screening centers, the authors invited 118 radiologists to bring up to five mammograms to their scientific exhibit at the 1993 meeting of the Radiological Society of North America (RSNA). Forty-three mammograms from 14 sites were brought to the exhibit, where they were digitized and analyzed. Results of the analysis on the RSNA cases were compared with those obtained on a standard database of 39 mammograms collected from two centers. The performance of the detection algorithm on the RSNA images was lower than that achieved on the standard database. This lower performance was due in part to the higher fraction of very subtle clustered microcalcifications in the RSNA cases, as well as the apparent dependence of the algorithm on image characteristics (eg, contrast and noise), which varied from center to center. The authors conclude that the algorithm is robust and accurate enough to undergo clinical testing. When it is implemented clinically, the computerized scheme must be customized to the image characteristics at each specific screening center to obtain optimal performance.

Breast Diseases↗

Visualization of oxygen level inside a single cardiac myocyte.

The present paper describes theoretical and experimental bases for quantitation of the oxygen level inside a single isolated ventricular rat myocyte. We applied three-wavelength microspectrophotometry to a single cardiomyocyte, where the sensitivity of the spectrophotometry was augmented by a digital image processing technique known as video-enhanced microscopy. Oxygen-dependent changes in light absorption of the intracellular pigments were detected and represented with the use of a newly defined variable, Z, where one pixel of the reconstructed cell image corresponded to 0.2 microns. Theoretically, Z is a single-valued function of the fractional oxygen saturation of the intracellular pigment. We demonstrated in quiescent cardiomyocytes that Z changed according to extracellular PO2, where the relationship was sigmoidal with the extracellular PO2 for a half-maximal Z of 3.2 Torr. In the aerobic cell, conversion of cytochromes to the reduced forms by NaCN did not affect Z value. Therefore, we conclude that Z mainly represents the fractional oxygen saturation of myoglobin, thus reporting cytosolic PO2. We also demonstrated that for extracellular PO2 of 1.3 Torr, abolition of mitochondrial oxygen consumption by NaCN significantly elevated the intracellular oxygen level, suggesting existence of oxygen pressure gradients in a quiescent single cardiomyocyte that were proportional to oxygen flux.

Animals↗

Analysis of PrPc mRNA by in situ hybridization in brain, placenta, uterus and testis of rats.

An amyloid-like isoform of a 33- to 34-kD glycoprotein, termed as the scrapie prion protein (PrPsc), plays a critical role in transmissible spongiform encephalopathies of animals and humans. It has even been suggested to present the responsible infectious agent. This protein is a posttranslationally modified form of the cellular isoform of prion protein (PrPc). Hitherto, little has been known about the functions of PrPc. In order to examine the localization of PrPc mRNA in rat tissues, the in situ hybridization technique was performed. In rat brain, PrPc mRNA was predominantly localized within pyramidal cells of the hippocampus, large neurons of the thalamus and neocortex, and Purkinje cells of the cerebellum. In the placenta, not only PrPc mRNA was localized to a subpopulation of decidual cells at the highest levels, it was also expressed in the amnion and mesodermal layer of the yolk sac. Furthermore, PrPc mRNA was also expressed in the myometrium of the uterus and seminiferous tubule in the testis. However, signals were not obtained in the lung, spleen, liver of prenatals and other fetus tissues. The distribution of rat PrPc mRNA portrayed the levels which were different among the various types of cells, suggesting that its expression may be regulated in a tissue-specific manner.

Animals↗

Early development of encephalomyocarditis (EMC) virus-induced orchitis in Syrian hamsters.

