Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 487 records · Page 27Linked to original sources

PubMed1994

Synaptic input-induced increase in intraneuronal Ca2+ in the medial vestibular nucleus of young rats.

In the medial vestibular nucleus (MVN), an input-dependent influx of Ca2+ into neurons through N-methyl-D-aspartate (NMDA) receptor-linked channels and/or voltage-dependent Ca2+ channels is suggested as underlying certain mechanisms of plasticity of the vestibular system. To see whether there is an increase in intracellular Ca2+ induced by afferent synaptic inputs to MVN neurons, we measured changes in [Ca2+]i with microfluorometry using a Ca2+ indicator, rhod-2, following electrical stimulation of ipsilateral vestibular afferents and commissural fibers in slice preparations of the brainstem of young rats (4-7 days postnatal). Single shock stimulation of ipsilateral afferents or commissural fibers induced an increase in fluorescence intensity lasting for several seconds. An application of 2-amino-5-phosphonovaleric acid (APV), an antagonist of NMDA receptors, almost completely blocked this stimulus-induced rise in fluorescence intensity. Nifedipine, an L-type Ca2+ channel blocker, also reduced the stimulus-induced rise in fluorescence intensity to 44-51% of the control value. These results suggest that synaptic inputs from the afferent and commissural pathways induce an influx of Ca2+ into MVN neurons due, at least in part, to the activation of NMDA receptors and the subsequent operation of L-type Ca2+ channels in young rats.

Animals↗

PubMed1994

Effects of chronic treatment with clofibric acid on response of rat hepatocytes to mitogenic stimuli.

Mitoinhibitory effects of clofibric acid (CA) were investigated in rat hepatocytes in vitro and in vivo. Female Sprague-Dawley rats, 11 weeks of age, were dietetically treated with CA at 9000 ppm for up to 13 weeks. In the in vitro study, hepatocytes were isolated from rats on day 4 and in weeks 1, 2, 5, 9 and 13, and cultured for 48 h in a medium containing epidermal growth factor. Over the last 24 h, bromodeoxyuridine (BrdU) was added to the medium to determine number of hepatocytes in S-phase. The labeling index (LI) of CA-treated hepatocytes in culture was below control values as early as day 4, and progressively declined with increasing treatment period. In the in vivo study, rats were 2/3 partially hepatectomized at week 13 and maintained for 24 h. BrdU was injected intraperitoneally 1 h prior to necropsy. The LI in the CA-treated liver was also decreased. These data indicated that continuous treatment of CA resulted in decreases in hepatocyte response to growth stimuli, and suggested a possible relation between the chronic growth inhibitory effect on cell multiplication and tumor promotion in rat hepatocarcinogenesis.

Animals↗

PubMed1994

Mineralocorticoid type I receptor in the rat cochlea: mRNA identification by polymerase chain reaction (PCR) and in situ hybridization.

Expression of mineralocorticoid type I receptor (MR) gene in the rat cochlea was determined using molecular biological techniques. We synthesized complementary DNA (cDNA) from rat cochlear total RNA and then amplified MR cDNA fragments by polymerase chain reaction (PCR). The amplified cDNA fragments were subcloned into an expression vector and the nucleotide sequence was analyzed to confirm the expression of mRNA encoding MR in the cochlea. We then synthesized digoxigenin-labeled riboprobes with this cloned DNA template and examined the localization of MR mRNA in the cochlea by in situ hybridization. The amino acid sequence of MR cDNA expressed in the cochlea was identical to that of the MR first cloned in the rat hippocampus. In situ hybridization showed the expression of MR mRNA in marginal cells of the stria vascularis, suggesting that aldosterone may regulate microhomeostasis of the endolymph, presumably by modulating Na, K-ATPase activity. Intense MR signal was also identified in spiral ganglion cells, the function of which remains to be determined.

Aldosterone↗

PubMed1994

Failure of forskolin to elevate the endocochlear potential in kanamycin-poisoned animals.

