Biomedical subjects
Publications and source records attributed to S Honda.
A hydropic fetus that exhibited intrapericardial teratoma with marked pericardial effusion was prenatally diagnosed. Intrauterine pericardiocentesis was performed to diagnose and to treat hydrops. Pericardiocentesis for tamponade secondary to a fetal intrapericardial teratoma might prevent fetal death and premature delivery.
In humans, the numbers of erythrocytes and granulocytes, but not that of lymphocytes, tend to increase in parallel. To determine the mechanism, we investigated how the administration of erythropoietin induces the expansion of erythroid cells and other lineage cells in the bone marrow, liver, and other organs of mice. When mice were injected twice (days 1 and 2) with erythropoietin at a dose of 20 or 200 IU/day/ mouse, a prominent expansion of TER 19+ (erythroid cells) and Gr-1high cells (granulocytes) occurred in the liver, spleen, and bone marrow day 3 after the initial injection. On the other hand, lymphoid cells, including NK cells, extrathymic T cells, and conventional T cells, did not expand. In parallel with the expansion of erythroid cells and granulocytes, the levels of c-kit(+)Lin- cells increased in the liver and bone marrow. Despite the increase in the proportion of c-kit(+) Lin(-) cells, the generation of lymphocytes (e.g., T cells) decreased when such bone marrow cells were injected to scid mice. These results suggest that erythropoietin has the ability to induce the expansion of not only erythroid cells but also granulocytes in the liver, spleen, and bone marrow. Furthermore, c-kit+ progenitors which may commit themselves to erythroid and myeloid cells, but not to lymphoid cells, were also activated in the liver and bone marrow of mice treated with erythropoietin.
BACKGROUND: Clinical significance of immunohistochemically detectable level of p53 protein has been reported, but with some limitation as a prognosticator of bladder cancer patients. Whether or not simultaneous evaluation of mdm2 and p53 expression in bladder cancer exceed the prognostic significance of conventional histological findings, cell proliferation markers and apoptotic parameters remains unclear. MATERIALS AND METHODS: The paraffin-embedded materials taken from 84 patients with transitional cell carcinoma of the bladder who were treated with total cystectomy were used in this study. Immunostainings of p53 protein, mdm2 protein and Ki67 antigen were performed using monoclonal antibodies (clone DO7, clone 1B10 and clone MIB1, respectively). In addition, the apoptotic cells were determined using a terminal deoxynucleotidyl transferase (TdT) mediated dUTP biotin nick end labeling (TUNEL) technique. The results were quantitatively evaluated using a CAS 200 Image Analyzer (Cell Analysis System, Elmhurst, Ill., USA) and were compared with histological findings and clinical course. RESULTS: The mean values of mdm2 expression, p53 immunoreactivity, Ki67 expression and apoptotic index were 19.2, 20.5, 22.4 and 0.96%, respectively. Histological grade and pT category were significantly positively correlated with 53 immunoreactivity (p < 0.05 and p < 0.05, respectively), Ki67 expression (p < 0.005 and p < 0.0001, respectively) and apoptotic index (p < 0.01 and p < 0.0001, respectively), while both were not correlated with mdm2 expression. Using univariate analysis, the prognostic relevance for both survival and disease progression was noted in histological grade, pT category, p53 expression, Ki67 index and apoptotic index, whereas it was not in mdm2 expression. However, when analyzing the simultaneous evaluation of mdm2 and p53 expression (mdm2-p53 category), the relationship of the mdm2-p53 category with Ki67 expression and apoptotic index showed a statistical significance and a borderline significance (p = 0.0085 and p = 0.0652, respectively). In addition, the patients with both mdm2(-) and p53(-) showed a significant better prognosis as compared with either counterpart of mdm2-p53 category (p < 0.05 for both). Multivariate analysis revealed only pT category and mdm2-p53 category as independent factors for both disease progression and survival. CONCLUSIONS: Clinical significance of simultaneous evaluation of mdm2 and p53 immunostaining proved to be superior over that of cell proliferation and/or apoptotic markers when elucidating the biological characteristics of bladder cancer.
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This study was carried out to clarify the frequency of detection of antibody activity to ribosomal protein S10 (anti-S10) in patients with systemic lupus erythematosus (SLE) with anti-Sm antibodies (anti-Sm), and clinical differences between anti-Sm-positive SLE patients with and without anti-S10. Twenty-seven of 31 serum samples containing anti-Sm reacted with ribosomal protein S10 along with Sm core proteins B/B' and D (87.1%). Four serum samples containing anti-Sm against only B/B' but not D did not react with S10 (12.9%). Patients who had both anti-Sm and anti-S10 showed lower serum complements levels, high frequency of skin lesion and anti-double-stranded DNA antibody. Many anti-Sm antibodies may recognize B/B', D, and S10 simultaneously, and such antibodies may appear in active disease.
