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Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 253 records · Page 14Linked to original sources
PubMed1998

Automated computerized classification of malignant and benign masses on digitized mammograms.

RATIONALE AND OBJECTIVES: To develop a method for differentiating malignant from benign masses in which a computer automatically extracts lesion features and merges them into an estimated likelihood of malignancy. MATERIALS AND METHODS: Ninety-five mammograms depicting masses in 65 patients were digitized. Various features related to the margin and density of each mass were extracted automatically from the neighborhoods of the computer-identified mass regions. Selected features were merged into an estimated likelihood of malignancy by, using three different automated classifiers. The performance of the three classifiers in distinguishing between benign and malignant masses was evaluated by receiver operating characteristic analysis and compared with the performance of an experienced mammographer and that of five less experienced mammographers. RESULTS: Our computer classification scheme yielded an area under the receiver operating characteristic curve (Az) value of 0.94, which was similar to that for an experienced mammographer (Az = 0.91) and was statistically significantly higher than the average performance of the radiologists with less mammographic experience (Az = 0.81) (P = .013). With the database used, the computer scheme achieved, at 100% sensitivity, a positive predictive value of 83%, which was 12% higher than that for the performance of the experienced mammographer and 21% higher than that for the average performance of the less experienced mammographers (P < .0001). CONCLUSION: Automated computerized classification schemes may be useful in helping radiologists distinguish between benign and malignant masses and thus reducing the number of unnecessary biopsies.

Breast Neoplasms↗
PubMed1998

Peritoneal macrophages play an important role in eliminating human cells from severe combined immunodeficient mice transplanted with human peripheral blood lymphocytes.

To elucidate the mechanism of human cell elimination from severe combined immunodeficient (SCID) mice transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice), we explored the immunocytes in the peritoneal cavity in SCID mice where human PBL were transferred. When the phenotype of peritoneal exudate cells (PEC) was compared by flow cytometry among three congenic strains of SCID mice that differ in their acceptability for human PBL, the PEC in NOD-scid mice, which exhibit the highest acceptability, contained the smallest number of F4/80lo/-Mac-1(+)-activated macrophages. Moreover, the proportions of natural killer cells in PEC of the three strains of SCID mice were not always correlated with the acceptability. These findings suggest the possibility that peritoneal macrophages eliminate human cells in hu-PBL-SCID mice. To verify this hypothesis, we evaluated the engraftment of human PBL into SCID mice that were treated with liposome-encapsulated dichloromethylene diphosphonate, which selectively depletes macrophages by inducing apoptosis, or 8-aminoguanidine hemisulphate salt, an inhibitor of inducible nitric oxide synthase of macrophages. As a result, both of these regimens improved engraftment of human PBL, indicating that peritoneal macrophages take part in human cell elimination in the peritoneal cavity of hu-PBL-SCID mice and that it is mediated, at least in part, by direct macrophage cytotoxicity utilizing nitric oxide.

Animals↗
PubMed1998

Encephalomyocarditis (EMC) virus infection in PC12 and C6 cells.

PC12 cells derived rom rat pheochromocytoma and C6 cells derived from rat glioma were infected with 0.3 plaque forming units (PFU)/cell of the D variant of encephalomyocarditis virus (EMC-D), after pretreatment with or without nerve growth factor (NGF). The virus titres in medium and cells were investigated at 6, 12, 24, 48 and 72 h post infection (HPI), and histopathology and viral antigens in cells were examined at 24 and 48 HPI, respectively. As a result, neither viral replication nor light and electron microscopic changes were observed in PC12 cell cultures without NGF-pretreatment. On the contrary, in PC12 cell cultures with NGF-pretreatment, the virus titre prominently increased at 12 HPI, and peaked at 48 HPI. In addition, distinct histological and ultrastructural changes with viral antigens in cells were observed. C6 cells showed similar morphology and susceptibility to EMC-D-infection irrespective of NGF-pretreatment. Namely, the virus titres in C6 cell cultures increased slightly and viral antigens were found in a small number of C6 cells, but there were no evident histological and ultrastructural changes. These results suggest that PC12 cells pretreated with NGF and C6 cells are susceptible to EMC-D infection in vitro.

