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Biomedical subjects

M Osada

Publications and source records attributed to M Osada.

At least 55 records · Page 3Linked to original sources

Comparative accuracy of automated computer analysis versus physicans in training in the interpretation of electrocardiograms.

We compared the interpretation of an electrocardiogram (ECG) made by computer with that made by physicians in training, as well as with the diagnosis made by cardiologists. ECGs were collected from 1058 Japanese adults (812 men and 246 women, mean age 49 +/- 19 years). With the computer program, the incidence of false-negative reports was 10.5% while that of false-positive reports was 16.5%, when compared with the physician's diagnosis. The incidence of a false-positive diagnosis with the computer was 18 times higher than that found by the physicians in training. The results show the advantages and the limitations in the use of computers for analysis of ECGs.

Adult↗

[Biological inter- and intra-individual variations of serum immunochemical constituents and their allowable limits of analytical error].

The biological inter- and intra-individual variations of serum immunochemical constituents were estimated by the analysis of variance. Twelve samples taken at weekly intervals were analyzed for 22 healthy individuals. As for immunoglobulin (Ig) G, IgA, IgM, IgE, C-reactive protein, anti-streptolysin O, alpha-fetoprotein, complement component 3 and 4, and ferritin, the intra-individual variations (with coefficient of variations (CVs) ranging from 4.8% to 51.7%) were smaller than the inter-individual variations (with CVs ranging from 14.6% to 107.6%). The values for carcinoembryonic antigen (with CVs of inter- and intra-individual variation being 31.6% and 39.6%, respectively) and beta 2-microglobulin (with CVs of inter- and intra-individual variation being 14.4% and 13.1%, respectively) were similar. The biological variations of serum immunochemical constituents, examined in this study, were larger than those of serum chemical constituents. Based on our data, we propose allowable limits of analytical error, which is less than one-half of the average intra-individual variation for evaluation of imprecision and is less than one-quarter of the inter- plus intra-individual variation for evaluation of inaccuracy.

Analysis of Variance↗

Downregulation of mRNA expression of Edg-3, a putative sphingosine 1-phosphate receptor coupled to Ca2+ signaling, during differentiation of HL-60 leukemia cells.

We measured the mRNA expression of the recently identified putative sphingosine 1-phosphate (S1P) receptors, i.e., Edg-1, AGR16/H218, and Edg-3, in HL-60 leukemia cells. Of these putative receptors, Edg-3 mRNA was abundantly expressed in undifferentiated HL-60 cells. Further, its mRNA expression was markedly downregulated by inducers of cell differentiation such as dibutyryl cAMP, retinoic acid, and 1alpha, 25-dihydroxyvitamin D3. The reduction of mRNA expression was associated with the attenuation of an S1P-induced increase in cytoplasmic free Ca2+ concentration. Thus, Edg-3, whose mRNA expression is downregulated during cell differentiation, may be responsible for the S1P-induced Ca2+ response in HL-60 leukemia cells.

3T3 Cells↗

The Ah receptor is not involved in 2,3,7,8-tetrachlorodibenzo- p-dioxin-mediated apoptosis in human leukemic T cell lines.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental pollutant causing public concern. Its toxic effects include disruption of the immune, endocrine, and reproductive systems, impairment of fetal development, carcinogenicity, and lethality in rodents. Here, we report that TCDD induces apoptosis in two cultured human leukemic lymphoblastic T cell lines. This cell death was found not to be dependent on an aryl hydrocarbon receptor and to be inhibited by the inhibitor of tyrosine kinases and caspases. Apoptosis-linked c-Jun N-terminal kinase is rapidly activated in these cells by the treatment with TCDD. A dominant-negative mutant of c-Jun N-terminal kinase prevented cell death in the treatment with TCDD. Furthermore, TCDD decreases the Bcl-2 protein level in these cell lines. These findings will help in the understanding of the molecular mechanism underlying TCDD-mediated immunotoxicity.

Apoptosis↗

Determination of antipituitary antibody in patients with endocrine disorders by enzyme-linked immunosorbent assay and Western blot analysis.

The identification of pituitary antigens recognized by human antipituitary antibodies (APAs) is important in evaluating the pathophysiology of multiendocrine disorders linked to autoimmune factors. However, there is no convenient method for the quantitative analysis of circulating APAs. This study reports the development of an enzyme-linked immunosorbent assay (ELISA) for the detection of APAs. APAs were measured by ELISA and confirmed by Western blot analysis in sera from patients with endocrine disorders. APAs were detected frequently in patients with autoimmune thyroiditis, insulin-dependent diabetes mellitus (IDDM), or pituitary dwarfism. Circulating APAs were detected in 18% of patients with autoimmune thyroiditis. Confirmation by Western blot revealed positivity for APAs in the serum of 36% of patients with Hashimoto disease and in 29% of patients with Graves disease. Notably, 39% of patients with IDDM were also positive for APAs by ELISA. The identification of APAs by ELISA may be useful in evaluating autoimmune mechanisms involved in patients with multiendocrine disorders.