OBJECTIVE: It is important for GH-deficient children to treat abnormal body composition associated with a metabolic consequence, not only short stature. In this study we evaluated long-term effects of GH therapy on body composition in GH-deficient boys and girls. SUBJECTS AND METHODS: Forty-nine subjects with GH deficiency, 35 boys and 14 girls, 6 to 14 years of age, were studied. All the subjects were treated for three years with recombinant human GH at a weekly dosage of 0.5 IU/kg by subcutaneous daily injection. Body composition was measured by bioelectrical impedance analysis (BIA 101, Spectrum II 287, RJL Systems, Detroit, Mich). RESULTS: Body fat (%) decreased significantly during the first three months of GH treatment. These values were maintained low thereafter in boys, in contrast to those which continued to tend upward in girls from the second year of the treatment. Lean body mass (kg) increased significantly with increasing extracellular water (kg) and body cell mass (kg) in both sexes during GH treatment. CONCLUSION: Our data demonstrate that GH can reduce body fat mass in GH-deficient boys and girls. The gender difference in changes in body fat with age during the course of this study is compatible with that observed in normal children. The rapid increase in extracellular water and the gradual increase in body cell mass both contributed to the steady increase in LBM during GH treatment.
This study aimed at identifying factors influencing satisfaction among employees who undergo health check-ups. Seven hundred and twenty two workers at a single working-site (669 male and 53 female) were recruited for a cross-sectional survey with a self-administered questionnaire that we newly developed through a pilot interview study. Multiple logistic regression analysis showed that overall satisfaction was significantly associated with the employee's age (p = 0.06), job type (p = 0.10), and waiting time during the examination (p < 0.01), the burden involved in filling out a check list before the examination (p = 0.06), and the courtesy of the health examination staff (p = 0.07). Our results may imply a role of satisfaction for quality assurance during work-site health check-ups.
National Space Development Agency of Japan (NASDA) has been developed aquatic animal experiment facilities for space experiments using NASA Space Shuttle. Vestibular Function Experiment Unit (VFEU) has been firstly designed and developed for Spacelab-J mission (STS-47), and 8 days space experiment with carp has been performed. Following, the VFEU, Aquatic Animal Experiment Unit (AAEU) has been developed to accommodate small aquatic animals second International Microgravity Laboratory mission (IML-2, STS-65). Four kinds of space experiments with goldfish, medaka, newt, and newt eggs have been performed for 15 days mission duration. Then, VFEU has been improved to accommodate marine fish under low temperature condition for Neurolab (STS-90) and STS-95 missions. 17 days (STS-90) and 9 days (STS-95) experiments with oyster toadfish have been performed by using the VFEU. This report summarizes the outline of these aquatic animal experiment facilities.
Reticulated platelets retain some residual mRNA in their cytoplasm and are thought to be newly produced platelets. In recent years, it has been reported that the reticulated platelet count (RP) correlates well with platelet production. For that reason, the measurement of RP (%) is considered useful for analyses of platelet kinetics and differential diagnoses of thrombocytopenic disorders. However, certain technical difficulties exist because fluorochrome thiazole orange (TO), which is used for staining purposes, stains platelet granules nonspecifically, and so far, only a few reports have documented the study of precision staining techniques. We evaluated staining criteria precisely in an effort to solve the issue of nonspecific staining by TO, and concluded that the important points for effective staining were (1) fixation of platelets, (2) 1:8 dilution of TO (ReticCount), (3) incubation for 1 to 2 hours, and (4) the capture of platelets using anti-CD42b monoclonal antibody. We stained reticulated platelet samples by the above method and achieved intra-assay reproducibility of 3.4-5.1% RP (%) in normal subjects was 8.7 +/- 2.2%. It was significantly higher (23.6 +/- 13.3%) in patients with idiopathic thrombocytopenic purpura (ITP), and elevated in 87% of all evaluated ITP patients. Our method is sensitive, provides reproducible results, and can be effectively utilized for the analysis of platelet kinetics and differential diagnosis of thrombocytopenia.
