Biomedical subjects
Publications and source records attributed to T Yasuda.
A case of Ewing's sarcoma with intracranial metastasis is reported with special reference to positron emission tomography (PET) evaluation of cerebral hemocirculation and metabolism after brain irradiation.
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We used a fluorescence differential display-PCR (FDD-PCR) technique to analyze the genes expressed in mouse brains collected at nine different developmental stages ranging from 3 days to 15 months after birth, and 5 age-dependently expressed genes were found. Age-dependent expression of each of these 5 genes was confirmed by quantitative real-time PCR analysis. Of the 5 genes, 4 (B1-B4) had high homology with the nucleotide sequences of cDNA clones of known mouse genes (myelin proteolipid protein, transferrin, embryo cDNA from the RIKEN full-length enriched library, and protein tyrosine phosphatase), and the rest (B5) with expressed sequence tags of an unknown gene. Sequencing analysis of the full-length cDNA constructed based on the B5 sequence demonstrated that the gene product of B5 was identical to G-substrate, a specific substrate for cGMP-dependent protein kinase. The expression patterns of known genes obtained in our study may provide a further opportunity to investigate the biological and physiological roles of the proteins they encode.
BACKGROUND: Although antimyosin scintigraphy detects myocyte necrosis associated with myocarditis, it has also been reported to yield positive results in a large number of patients with clinical dilated cardiomyopathy without histologic evidence of myocarditis. The question to be resolved is whether this discordance represents false-positive results of antimyosin scans or whether antimyosin scintigraphy more accurately identifies the presence of myocyte necrosis than does endomyocardial biopsy testing. METHODS AND RESULTS: Forty patients with the acute onset of dilated cardiomyopathy (left ventricular ejection fraction < 45%; mean 27% +/- 11%) but no endomyocardial biopsy evidence of myocarditis, were identified from a consecutive series of 50 patients who had undergone indium 111 antimyosin antibody scintigraphy and endomyocardial biopsy for suspected myocarditis. The endomyocardial biopsy specimens were analyzed to identify features correlating with antimyosin uptake or improvement in left ventricular ejection fraction (LVEF) over time. Twenty-five patients showed left ventricular myocardial uptake of radiolabeled antimyosin antibody by both planar and tomographic imaging. The remaining 15 patients had no antimyosin uptake. Of the 25, 22 (88%) patients with positive findings on antimyosin scans had degenerated, myofibrillarlytic myocytes in their biopsy specimens. Of the 15 patients with negative findings on antimyosin scans, only 6 (40%) had similar myofibrillarlytic myocytes (chi 2 = 8.13; p < 0.0047). No other histological feature correlated with the antimyosin positivity. Stepwise multiple regression analysis was performed for identification of predictors of short-term improvement in LVEF. Patients with positive findings on antimyosin scans showed a trend toward improvement with time (F = 3.97; p > 0.05). None of the histologic features predicted improvement in the LVEF. However, the combination of positive findings on an antimyosin scan and myofibrillarlysis did correlate significantly with spontaneous improvement in ejection fraction (F = 4.53; 0.01; < p < 0.05). CONCLUSIONS: This study identifies myofibrillarlysis as a common pathologic alteration in patients with recent onset of dilated cardiomyopathy and positive findings on antimyosin scan, who lack right ventricular biopsy evidence of myocarditis. Because myofibrillarlytic cell population may represent a histologic spectrum of viable to necrotic myocytes, it appears that antimyosin uptake detects necrotic myofibrillarlytic myocytes that are not identified by light microscopy.