The effect of forskolin (FSK) on the endocochlear potential (EP), K+ activity (AK), Na+ activity (ANa) and Cl- activity (ACl) in scala media (SM) was compared between normal and kanamycin (KM)-poisoned guinea pigs by means of double-barrelled ion-selective microelectrodes. The perfusion of the scala vestibuli (SV) with FSK (200 microM) produced EP elevation in normal animals whereas FSK failed to do it in KM-poisoned animals. FSK increased ACl of SM with no significant change in AK and ANa of SM in both groups of animals. Histological examination of KM-poisoned animals showed damaged outer and inner hair cells with an intact appearance of the stria vascularis. The mechanism underlying the failure of FSK to elevate the EP in KM-poisoned animals is discussed.

Animals↗

PubMed1994

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

Hepatic changes of mice in the subacute phase of streptozotocin (SZ)-induced diabetes were investigated biochemically and pathologically. Biochemically, the contents of serum glucose and of serum and liver lipids increased while the content of liver glycogen decreased in SZ-induced diabetic mice. Histopathologically, hypertrophy of hepatocytes due to an increase in number of intracytoplasmic acidophilic granules was common to SZ-induced diabetic mice. Electron microscopically, these hepatocytes were characterized by a prominent increase in number of mitochondria showing normal structure, a marked decrease of glycogen granules and poorly developed rough endoplasmic reticulum, which were common to so-called oncocytic cells. In some SZ-induced diabetic mice, bile duct hyperplasia with an appearance of cytomegalic hepatocytes was also observed.

Animals↗

PubMed1994

The outcome of neurovascularized allogeneic muscle transplantation under immunosuppression with cyclosporine.

A model of neurovascularized rectus femoris muscle transplantation was established using inbred rats, and histologic and electrophysiologic investigations were carried out with respect to: 1) whether allogeneic muscle grafts could be established during low-dose, continuous, cyclosporine administration; 2) whether functional restoration of the grafted muscle was possible; and 3) whether immunologic tolerance could be induced by administering a 6-week, low-dose, continuous course of cyclosporine. In the animals continuously administered cyclosporine, no rejection was observed until 12 weeks after surgery; the grafts were completely viable; and M waves could be induced by stimulation of the femoral nerve motor branch. In the animals administered cyclosporine for 6 weeks, rejection was observed 7 weeks after surgery (1 week after discontinuation of immunosuppression), and the grafts became completely necrotic after 10 weeks. These findings suggest that neurovascularized muscle allografts show functional recovery similar to autografts under continuous, low-dose administration of cyclosporine, but that rejection occurs early, and immunologic tolerance does not develop, if the administration is discontinued.

Animals↗

PubMed1994

Vascularized allogeneic nerve transplantation with cyclosporine immunosuppression.

Allogenic grafts have many advantages over autogenous grafts. An experimental rat model using the great saphenous nerve was developed to study the reconstruction of long peripheral nerve defects with vascularized allogeneic nerve grafts, and the effects of cyclosporine therapy on graft survival were assessed. In animals receiving short-term immunosuppression, the number of regenerated axons increased steadily during the treatment, but rejection began immediately after cyclosporine was discontinued. As the tissues transplanted with the nerves underwent necrosis, the grafts showed demyelination. In contrast, in animals receiving long-term cyclosporine therapy, nerve regeneration assessed in terms of the myelinated axon count was excellent until at least 12 weeks postoperatively but was less active than in vascularized autografts or conventional allografts. These results indicate that the short-term immunosuppressive therapy with cyclosporine cannot produce immunological tolerance of vascularized nerve allografts. In addition, even when administration of cyclosporine was prolonged, nerve regeneration did not exceed that in autografts.

Animals↗

PubMed1994

Activation of chloride current by P2-purinoceptors in rat ventricular myocytes.

