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Biomedical subjects

M Shima

Publications and source records attributed to M Shima.

At least 127 records · Page 7Linked to original sources

Molecular genetic analysis of the ABO blood group system: 2. cis-AB alleles.

We have determined the nucleotide sequence of the coding region in the last two coding exons of ABO genes from two cis-AB individuals (genotype cis-AB/O) with no consanguinity. In this region, cis-AB alleles from these 2 individuals were identical to one another while different from the A1 allele by two nucleotide substitutions. Both of these nucleotide substitutions result in amino acid substitutions. The first substitution is identical to the one previously found in the A2 allele. The other substitution is found at the fourth position of the four amino acid substitutions which discriminate A1 and B transferases.

ABO Blood-Group System↗

[Investigation of subjective symptoms among visual display terminal users and their affecting factors--analysis using log-linear models].

In order to evaluate factors affecting visual and musculoskeletal symptoms by visual display terminal (VDT) operation, a questionnaire survey was conducted among clerical workers in Chiba university. The results were as follows: 1) Of these workers, 81.9% engaged in VDT operation. For most of the subjective symptoms, the prevalence rates tended to increase with the degree of VDT use. 2) These complaints were combined to give visual and musculoskeletal symptom scores. Both of the scores were higher among females than males, and the musculoskeletal symptom score was significantly higher. No difference was found in regard to age. 3) Analysis using log-linear models was performed to evaluate the effects of sex and age. The results showed that the visual and musculoskeletal symptom scores were significantly higher among the workers operating VDTs for one or more hours per day than among those who did not operate them at all. Analysis of the effects of VDT workloads revealed that VDT use for five or more days per week significantly increased the prevalence rates of both symptoms. Their use for less than four days per week affected neither of the symptoms. With regard to operating time per day or length of VDT use, no differences were found. 4) This investigation suggested that the VDT workloads were not so heavy and that the effects on each symptom were minor among the subjects of the present survey. However, it is important that consideration be given to ensure that the workloads for workers who operate VDTs every day not be too heavy.

Adult↗

[Quantitative analysis of right ventricular overloading by 201Tl myocardial SPECT].

Clinical usefulness of quantitative analysis of right ventricular overloading was evaluated by 201Tl myocardial SPECT in comparison with cardiac catheterization and MRI. Seventy-four MBq of 201TlCl was intravenous injected and 201Tl myocardial SPECT was performed on 40 patients (mean age: 61.0 +/- 11.8) with right ventricular overloading. Regions of interest (ROI) were selected on right and left ventricular walls in a midventricular short axis image of SPECT and uptake of each ROI were counted. The right ventricle (RV)/left ventricle (LV) 201Tl uptake ratio (R/L-Tl) was calculated. Wall thickness of RV and LV were measured on MRI and the RV/LV wall thickness ratio (R/L-WT) was calculated. RV and LV pressure were recorded in cardiac catheterization, and the RV/LV systolic pressure ratio (R/L-P) was calculated. There was significant positive correlation (Y = 0.73X + 0.19, r = 0.71, p < 0.001) between R/L-Tl and R/L-WT. R/L-Tl was positively correlated with R/L-P in patients with pressure overload (Y = 1.14X - 0.049, r = 0.85, p < 0.001) and in patients with volume overload (Y = 0.51X + 0.023, r = 0.88, p < 0.001) and the slope of the regression line in patients with pressure overload was significantly steeper than that in patients with volume overload (p < 0.001). In conclusion, quantitative analysis of right ventricular overload by 201Tl myocardial SPECT is useful to estimate RV/LV wall thickness ratio and pressure ratio.

Adult↗

Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product.