BACKGROUND: Radiolabeled antibody specific for cardiac myosin administered intravenously has been used to define noninvasively regions of myocardial necrosis. Inflammatory heart disorders such as myocarditis and heart transplant rejection demonstrate diffuse and often faint myocardial uptake of antimyosin antibody. This study was undertaken to evaluate the reproducibility and diagnostic accuracy of antimyosin antibody imaging for the detection of patients with suspected myocarditis. METHODS AND RESULTS: Fifty antimyosin scans, performed consecutively in patients with suspected myocarditis, were evaluated by one independent observer and two panels of observers. Antimyosin scan interpretations were compared with endomyocardial biopsy results and also with serial changes in left ventricular function. An independent observer (A) and a panel of five observers (A through E) interpreted the antimyosin scans as positive or negative on the basis of both planar images and tomographic reconstructions. Three of the five observers (A through C) again interpreted the scans but based interpretation only on planar images. Blinded random sequence evaluation of antimyosin scans based on the planar and tomographic interpretations revealed moderate agreement between the independent observer (A) and the group of observers (A through E) (kappa = 0.58). There was also moderate agreement between interpretations based on planar images alone and interpretations based on both planar and tomographic images (kappa [A through E]/[A through C] = 0.57; kappa [A through C]/A = 0.48). Comparison of antimyosin scan results with histologic evidence of myocarditis in endomyocardial biopsy specimens demonstrated that all scan results obtained from the individual or the panels of observers had a very high sensitivity (91% to 100%) and a high negative predictive value (93% to 100%). The specificity (31% to 44%) and positive predictive value (28% to 33%) were less impressive. We also compared the scan and biopsy results with the composite clinical standard of significant left ventricular functional improvement. Endomyocardial biopsy demonstrated poor sensitivity (35%) compared with antimyosin scans (82% to 94%) but had superior specificity (endomyocardial biopsy, 79%; antimyosin scan, 25% to 42%). The specificity of interpretations based on planar and tomographic interpretations (38% to 42%) was better than the planar images alone (25%). If reversible left ventricular dysfunction is considered clinical evidence of myocarditis, this study suggests that a negative endomyocardial biopsy significantly misses the presence of the disease. On the other hand, a negative antimyosin scan almost invariably excludes myocarditis. CONCLUSIONS: This study demonstrates a high degree of interobserver reproducibility of antimyosin interpretation. Comparison of the scintigraphic results with histologic and clinical standards indicates a high sensitivity of antimyosin scans for the detection of myocarditis. The antimyosin scan is also not likely to miss clinically or pathologically diagnosed myocarditis, in contrast to the endomyocardial biopsy, which missed clinically validated myocarditis 65% of time. The combination of high sensitivity and negative predictive value suggests that antimyosin scintigraphy may be an effective screening procedure for obviating biopsies in patients with suspected myocarditis.
BACKGROUND: Age characteristics of patients undergoing various types of stress tests are important because of differences in clinical background and exercise performance between the young and elderly. Adverse effects of pharmacologic agents are known to be more common in the elderly, who are less able to perform vigorous exercise stress testing. We investigated the clinical background, performance characteristics, and complication rate of various stress tests in younger (<75 years old) and elderly (>75 years old) patient populations. METHODS: A total of 3412 patients (2796 younger, 616 elderly) underwent 5 types of stress tests with (1) technetium-99m sestamibi (MIBI) single photon emission computed tomography: symptom-limited exercise (Ex, 1598 younger, 173 elderly), (2) dipyridamole infusion (0.14 mg/kg/min, 4 minutes) without exercise (D, 260 younger, 114 elderly), (3) with exercise (DEx, 339 younger, 112 elderly), (4) adenosine infusion (0.14 mg/kg/min, 5 minutes) without exercise (A, 253 younger, 101 elderly), and (5) with exercise (AEx, 346 younger, 116 elderly). RESULTS: Sixty-seven percent of patients in the younger population were able to achieve 85% of the maximum predicted heart rate, whereas 54% of the elderly reached this level of exercise. No patient had life-threatening complications. In both the younger and elderly groups, chest discomfort, feelings of impending syncope, flushing, and fall in blood pressure occurred less frequently in DEx than D and in AEx than A. Sinus bradycardia occurred less frequently in AEx than A in the younger (1.2% vs 4.3%, P < .05) and elderly groups (0.9% vs 6.9%, P < .05). Atrioventricular block was less frequent in AEx than A in the younger group (3.2% vs 7.9%, P < .05) but not so in the elderly group (13.0% vs 17.8%, not significant). The frequency of ischemic electrocardiographic changes in DEx and AEx was very similar to that of Ex in both the younger and elderly groups, although ischemic electrocardiographic changes in D and A are known to be less frequent. CONCLUSION: Of the elderly group who were judged to be fit to exercise to 85% of maximum predicted heart rate, nearly half failed to reach this level. In contrast, the younger patients were able to achieve this level in 67% of tests. Supplementation with modest exercise reduced most of the pharmacologically related adverse effects. The elderly group was not protected from atrioventricular block as effectively as the younger group by additional exercise in the adenosine stress test. Ischemic electrocardiographic changes in the pharmacologic stress test were as frequent as in the exercise stress test when modest supplementary exercise was added to the pharmacologic protocol. There were no deaths, myocardial infarction, or other major complications. These observations suggest that exercise and pharmacologic stress tests are safe in the elderly, including those patients more than 75 years old.