Animals↗
PubMed1998

Free vascularized fibular grafts for large bone defects in the extremities after tumor excision.

Free vascularized fibular grafts were used in nine selected patients with bone tumors in the involved extremity. There were five locally aggressive tumors and four malignant tumors. Each skeletal defect was longer than 10 cm, and the mean length was 13 cm. Ten grafts of 17.4 cm in mean length were harvested in these nine patients. In two cases with upper-extremity involvement, arthroplasty using the fibular head was the procedure of choice, while interacalary grafting was performed in the lower extremity. Dual grafting was performed for complete defects of the femur. The viability of each graft was demonstrated through survival of the combined skin flaps or with a positive bone scan. Primary bony union was obtained in all cases, and the mean time to union was 5.2 months. In the lower extremity, significant hypertrophy of the graft was seen. Satisfactory functional results were obtained in all the patients.

Adolescent↗
PubMed1998

The effect of forskolin on the sound-evoked potentials in the guinea pig cochlea.

The effect of forskolin (FSK) on cochlear sound-evoked potentials was examined in the guinea pig. The perfusion of the scala vestibuli (SV) with FSK (2 x 10(-4) M) produced a significant increase in the amplitude of negative summating potential (- SP) with no change in cochlear microphonics (CM) amplitude, and a significant decrease in the amplitude of compound action potential (CAP) with a significant prolongation of N1 latency and a 20 dB CAP threshold elevation. The results lead us to speculate that FSK-induced changes may be involved in the transient formation of endolymphatic hydrops.

Animals↗
PubMed1998

A new immunosuppressant, FTY720, prolongs limb allograft survival in rats.

A new immunosuppressant, FTY720, was applied to limb allotransplants and its effectiveness was investigated. Using inbred rats, for which the major histocompatibility complexes were completely mismatched, 31 limb transplantations were performed and FTY720 was administered at a dose of 1.5 or 3 mg per kilogram per day for 10 days postoperatively. Rejection was monitored by the appearance of the skin of the grafted hind limb, soft radiograph, microangiography, and histology. In animals receiving no immunosuppressive therapy, the mean onset of rejection was 4.2+/-1.0 days postoperatively, and the grafted limbs became acutely necrotic. The mean onset of rejection was 6.0+/-0.9 days in animals receiving FTY720 at a dose of 1.5 mg per kilogram per day and 7.9+/-1.5 days in animals receiving FTY720 at a dose of 3 mg per kilogram per day. Survival of the grafted limbs was significantly prolonged compared with that in animals without immunosuppression. The immunosuppressive effect of FTY720 appeared to be dose dependent; however, complete suppression of rejection could not be obtained with FTY720 therapy alone.

Animals↗
PubMed1998

Physiologic shear stress suppresses endothelin-converting enzyme-1 expression in vascular endothelial cells.

Shear stress dilates blood vessels and exerts an antiproliferative effect on vascular walls. These effects are ascribed to shear stress-induced, endothelium-derived vasoactive substances. Endothelin-converting enzymes (ECEs), the enzymes that convert big endothelin-1 (ET-1) to ET-1, have recently been isolated and the corresponding proteins have been termed ECE-1 and ECE-2. Furthermore, two isoforms of human ECE-1 have been demonstrated and termed ECE-1 alpha and ECE-1 beta. In this study, to elucidate the role of ECE-1 under shear stress we examined the effect of physiologic shear stress on the mRNA expression of ECE-1 and ET-1 in cultured bovine carotid artery endothelial cells (BAECs) and human umbilical veins (HUVECs), and also ECE-1 alpha mRNA expression in HUVECs. ECE-1 mRNA expression was significantly downregulated by shear stress in 24 h, both in BAECs and HUVECs, in a shear stress intensity-dependent manner. The expression of ECE-1 alpha mRNA was also attenuated by shear stress in HUVECs. ET-1 mRNA expression showed a concordant decrease with ECE-1 mRNA expression. These results suggest that shear stress-induced gene regulation of ET-1 and ECE-1 mRNA expression can contribute to the decrease of ET-1 peptide level by shear stress.