BACKGROUND: Expression of nucleoside diphosphate (NDP) kinase, which is highly homologous to the nm23 gene product in a variety of species, has been found to be inversely associated with metastatic potential in human breast cancer. PURPOSE: The present study was conducted to clarify the association of NDP kinase expression with metastatic potential in human hepatocellular carcinoma. METHODS: The immunohistochemical expression of NDP kinase was analyzed in 30 patients with histopathologically proven hepatocellular carcinoma. These patients included nine with distant metastases and 21 without distant metastases. Tissue specimens were reacted with rabbit anti-rat NDP kinase antibody and stained by the biotin-streptavidin complex method. The relative staining intensities were evaluated by comparing primary tumor sites with adjacent nontumorous liver tissue or with metastatic sites, RESULTS: The expression of NDP kinase in primary sites in patients with distant metastases was significantly less intense than that in patients without distant metastases (P = .018). NDP kinase was expressed significantly less intensely in metastatic sites than in primary sites (P = .005). The intensity of NDP kinase expression did not statistically correlate with tumor size or number of lesions in the liver, histopathological classification of tumor, associated liver diseases, hepatitis virus markers, or tumor markers. CONCLUSION: These results suggest that the reduced expression of NDP kinase is closely associated with distant metastatic potential in hepatocellular carcinoma. IMPLICATIONS: It is possible that both NDP kinase and the nm23 gene product may be active in the progression and differentiation of tumor cells and that their reduced expression induces a high metastatic potential in tumor cells. Studies using Northern blotting or in situ hybridization should be planned to confirm our findings.

Adult↗

Enhanced DNA synthesis in rat hepatoma cells by conditioned media from Kupffer cells incubated with supernatants of tumor necrosis factor-alpha-pretreated hepatocytes.

The effects of tumor necrosis factor-alpha (TNF-alpha) on DNA synthesis in AH66 rat hepatoma cells and rat hepatocytes were analysed by means of [3H]thymidine incorporation. DNA synthesis in AH66 cells was suppressed when AH66 cells were directly incubated with TNF-alpha. When primary culture of rat Kupffer cells was incubated with hepatocyte conditioned media pretreated with TNF-alpha (0-200 U/ml), and AH66 cells were then treated with these hepatocyte/Kupffer cell-conditioned media, TNF-alpha used in the pretreatment caused a dose-dependent increase in DNA synthesis in AH66 cells with a maximum effect amounting to a more than 10-fold increase. In contrast, DNA synthesis in primary culture of rat hepatocytes was not stimulated by the TNF-alpha-pretreated hepatocyte/Kupffer cell conditioned media. These results suggest that TNF-alpha-mediated hepatocyte-Kupffer cell interaction selectively promotes proliferation of rat hepatoma cells.

Animals↗

Interaction of interferon-alpha with interleukin-1 beta or tumor necrosis factor-alpha on hepatitis B virus enhancer activity.

The interaction of IFN-alpha with IL-1 beta or TNF-alpha on hepatitis B surface antigen (HBsAg) expression was analysed in hepatitis B virus (HBV)-DNA integrated PLC/PRF/5 and non-integrated HuH-7 human hepatoma cells. Secretion of HBsAg in PLC/PRF/5 cells was reduced by IFN-alpha, IL-1 beta or TNF-alpha, and synergistically depressed when IFN-alpha was used in combination with IL-1 beta or TNF-alpha. By Northern blot analysis, the levels of HBsAg mRNA were suppressed by IFN-alpha in combination with IL-1 beta or TNF-alpha. In the chloramphenicol acetyltransferase plasmid transfection assay, IFN-alpha in combination with IL-1 beta or TNF-alpha caused a much greater suppression of HBV enhancer activity than IFN-alpha, IL-1 beta or TNF-alpha alone in both hepatoma cells. These findings suggest that the interaction of IFN-alpha with IL-1 beta or TNF-alpha synergistically represses HBV enhancer activity, resulting in depressed expression of HBsAg.

Carcinoma, Hepatocellular↗

Inhibitory effect of prostaglandin delta 12-PGJ2 on cell proliferation and alpha-fetoprotein expression in HuH-7 human hepatoma cells.