Adult↗

Beneficial effect of ischemic preconditioning on Ca2+ paradox in the rat heart.

The effect of ischemic preconditioning (IP; 3 min ischemia plus 3 min reperfusion) on the recovery of cardiac function after Ca2+ depletion was investigated. Isolated rat hearts were subjected to different cycles of IP episodes followed by Ca2+ free perfusion and repletion. Perfusion of control hearts with Ca2+ free medium for 5 min followed by repletion of Ca2+ for 30 min resulted in a marked decrease in the left ventricular (LV) developed pressure and an increase in LV end-diastolic pressure (Ca2+ paradox). The depressed function due to Ca2+ paradox recovered with three cycles of IP. Myoglobin release during Ca2+ repletion also decreased significantly by three cycles of IP. The beneficial effects of IP were also evident when the hearts were subjected to a mild form of Ca2+ paradox involving 3 min Ca2+ depletion. The protective effect rendered by IP disappeared when 10 microM of 8-(p-sulfophenyl)-theophylline, adenosine antagonist was perfused for 10 min before IP. These results suggest that IP exerts beneficial effects on Ca2+ paradox which may be mediated by adenosine.

Animals↗

Cloning and functional analysis of human p51, which structurally and functionally resembles p53.

The p53 tumor suppressor gene, which is induced by DNA damage and/or stress stimuli, causes cells to undergo G1-arrest or apoptotic death; thus it plays an essential role in human carcinogenesis. We have searched for p53-related genes by using degenerate PCR, and have identified two cDNA fragments similar to but distinct from p53: one previously reported, p73, and the other new. We cloned two major splicing variants of the latter gene and named these p51A and p51B (a human homologue of rat Ket). The p51A gene encodes a 448-amino-acid protein with a molecular weight of 50.9 kDa; and p51B, a 641-amino-acid protein with a molecular weight of 71.9 kDa. In contrast with the ubiquitous expression of p53, expression of p51 mRNA was found in a limited number of tissues, including skeletal muscle, placenta, mammary gland, prostate, trachea, thymus, salivary gland, uterus, heart and lung. In p53-deficient cells, p51A induced growth-suppression and apoptosis, and upregulated p21waf-1 through p53 regulatory elements. Mutations in p51 were found in some human epidermal tumors.

Alternative Splicing↗

Modification of ischemia-reperfusion-induced changes in cardiac sarcoplasmic reticulum by preconditioning.

To examine the effects of ischemic preconditioning on ischemia-reperfusion-induced changes in the sarcoplasmic reticulum (SR) function, isolated rat hearts were either perfused with a control medium for 30 min or preconditioned with three episodes of 5-min ischemia and 5-min reperfusion before sustained ischemia for 30 min followed by reperfusion for 30 min was induced. Preconditioning itself depressed cardiac function (left ventricular developed pressure, peak rate of contraction, and peak rate of relaxation) and SR Ca2+-release and -uptake activities as well as protein content and Ca2+/calmodulin-dependent protein kinase (CaMK) phosphorylation of Ca2+-release channels by 25-60%. Global ischemia for 30 min produced marked depressions in SR Ca2+-release and -uptake activities as well as SR Ca2+-pump protein content in control hearts; these changes were significantly attenuated by preconditioning. Compared with the control preparations, preconditioning improved the recovery of cardiac function and SR Ca2+-release and -uptake activities as well as Ca2+-release channel and Ca2+-pump protein contents in the ischemic-reperfused hearts. Unlike the protein kinase A-mediated phosphorylation in SR membranes, the CaMK-mediated phosphorylations at Ca2+-release channels, Ca2+ pump, and phospholamban were depressed in the ischemic hearts; these changes were prevented by preconditioning. These results indicate that ischemic preconditioning may exert beneficial effects on ischemia-reperfusion-induced alterations in SR function by preventing changes in Ca2+-release channel and Ca2+-pump protein contents in the SR membrane.

Animals↗

Prolonged P300 latency in eating disorders.

This study investigated event-related potential (ERP) indices of information-processing in eating disorders. ERPs during an auditory two-tone discrimination task were recorded at midline at 3 sites in 28 anorexic patients, 12 low-weight bulimic patients (body mass index (BMI) under 17.5), 12 normal-weight bulimic patients (BMI over 17.5), and 40 control subjects. The P300 latency was significantly prolonged at all sites in both bulimic groups compared with that in controls, and at frontal and central electrode sites in anorexics. In contrast, the P300 amplitude did not differ between these groups at any site. The prolonged P300 latency in eating disorders suggests a task-related slowing of perceptual decisions that reflects their cognitive impairment.