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Longevity is regulated by the daf-2 gene network in Caenorhabditis elegans. Mutations in the daf-2 gene, which encodes a member of the insulin receptor family, confer the life extension (Age) phenotype and the constitutive dauer (a growth-arrested larval form specialized for dispersal) formation phenotype. The Age phenotype is mutually potentiated by two life extension mutations in the daf-2 gene and the clk-1 gene, a homologue of yeast CAT5/COQ7 known to regulate ubiquinone biosynthesis. In this study, we demonstrated that the daf-2 mutation also conferred an oxidative stress resistance (Oxr) phenotype, which was also enhanced by the clk-1 mutation. Similar to the Age phenotype, the Oxr phenotype was regulated by the genetic pathway of insulin-like signaling from daf-2 to the daf-16 gene, a homologue of the HNF-3/forkhead transcription factor. These findings led us to examine whether the insulin-like signaling pathway regulates the gene expression of antioxidant defense enzymes. We found that the mRNA level of the sod-3 gene, which encodes Mn-superoxide dismutase (SOD), was much higher in daf-2 mutants than in the wild type. Moreover, the increased sod-3 gene expression phenotype is regulated by the insulin-like signaling pathway. Although the clk-1 mutant itself did not display Oxr and the increased sod-3 expression phenotypes, the clk-1 mutation enhanced them in the daf-2 mutant, suggesting that clk-1 is involved in longevity in two ways: clk-1 composes the original clk-1 longevity program and the daf-2 longevity program. These observations suggest that the daf-2 gene network controls longevity by regulating the Mn-SOD-associated antioxidant defense system. This system appears to play a role in efficient life maintenance at the dauer stage.
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The distribution of the conduction velocity (DCV) of peripheral nerve fibers was estimated from two compound action potentials (CAPs) that were evoked at two sites by electrical stimulation and recorded at a different site. In this paper, a regularized least-squares method with a smoothness constraint and self-adaptation of the regularization parameter was adopted. Computer simulation showed it to be effective, especially for noisy CAP signals. In addition, the conduction lengths of nerve fibers were automatically determined by a Fibonacci search, since the conduction lengths of nerve fibers could not be measured accurately due to slack in fibers or changes in length associated with the contraction of adjacent muscles.
We evaluated measurements of PAIgG, reticulated platelets (RP), plasma thrombopoietin (TPO) levels, and platelet size to determine whether these parameters were useful for the differential diagnosis of idiopathic thrombocytopenic purpura (ITP), aplastic anemia (AA), and hypoplastic thrombocytopenia (HypoT). The percentage of RP (%RP) in patients with ITP was significantly higher (25.2 +/- 11.0%, P < 0.001) than in normal subjects (7.9 +/- 2.8), and the sensitivity, specificity, and predictive value of %RP in diagnosing ITP were 82%, 95%, 96%, respectively. On the other hand, TPO levels in patients with AA and HypoT were significantly higher (355.5 +/- 218.7 pg/ml, P < 0.001, and 376.4 +/- 347.2, P < 0.001, respectively) than in normal subjects (36.7 +/- 23.0). The sensitivity, specificity, and predictive value of TPO in diagnosing AA and HypoT were 88%, 89% and 86%, respectively. We also sought to determine whether the simultaneous measurement of %RP and TPO improved their value in the differential diagnosis of ITP, AA, and HypoT. However, simultaneous measurement did not yield significant improvements in sensitivty, specificity, or predictive value. These results indicated that measurements of %RP will suffice for the diagnosis of ITP, and that measurements of TPO are adequate for the diagnosis of AA and HypoT.
Aromatase is known to be involved in the control of morphological, neuroendocrine, and behavioral sex differences in the brain. To study the detailed functions of aromatase in mouse brain, we generated aromatase-deficient mice that lack exons 1 and 2 and the proximal promoter region of the cyp19 gene by homologous recombination. The genotypes of offspring from heterozygous matings conformed to the Mendelian rule. The aromatase knockout (ArKO) male and female mice displayed no significant external morphological abnormalities, although the uteri of adult ArKO female mice were remarkably underdeveloped. Male-typical sexual behavior directed toward females was, however, strongly modified in the ArKO male mice. The ArKO male mice showed significantly prolonged latencies to mount and decreased numbers of mounts in response to receptive stimulus females. These results suggest an important participation of the aromatase gene in the reproductive behaviors.
