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Biomedical subjects

Y Sasaki

Publications and source records attributed to Y Sasaki.

At least 19 recordsLinked to original sources

[Quantitative analysis of pneumoconiosis in standard chest radiographs].

A computerized method to quantify and characterize interstitial diseases by using physical texture measures obtained from an analysis of the power spectrum of lung textures in digital chest radiographs was applied to Japanese standard radiographs of pneumoconiosis. Texture measures were determined from standard radiographs of silicosis, asbestosis, and other types of pneumoconiosis as well as chest radiographs of normal lungs. Our preliminary results indicated that the texture measures obtained from computer analysis corresponded closely with the standard categories of silicosis. However, there was no significant correlation between texture measures and the categories for asbestosis and other types of pneumoconiosis in terms of texture pattern. Japanese standard radiographs of pneumoconiosis are categorized according to the profusion of opacities, without reference to the size and shape of the opacities. Furthermore, in some films the size and shape of the opacities vary considerably within the same category. Therefore, it is considered that these characteristics of the standard films affected the results of our texture measures. It also considered that a large ROI and other texture measures are needed to characterize large opacities and mixed-shaped opacities of pneumoconiosis.

Humans

Role of lysophosphatidylcholine in T-lymphocyte activation: involvement of phospholipase A2 in signal transduction through protein kinase C.

2-Lysophosphatidylcholine (lysoPtdCho), a product of the hydrolysis of phosphatidylcholine catalyzed by phospholipase A2, greatly potentiates the activation of human resting T lymphocytes that is induced by a membrane-permeant diacylglycerol plus a calcium ionophore, as determined by the expression of the alpha subunit of the interleukin 2 receptor and thymidine incorporation into DNA. LysoPtdCho per se is inactive unless both diacylglycerol and a calcium ionophore are present. This effect of lysoPtdCho is also observed when diacylglycerol is replaced by a tumor-promoting phorbol ester. Other lysophosphatides including lysophosphatidylserine, lysophosphatidylinositol, and lysophosphatidic acid are inert except for lysophosphatidylethanolamine, which is far less effective than lysoPtdCho. Tracer experiments with radioactive choline indicate that, when T lymphocytes are stimulated with an antigenic signal, lysoPtdCho is indeed produced in a time-dependent fashion, although the concentration of this lysophospholipid accumulated remains to be quantitated. It suggests that phospholipase A2 is directly involved in the signal transduction pathway through protein kinase C to induce long-term cellular responses.

Calcium

Efficient in vitro folding of the three-disulfide derivatives of hen lysozyme in the presence of glycerol.

Four derivatives of hen lysozyme, each lacking one native disulfide bond of the four in authentic lysozyme, were produced in Escherichia coli by expressing synthetic mutant genes. In the reoxidation reaction of the reduced derivatives purified from inclusion bodies, the addition of glycerol significantly enhanced the efficiency of folding and 'correct' disulfide bond formation. This enabled simple chromatographical purification of refolded materials. Purified 3SS-derivatives all showed lytic activities and secondary structures comparable to authentic lysozyme, which directly showed that none of the four native disulfide bonds is a prerequisite for 'correct' in vitro folding.

Animals

[Evaluation of an automated adaptive unsharp masking technique in digital chest radiographs].

We are developing a fully automated adaptive unsharp masking technique with parameters that depend on the regional image features of digital chest radiographs. Regions such as the lung fields, retrocardiac area, and spine have extremely different texture patterns and optical densities on chest radiographs. Therefore, it is necessary to enhance the image contrast of each region by an optimum parameter for the regional image. In this study, a chest radiograph was automatically divided into three segments (lung field, retrocardiac area, and spine) by histogram analysis of pixel values. Then, the lung field and retrocardiac area were selectively enhanced with a small mask size and mild weighting factors that had been previously determined as optimum parameters. The spine was enhanced with a large mask size and adequate weighting factors. An observer performance test indicated that this technique provides excellent diagnostic accuracy for simulated nodules over the mediastinum and diaphragm without sacrificing diagnostic accuracy for nodules over the lung field. We believe that this adaptive processing technique may have the potential to be a useful aid for the diagnosis of chest radiographs.