Adolescent↗

Rhabdomyolysis after infection and taking a cold medicine in a patient who was susceptible to malignant hyperthermia.

A case of rhabdomyolysis after a possible viral infection and the use of a cold medication is reported. A 41-year-old man who presented with dysarthria, dysphagia, progressive weakness of his muscles and a high grade fever was admitted. He suffered from massive rhabdomyolysis, acute renal failure, and bronchopneumonia. Hemodialysis, antibiotics, and hydration therapy were effective in the treatment of his illness. Although the cause of the rhabdomyolysis was not completely clear, he was subsequently shown to be susceptible to malignant hyperthermia (MH) based on the results of a caffeine-halothane contracture test. When a mild recurrence occurred during a follow-up muscle biopsy, intravenous dantrolene sodium was administered and he improved immediately. This case suggests that MH should be considered in patients with rhabdomyolysis when the cause is unclear. The caffeine-halothane contracture test may also be helpful in the diagnosis.

Adult↗

Detection of left ventricular enlargement by electrocariography.

Cardiomegaly is one of the commonest findings encountered in daily clinical practice, and its differential diagnosis is a common clinical problem. There are many electrocardiological (ECG) criteria known for left ventricular hypertrophy (LVH), but its limitations have also been suggested. We evaluated 102 patients fulfilling the ECG criteria of precordial and limb lead for LVH with echocardiographic findings as a gold standard. Among these 102 patients, the echocardiogram revealed 38 subjects with LVH, 26 subjects with left ventricular dilatation (LVD), 7 subjects with both findings, and 31 subjects with neither findings. Precordial criteria such as SV1+RV5 or RV6 > 30 mm, SV1 or SV2+RV5 > 35 mm, R+S > 40 mm, SV1 or SV2+RV5 or RV6 > 35 mm, SV2+RV4 or RV5 > 35 mm, high in sensitivity and low in specificity for LVD and LVH, are appropriate for screening LVD and LVH. Cornell limb lead criterion, SV3+RaVL > 28 mm (male), SV3+RaVL > 20 mm (female), high in sensitivity and specificity only for LVH, is the best elecrocardiographic criterion to evaluate LVH. Precordial and limb lead criteria such as R> 13 mm, RaVL > 12 mm, RaVF > 20 mm, onset of intrinsicoid deflection in V5 or V6> 0.05 sec, left axis deviation -30 degrees to -90 degrees, low in sensitivity, and high in specificity, are useful to rule out LVH and/or LVD. Our findings suggest LVD and LVH can be evaluated by ECG, but similar sensitivity and specificity for both LVH and LVD makes separation of LVH from LVD unattainable.

Electrocardiography↗

["If only I had known it earlier"--the best time to bring a terminal cancer patient back home].

We gave 44 patients palliative care at home for a period of six years from June 1992 to May 1998. Judging from the satisfaction with medical staff caring for the peaceful passing of 37 cancer patients at home, we considered the factors that prevent patients from gaining access to QOL (Quality of Life) enrichment. In most cases, it is too late to switch from hospital care to home care for the sake of QOL enrichment. We believe it better that a home doctor or visiting nurse have access to such patients as early as possible. To make this possible, it is necessary for the patients, his or her family and the medical staff at the hospital to be aware of the realities and possibilities of palliative care at home. At the same time, it is imperative that the staff working in home medical care endeavor to enhance their readiness to accept the patients and to improve their medical standard.

Home Care Services, Hospital-Based↗

Identification and characterization of R-ras3: a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution.

Members of the Ras subfamily of GTP-binding proteins, including Ras (H-, K-, and N-), TC21, and R-ras have been shown to display transforming activity, and activating lesions have been detected in human tumors. We have identified an additional member of the Ras gene family which shows significant sequence similarity to the human TC21 gene. This novel human ras-related gene, R-ras3, encodes for a protein of 209 amino acids, and shows approximately 60-75% sequence identity in the N-terminal catalytic domain with members of the Ras subfamily of GTP-binding proteins. An activating mutation corresponding to the leucine 61 oncogenic lesion of the ras oncogenes when introduced into R-ras3, activates its transforming potential. R-ras3 weakly stimulates the mitogen-activated protein kinase (MAPK) activity, but this effect is greatly potentiated by the co-expression of c-raf-1. By the yeast two-hybrid system, R-ras3 interacts only weakly with known Ras effectors, such as Raf and RalGDS, but not with RglII. In addition, R-ras3 displays modest stimulatory effects on trans-activation from different nuclear response elements which bind transcription factors, such as SRF, ETS/TCF, Jun/Fos, and NF-kappaB/Rel. Interestingly, Northern blot analysis of total RNA isolated from various tissues revealed that the 3.8 kilobasepair (kb) transcript of R-ras3 is highly restricted to the brain and heart. The close evolutionary conservation between R-ras3 and Ras family members, in contrast to the significant differences in its biological activities and the pattern of tissue expression, raise the possibility that R-ras3 may control novel cellular functions previously not described for other GTP-binding proteins.