1. Rat ventricular myocytes were dissociated and their responses to extracellularly applied ATP were recorded using patch pipettes under the whole cell configuration. 2. ATP initially induced an inward current followed by an outward current at -50 mV. With a Cs-rich pipette solution the late outward current was blocked, leaving a sustained inward current (IATPs) suggesting that a K+ conductance underlies the late response. 3. When the extracellular Cl- concentration was changed, the reversal potential of IATPs corresponded well to the shift of the Cl- equilibrium potential. IATPs was reversibly blocked by the chloride channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS). 4. The concentration-response curve of IATPs had a Hill coefficient of 0.98 and an EC50 value of 5.2 x 10(-6) M. 5. ATP was more potent than ADP, while AMP and adenosine were ineffective, suggesting that P2-purinoceptor activation induced IATPs. 6. The activation of IATPs was depressed by depleting the extracellular Mg2+ and increased by adding Mg2+. 7. Our results strongly suggest that P2-purinoceptor activation by ATP induces both a Cl(-)-conductance (IATPs) and a K(+)-conductance in rat ventricular myocytes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1994

Computerized detection of clustered microcalcifications in digital mammograms using a shift-invariant artificial neural network.

A computer-aided diagnosis (CAD) scheme has been developed in our laboratory for the detection of clustered microcalcifications in digital mammograms. In this study, we apply a shift-invariant neural network to eliminate false-positive detections reported by the CAD scheme. The shift-invariant neural network is a multilayer back-propagation neural network with local, shift-invariant interconnections. The advantage of the shift-invariant neural network is that the result of the network is not dependent on the locations of the clustered microcalcifications in the input layer. The neural network is trained to detect each individual microcalcification in a given region of interest (ROI) reported by the CAD scheme. A ROI is classified as a positive ROI if the total number of microcalcifications detected in the ROI is greater than a certain number. The performance of the shift-invariant neural network was evaluated by means of a jackknife (or holdout) method and ROC analysis using a database of 168 ROIs, as reported by the CAD scheme when applied to 34 mammograms. The analysis yielded an average area under the ROC curve (Az) of 0.91. Approximately 55% of false-positive ROIs were eliminated without any loss of the true-positive ROIs. The result is considerably better than that obtained in our previous study using a conventional three-layer, feed-forward neural network. The effect of the network structure on the performance of the shift-invariant neural network is also studied.

Biophysical Phenomena↗

PubMed1994

Evaluation of an asymmetric screen-film system for chest radiography.

To evaluate the potential utility of an asymmetric screen-film system for chest radiography, its image quality and detail visibility compared with a conventional screen-film system are investigated. The basic imaging properties were evaluated by measuring Hurter and Driffield curves, resolution properties, and noise Wiener spectra. The visibility of simulated anatomical and pathological details in radiographs of a chest phantom and normal anatomy in chest radiographs of patients were evaluated subjectively. The dynamic range of each system is comparable, though the asymmetric screen-film system can provide an advantage over the conventional system due to a relative dose reduction of approximately 35% and higher resolution properties at high optical densities. The noise level of the asymmetric screen-film system is slightly greater at low optical densities and much greater at high optical densities. However, the visibility of lung details with the asymmetric screen-film system is slightly superior to the conventional screen-film system despite the increase in noise. Mediastinal and retrodiaphragmatic details are similar, though marginally superior with the asymmetric screen-film system. It is concluded that the asymmetric screen-film system provided slightly superior image quality to the conventional screen-film system for chest radiography, provided the average lung density is maintained at a higher level than is customary with conventional systems.

Biophysical Phenomena↗

PubMed1994

Effect of case selection on the performance of computer-aided detection schemes.

The choice of clinical cases used to train and test a computer-aided diagnosis (CAD) scheme can affect the test results (i.e., error rate). In this study, we deliberately modified the components of our testing database to study the effects of this modification on measured performance. Using a computerized scheme for the automated detection of breast masses from mammograms, it was found that the sensitivity of the scheme ranged between 26% and 100% (at a false positive rate of 1.0 per image) depending on the cases used to test the scheme. Even a 20% change in the cases comprising the database can reduce the measured sensitivity by 15%-25%. Because of the strong dependence of measured performance on the testing database, it is difficult to estimate reliably the accuracy of a CAD scheme. Furthermore, it is questionable to compare different CAD schemes when different cases are used for testing. Sharing databases, creating a common database, or using a quantitative measure to characterize databases are possible solutions to this problem. However, none of these solutions exists or is practiced at present. Therefore, as a short-term solution, it is recommended that the method used for selecting cases, and histograms or mean and standard deviations of relevant image features be reported whenever performance data are presented.