Evaluation Studies as Topic

Different effects of peptidase inhibitors on dermorphin- and on [D-Arg2]dermorphin-induced antinociceptive activity.

The antinociceptive effects produced by the intracerebroventricular (i.c.v.) injection of dermorphin and [D-Arg2]dermorphin were compared in conscious mice, using the combined administration of peptidase inhibitors. Nociception was assessed using a tail pressure assay. Dermorphin-induced antinociception was not potentiated by simultaneous administration of amastatin or captopril as judged from the ED50 values. Co-administration of dermorphin and amastatin gave a longer duration than with dermorphin alone, whereas there was no significant effect on duration with captopril. The antinociceptive activity of dermorphin was significantly enhanced when the heptapeptide was injected simultaneously with both peptidase inhibitors. This result indicates that the heptapeptide sequence is required for the full expression of intrinsic opioid activity of dermorphin. In contrast, co-administration of amastatin brought about a significant enhancement of the antinociceptive activity induced by i.c.v. administration of [D-Arg2]dermorphin, whereas the effect of [D-Arg2]dermorphin was markedly decreased by the concurrent administration of captopril or thiorphan. The potency of captopril was much greater than that of thiorphan. The present results suggest that [D-Arg2]dermorphin may be transformed metabolically to a peptide which has potent antinociceptive activity.

Analgesics, Opioid

Analysis of laryngeal movement by digital subtraction laryngography.

Fine movement of laryngeal components was analyzed by digital subtraction laryngography with the use of a digital fluorography system. Two kinds of image processing modes, the super pulse image subtraction mode and the time interval difference mode, were used for this purpose. By the super pulse image mode, the distance and extent of movement of laryngeal components at vocal initiation and during phonation could be observed. By the time interval difference mode, the amount and direction of motion for a certain interval and fine movement, such as vocal initiation, were determined.

Fluoroscopy

Intracellular calcium as a second messenger for human hepatocyte growth factor in hepatocytes.

Human hepatocyte growth factor is a newly discovered substance that stimulates DNA synthesis in vitro. In this study, we examined intracellular Ca2+ movement as one of the second messengers for human hepatocyte growth factor in primary-cultured hepatocytes. The addition of hHGF induced Ca2+ oscillation, but the frequency of oscillations varied from cell to cell. We also saw marked intercellular heterogeneity in the initial latent period for the Ca2+ response; the mean latent period was rather longer than those seen with phenylephrine and vasopressin. This difference in the initial latent period may be due to the difference in the pathways of Ca2+ elevation. Duration of culture determined the number of human hepatocyte growth factor-responsive cells; their number peaked at 2 to 5 hours of confluent culture, whereas the peak was earlier in a low-density culture. These changes in responsiveness during culture can be explained by the cell cycle-dependent sensitivity to human hepatocyte growth factor of hepatocytes. The Ca2+ response to human hepatocyte growth factor was dose dependent; 10(-10) mol/L hHGF gave the highest Ca2+ response, similar to the dose-response curve of DNA synthesis. We even observed the Ca2+ response in the Ca(2+)-free buffer, so the increase in Ca2+ was considered due to release from intracellular Ca2+ stores. These results suggest that human hepatocyte growth factor causes the intracellular Ca2+ elevation in the early stage of the cell cycle and that it plays important roles in the signal transduction systems for human hepatocyte growth factor and the proliferation of hepatocytes.

Animals

Epidermal growth factor induces dose-dependent calcium oscillations in single fura-2-loaded hepatocytes.