3T3 Cells↗

Oligomerization is not essential for growth suppression by p53 in p53-deficient osteosarcoma Saos-2 cells.

The carboxy-terminal portion of the p53 protein contains the tetramerization domain, and the introduction of multiple missense mutations in this domain disrupts the formation of p53 tetramers, resulting in the production of dimeric or monomeric forms of p53. It has recently been shown that a single missense or nonsense mutation in this domain affects the functional properties of p53 both in yeast and in mammalian cells. In this study, we tested the oligomerization of p53 with mutations in the oligomerization domain, when expressed in a human osteosarcoma cell line, Saos-2, in vivo. We found that single point mutations, including two missense and two nonsense mutations, in the alpha-helix of the oligomerization domain disrupted the oligomerization of p53, but that p53 still retained its ability to inhibit colony formation of cells to some degree. These results suggest that oligomerization and the carboxy-terminal basic domain are not prerequisite for p53-dependent tumor suppression, and this may explain why few of the tumor-derived p53 mutations that have been examined so far are carboxy-terminal mutations.

Biopolymers↗

Screening the p53 status of human cell lines using a yeast functional assay.

We have screened the p53 status of 156 human cell lines, including 142 tumor cell lines from 27 different tumor types and 14 cell lines from normal tissues by using functional analysis of separated alleles in yeast. This assay enables us to score wild-type p53 expression on the basis of the ability of expressed p53 to transactivate the reporter gene HIS3 via the p53-responsive GAL1 promotor in Saccharomyces cerevisiae. Of 142 tumor cell lines, at least 104 lines (73.2%) were found to express the mutated p53 gene: 94 lines (66.2%) were mutated in both alleles, three lines (2.1%) were heterozygous, and no p53 cDNA was amplified from seven lines (4.9%). Of the 14 cell lines originating from normal tissues, all the transformed or immortalized cell lines expressed mutant p53 only. Yeast cells expressing mutant p53 derived from 94 cell lines were analyzed for temperature-sensitive growth. p53 cDNA from eight cell lines showed p53-dependent temperature-sensitive growth, growing at 30 degrees C but not at 37 degrees C. Four temperature-sensitive p53 mutations were isolated: CAT-->CGT at codon 214 (H214R), TAC-->TGC at codon 234 (Y234C), GTG-->ATG at codon 272 (V272M), and GAG-->AAG (E285K). Functionally wild-type p53 was detected in 38 tumor cell lines (26.8%) and all of the diploid fibroblasts at early and late population doubling levels. These results strongly support the previous findings that p53 inactivation is one of the most frequent genetic events that occurs during carcinogenesis and immortalization.

Alleles↗

Changes in auditory P300 in patients with major depression and silent cerebral infarction.

We examined event-related potentials in patients with senile depression and silent cerebral infarction (SCI) to clarify the features of the P300 component. P300 event-related potentials were recorded in drug-free depressed patients (N = 16) and normal controls (N = 17). All patients underwent magnetic resonance imaging and were classified as SCI-positive (N = 7) or SCI-negative (N = 9). In depressed patients, the P300 was reexamined after antidepressant treatment. Prior to treatment, P300 amplitudes in depressed patients were significantly smaller than those in normal controls (P < 0.01). P300 amplitudes increased significantly in SCI-negative patients following recovery (P < 0.05), but did not change in SCI-positive patients. SCI may interrupt the treatment-related P300 amplitude increase in depressed patients.

Age Factors↗

The influence of different types of hard-palate closure in two-stage palatoplasty on maxillary growth: cephalometric analyses and long-term follow-up.

Using cephalometric analysis we investigated the influence on maxillary growth of two different types of hard-palate closure in two-stage palatoplasty. In 12 patients with complete unilateral cleft lip, alveolus, and palate, the lip and soft-palate were closed between 3 and 7 months of age. These 12 patients were then assigned to two groups of 6. In one group the hard palate was closed at 1 year 5 to 11 months of age by a vomer flap with a skin graft (VF group, Osada's two-stage palatoplasty) and in the other group it was closed by the mucoperiosteal pushback procedure (PB group). Sella-nasion-point A (SNA) in the VF group at 3 to 4 and after 10 years of age were within normal range and significantly larger than in the PB group. Two patients in the PB group required orthognatic surgery to obtain normal occlusion and a well-balanced profile. We concluded that in two-stage palatoplasty better maxillary growth can be obtained using the vomer flap method than using the pushback procedure.

Adolescent↗