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Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 559 records · Page 31Linked to original sources

Potential usefulness of computerized nodule detection in screening programs for lung cancer.

RATIONALE AND OBJECTIVE: To alert radiologists to possible nodule locations and subsequently to reduce the number of false-negative diagnoses, the authors are developing a computer-aided diagnostic (CAD) scheme for the detection of lung nodules in digital chest images. METHODS: A computer-vision scheme was applied to photofluorographic films obtained in a mass survey for detection of asymptomatic lung cancer in Japan. Ninety-five patients with abnormal test results who had primary and metastatic lung cancers and 103 patients with normal test results were included. RESULTS: The sensitivity of the computer output was comparable with that of physicians in this mass survey (62%). The computer detected approximately 40% of all nodules missed in the mass survey, but missed 17 true-positive results identified in the mass survey. The CAD scheme produced an average of 15 false-positive findings per image. CONCLUSION: If the number of false-positive results can be significantly reduced, computer-vision schemes such as this may have a role in lung cancer screening programs.

False Positive Reactions↗

Image feature analysis of false-positive diagnoses produced by automated detection of lung nodules.

RATIONALE AND OBJECTIVES: To reduce the number of false-negative diagnoses by radiologists, the authors are developing a computer-aided diagnosis scheme for detection of lung nodules in digital chest images. In this study, the authors attempted to reduce the number of false-positive diagnoses obtained with a previous computer scheme by incorporating additional knowledge from experienced chest radiologists into the computer scheme. METHODS: The authors applied their previous computer scheme, using less-strict criteria, to 60 clinical chest radiographs; this yielded 735 candidate nodules (23 true nodules and 712 false-positive diagnoses). These candidates were analyzed using region-growing, trend-correction, and edge-gradient techniques to determine measures by which to quantify image features of candidate nodules. RESULTS: The 712 false-positive diagnoses represented various anatomic structures that were located throughout the chest image. From this analysis, we were able to decrease the number of false-positive errors from an average of 12 to approximately 5 per image without eliminating any true nodules. CONCLUSION: Our results show that incorporating knowledge from experienced chest radiologists into the computer algorithm will play an important role in the development of computerized schemes for the detection of pulmonary nodules.

Diagnostic Errors↗

Haematological and serum biochemical values in hairless and haired descendants of Mexican hairless dogs.

Haematological and serum biochemical measurements were carried out in 1-year-old hairless and haired hybrids derived from the Mexican hairless dog (MHD). These hybrids included F1 hybrids obtained from male MHD and female Beagles, and BCF1 hybrids obtained from male hairless F1 and female Beagles. There were no significant differences between F1 and BCF1 hybrids, nor between male and female hybrids. Except for red blood cell counts, haemoglobin concentrations and packed cell volumes which were slightly higher in MHD-descendants than in Beagles, there were no differences for haematological and serum biochemical findings between hairless and haired hybrids when compared to age-matched Beagles.

Animals↗

Glomerular lesions in unilateral nephrectomized and diabetic (UN-D) mice.

Experimental diabetes was induced in both control and unilaterally nephrectomized male mice by injecting streptozotocin (SZ) (50 mg/kg x 5 days) one week after nephrectomy. The time course changes in the glomerular lesions were examined for up to 12 weeks after completion of the SZ-injection (12WAI). In unilateral nephrectomized and diabetic mice, mild segmental expansion of the mesangial area developed at 4WAI, and it progressed to prominent segmental glomerulosclerosis at 12WAI. In the electron microscopic examination at 12WAI, marked expansion of the mesangial area, segmental thickening of the glomerular basement membrane, fusion of the foot processes of podocytes and a prominent increase in the number of microvilli of capillary endothelial cells were observed. On the other hand, mild to moderate expansion of the glomerular mesangial area was only sporadically found in unnephrectomized diabetic mice at 12WAI. Interestingly, Bowman's capsules of diabetic mice were generally lined with flattened epithelia but those of non-diabetic mice with cuboidal or low columnar epithelia.

Animals↗

Encephalomyocarditis (EMC) virus-induced myocarditis by different virus variants and mouse strains.