Digital imaging fluorescence microscopy has been used to investigate epidermal growth factor-induced calcium responses of fura-2-loaded hepatocytes in primary culture at the single-cell level. Epidermal growth factor induced oscillations in cytosolic free calcium ([Ca2+]i) consisting of a periodic train of spikes unlike the monophasic elevation in cell suspensions reported previously. In this study, 79% of the cells in the microscopic field responded to 0.1 nmol/L epidermal growth factor, and 78% of the responsive cells displayed oscillations. However, the frequency of oscillations differed considerably from cell to cell. [Ca2+]i measurement in a cell population was simulated using these data, but only a slightly biphasic pattern was obtained, indicating the significance of single-cell measurement of [Ca2+]i. Because considerable heterogeneity existed in the sensitivity to epidermal growth factor between the cells, single hepatocytes were stimulated sequentially with increasing concentrations of epidermal growth factor to investigate the dose dependence of the oscillations. The frequency of the oscillations increased with increasing epidermal growth factor concentration, but the amplitude was similar for all concentrations, suggesting the existence of frequency-encoded information even in the pathway through tyrosine kinase for epidermal growth factor signaling. The pattern of the oscillations with epidermal growth factor, especially the latency, was considerably different from that with phenylephrine, which is known to use the phosphatidylinositol pathway, possibly because of the difference in the pathway toward phosphatidylinositol turnover between these agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A prognostic-factor risk index in advanced non-small-cell lung cancer treated with cisplatin-containing combination chemotherapy.

Prognostic factors for response and survival were retrospectively evaluated in 192 previously untreated patients with advanced non-small-cell lung cancer (NSCLC) who had received either vindesine plus cisplatin or mitomycin plus vindesine plus cisplatin as initial treatment. Univariate analysis demonstrated that squamous-cell histology, early stage, and a small number of metastatic sites were favorable prognostic factors for response to chemotherapy. Multivariate analysis using Cox's proportional hazard model indicated that the number of metastatic sites was the only significant pretreatment factor for response (P = 0.0005). Multivariate regression analysis revealed that the number of metastatic sites (P = 0.0002), sex (P = 0.0009), serum albumen levels (P = 0.0018), performance status (P = 0.0026) and lactic dehydrogenase values (P = 0.0026) contributed independently to survival. On the basis of these five prognostic factors, a prognostic index for survival was used to define three prognostic groupings (good, intermediate, and poor) for survival (median survival, 16.5 vs 9.4 vs 4.6 months; P = 0.0001). This particular regression model should aid in the design and analysis of new treatment strategies and may be useful for indirect comparisons of different studies carried out in similar patient populations.

Adenocarcinoma

A case of pediatric cardiomyopathy with severely restrictive physiology.

A rare case of a 6-year-old male with idiopathic familial cardiomyopathy manifesting severely restrictive physiology is reported. The patient showed congestive heart failure with dilatation of both atria with a normal ventricular cavity. A square-root configuration was revealed in the ventricular pressure tracings. His elder brother had died of hypertrophic cardiomyopathy at the age of 3 years. Endomyocardial biopsy disclosed marked disorganization of muscle bundles with hypertrophy of the myocytes and interstitial fibrosis. The patient died suddenly during hospitalization. Autopsy revealed diffuse hypertrophy of both the ventricular walls and the ventricular septum with extensive myocardial disorganization and interstitial fibrosis. These advanced myopathic changes in the myocardium may have been related to the restrictive physiology in this case.

Bundle-Branch Block

Pseudomyxoma peritonei with progressive calcifications: CT findings.

Development of abdominal calcifications due to pseudomyxoma peritonei is rare. The authors present three cases whereby computed tomographic (CT) studies during or after chemotherapy for pseudomyxoma peritonei demonstrated development and progression of punctate calcifications in the abdomen. The clinical and CT findings of these cases are presented together with a brief review of the pertinent literature.

Adult

Dependence of ultrasonic attenuation of liver on pathologic fat and fibrosis: examination with experimental fatty liver and liver fibrosis models.