9-deoxy-delta 9,delta 12-13,14-dihydro-prostaglandin D2 (delta 12-PGJ2) is a potent inhibitor of proliferation of tumor cells. In the present study, the effect of delta 12-PGJ2 on the alpha-fetoprotein(AFP) and the albumin gene expression was analyzed in HuH-7 human hepatoma cells. delta 12-PGJ2 inhibited the cell growth and reduced the medium AFP concentrations dose-dependently. To determine whether this decline of AFP depends only on the relative decrease in cell numbers by delta 12-PGJ2, or is in part, due to the decrease in the cellular AFP synthesis by delta 12-PGJ2, Northern blot analysis was performed in this study. By Northern blotting, it was shown that delta 12-PGJ2 caused a marked reduction in the levels of the AFP mRNA and the albumin mRNA. In contrast, the level of the beta-actin mRNA was not changed by delta 12-PGJ2. In the transient chloramphnicol acetyltransferase plasmid transfection experiments, delta 12-PGJ2 did not suppress the AFP enhancer activity, which possibly regulates both the AFP and the albumin gene expression in HuH-7 hepatoma cells, but resulted in the selective repression of the AFP and the albumin promoter activity. These results suggest that delta 12-PGJ2 suppresses not only cell growth but also expression of the AFP gene and the albumin gene at the transcriptional level in human hepatoma cells.

Albumins↗

Echocardiographic determination of stroke volume during rapid atrial pacing and volume loading in normal rats.

OBJECTIVE: The aim was to validate echocardiographic assessment of acute changes of left ventricular stroke volume in normal rats. METHODS: By transthoracic use of a 7.5 MHz ultrasonic transducer, the left ventricular dimensions were determined before and during rapid atrial pacing and saline infusion in seven Wistar rats weighing 310-470 g. Left ventricular volume was calculated from short axis dimensions according to a cube function formula. Echo stroke volume (SVE) was then compared with that obtained simultaneously using a pulsed Doppler flow meter placed around the ascending aorta (SVF). RESULTS: The SVE (ml) was decreased from 0.30(SD 0.12) to 0.13(0.06) by rapid pacing and increased from 0.27(0.12) to 0.63(0.16) by volume loading. Regression analysis showed high correlations between SVE and SVF during both pacing (r = 0.84) and infusion (r = 0.91) studies. Furthermore, correlations between SVE and SVF in individual animals were very close (r = 0.87-0.99 in the pacing study and 0.92-0.99 in the volume study). Interobserver and intraobserver variances were small, with close correlations (r = 0.96-0.99) and modest standard errors of the estimate (0.02-0.04 ml) between the two measurements. CONCLUSIONS: Echocardiography allows reliable in vivo measurement of cavity dimensions and assessment of acute alterations in stroke volume in normal rats.

Animals↗

A monoclonal antibody (NMC-VIII/10) to factor VIII light chain recognizing Glu1675-Glu1684 inhibits factor VIII binding to endogenous von Willebrand factor in human umbilical vein endothelial cells.

The monoclonal antibody NMC-VIII/10 is a neutralizing antibody which recognizes the Glu1675-Glu1684 sequence of the factor VIII light chain and inhibits factor VIII (FVIII) binding to immobilized von Willebrand factor (vWf). In this study we immunohistochemically determined, using human umbilical cord tissue, whether or not NMC-VIII/10 has an inhibitory effect on FVIII binding to endogenous vWF in endothelial cells. Tissue sections were reacted with purified FVIII followed by peroxidase-conjugated monoclonal antibody (C5) recognizing the 54 kD fragment of the FVIII heavy chain. The labelling pattern of bound FVIII was similar to that of endogenous vWF and appeared as a fine granular deposit in the endothelial cells. Addition of purified vWF completely inhibited the binding of FVIII to endothelial cells. Furthermore, FVIII did not bind to endothelium in the presence of 0.25 M CaCl2, and similarly, thrombin-treated FVIII did not bind to the vascular site. These findings suggested that FVIII was bound to endogenous vWF in the endothelial cells. The binding reaction was completely inhibited by NMC-VIII/10, confirming that the monoclonal antibody recognizes the specific epitope responsible for FVIII binding to endogenous vWF.

Antibodies, Monoclonal↗

Synergistic effect of 1,25-dihydroxyvitamin D3 and retinoic acid in inducing U937 cell differentiation.