The mode of occurrence of encephalomyocarditis (EMC) virus-induced myocarditis in mice was pathologically and virologically investigated using 2 virus variants (highly diabetogenic EMC-D and non-diabetogenic EMC-B) and 2 mouse strains (diabetes-susceptible BALB/c and diabetes-resistant C57BL/6). Mice were inoculated with 10(5) PFU/head of the virus intraperitoneally and observed up to 7 days post inoculation (7DPI). As compared with EMC-B-infected BALB/c and EMC-D-infected C57BL/6 mice, EMC-D-infected BALB/c mice developed marked myocarditis and exhibited a heart virus titer of more than 100 times above that of the others after 4DPI. Electron microscopically, small aggregations of virus-like particles, with 20-25 nm in diameter, were found in the cytoplasm of degenerated cardiomyocytes showing mitochondrial and myofibrillar degeneration in EMC-D-infected BALB/c mice.

Animals↗

Effect of hyperlipidemia on cardiovascular responses to adrenergic stimulation in piglets.

This study was designed to assess the effect of hyperlipidemia on cardiovascular responses to adrenergic stimulation in a porcine model. Four-week-old piglets (n = 10) were divided into two groups; one fed a control diet and the other was fed an atherogenic diet for 8 weeks. Cardiovascular responses were evaluated to both norepinephrine (NE; 0.5 and 2.5 micrograms/kg) and isoproterenol (ISO; 0.1 and 0.5 microgram/kg) from simultaneous recordings of femoral arterial pressure, heart rate, left intraventricular pressure and left intraventricular dP/dt. It was found that no significant difference in the baseline values of cardiovascular function was observed between the control and hyperlipidemic groups. However, in the hyperlipidemic group as compared with the control group: 1) arterial blood pressure responses to NE were significantly increased (P less than 0.05), 2) cardiac contractile responses to NE and ISO were significantly potentiated (P less than 0.05), and 3) reflex bradycardia in response to increasing arterial blood pressure did not occur. These findings indicate that hyperlipidemia can potentiate the cardiovascular responses to adrenergic stimulation, whereas reflex cardiovascular regulation is somewhat altered by hyperlipidemia. Conceivably, these observations may have relevance to the possible role of the mechanism of the interaction of hyperlipidemia and hypertension in atherogenesis.

Analysis of Variance↗

Measurements of CO2 diffusivity and buffering capacity in myoglobin solutions.

Diffusion processes of CO2 into or out of a thin layer of myoglobin (Mb) solution were followed by pH-sensitive fluorescence of 4-methylumbelliferone. Mb solutions were prepared by dissolving horse heart Mb at 0.1 to 4 mM in a modified Krebs solution containing NaHCO3 of 30 mM. Carbonic anhydrase was added to observe the diffusion-limited pH changes. The PCO2 in the layer were calculated as the numerical solution of a diffusion equation. For the simulation of the observed pH-time curves, the PCO2 changes were converted to the pH changes using a linear relation between logPCO2 and pH. The diffusion coefficients of CO2 and HCO3- (DCO2 and DHCO3) were determined as the optimum parameters to fit the calculated pH-time curves to the observed ones. Both the DCO2 and DHCO3 decreased exponentially as the Mb concentration was increased. At a physiological concentration of Mb in cardiomyocytes (0.2 mM) and at 37 degrees C, the DCO2 and DHCO3 values were 9.8 x 10(-5) and 16 x 10(-5) cm2.s-1, respectively. The buffer value (beta) was calculated as the slope of a pH-bicarbonate diagram by measuring the CO2 content and pH of the Mb solutions equilibrated with known PCO2 gases. The beta was found to increase with increasing Mb concentration with a value of 6.2 mEq.l-1.pH-1 at 0.2 mM.

Animals↗

Adenylate cyclase modulation of ion permeability in the guinea pig cochlea: a possible mechanism for the formation of endolymphatic hydrops.

