Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 397 records · Page 22Linked to original sources

PubMed1996

An improved shift-invariant artificial neural network for computerized detection of clustered microcalcifications in digital mammograms.

A shift-invariant artificial neutral network (SIANN) has been applied to eliminate the false-positive detections reported by a rule-based computer aided-diagnosis (CAD) scheme developed in our laboratory. Regions of interest (ROIs) were selected around the centers of the rule-based CAD detections and analyzed by the SIANN. In our previous study, background-trend correction and pixel-value normalization were used as the preprocessing of the ROIs prior to the SIANN. A ROI is classified as a positive ROI, if the total number of microcalcifications detected in the ROI is greater than a certain number. In this study, modifications were made to improve the performance of the SIANN. First, the preprocessing is removed because the result of the background-trend correction is affected by the size of ROIs. Second, image-feature analysis is employed to the output of the SIANN in an effort to eliminate some of the false detections by the SIANN. In order to train the SIANN to detect microcalcifications and also to extract image features of microcalcifications, the zero-mean-weight constraint and training-free-zone techniques have been developed. A cross-validation training method was also applied to avoid the overtraining problem. The performance of the SIANN was evaluated by means of ROC analysis using a database of 39 mammograms for training and 50 different mammograms for testing. The analysis yielded an average area under the ROC curve (A(z)) of 0.90 for the testing set. Approximately 62% of false-positive clusters detected by the rule-based scheme were eliminated without any loss of the true-positive clusters by using the improved SIANN with image feature analysis techniques.

Biophysical Phenomena↗

PubMed1996

Density correction of peripheral breast tissue on digital mammograms.

When digital mammograms are viewed on video displays, evaluation of the skin and subcutaneous tissue is often difficult and may require special window settings. An algorithm has been developed for selective enhancement (ie, density correction) of the dark peripheral portions of the breast on mammograms. After an automated segmentation of the digital mammogram and identification of the skin line, a fitted enhancement curve is generated to selectively enhance all pixels within a certain distance from the skin to match the density of the center part of the breast. After enhancement, skin and breast parenchyma can be evaluated simultaneously without the need for different window settings. When tested on a set of 400 digitized mammograms, the density correction algorithm significantly (P < .0001) increased the maximum area of breast tissue visualized simultaneously at window width settings of 0.5-2.0 delta OD (optical density). Artifacts interfering with interpretation were observed in less than 1%. The algorithm for correcting the density of peripheral breast tissue substantially facilitates and improves the display of digital mammograms and thus will be a valuable component of an integrated workstation for computer-aided diagnosis in mammography.

Algorithms↗

PubMed1996

Malignant and benign clustered microcalcifications: automated feature analysis and classification.

PURPOSE: To develop a method for differentiating malignant from benign clustered microcalcifications in which image features are both extracted and analyzed by a computer. MATERIALS AND METHODS: One hundred mammograms from 53 patients who had undergone biopsy for suspicious clustered microcalcifications were analyzed by a computer. Eight computer-extracted features of clustered microcalcifications were merged by an artificial neural network. Human input was limited to initial identification of the microcalcifications. RESULTS: Computer analysis allowed identification of 100% of the patients with breast cancer and 82% of the patients with benign conditions. The accuracy of computer analysis was statistically significantly better than that of five radiologists (P = .03). CONCLUSION: Quantitative features can be extracted and analyzed by a computer to distinguish malignant from benign clustered microcalcifications. This technique may help radiologists reduce the number of false-positive biopsy findings.

Breast Diseases↗

PubMed1996

Effect of a computer-aided diagnosis scheme on radiologists' performance in detection of lung nodules on radiographs.

PURPOSE: To evaluate the effect of a computer-aided diagnosis (CAD) scheme on radiologists' performance in the detection of lung nodules, and to examine a new method of receiver operating characteristic (ROC) analysis. MATERIALS AND METHODS: One hundred twenty radiographs (60 normal and 60 abnormal with lung nodules of varying subtlety) were used. Sixteen radiologists (two thoracic, six general, and eight residents) participated in an observer study in which they read both conventional radiographs and digitized radiographs. The radiologists' performance was evaluated with ROC analysis with two different methods (independent testing and sequential testing) and a continuous rating scale. RESULTS: Az (area under the best fit binormal ROC curve when it is plotted in the unit square) values obtained from ROC analysis with and without CAD output were 0.940 and 0.894, respectively, in the independent test and 0.948 and 0.906, respectively, in the sequential test. Findings with both methods indicated that the CAD scheme statistically significantly improved diagnostic accuracy, particularly for radiologists with less experience (P < .001). Reading time was not increased when CAD was used. CONCLUSION: The CAD scheme can assist radiologists in the detection of lung nodules on chest radiographs.