We examined the effects of retinoic acid (RA), 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), and its synthetic analogue, 22-oxa-1,25-(OH)2D3, on differentiation of U937 cells by studying the cellular growth, surface marker expression and cytosolic free Ca2+ concentration ([Ca2+]i). RA inhibited cellular growth but did not induce expression of Mo2 (CD14), a monocyte/macrophage specific surface marker. To the contrary, 1,25-(OH)2D3 did not inhibit cellular growth, but increased CD 14-positive cells. Simultaneous addition of 1,25-(OH)2D3 and RA had no additive effect on cellular growth inhibition or CD14 expression. With regard to [Ca2+]i, however, 5 days' incubation with either of them increased the basal [Ca2+]i level and induced U937 cells to respond to formyl-methionyl-leucyl-phenylalanine (FMLP). When the cells were incubated with both 10(-6) M RA and 10(-8) M 1,25-(OH)2D3, basal [Ca2+]i was higher and FMLP caused a greater increase in [Ca2+]i than when only RA or 1,25-(OH)2D3 was added. These data suggest that RA and 1,25-(OH)2D3 induce monocytoid differentiation in U937 cells through different pathways and act synergistically in the differentiation process. The 22-oxa-1,25-(OH)2D3 induced CD14 expression, basal [Ca2+]i increase and [Ca2+]i response to FMLP, but did not cause cellular growth inhibition in U937 cells, and in these points, 22-oxa-1,25-(OH)2D3 exhibited no significantly different effects from 1,25-(OH)2D3. Thus, 22-oxa-1,25-(OH)2D3 has the same potent activity as 1,25-(OH)2D3 in inducing differentiation of U937 cells.

Antigens, CD↗

[Evaluation of hepatectomy in small hepatocellular carcinoma--comparison with transcatheter arterial embolization therapy].

Therapeutic effect on 81 hepatectomized patients with hepatocellular carcinoma (HCC) less than 5cm in diameter was compared to that achieved by transcatheter arterial embolization therapy (TAE) in 61. The 5-year cumulative survival rate after hepatectomy was 38%, which was better than that of TAE (8%). Outcome after hepatectomy was better than that after TAE, according to tumor size in less than 2cm in diameter and single nodule. The 3-, and 5-year survival rates for curative hepatectomy were significantly better than those for TAE. But there was no significant difference in survival curves between relative noncurative hepatectomy and TAE. In terms of hepatic reserve with reference to Child's classification, the survival curve for TAE was better than that for relative noncurative hepatectomy in patients with Child-A, but there was no significantly difference between these two methods. Survivors more than 3 years after hepatectomy and TAE were 24 (48.0%) and 11 (23.4%) patients, respectively. Nineteen of 24 patients with hepatectomy had recurrent HCCs, of which reresection was done in 6, TAE in 11 and other treatments in 2. The advantage of hepatectomy in comparison with TAE is a possibility of long-term survival, if curative hepatectomy is performed.

Adolescent↗

[A study of mortality among male physicians in Chiba prefecture].

In order to assess mortality patterns of Japanese physicians, the mortality during a 12 year period (July 1978-June 1990) among male members of the Chiba Medical Association was studied. The overall mortality among physicians was significantly lower than the general male population in Chiba prefecture (standardized mortality ratio [SMR] = 0.69). Physicians were found to have lower cause-specific mortality from cancer (SMR = 0.71), cerebrovascular disease (SMR = 0.42), pneumonia and bronchitis (SMR = 0.63), accidents (SMR = 0.37), and suicide (SMR = 0.29) than the general population, but to have higher mortality from senility (SMR = 1.75). When compared to the total working population and the professional and technical workers, all-cause mortality for physicians did not differ. Mortality from ischemic heart disease was significantly higher during 1979-1983, but was similar during 1984-1988. Analysis by specialty showed that during 1979-1983 internal medicine physicians had a lower mortality than surgeons, but this reversed during 1984-1988 with the former having a higher mortality than the latter. Over the whole period, no difference in mortality existed between internists and surgeons. A cohort of 2,502 male members that is being followed, showed that the mortality of physicians was lower than the general population. However, no significant difference between the internists and surgeons was observed in both overall and major cause-specific mortality.