The pathophysiological mechanisms leading to endolymphatic hydrops in Meniere's disease are unknown. Changes in ionic permeability of the cellular membranes between the endolymph and the perilymph, which alter the composition and osmolarity of the inner ear fluid, may be a major factor in the etiology of endolymphatic hydrops. To determine the possible involvement of adenylate cyclase in the formation of endolymphatic hydrops, we measured the endolymphatic K+, Na+, Cl- activities (AK, ANa, ACl) and the endocochlear potential (EP) by means of ion-selective microelectrodes while inner ear adenylate cyclase was activated by perilymphatic perfusion with forskolin. We observed a large ACl increase accompanied by an EP increase during forskolin (2 x 10(-4) M) perfusion and a delayed AK decrease after perfusion. No measurable ANa change was observed. These results suggest that adenylate cyclase may regulate Cl- permeability of the endolymph-perilymph barrier and that adenylate cyclase plays a critical role in acute endolymphatic hydrops in Meniere's disease by altering the osmolarity of the endolymph.

Adenylyl Cyclases↗

smg/rap1/Krev-1 p21s inhibit the signal pathway to the c-fos promoter/enhancer from c-Ki-ras p21 but not from c-raf-1 kinase in NIH3T3 cells.

smg/rap1A/Krev-1 p21 cDNA is known to inhibit v-Ki-ras p21-induced cell transformation in NIH3T3 cells, but the inhibitory mechanism is not clear at present. In the present study, we examined the effect of smg p21s on the c-fos promoter/enhancer linked to the luciferase reporter gene (c-fos-luciferase). After transfection of c-fos-luciferase into NIH3T3 cells constitutively expressing c-Ki-ras(val-12) p21 or activated c-raf-1 kinase, expression of c-fos-luciferase was much higher than after transfection into control NIH3T3 cells. Addition of platelet-derived growth factor (PDGF), 12-O-tetradecanoyl phorbol 13-acetate (TPA) or dibutyryl cyclic AMP (Bt2cAMP) to the control NIH3T3 cells stimulated c-fos-luciferase expression. Transfection of the smg p21 cDNAs inhibited the activated ras p21-, PDGF- or TPA-stimulated c-fos-luciferase expression, but did not inhibit the activated c-raf-1 kinase- or Bt2cAMP-stimulated reaction. These results indicate that smg p21s inhibit the signal pathways from the PDGF receptor, protein kinase C, and ras p21s to the c-fos promoter/enhancer, but not those from c-raf-1 kinase and cyclic AMP-dependent protein kinase to the c-fos promoter/enhancer.

3T3 Cells↗

Neurotransmission in the auditory system.

Neurotransmitters and neuromodulators thought to be active on neurons in the cochlea, CN, and SOC have been reviewed. The variety of neurotransmitters and neuromodulators present and likely colocalized in these neurons are the chemical substrates that link morphologically and physiologically diverse neurons to process sound information. The impact of the limited number of neurotransmitters and neuromodulators in the auditory system is magnified by their interaction with structurally diverse receptors; thus great functional diversity is possible. Moreover, the effects of neurotransmitters and neuromodulators are not limited to synaptic transmission but serve as trophic agents for the establishment of neuronal circuitry during development and the rearrangement of synapses as a result of sensory experience or injury. An understanding of the neurochemical aspects of sensory processing at these diverse synapses then is of fundamental importance in understanding the organization of the auditory system.

Auditory Pathways↗

Morphometric study on the renal glomeruli of streptozotocin (SZ)-induced diabetic APA hamsters.

Morphometrical analysis was done on the renal glomeruli of streptozotocin (SZ)-induced diabetic and control APA hamsters. In coincidence with the histopathological and ultrastructural findings, the areas of whole glomerulus (WG) and mesangial region (MR) were significantly larger in diabetic animals than in controls at 1 and 3 months after SZ-injection (1 and 3MAI). The area of capillary lumen in diabetic animals was larger than that in controls at 1MAI but it became similar between both groups at 3MAI probably due to an increase in the area of MR. The thickness of basement membrane was significantly larger in diabetic animals than in controls at 3MAI. The present morphometrical findings, together with histological and ultrastructural ones, suggest that SZ-induced diabetic APA hamsters are useful as a model system for the investigation of focal and segmental glomerulosclerosis.