Adult↗

PubMed1996

Regulation of oxygen diffusion in hypoxic isolated cardiac myocytes.

In the normal beating heart, oxygen pressure (PO2) gradients between capillary blood and intracellular space are so large that cytosolic PO2 may decline to around PO2 at half saturation of myoglobin (2-5 Torr). Hence, a decrease in capillary blood PO2 of a few Torr would easily deplete oxygen in mitochondria if PO2 gradients are unchanged. The aim of the present study was to demonstrate, in a single isolated cardiac myocyte of the rat, a mechanism that reduces PO2 gradients in hypoxia so that oxygenation of the intracellular space would be sustained. Using a newly developed microspectrophotometric device, we were able to follow changes in cytosolic PO2 of an individual ventricular myocyte in an hypoxic medium. For extracellular PO2 of 4.4 Torr, we found an elevation (2.1 Torr) of the cytosolic PO2 when oxygen consumption of the cell was abolished by 2 mM NaCN, thus demonstrating PO2 gradients from extracellular medium to cytosolic space in a single individual cardiomyocyte. The magnitude of these PO2 gradients was reduced as extracellular PO2 was further lowered, and they were no longer detectable for extracellular PO2 of 0.6 Torr. To further elucidate physiological effects of the PO2-dependent changes in PO2 gradients demonstrated above, we conducted a simulation of ischemia in a single cardiac myocyte. The stop-flow procedure (simulated ischemia) quickly decreased cytosolic PO2 from 7.3 to 1.8 Torr in 5 min, while the rate of fall of PO2 considerably decreased when the cytosolic PO2 decreased to < 2 Torr. Consequently, even 30 min after the onset of the stop flow, cytosolic PO2 was significantly higher than that of the anoxic perfusion. These results together suggest that in severe hypoxia oxygenation of the intracellular space might be partially maintained by relative elevation of cytosolic PO2, resulting from progressive decrease in PO2 gradients from extracellular space to cytosol.

Animals↗

PubMed1996

Vascular endothelial growth factor suppresses C-type natriuretic peptide secretion.

Angiogenesis plays a pivotal role not only in wound healing and tumor progression but also in diabetic angiopathy, arteriosclerosis, and collateral formation of obstructive vascular diseases. Vascular endothelial growth factor (VEGF) is now thought to be an endothelium-specific and potent angiogenic factor. We previously demonstrated that C-type natriuretic peptide (CNP), originally isolated from porcine brain, is produced by endothelial cells and proposed that CNP can exert control over vascular tone and growth as a local vascular regulator. In the present study, we examined the effect of VEGF on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP we developed. VEGF (1 to 100 ng/mL) dose-dependently suppressed CNP secretion from cultured bovine endothelial cells, and 100 ng/mL VEGF suppressed endothelial CNP secretion to 28% of control levels (31.7 +/- 5.5 versus 8.9 +/- 0.8 fmol/mL, vehicle versus VEGF). VEGF also suppressed CNP mRNA expression in endothelial cells 9 hours after administration. In contrast, basic fibroblast growth factor (20 ng/mL), an endothelium-nonspecific angiogenic factor, significantly stimulated CNP secretion by 290%. These results indicate that VEGF can regulate vascular tone and growth in the process of angiogenesis through suppression of endothelial secretion of CNP, which is an endothelium-derived vasorelaxing and growth-inhibitory peptide.

Animals↗

PubMed1996

Regulation of endothelial production of C-type natriuretic peptide in coculture with vascular smooth muscle cells. Role of the vascular natriuretic peptide system in vascular growth inhibition.