Humans↗

Evaluation of nontumorous tissue damage by transcatheter arterial embolization for hepatocellular carcinoma.

The serial changes in serum hepatic enzyme activities by transcatheter arterial embolization (TAE) were analyzed in 17 patients with hepatocellular carcinoma to estimate the contribution to the value by the damage of tumor or nontumorous hepatic cells. The serum levels of relatively tumor-specific fructose 1,6-diphosphate (FDP) aldolase were elevated after TAE in the cases of both superselective and nonsuperselective TAE that were performed from the segmental and the nonsegmental hepatic artery, respectively, but we found the marked elevation of FDP aldolase in the cases of the superselective TAE. In contrast, the non-tumor-specific fructose 1-phosphate (F1P) aldolase was markedly elevated only in the cases of nonsuperselective TAE. The total amount of FDP aldolase released by TAE correlated significantly with the integrated tumor tissue volume (P less than 0.005), whereas the total amount of F1P aldolase output correlated significantly with the integrated nontumorous tissue volume (P less than 0.005) as defined by lipiodol accumulation on computerized tomography scan. The consequent changes in the total nontumorous liver volumes after TAE were also analyzed by the follow-up computerized tomography scan. The nonsuperselective TAE caused the significant total nontumorous liver atrophy when compared with the superselective TAE. The progression of the total nontumorous liver atrophy correlated significantly with F1P aldolase output by TAE (P less than 0.001) but not with FDP aldolase output. These results suggest that the outputs of FDP and F1P aldolase are useful to estimate the degree of the tumorous and nontumorous tissue damage by TAE, respectively, and F1P aldolase output can be used to predict the progression of liver atrophy caused by TAE.

Adult↗

Transforming growth factor beta 1 differentially regulates alpha-fetoprotein and albumin in HuH-7 human hepatoma cells.

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit hepatocyte growth in vitro and in vivo. In this study, we analyzed the effect of TGF-beta 1 on alpha-fetoprotein (AFP) and albumin gene expression in HuH-7 human hepatoma cells. TGF-beta 1 inhibited cell growth in a dose dependent manner. The cellular secretion rate of AFP but not albumin was suppressed significantly by TGF-beta 1. TGF-beta 1 caused a significant reduction in the level of AFP mRNA. In contrast, the levels of albumin mRNA or beta-actin mRNA were not changed by TGF-beta 1. In transient transfection experiments, TGF-beta 1 resulted in selective repression of AFP promoter activity. These results suggest that TGF-beta 1 is one of the key factors involved in the differential regulation of the AFP gene and the albumin gene.

Carcinoma, Hepatocellular↗

[An adult case of virus-associated hemophagocytic syndrome (VHAS) and a review of this syndrome in adults in Japan].

An adult case of Virus-associated hemophagocytic syndrome (VAHS) was reported and a review of this syndrome in adults in Japan was also made. A 79 year-old woman was referred to our hospital for detailed examination for sustained generalized fatigue lasting for about two weeks. Other clinical manifestations of this patient included fever, generalized lymphadenopathy, hepatosplenomegaly, anemia and mild liver dysfunction. The biopsy of the lymph node revealed hyperplasia of histiocyte with hemophagocytosis. There was also an elevation of IgG antibody against EB virus and the patient was therefore diagnosed to have VAHS. The prednisolone therapy was then initiated and the patient responded to this treatment very well. By the review of the Japanese literatures, seven adult cases of VAHS were found. Based on the descriptions on these cases, the prognosis of this syndrome appeared to be extremely poor which is totally different from VAHS in children. Our case showed a very favourable clinical course following steroid therapy and this suggested that steroid therapy should be considered even at the early stage of this syndrome in adults.

Aged↗

[Changes of procoagulant and fibrinolytic activities in the alveoli of rats exposed to ozone].