Animals↗

The functional domain of the stimulatory GDP/GTP exchange protein (smg GDS) which interacts with the C-terminal geranylgeranylated region of rap1/Krev-1/smg p21.

rap1/Krev-1/smg p21 (smg p21), a member of the small GTP-binding protein (G protein) superfamily, has a geranylgeranylated cysteine residue and clustered basic amino acids in the C-terminal region. The GDP/GTP exchange reaction of smg p21 is regulated by smg GDS, which is also active on Ki-ras p21 and rho p21. The C-terminal region of smg p21 is essential for its interaction with smg GDS. Moreover, smg p21 is phosphorylated by cyclic AMP- and cyclic GMP-dependent protein kinases at the serine residue between the polybasic region and the prenylated cysteine residue, and this phosphorylation initiates the smg GDS-induced smg p21 activation. Thus, the C-terminal cationic and hydrophobic region is important for the regulation of the smg p21 activity. In the present study, we attempted to determine the functional domain of smg GDS which interacts with the C-terminal region of smg p21 by use of a cross-link method and a site-directed mutagenesis method. The region of smg GDS cross-linked with the C-terminal region of smg p21B was residues 444-492, which is located at the C-terminal fifth of smg GDS. On deletion of these residues, smg GDS became inactive on smg p21B, Ki-ras p21 and rhoA p21. These results indicate that residues 444-492 of smg GDS are at least one of the domains which interact with the C-terminal region of its substrate small G proteins.

Amino Acid Sequence↗

Rapid induction of atherosclerosis in rabbits.

Japanese white rabbits fed a restricted amount (100 g/head/day) of an atherogenic diet (AD) containing 0.2% cholesterol and 6% peanut oil showed mild and persistent hypercholesterolemia (338 +/- 79 mg/dl). They developed atherosclerotic lesions 4 weeks after deendothelialization of aorta carried out at the 4th week of AD-feeding. This rabbit model of atherosclerosis has such advantages as being able to be produced in a short period and having similar biochemical and pathological characteristics with those in human atherosclerosis.

Animals↗

Rapid induction of glomerular lipidosis in APA hamsters by streptozotocin.

The pathology of male Syrian hamsters of APA strain which were injected intraperitoneally with 40 mg/kg body weight of streptozotocin (SZ) at 2 months of age was examined. It showed long-lasting prominent hyperglycaemia and hyperlipidaemia with glucosuria and the development of glomerular lipidosis from 1 month after SZ-injection (1 MAI). Glomerular lesions were restricted to the juxtamedullary cortex at 1 MAI and then extended to the subcapsular cortex. At 3 MAI, glomerular lesions were characterized by focal segmental glomerulosclerosis showing segmental expansion of the mesangial area due to an increase of basement membrane-like material and mesangial cells with lipid droplets and foam cells. SZ-induced diabetic APA hamsters will be a useful model for the investigation of glomerular lipidosis and focal segmental glomerulosclerosis.

Animals↗

Computer-aided diagnosis: development of automated schemes for quantitative analysis of radiographic images.

Preliminary results obtained with computer-aided diagnosis (CAD) from various radiographic examinations are very encouraging. However, CAD is still at an early stage of its development. It will be necessary to increase further the understanding of image features of normal and abnormal patterns, to establish databases, and to devise specific approaches for particular types of pathology. Although the existing schemes are designed to be applied to digital radiographs, similar techniques can be applied in the future to cross-sectional images such as CT, MRI, and ultrasound. We believe that CAD will become clinically practical in the near future.

Angiography↗

Major component of Ra-reactive factor, a complement-activating bactericidal protein, in mouse serum.

A complement-activating bactericidal protein, Ra-reactive factor was isolated from mouse serum by an affinity method. The m.w. of the isolated RaRF estimated by glycerol density gradient sedimentation (around 300,000) was the same as that of the active material in mouse serum. As evidenced by gel filtration, the intact RaRF was decomposed into high (higher than 200,000) and low (50,000 to 200,000) m.w. components by treatment with 10% acetonitrile. SDS- and acid/urea-PAGE demonstrated that the high m.w. component was completely dissociated into equimolar quantities of two kinds of 28 kDa polypeptides, P28a and P28b, under reducing conditions, indicating that the association of these polypeptides was stabilized by disulfide bonds. The ability to bind specifically to the Ra determinant was retained in the high m.w. component, although the complement-activating potency was lost. The amino acid compositions of P28a and P28b polypeptides were compared with those of related serum proteins. The P28a and P28b polypeptides were found to have the highest homology to rat mannan-binding protein and mouse and human C1q subcomponent of complement.

Amino Acids↗