The distribution of deoxyribonuclease I (DNase I) in human and rat stomachs was examined by biochemical, molecular biological and immunohistochemical techniques. By the use of monoclonal anti-human DNase I and polyclonal anti-rat DNase I antibodies, we determined that strong immunoreactivity was present in the cytoplasm of chief cells of the human fundus and the rat pars glandularis, respectively. High DNase I enzyme activity was detected in tissue homogenates of both human fundus and rat pars glandularis. The presence of DNase I-specific mRNA was verified by reverse transcriptase-polymerase chain reaction analysis of the total RNAs extracted from human and rat stomachs. Immunoelectron microscopy revealed gold particles localized in the chief cells, with most labelling in exocrine secretory granules. These results show that the chief cells of human and rat stomach produce DNase I. This is the first report to demonstrate that secretion of DNase I is controlled by the chief cells in human and rat stomachs.
BACKGROUND: Some of the major blood group antigens are on lipids and proteins of the red cell membrane. Incubation of intact red cells with liposomes containing specially designed artificial lipids has been shown to result in the extraction of membrane proteins by the liposomes. The extraction of blood group structures and the retention of their antigenicity have not been reported. STUDY DESIGN AND METHODS: After the incubation of red cells with liposomes, the extraction of the antigens from human red cells by liposomes was examined by evaluation of the agglutination of the liposomes by respective antisera. RESULTS: Agglutination specific to the A and B blood group antigens was seen, which indicated that the antigenicity of the blood group antigens was retained even after the extraction by the liposomes. The presence of an artificial boundary lipid, 1,2-dimyristamido-1,2-deoxyphosphatidylcholine, in the liposome was crucial to the efficient extraction of the A and B antigens. On the other hand, the extraction of D, M, N, and P1 was not always detectable by agglutination. CONCLUSION: The A and B blood group antigens were directly extracted from red cells by liposomes without loss of antigenicity.
In our previous study, in vitro hemolysis tests showed that collision flow against wall roughness had an effect on hemolysis when the flow velocity was more than 3 m/s and surface roughness was more than Ra = 1.54 microm. However, the specific portion of the flow on the wall that induced hemolysis was not clarified. Therefore, the purpose of this study was to present the relationship between flow behavior and hemolysis by means of in vitro tests and computational fluid dynamics (CFD) analysis. We investigated the relationship between the location of surface roughness and hemolysis. In CFD, we investigated the flow behavior on the wall. The highest rate of hemolysis was observed in a region around the center of the surface roughness on the bottom plate. On CFD analyses, the flow behavior included the highest wall shear stress (304 Pa) and the highest flow acceleration (2.8 m/s2) around the center of the bottom plate. Therefore, it is concluded that the causes of hemolysis during collision flow depend upon wall shear stress and flow acceleration.
The purpose of this study was to investigate the effect of multiple mechanical forces in hemolysis. Specific attention is focused on the effects of shear and pressure. An experimental apparatus consisting of a rotational viscometer, compression chamber, and heat exchanger was prepared to apply multiple mechanical forces to a blood sample. The rotational viscometer, in which bovine blood was subjected to shear rates of 0, 500, 1,000, and 1,500 s(-1), was set in the compression chamber and pressurized with an air compressor at 0, 200, 400, and 600 mm Hg. The blood temperature was maintained at 21 degrees C and 28 degrees C. Free hemoglobin at 600 mm Hg was observed to be approximately four times higher than at 0 mm Hg for a shear rate of 1,500 s(-1) (p < 0.05). The results suggest that the increase in hemolysis is strongly related to pressure when high shear rates are applied to the erythrocytes. The data acquired in this study will be helpful in the development of artificial organs, where it will facilitate the prediction of hemolysis in flow dynamics analysis, flow visualization, and computational fluid dynamics.