The purpose of this study was to evaluate the role of ozone, a reactive product of environmental photochemical oxidation, in the development of pulmonary fibrosis. Male Wistar rats were exposed continuously to 0.5 ppm ozone for 1,4,7 and 14 days, and alveolar macrophages and lavage fluid obtained by bronchoalveolar lavage were examined. The results were as follows: 1) The total protein content in the lavage fluid was significantly increased compared to the control at 1 to 7 days by ozone exposure. Both alveolar macrophage and neutrophil counts increased in response to ozone exposure. However, approximately 90% of the free cells recovered were alveolar macrophages throughout the exposure period. 2) The plasminogen activator (PA) activity released from alveolar macrophages did not change in the group exposed for 1 day. But the activities were significantly high in the groups exposed for 4 to 14 days. 3) The PA activity of the lavage fluid showed a marked increase on the 1st day of ozone exposure, and subsequently decreased rapidly. However, the significantly increased activity was maintained throughout the exposure period. 4) In contrast, the procoagulant (PC) activity was unchanged on the 1st day of ozone exposure but the activity increased significantly on the 4th day, and was maintained at a high level until the 14th day. 5) The elastase inhibitory capacity (EIC) of the lavage fluid was significantly increased compared to the control by ozone exposure, but this difference was not seen throughout the exposure period when the EIC was corrected for the total protein content in the lavage fluid. These results revealed that both PA and PC activities increased in the alveolar fluid of rats exposed to 0.5 ppm ozone. The transition in the respective activities suggested that the fibrinolytic pathway in the alveoli was enhanced early in the exposure to ozone, while the coagulation pathway was enhanced later. This imbalance in coagulation homeostasis may be important in the regulation of fibrotic responses in the lungs of rats exposed to ozone. These findings are in agreement with morphological reports indicating that ozone exposure initially damaged the alveoli and later caused pulmonary fibrosis.

Animals↗

Visualization of the heart and determination of left ventricular mass in rats by echocardiography.

A high-frequency transducer was used to determine the optimal parameters for visualizing the heart in 40 normal Wistar, 15 SHR, and 10 aorta-banded rats. The rats were 5 to 30 weeks old and weighed between 105 and 705 grams. Two-dimensional and M-mode views of the ventricles, atria, valves, and great arteries were obtained by placing the transducer beneath the rats through the left or right parasternal window in either the prone or the right decubitus positions, respectively. Left ventricular (LV) mass was determined on the basis of a spheroid model; these values correlated well with the LV weight for both the Wistar rats (r = 0.94, p less than 0.001) and the rats with cardiac hypertrophy due to pressure load (r = 0.87, p less than 0.001). These results were highly reproducible. This indicates that echocardiography is useful for obtaining quantitative measurements in rats.

Animals↗

Epitope localization of monoclonal antibodies against factor VIII light chain which inhibit complex formation by factor VIII with von Willebrand factor.

We obtained three clones of monoclonal antibodies against factor VIII by immunization with purified human factor VIII. The anti-factor VIII procoagulant activity of these antibodies ranged from 2 to 53 Bethesda units/mg of IgG. According to an immunoblotting study, all antibodies reacted with the 80 kDa light chain but not with 72 kDa peptides derived from thrombin digestion of factor VIII. We attempted to localize the antigenic epitopes of these antibodies by a competitive blocking assay using synthetic peptides and recombinant fragments of the amino-terminal region of factor VIII light chain. In the former assay, a 50 microM peptide containing the fifteen amino acid residues from the Val1670-Glu1684 completely inhibited the binding of the three monoclonal antibodies to immobilized factor VIII. In the latter experiment, 13 reactive recombinant peptides were obtained. Sequences of these peptides revealed fourteen overlapped amino acid residues from Glu1675 to Pro1688. All three antibodies at a final concentration of around 10 micrograms/ml completely inhibited the binding of 125I-labelled factor VIII to immobilized von Willebrand factor (vWF). We conclude that ten amino acid residues, 1675EDFDIYDEDE1684 in the factor VIII light chain are important for complex formation with vWF.

Antibodies, Monoclonal↗