To clarify the effect of the pathological state of the liver on ultrasonic attenuation, we produced two experimental rabbit models. The influence of fat on ultrasonic attenuation was examined using a fatty liver model without liver fibrosis, and that of fibrosis on attenuation using a liver fibrosis model without fatty infiltration. Ultrasonic data were obtained in vivo directly from the liver, and an acoustic attenuation coefficient slope was obtained by the spectral difference method. Tissue components of the liver, namely the total lipid, hydroxyproline and water contents, were measured precisely by quantitative methods. We revealed that ultrasonic attenuation depends mainly on fatty infiltration of the liver and to a lesser extent on fibrosis, but not on the water content.

Adipose Tissue

Production of IL-4, IL-2, IFN-gamma, and TNF-alpha by peripheral blood mononuclear cells of patients with atopic dermatitis.

Recently, T cell-derived cytokines have been postulated to be involved in the pathogenesis of atopic dermatitis (AD) since the synthesis of IgE is profoundly regulated by cytokines such as IL-4, IFN-gamma and IL-2. IL-4 enhances the production of IgE and in contrast, IFN-gamma inhibits this IL-4-mediated IgE production. IL-2 also prevents IL-4-induced production of IgE by a different mechanism from IFN-gamma, suggesting that the level of IgE is regulated by the quantitative balance of these antagonizing cytokines. We examined the production of IL-4, IL-2, IFN-gamma and TNF-alpha by PBMC of AD patients and non-AD controls. Although the production of IL-2 and TNF-alpha by AD patients was significantly lower than that of non-AD controls, the production of IL-4 and IFN-gamma did not show significant differences between AD and non-AD individuals. There was no significant correlation between cytokine production and clinical symptoms in AD patients. There was significant positive correlation between IL-4 and IL-2 production, and between IFN-gamma and TNF-alpha production. Serum IL-4 levels showed no significant difference between AD group and non-AD group.

Adolescent

Congenital polyneuropathy in Walker-Warburg syndrome.

Polyneuropathy was found in a patient with the Walker-Warburg syndrome. The most dominant features were the presence of extremely and tortuously proliferated myelin sheaths, the most of which having no neurofilaments and neurotubules. The other peculiar findings were the presence of microfilaments in Schwann cell cytoplasms, which were very similar to neurofilaments, and the presence of partial and abrupt disappearance of myelin sheaths. The severity of neuropathy was variable among nerve bundles, and a few nerve bundles looked normal on light microscopy. The above-mentioned lesions did not suggest the degeneration and/or regeneration of normally developed nerve fibers. We could not conclude the pathogenesis of this neuropathy, however, it was logical to consider that they reflected dysplastic myelination due to Schwann cell dysmaturity as well as the cerebral dysplasia.

Axons

Ovarian juvenile granulosa cell tumor associated with Maffucci's syndrome.

A 15-year-old girl developed a juvenile granulosa cell tumor associated with Maffucci's syndrome (enchondromatosis + hemangiomas). Clinical manifestations of the disease included an abdominal mass and progressive anemia. She underwent the removal of a Stage Ic juvenile granulosa cell tumor and subsequent adjuvant chemotherapy. On follow-up examination 4 years later, no recurrence of the ovarian tumor was noted. A review of the literature showed 10 previous cases of juvenile granulosa cell tumor associated with enchondromatosis, two associated with Maffucci's syndrome, and the rest with Ollier's disease (enchondromatosis). Ovarian juvenile granulosa cell tumor may occur not infrequently in female patients with enchondromatosis in the first or second decades, in contrast to the widely recognized sarcomatous changes of enchondromas that usually occur after the second decade. Data provided from these cases also emphasize the concept of a generalized mesodermal dysplasia.

Adolescent

Chemotherapy-induced anemia in patients with primary lung cancer.

To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05).

Adult