Lesions associated with encephalomyocarditis (EMC) virus in the testes of Syrian hamsters were investigated. Histopathologic changes were first detectable by light microscopy at 3 days postinoculation (DPI). Immunohistochemically, virus antigens were detected in the cytoplasm of germ cells and Sertoli cells in some seminiferous tubules beginning at 2 DPI. The following ultrastructural changes were observed: 1) swelling of mitochondria and dilatation of endoplasmic reticulum in germ cells, 2) large number of residual bodies in seminiferous tubules, 3) aggregates of virus-like particles in the cytoplasm of degenerated cells and tubular lumen, 4) condensation of cytoplasm and dilatation of endoplasmic reticulum in Sertoli cells, and 5) degenerative changes in capillary endothelial cells.

Animals↗

Therapeutic efficacy of 5-fluorouracil prodrugs using endogenous serum proteins as drug carriers: a new strategy in drug delivery system.

To establish a novel drug delivery system for 5-fluorouracil (5FU), we have developed a system in which the low-molecular-weight prodrugs of 5FU bound to endogenous serum proteins, thus circulating like those proteins. Subsequently, the prodrugs were slowly hydrolyzed to generate active 5FU in the bloodstream. To examine the therapeutic effect of these prodrugs, we injected them into BALB/c mice previously implanted subcutaneously with Meth A sarcoma. Among the prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil (5FU-1pCPMC) was effective in reducing tumors and prolonging survival time. The non-hydrolyzable compound, 1-(4-chlorobenzyl)-5-fluorouracil, did not show any therapeutic effect, suggesting that the therapeutic efficacy of 5FU-1pCPMC is due to the sustained release of 5FU from the serum protein-prodrug complex. The data shown here may create a new field in drug delivery system technology.

Animals↗

Encephalomyocarditis (EMC) virus infection in the common vole, Microtus arvalis.

Encephalomyocarditis (EMC) virus infection in the common vole was examined for the first time. Sixteen 8-week-old males inoculated intraperitoneally with 10(5) plaque-forming units (pfu)/animal of the D variant of EMC virus were killed 3 and 7 days after inoculation (3 and 7 DAI). Viral replication was detected in the brain (10(5) pfu/g), heart (10(4) pfu/g) and pancreas (10(7) pfu/g) of all 8 animals at 3DAI. It was found in the pancreas (10(3) pfu/g) of all 8 animals and in the brain (10(4) pfu/g) of 2 of 8 animals at 7 DAI. Histopathological changes were observed in the brain (mild mononuclear cell infiltration around capillaries and sporadic pyknosis of neurons), heart (minimal myocardial necrosis) and pancreas (prominent acinar cell necrosis with inflammatory exudation) at 3DAI. At 7 DAI, replacement of necrotic tissues by mesenchymal cells and regeneration of acinar cells were conspicuous in the pancreas. Throughout the experimental period, no evidence for diabetogenic effect was found.

Animals↗

Long-term effects of dietary fiber supplementation on serum glucose and lipoprotein levels in diabetic rats fed a high cholesterol diet.

We have shown that cholesterol-fed diabetic rats developed atheromatous lesions in the aorta and coronary arteries, which were not observed in cholesterol-fed diabetic rats receiving concomitant supplementation with 15% glucomannan, a soluble dietary fiber concentrate. The present study was designed to examine the effects of the dietary fiber supplementation on serum levels of glucose and lipoproteins in cholesterol-fed diabetic rats. Feeding a diet containing 1.5% cholesterol (wt/wt) and 0.37% cholic acid for 18 weeks to rats made diabetic by streptozotocin (35 mg/kg body weight, iv) produced moderate hyperglycemia and moderate hypercholesterolemia, the latter being characterized by high concentrations not only of low density lipoproteins but also intermediate density lipoproteins and very low density lipoproteins. These changes in serum lipoproteins and hyperglycemia were substantially reduced by 18 weeks of supplementation with glucomannan but high density lipoprotein cholesterol and triglyceride levels did not change after feeding a cholesterol-rich diet in the presence or absence of glucomannan supplementation. These results suggest that amelioration in hyperlipoproteinemia and hyperglycemia induced by the dietary fiber supplementation may help retard or prevent the atheromatous formation found in cholesterol-fed diabetic rats.

Animals↗