Recently, we have demonstrated that C-type natriuretic peptide (CNP) is produced in vascular endothelial cells (ECs). In the present study, we investigated the interaction of ECs and vascular smooth muscle cells (SMCs) for endothelial production of CNP and its action on vascular growth, using the EC/SMC coculture system. The concentration of CNP-like immunoreactivity in the medium was increased 60-fold within 48 hours in the EC/SMC coculture with direct contact compared with that in EC alone. Northern blot analysis revealed the augmented expression of CNP mRNA in the EC/SMC coculture. The accumulation of intracellular cGMP in the coculture was concomitantly increased, and this response was blocked by anti-CNP monoclonal antibody and HS-142-1, a nonpeptide atrial natriuretic peptide receptor antagonist. The concentration of biologically active transforming growth factor-beta (TGF-beta) in the culture medium of the coculture with direct contact of ECs and SMCs was elevated to the level to stimulate endothelial production of CNP. Actually, the neutralizing antibody against TGF-beta abrogated the cGMP accumulation in the coculture. These results show that endothelial production of CNP in the EC/SMC coculture is at least in part regulated by TGF-beta. Furthermore, the conditioned medium from ECs stimulated by TGF-beta was demonstrated to have a growth-inhibitory effect on SMCs, which was abolished by anti-CNP monoclonal antibody and HS-142-1. The treatment with anti-CNP monoclonal antibody and HS-142-1 also significantly increased the cell number of the EC/SMC coculture. The present study reveals the pathophysiological significance of endothelial CNP as a paracrine/autocrine vascular regulator for vascular growth in the interaction of ECs and SMCs.

Animals↗

PubMed1996

Renal glomerular fibrosis in a cat.

Renal glomerular fibrosis was observed in a 1-year-old spayed female Japanese domestic cat that showed clinically advanced renal failure. In the glomeruli, increased homogeneous materials were stained strongly with aniline blue by Masson's trichrome and positive for anti-type III collagen antibody by immunohistochemical staining, causing mesangial sclerosis and capillary collapse. By electron microscopy, randomly arranged fibrils were observed in the expanded subendothelial and mesangial areas, and the fibrils showed periodicity characteristic of collagen fibers in longitudinal sections. These findings of glomerular lesions closely resemble those of human "collagenofibrotic glomerulonephropathy," which has recently been described as a new type of glomerulonephropathy.

Animals↗

PubMed1996

Histochemical, lectin-histochemical and morphometrical characteristics of intestinal goblet cells of germfree and conventional mice.

Histochemical, lectin-histochemical and morphometrical studies were carried out on intestinal goblet cells of 8-week-old germfree (GF) and conventional (CV) mice of the BALB/c strain. Except for the reactivity of cecal goblet cells to Dolichos biflorus agglutinin (DBA) and Ulex europeus-I agglutinin (UEA-I), there was no difference between GF and CV mice in histochemical and lectin-histochemical properties. In the cecal mucosa, DBA stained the goblet cells strongly in CV mice but not in GF mice and UEA-I stained the goblet cells strongly in the lower part of crypts in CV mice but only faintly in GF mice. These findings suggest that terminal residues of cecal goblet cell mucin were different in GF and CV mice. Morphometrically, cecal goblet cells were fewer in number and smaller in size in GF mice than in CV mice. In addition, high iron diamine-alcian blue staining made a very clear border between the cecum and colon, because cecal goblet cells were exclusively positive for sulfomucin and colonic goblet cells were predominantly positive for sialomucin.

Alcian Blue↗

PubMed1996

Immunohistochemical study on the deposition of apolipoprotein E in cerebral and islet amyloidoses in cynomolgus monkeys (Macaca fascicularis).

To investigate the role of apolipoprotein E (apo E) in amyloidoses of cynomolgus monkeys, the localization of apo E in cerebral amyloid, including senile plaques and cerebrovascular amyloid, and in islet amyloid was examined immunohistochemically. Mature types of senile plaques with amyloid deposits and cerebrovascular amyloid showed intense immunoreactivity to both antisera to apo E and amyloid beta protein (A beta). In contrast, diffuse plaques without obvious Congophilic amyloid showed weak immunoreactivity to antiserum to apo E, but intense reactivity to antiserum to A beta. In addition, the number of these apo E-positive diffuse plaques was small compared with that of A beta-positive plaques. On the other hand, diabetic islet amyloid that was negative with A beta, reacted intensely with antiserum to apo E. These findings suggest that apo E plays an important role in amyloid fibril formation in several types of amyloidoses.