The aim of this study was to develop a new cellular restoration model using primary cultured rabbit gastric mucosal cells, and to evaluate the role of cytoskeleton and calmodulin in this process. Confluent monolayer mucosal cell sheets consisting mainly of mucous cells were wounded, and a rotating silicon tip was used to make cell-free areas of constant size. The process of restoration was monitored, and the cell-free area was measured and analysed quantitatively. Artificial wounds recovered in 36 h in controls; however, mucosal cell repair was inhibited by treatment with the actin inhibitor, cytochalasin B, and the calmodulin inhibitor, W-7. In the process of restoration, bromodeoxyuridine (BrdU)-positive cells appeared around the wound 24 h after injury and then disappeared after the complete repair. Because BrdU-positive cells were never detected within 24 h after wounding, initial recovery of the wound occurred only by cell migration. Both the migration and the proliferation stage are seen with this model. This culture model is suitable for the analysis of gastric mucosal restoration. Present data are consistent with the hypothesis that the integrity of the cytoskeletal system is important for restoration after damage of the gastric mucosa.
We studied the relationship between serum calcium and urinary calcium excretion in association with the parathyroid function in 28 neonates at birth and at five days of age. At birth, the urine calcium was low in spite of high cord serum calcium and a low parathyroid hormone level. On the fifth day of birth, urinary calcium excretion increased despite the reduction in serum calcium and an increase in the parathyroid hormone. These results suggest that the large increase in renal blood flow and the consequent increase in calcium load on the immature renal tubule occurring after birth may be the main cause for the change in this serum calcium-urinary calcium relationship. This finding can in part explain the temporary hypocalcemia during this period.
An example of red cells having no reaction with any Rh antisera was found in a Japanese woman. Results of a serological investigation of the family indicated the action of a 'regulator' gene. Her serum contained an antibody which agglutinated all cells of common Rh types, except for Rhnull, by the saline, anti-globulin and papain techniques.
Angiotensin II (Ang II) may play a significant role mediating intraglomerular hypertension and glomerular sclerosis. Therefore, we investigated whether a model of pressure-induced stress, mechanical stretch/relaxation, affected the renin-angiotensin system (RAS) in cultured rat mesangial cells. Type 1 Ang II receptor (AT1R) expression was assessed by 125I-Ang II binding and quantitative reverse-transcription polymerase chain reaction. Stretch/relaxation increased steady-state AT1R mRNA levels as well as specific [125I]Ang II binding. Increased AT1R expression was associated with altered AT1R signaling. Ang II (100 nM) increased total phosphoinositide hydrolysis in control cells (186 +/- 25%, n = 6; p < 0.025 vs. no treatment). However, stretch/relaxation for 48 h further augmented AT1R-mediated PI hydrolysis (293 +/- 38%, n = 6; p < 0.025 vs. Ang II treatment alone). We examined other RAS components in mesangial cells subjected to stretch/relaxation. Angiotensinogen, determined by radioimmunoassay of Ang I generation in conditioned media, increased with stretch/relaxation, and reverse-transcription polymerase chain reaction demonstrated increased angiotensinogen gene expression in stretch/relaxation-treated cells. However, renin activity and angiotensin-converting-enzyme-like activity were unaffected by stretch/relaxation. Thus, mesangial cells maintain a local RAS similar to those described in other tissues, and AT1R expression and angiotensinogen production in this cellular RAS are increased by stretch/relaxation. It is likely that mesangial cells in vivo, exposed to variations in intraglomerular pressure, may regulate their responses via a local RAS.