Platelet IIbbeta3 is a prototypic integrin and plays a critical role in platelet aggregation. Occupancy of IIbbeta3 with multivalent RGD ligands, such as fibrinogen, induces both expression of ligand-induced binding sites (LIBS) and IIbbeta3 clustering, which are thought to be necessary for outside-in signaling. However, the association between LIBS expression and outside-in signaling remains elusive. In this study, we used various IIbbeta3-specific peptidomimetic compounds as a monovalent ligand instead of fibrinogen and examined the association between LIBS expression and outside-in signaling such as IIbbeta3-mediated intracellular Ca2+ signaling. Using a set of monoclonal antibodies (MoAbs) against LIBS, we showed that antagonists can be divided into two groups. In group I, antagonists can induce LIBS on both IIb and beta3 subunits. In group II, antagonists can induce LIBS on the IIb subunit, but not on the beta3 subunit. Inhibition studies suggested that group I and group II antagonists interact with distinct but mutually exclusive sites on IIbbeta3. Neither group I nor group II antagonist increased intracellular Ca2+ concentrations ([Ca2+]i) in nonactivated platelets. All antagonists at nanomolar concentrations abolished the increase in [Ca2+]i in 0.03 U/mL thrombin-stimulated platelets, which is dependent on both fibrinogen-binding to IIbbeta3 and platelet-aggregation. However, only group I antagonists at higher concentrations dose-dependently augmented the [Ca2+]i increase, which is due to aggregation-independent thromboxane A2 production. This increase in [Ca2+]i was not observed in thrombasthenic platelets, which express no detectable IIbbeta3. Thus, only the group I antagonists, albeit a monovalent ligand, can initiate IIbbeta3-mediated intracellular Ca2+ signaling in the presence of thrombin stimulation. Our findings strongly suggest the association between beta3 LIBS expression and IIbbeta3-mediated intracellular Ca2+ signaling in platelets.
The platelet integrin IIbbeta3 has become a new target for the treatment of pathological thrombosis. It becomes apparent that the affinity of IIbbeta3 for its ligands is dynamically regulated by inside-out signaling. However, the components that couple diverse intracellular signals to the cytoplasmic domains of IIbbeta3 remain obscure. Employing a chymotrypsin-induced IIbbeta3 activation model, we previously proposed the hypothesis that Na+/Ca2 + exchanger (NCX) may be involved in inside-out signaling (Shiraga et al: Blood 88:2594, 1996). In the present study, employing two unrelated Na+/Ca2+ exchange inhibitors, 3',4'-dichlorobenzamil (DCB) and bepridil, we investigated the role of NCX in platelet activation induced by various agonists in detail. Both inhibitors abolished platelet aggregation induced by all agonists examined via the inhibition of IIbbeta3 activation. Moreover, these inhibitors abolished IIbbeta3 activation induced by phorbol 12-myristate 13-acetate or A23187. On the other hand, neither of these inhibitors showed apparent inhibitory effects on protein phosphorylation of pleckstrin or myosin light chain, or an increase in intracellular calcium ion concentrations evoked by 0.1 U/mL thrombin. These effects of the NCX inhibitors are in striking contrast to those of protein kinase C inhibitor, Ro31-8220. Biochemical and ultrastructural analyses showed that NCX inhibitors, particularly DCB, made platelets "thrombasthenic". These findings suggest that the NCX is involved in the common steps of inside-out signaling through integrin IIbbeta3.
First, we determined the cerebral localization of reduced glutathione (GSH) in normal mice by means of autoradiography using 99mTc-meso-hexamethyl propylene oxime. A highly specific localization of GSH in the cerebellum and hippocampus was observed. Secondly, we measured the elevation of GSH level in the brain after low-dose gamma-irradiation. The cerebral GSH levels increased soon after irradiation with 50 cGy of gamma-rays, reaching a maximum at 3 h post-treatment, then remaining significantly higher than that of the non-irradiated control until 12 h and returning to the control level by 24 h. Thirdly, we examined the induction of the activities and the mRNAs of proteins involved in the synthesis and regeneration of GSH in the brain of mice subjected to low-dose gamma-ray irradiation. The level of mRNA for gamma-glutamylcysteine synthetase was significantly increased at 0.5 h, and remained high until 2 h post-irradiation (50 cGy). The level was transiently lowered to the non-irradiated control level at 3 h and slightly increased again after 6 h post-irradiation. gamma-Glutamylcysteine synthetase activity was significantly increased 3 h after irradiation, and remained high up to 24 h post-irradiation. As for glutathione reductase, the mRNA level was increased at 0.5 h, and peaked strongly at 2 h, while the enzyme activity was significantly increased at 6 h after irradiation, and continued to increase up to 24 h. The level of mRNA for thioredoxin, which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked between 0.5 h and 2 h post-irradiation, and rapidly declined thereafter. The content of thioredoxin showed a transient decrease immediately after irradiation, but was then remarkably elevated, reaching a maximum at 3 h, and thereafter declining sharply. These results indicate that the increase in endogenous GSH in mouse brain soon after low-dose gamma-ray irradiation is a consequence of the induction of GSH synthesis-related proteins and occurs via both the de novo synthesis and the regeneration pathways.