Amyloid↗

PubMed1996

Variation in serum creatine phosphokinase activity as indicated in two-phase EMC-D virus-induced myocarditis.

In this study, myocardial damage in the D-variant of encephalomyocarditis (EMC-D) virus-induced myocarditis has been investigated consecutively by measuring serum creatine phosphokinase (CPK) activity. CPK activity in 8 week-old male BALB/cAJcl mice inoculated with EMC-D virus increased to a peak at 4 or 5 days postinoculation (DPI) and then gradually decreased. The CPK activity rose again after 7 DPI until it reached a second peak. In view of the kinetics of CPK activity, two-phase (early and late phase) myocardial damage in EMC virus infection were considered. In the late phase, an increase in cellular infiltration in the myocardium and a decrease in viral titer in the heart were observed. It was therefore suspected that the increase in CPK in the late phase may be caused by cellular infiltration, but not by viral replication. In our results, we suggested that a serial measurement of serum CPK activity might be a useful method for throwing more light on the myocardial damage caused by the autoimmune response. We also used a pathological (TUNEL) method to detect apoptotic cells and some apoptotic myocytes in the myocardium in late phase EMC virus-induced myocarditis.

Animals↗

PubMed1996

Age-related histochemical and ultrastructural changes in renal glomerular mesangium of APA hamsters.

Syrian hamsters of the APA strain (APA hamsters) develop spontaneous mesangial thickening in the renal glomeruli from an early age. They also develop focal and segmental glomerulosclerosis (FSG) at and after 6 months of age. In this study, histopathological, histochemical and electron microscopical examinations were conducted to clarify the age-related renal glomerular changes in spontaneous FSG of APA hamsters. Histopathological analysis revealed that expansion of the mesangial region and thickening of the glomerular basement membrane (GBM) in the glomeruli of APA hamsters progressed with age. These age-related changes appeared earlier in male animals. Immunohistochemical analysis suggested that type IV collagen was responsible for the expansion of the mesangial region and thickening of the GBM. In lectin histochemical analysis, positive sites for WGA with and without neuraminidase pretreatment and PNA with neuraminidase pretreatment were detected mainly in podocytes and were expanded with age. Ultrastructurally, the increase in basement membrane-like materials in the mesangial matrix, development of intracellular organella of mesangial cells and migration of a part of the mesangial cell cytoplasm into the GBM were observed at and after 6 months of age. These features suggested that mesangial cells played an important role in the age-related expansion of the mesangial region and thickening of the GBM.

Aging↗

PubMed1996

Spontaneous comedones on the skin of hairless descendants of Mexican hairless dogs.

In the first experiment, the skin sebum and humidity, perspiration ability of sweat glands, and histology of spontaneous comedones were examined in hairless descendants of Mexican hairless dogs. The skin of females showed lower humidity than that of males. Some animals with a large number of comedones exhibited remarkably high skin sebum scores. The comedones were distributed throughout the dorsal skin, and a cluster of lesions was found mainly in the limbs and prepuces. The sweat glands showed no perspiration in the sudorific test. Histologically, both infant and adult animals had lesions of micro- and/or "blackhead" comedones. Plugged follicles containing abundant keratic substances associated well-developed sebaceous glands. Spontaneous comedones in the skin of hairless dogs were grossly and histologically similar to the acne vulgaris observed in human beings. The skin of some adult animals showed a large number of protrusive comedones which were solid cystic structures containing organized substances. In the second experiment, three kinds of antiacne agents (sulfur and camphor, sulfur and resorcinol, and ibuprofen piconol) were applied daily to the test sites for one month. These antiacne agents caused prominent extrusion of keratin plugs from follicular sites. The results suggest that the hairless dogs are a predictive model for evaluating the efficacy of antiacne agents proposed for acne treatment.

Acne Vulgaris↗

PubMed1996

Involvement of macrophages in the development of encephalomyocarditis (EMC) virus-induced diabetes in mice.