Interleukin 1 alpha (IL-1alpha) production and invasiveness through mouse lung endothelial cells (MLE) were investigated in high-metastatic RCT+ and low-metastatic RCT- clones established from poorly differentiated murine sarcoma. Apparently, a higher level of IL-1alpha was derived from RCT+ cells than from RCT- cells. In an invasion assay, the number of cells which penetrated the MLE monolayer in RCT+ was significantly greater than that in RCT-. The invasiveness of RCT+ and RCT- cells was stimulated by additional recombinant mouse IL-1alpha (rIL-1alpha) in a dose-dependent manner. Anti-mouse IL-1alpha monoclonal antibody (anti-IL-1alpha mAb) significantly inhibited the invasiveness of RCT+ and RCT- cells through the MLE monolayer. However, in RCT+ cells these effects were higher than in RCT- cells. In an attachment assay, the ability of RCT+ cells to attach to the MLE monolayer was significantly higher than that of RCT- cells. The attachment ability of RCT+ and RCT- cells to the MLE monolayer was significantly increased by the pretreatment with rIL-1alpha in a dose-dependent manner. In a retraction assay, conditioned medium of RCT+ stimulated the retraction of the MLE monolayer more markedly in comparison with conditioned medium of RCT-. The retraction of the MLE monolayer was stimulated by additional rIL-1alpha in a dose-dependent manner. The increased retraction of the MLE monolayer was closely associated with the enhancement in tumor cell invasiveness. These findings suggest that IL-1alpha derived from RCT+ and RCT- cells might contribute to the enhancement of tumor cell invasion by stimulating the attachment to the MLE monolayer and retraction of the MLE monolayer.
The relationship between vascular endothelial growth factor (VEGF) and induction of angiogenesis in high-metastatic RCT(+) or low-metastatic RCT(-) clones of the poorly differentiated murine RCT sarcoma was investigated. The association with E-selectin in VEGF-induced angiogenesis was also evaluated. RCT(+) cells produced significantly larger amounts of VEGF than RCT(-) cells. In a tube formation assay with murine lung microvascular endothelial (MLE) cells, conditioned medium from RCT(+) cells showed a significantly greater effect on tube formation than that from RCT(-) cells. Induction of tube formation was suppressed by anti-mouse VEGF monoclonal antibody. Furthermore, anti-mouse E-selectin monoclonal antibody suppressed the tube formation induced by recombinant mouse VEGF. In a flow-cytometric analysis, the expression of E-selectin on MLE cells was upregulated after pretreatment with conditioned medium from RCT(+) and RCT(-) cells. Conditioned medium from RCT(+) cells induced a higher expression of E-selectin compared to medium from RCT(-) cells. Anti-VEGF monoclonal antibody prevented the upregulation of E-selectin by the RCT cell-conditioned medium. These findings suggest that E-selectin plays an important role in the angiogenesis induced by VEGF. VEGF derived from tumor cells may enhance angiogenesis by upregulating the expression of E-selectin on vascular endothelial cells.
A pediatric case of multifocal glioblastoma is reported with special reference to positron emission tomography (PET) evaluations in the diagnosis and therapy. A PET scan employing 15O and 18F positron tracers disclosed a right thalamic lesion high in regional cerebral blood flow, cerebral blood volume and metabolic glucose rate, suggesting a malignant tumor. In contrast, a left frontal lesion with low regional cerebral blood flow, cerebral blood volume and metabolic glucose rate was presumed to be rather hypodynamic and hypometabolic. Histological examination of these isolated masses showed both to be glioblastomas, and, as predicted by the PET findings, there were minor histological distinctions. In repeated PET scans following postoperative combined radiochemotherapy, metabolic glucose rate values at the thalamic tumor decreased to about 50% the levels before therapy, although there was no distinguishable change in tumor size on the concurrent computerized tomography scans. This therapeutic efficacy on tumor metabolism was highly consistent with the period of clinical relief.
The deoxyribonuclease I (DNase I) system was studied in 120 unrelated Japanese patients with liver disease, malignant neoplasms, alimentary-canal disease and inflammatory conditions with respect to the distribution of phenotypes and gene frequencies in serum samples. In patients with alimentary-canal disease a significant deficit of the DNase I phenotype 1-2 was demonstrated, which suggests that heterozygosity may confer protection against such disease. Furthermore, a significant association between the DNase I phenotype 2 and liver disease was found. The possible involvement of these phenotypes in the response to these diseases would appear to merit further study.