Breast Neoplasms↗

PubMed1994

Computerized detection of masses in digital mammograms: automated alignment of breast images and its effect on bilateral-subtraction technique.

An automated technique for the alignment of right and left breast images has been developed for use in the computerized analysis of bilateral breast images. In this technique, the breast region is first identified in each digital mammogram by use of histogram analysis and morphological filtering operations. The anterior portions of the tracked breast border and computer-identified nipple positions are selected as landmarks for use in image registration. The paired right and left breast images, either from mediolateral oblique or craniocaudal views, are then registered relative to each other by use of a least-squares matching method. This automated alignment technique has been applied to our computerized detection scheme that employs a nonlinear bilateral-subtraction method for the initial identification of possible masses. The effectiveness of using bilateral subtraction in identifying asymmetries between corresponding right and left breast images is examined by comparing detection performances obtained with various computer-simulated misalignments of 40 pairs of clinical mammograms. Based on free-response receiver operating characteristic and regression analyses, the detection performance obtained with the automated alignment technique was found to be higher than that obtained with simulated misalignments. Detection performance decreased gradually as the amount of simulated misalignment increased. These results indicate that automatic alignment of breast images is possible and that mass-detection performance appears to improve with the inclusion of asymmetric anatomic information but is not sensitive to slight misalignment.

Breast Neoplasms↗

PubMed1994

Digital image subtraction of temporally sequential chest images for detection of interval change.

An automated digital image subtraction technique for temporally sequential chest images has been developed in order to aid radiologists in the detection of interval changes. A number of small regions of interest (ROIs) are selected automatically in the lung areas of two temporally sequential chest images. A local matching, based on a cross-correlation method, is performed on each pair of corresponding ROIs in order to determine shift values for the coordinates of two images. A proper warping of x,y coordinates is obtained by fitting two-dimensional polynomials to the distributions of shift values. One of the images is warped and then subtracted from the other. Forty six pairs of chest images (42 with interval changes and 4 without interval change) were processed using this method. The subtraction images were able to enhance various important interval changes, such as differences in the size of tumor masses, changes in heart size, and changes in pulmonary infiltrates or pleural effusions. Approximately 70% of the pairs showed reasonably good registration.

Humans↗

PubMed1994

Progressive encephalopathy in a Crohn's disease patient on long-term total parenteral nutrition: possible relationship to selenium deficiency.

The case of a patient with Crohn's disease complicated by progressive and irreversible encephalopathy, who had been on long-term total parenteral nutrition due to short bowel syndrome, is described. He initially experienced a disturbance of his vision, which was followed by various neurological symptoms during the next 3 years. These symptoms rapidly progressed until he finally developed consciousness disturbance. He also manifested erythrocytic macrocytosis, a low serum level of tri-iodothyronine and a high level of thyroxine. His blood levels of various trace minerals and vitamins were normal, except for selenium, which showed extremely low values. In addition, impaired plasma glutathione peroxidase activity was confirmed. After intravenous supplementation of selenium, macrocytosis, tri-iodothyronine and thyroxine values, and glutathione peroxidase activity all became normalized, yet he improved little neurologically. Our case suggests that long-term selenium deficiency may cause progressive and irreversible encephalopathy, and that careful monitoring of this mineral is necessary when an excessive period of total parenteral nutrition is being considered in the clinical setting.

Adult↗

PubMed1994

Therapeutic effect of reticuloendothelial system (RES)-avoiding liposomes containing a phospholipid analogue of 5-fluorouracil, dipalmitoylphosphatidylfluorouridine, in Meth A sarcoma-bearing mice.