The role of macrophages in the development of diabetes following infection with encephalomyocarditis (EMC) virus was examined in 3 strains of mice (DBA/2 and BALB/c: susceptible, C57BL/6: resistant). After infection with 100 plaque forming units (PFU)/head of EMC-D (highly diabetogenic variant), the incidence of diabetes at 3 days post infection (DPI) (DBA/2: 7/8, BALB/c: 3/8, C57BL/6: 0/8) was well correlated with the severity of macrophage infiltration with beta cell damage in the pancreatic islets (DBA/2: sever, BALB/c: moderate, C57BL/6: slight). Silica-pretreatment depleted macrophage infiltration in the pancreatic islets and decreased the incidence of diabetes at 7 DPI from 100% to 40% in DBA/2 and from 80% to 0% in BALB/c mice, respectively. These results suggest that macrophages play a critical role in the process of pancreatic beta cell damage in EMC virus infection in mice.

Animals↗

PubMed1996

Insulin suppresses endothelial secretion of C-type natriuretic peptide, a novel endothelium-derived relaxing peptide.

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells (ECs) and acts as an endothelium-derived relaxing peptide. We further demonstrated the detection of the gene transcripts of CNP and atrial natriuretic peptide (ANP) B receptor, a specific receptor for CNP, in human blood vessels. We thus propose the existence of a vascular natriuretic peptide system (NPS). CNP secretion was also demonstrated to be stimulated by various growth factors and cytokines. To clarify the significance of vascular NPS in proliferative vascular complications associated with diabetes, hypertension, or atherosclerosis, in the present study we examined the effect of insulin on CNP secretion from cultured ECs. Insulin at a concentration in the physiological range (10(-10)-10(-7) mol/l) potently suppressed CNP secretion, whereas insulin at the same concentration did not suppress endothelin (ET) secretion from EC. IGF-I had no significant effect on CNP secretion. Insulin, therefore, can be a potent inhibitor of CNP secretion through the activation of insulin receptor. Since CNP has been shown to be a potent inhibitor of vascular smooth muscle cell proliferation, the present study suggests the possibility that attenuated activity of vascular NPS is associated with hyperinsulinemia, which might result in proliferative vascular lesions.

Animals↗

PubMed1996

Auditory plasticity in cochlear implant patients.

Dynamic range (DR) of cochlear implant electrodes and speech recognition scores (SRS) were chronologically studied in 23 post-lingually deaf subjects over a period of one year. DR significantly increased over one year (ANOVA, p = 0.03). When DR was compared among three groups of electrodes which were located in the inferior, ascending and superior segments of the cochlear basal turn, that in the superior segment showed the largest increase (p = 0.001), followed by those in the ascending and inferior segments. Vowel and consonant recognition scores with auditory cue were best 6 months after operation and were maintained at the level for one year. Although the time course of improvement differed between DR and SRS, a significant positive correlation was observed at 12 months after operation. Improvement of SRS could be a result of a DR increase in the superior segment of the cochlea, which should convey pitch information over the mid-frequency region.

Adolescent↗

PubMed1996

Nerve-regenerating effect of 15-deoxyspergualin. Peripheral nerve allotransplants in the rat.

We studied the effect of two immunosuppressive agents, 15-deoxyspergualin and cyclosporine A, on various nerve allografts in inbred rats whose major histocompatibility complex was mismatched. As allografts, we used the sciatic nerve (20 mm) and the saphenous nerve (20 mm). We found that 1) fresh peripheral nerve allografts with a short course of 15-deoxyspergualin and cyclosporine A therapy induced more regenerated axons than autografts did, 2) a short course of 15-deoxyspergualin therapy provided better nerve regeneration than cyclosporine A therapy in all forms of nerve allografts and large caliber nerve allografts induced more regenerated axons.

Animals↗

PubMed1996

Reconstruction of irreparable brachial plexus injuries with reinnervated free-muscle transfer. Case report.

The complete avulsion of the brachial plexus is a severe injury usually caused by high-energy trauma. Even with the advent of modern microsurgical techniques, many patients have been rendered severely handicapped following this injury. The authors present a new reconstructive procedure that uses a microsurgical reinnervated free-muscle transfer to return prehensile function to an upper limb that is completely paralyzed. Although the procedure is still preliminary, a successful case is briefly described.

Adult↗