Animals↗
PubMed1998

Oxidative stress suppresses the endothelial secretion of endothelin.

To address endothelial function on vascular walls exposed to oxidative stress, we investigated the effect of oxidative stress on the secretion of endothelin-1 (ET-1) from cultured bovine carotid artery endothelial cells (BAECs). Concentrations of ET-1 in the media were measured by a specific radioimmunoassay and ET-1 mRNA expression was estimated by Northern blot analysis. Treatment of BAECs with 0.5-2.0 mM H2O2 for 3 h suppressed both ET-1 secretion and ET-1 mRNA expression in a dose-dependent manner compared to control. Attenuation of ET-1 mRNA expression by H2O2 was revealed to take place at the transcriptional level. The addition of NG-nitro-L-arginine-methyl ester (L-NAME) 10 microns, a specific nitric oxide synthase inhibitor, had no effect on H2O2-induced suppression of ET-1 mRNA expression. Suppression of ET secretion under oxidative stress observed in the present study is proposed to be a compensatory mechanism of endothelial cells to inhibit vasoconstriction and proliferation during oxidative stress.

Animals↗
PubMed1998

Treatment of chronic regional pain syndrome using manipulation therapy and regional anesthesia.

In a 4-year period, 17 consecutive patients with posttraumatic chronic regional pain syndrome were treated with a new technique, Movelat manipulation therapy. At average follow-up of 8 months, satisfactory results were achieved in 15 patients (88%), but 2 patients, 1 with digital nerve injury and 1 with ulnar nerve injury, did not respond to the therapy. Factors associated with good clinical response include chronic regional pain syndrome type I, i.e., dystrophy produced by a trauma to the hand but not involving a specific nerve injury, early-stage disease (within 3 months after trauma), and involvement of the upper limbs. Complications were rare and mild (pain over the tourniquet site in 3%, temporary dizziness in 1%). This therapy is simple and safe and recommended for early treatment of chronic regional pain syndrome.

Adult↗
PubMed1998

Revascularized intercalary bone allografts with short-term immunosuppression with cyclosporine in the canine.

To study the healing process of vascularized intercalary bone allograft after withdrawal of immunosuppressive drugs, allotransplantation of the tibia diaphysis with a vascular pedicle was performed in eight adult mongrel dogs (group 2) and assessments were made both during administration and after discontinuation of cyclosporin A. As controls, similar grafts with the vascular pedicles were removed and reimplanted back to the same animals (five dogs, group 1). Allotransplantation of frozen stored bone without a vascular pedicle (10 dogs, groups 3A and 3B) were also compared. No union occurred in most cases of frozen stored bone allotransplant because the transplanted bone was resorbed, leading to loosening and subsequent failure of osteosynthesis with the plate and screws used. Under cyclosporin A immunosuppression, bony union (i.e., when trabeculae were seen crossing the graft-recipient junction with obliteration of the junction line) occurred at almost similar time intervals in all dogs of group 2 (bone allotransplant with a vascular pedicle) by 3 months postoperatively, which was similar to those of group 1. No systemic side effects of cyclosporin A were observed. Cyclosporin A was discontinued 3 months following graft implantation. The bone graft became avascular within a week following withdrawal of cyclosporin A. However, bone union was maintained, and the transplanted bone never showed bone resorption, sclerosis, or fracture on serial radiographs up to the time the animals were sacrificed, between 5 and 14 months later. Histology at sacrifice showed that the transplanted allografts were being replaced at both ends by fresh bone derived from the transplantation bed. We conclude on the basis of the results of this study that solid bony union can be obtained in allotransplanted bone with a vascular pedicle if cyclosporin A is given for a brief period. After cyclosporin A is withdrawn, although the bone becomes nonviable secondary to rejection occurring in the blood vessels, its skeletal structure remains intact, enabling it to maintain its structural support while awaiting replacement by bony ingrowth from both ends of the graft.