Reticuloendothelial system (RES)-avoiding liposomes are known to accumulate in tumor tissues due to passive targeting. Dipalmitoylphosphatidylfluorouridine (DPPF), a potent antitumor agent readily incorporated into the lipid bilayer, was embedded in RES-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). The therapeutic effect of DPPF in PGlcUA-liposomes was examined in tumor-bearing mice. Free or liposomal DPPF was injected intravenously into BALB/c mice bearing subcutaneously implanted Meth A sarcomas. The RES-avoiding liposomal formulation using PGlcUA was effective in reducing tumors, and prolonging survival time compared with free DPPF and also DPPF in conventional liposomes. Therefore, PGlcUA-liposomes might be of practical use as drug carriers for anticancer agents, especially their derivatives for embedding in liposomal membranes.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1994

Encephalomyocarditis (EMC) virus-induced testicular lesion in BALB/c mice.

Characteristics of encephalomyocarditis (EMC) virus-induced testicular lesions were investigated in 4- and 8-week-old BALB/c male mice after intraperitoneal (i.p.) and intratesticular (left) (i.t.) inoculation of the D variant of EMC virus (EMC-D). Apart from variation in severity and incidence, the histopathological nature of the resultant testicular lesion was similar in all infected mice, and was characterized by degeneration and necrosis of germinal cells and spermatogonia with inflammatory infiltration. Almost all the inoculated left testes of the i.t. group developed marked lesions. In general, the virus titre in the testis and incidence of testicular lesions were higher in 4-week-old mice than in 8-week-old mice. In addition, testicular lesions developed earlier and with a higher incidence in the PBS-inoculated right testis of the i.t. group than in either testis of the i.p. group of the same age.

Animals↗

PubMed1994

Glucose effectiveness in two subtypes within impaired glucose tolerance. A minimal model analysis.

To clarify the event that is involved in the pathogenesis of impaired glucose tolerance (IGT), we studied 15 individuals with IGT and 15 subjects with normal tolerance using the minimal model approach. Our IGT subjects were characterized by normal insulin secretory responses to oral glucose and mild impairments in insulin sensitivity (SI) and glucose effectiveness (SG) at basal and zero insulin. Next, we classified our IGT subjects into two subpopulations: one with normal insulin sensitivity (SI: 0.92 +/- 0.11 x 10(-4) min-1.pmol/l-1 and the other with insulin resistance (SI:0.31 +/- 0.06 x 10(-4)min-1.pmol/l-1, P < 0.05). The populations did not differ with respect to body mass index and fasting plasma glucose level. Basal plasma insulin level was higher in the insulin-resistant group (84.8 +/- 23.3 pmol/l) than in the insulin-sensitive group (48.7 +/- 6.8 pmol/l), but the difference was not statistically significant. The absolute insulin secretory responses to oral glucose were significantly higher in the resistant group (83,205 +/- 17,787 pmol/l x min) than in the sensitive group (24,727 +/- 3,591 pmol/l x min, P < 0.01), whose absolute responses were similar to those of normal control subjects (24,576 +/- 2,767 pmol/l x min). No significant difference was observed in SG between the resistant (0.016 +/- 0.002 min-1) and sensitive (0.013 +/- 0.002 min-1, P > 0.05) type of IGT, but SG was significantly type of IGT, but SG was significantly decreased in both groups compared with normal control subjects (0.023 +/- 0.002 min-1, P < 0.05-0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Strial dysfunction in a melanocyte deficient mutant rat (Ws/Ws rat).

A homozygous mutant rat at the white spotting (Ws) locus showing a deficiency of melanocytes has recently been found (4, 5). The function and morphology of the inner ear of the Ws/Ws rat were examined by auditory brainstem response (ABR), endocochlear DC potential (EP), and electron microscopy. The mean ABR threshold of the Ws/Ws rat was significantly higher than that of the control +/+ rat. Most Ws/Ws rats showed no or very little EP. In electron microscopy, the stria vascularis of the Ws/Ws rat proved to be very thin and flat with poor interdigitation of marginal cells, and absence of intermediate cells. The organ of Corti appeared to be intact in both the +/+ rat and the Ws/Ws rat. These electrophysiological and morphological findings suggest that the Ws/Ws rat suffered from severe hearing loss caused by strial dysfunction.

Acoustic Stimulation↗