Animals↗
PubMed1998

Optimally weighted wavelet transform based on supervised training for detection of microcalcifications in digital mammograms.

We are developing a computer-aided diagnosis (CAD) scheme for detection of clustered microcalcifications in digital mammograms. The use of an empirically chosen wavelet and scale combination for detection of microcalcifications as an initial step of the CAD scheme has been reported by us previously. In this study, we developed a technique for optimizing the weights at individual scales in the wavelet transform to improve the performance of our CAD scheme based on the supervised learning method. In the learning process, an error function was formulated to represent the difference between a desired output and the reconstructed image obtained from weighted wavelet coefficients for a given mammogram. The error function was then minimized by modifying the weights for wavelet coefficients by means of a conjugate gradient algorithm. The Least Asymmetric Daubechies' wavelets were optimized with 297 regions of interest (ROIs) as a training set by a jackknife method. The performance of the optimally weighted wavelets was evaluated by means of receiver-operating characteristic (ROC) analysis by use of the above set of ROIs. The analysis yielded an average area under the ROC curve of 0.92, which outperforms the difference-image technique used in our existing CAD scheme, as well as the partial reconstruction method used in our previous study.

Biophysical Phenomena↗
PubMed1998

Analysis of methods for reducing false positives in the automated detection of clustered microcalcifications in mammograms.

Clustered microcalcifications are often the first sign of breast cancer in a mammogram. Nevertheless, all clustered microcalcifications are not found by an individual radiologist reading a mammogram. The use of a second reader may find those clusters of microcalcifications not found by the first reader, thereby improving the sensitivity of detecting clustered microcalcifications. Our laboratory has developed a computerized scheme for the detection of clustered microcalcifications, which can act like a second reader, that is undergoing clinical evaluation. This paper concerns the feature analysis stage of the computer scheme, which is designed to remove some of the false-computer detections. We have examined three methods of feature analysis, namely, rule based (the method currently used), an artificial neural network (ANN), and a combined method. In an independent database of 50 images, at a sensitivity of 83%, the average number of false positive (FP) detections per image was: 1.9 for rule-based, 1.6 for ANN, and 0.8 for the combined method. We demonstrate that the combined method performs best because each of the two stages eliminates different types of false positives.

Breast Neoplasms↗
PubMed1998

A genetic algorithm-based method for optimizing the performance of a computer-aided diagnosis scheme for detection of clustered microcalcifications in mammograms.

Computer-aided diagnosis (CAD) schemes have the potential of substantially increasing diagnostic accuracy in mammography by providing the advantages of having a second reader. Our laboratory has developed a CAD scheme for detecting clustered microcalcifications in digital mammograms that is being tested clinically at the University of Chicago Hospitals. Our CAD scheme contains a large number of parameters such as filter weights, threshold levels, and region of interest (ROI) sizes. The choice of these parameter values determines the overall performance of the system and thus must be carefully set. Unfortunately, when the number of parameters becomes large, it is very difficult to obtain the optimal performance, especially when the values of the parameters are correlated with each other. In this study, we address the problem of identifying the optimal overall performance by developing an automated method for the determination of the parameter values that maximize the performance of a mammographic CAD scheme. Our method utilizes a genetic algorithm to search through the possible parameter values, and provides the set of parameters that minimize a cost function which measures the performance of the scheme. Using a database of 89 digitized mammograms, our method demonstrated that the sensitivity of our CAD scheme can be increased from 80% to 87% at a false positive rate of 1.0 per image. We estimate the average performance of our CAD scheme on unknown cases by performing jackknife tests; this was previously not feasible when the parameters of the CAD scheme were determined in a nonautomated manner.

Algorithms↗
PubMed1998

Murine coronavirus-induced subacute fatal peritonitis in C57BL/6 mice deficient in gamma interferon.

Gamma interferon-deficient (IFN-gamma-/-) mice with a C57BL/6 background were infected intraperitoneally with mouse hepatitis virus strain JHM (JHMV). In contrast to IFN-gamma-+/- and IFN-gamma+/+ mice, JHMV persisted in IFN-gamma-/- mice and induced death during the subacute phase of the infection. Unexpectedly, infected IFN-gamma-/- mice showed severe peritonitis accompanying the accumulation of a viscous fluid in the abdominal and thoracic cavities in the subacute phase. Destructive changes of hepatocytes were not observed. Administration of recombinant IFN-gamma protracted the survival time of IFN-gamma-/- mice after JHMV infection. These results demonstrate that IFN-gamma plays a critical role in viral clearance in JHMV infection. They also show that a resultant persistent JHMV infection induces another form of disease in IFN-gamma-/- mice, which bears a resemblance to feline infectious peritonitis in cats.

Alanine Transaminase↗
PubMed1998

Threshold number of provirus copies required per cell for efficient virus production and interference in moloney murine leukemia virus-infected NIH 3T3 cells.

The gag-pol readthrough mutant of Moloney murine leukemia virus, MLV-B(CAG) (T. Odawara, H. Yoshikura, M. Oshima, T. Tanaka, D. S. Jones, F. Nemoto, Y. Kuchino, and A. Iwamoto, J. Virol. 65:6376-6379, 1991), was poorly complemented by a mutant encoding only Gag. This is because with all the genetic elements necessary for env expression present in MLV-B(CAG), insufficient Env protein was produced by the cells expressing MLV-B(CAG) for efficient virus production. Since the env mRNA expression per provirus in the MLV-B(CAG)- and wild-type-MLV-producing cells were the same and since the cells expressing the former contained eightfold fewer proviral copies, the insufficient Env expression by the former was found to be due to insufficient proviral copies in the cells. Examination of the cell clones having various proviral copies of Deltawt MLV (M. Oshima, T. Odawara, T. Matano, H. Sakahira, Y. Kuchino, A. Iwamoto, and H. Yoshikura, J. Virol. 70:2286-2295, 1996) showed that mRNA level was proportional to the number of proviral copies while interference and virus production followed a sigmoid curve with a sharp rise at the threshold number of proviral copies of around four per cell. Multicycle infection probably continues until the threshold level of proviral copies is attained in natural infection too.

3T3 Cells↗
PubMed1998

Apoptosis in feline panleukopenia virus-infected lymphocytes.

Feline panleukopenia virus (FPLV) was shown to induce apoptosis to feline lymphoid cells and to reduce the expression of interleukin-2 receptor alpha on the cells. FPLV-induced apoptosis might be a key element in the pathophysiology of atrophy of lymphoid tissues associated with feline panleukopenia caused by FPLV.

Animals↗
PubMed1998

Direct observation of radial intracellular PO2 gradients in a single cardiomyocyte of the rat.

The purpose of the present study was to directly visualize radial gradients of intracellular PO2 in a single individual cardiomyocyte isolated from the rat ventricle. Microspectrophotometry with the use of cytosolic myoglobin as an oxygen probe was conducted at 410 nm. When the quiescent cell was incubated with 1 microM carbonyl cyanide m-chlorophenylhydrazone to increase oxygen consumption approximately eightfold, gradual decreases in myoglobin oxygen saturation (SMb) were demonstrated toward the core of the cell, whereas these decreases disappeared when the cell was treated with 2 mM NaCN. These results highlighted the importance of diffusional oxygen transport in determining intracellular oxygenation in cardiac cells. From the measured SMb, we assessed the profile of radial changes in intracellular PO2 at the mean SMb comparable to that in vivo ( approximately 0.5). Quite steep PO2 gradients were demonstrated in the vicinity of the sarcolemma that were rapidly attenuated toward the cell core. These radial profiles of intracellular PO2 demonstrate the significance of myoglobin-facilitated diffusion of oxygen. Furthermore, the shallow gradients of PO2 near the center of the cell might arise from partial depression of oxygen consumption near the cell core.

Animals↗