[Hereditary giant neutrophil leucocytes].
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Humans↗
Biomedical subjects
A Shibata
Publications and source records attributed to A Shibata.
[Wiskott-Aldrich syndrome].
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Diagnosis, Differential↗
Serum levels of prostate-specific antigen among Japanese-American and native Japanese men.
BACKGROUND: Fourfold to sixfold higher prostate cancer rates in Japanese-American men in the United States compared with Japanese men in Japan have been cited to support a role for environmental risk factors in the etiology of the disease. To examine the hypothesis that part or all of the elevated prostate cancer rates in Japanese-American men may reflect more intensive prostate cancer screening in the United States than in Japan, we compared prostate-specific antigen (PSA) levels in community-based samples of serum from men without prostate cancer. METHODS: Japanese-American men aged 40-85 years and native Japanese men aged 40-89 years with no history of prostate cancer provided sera, respectively, in the United States from March 1990 through March 1992 (n = 237) or in Japan from January 1992 through December 1993 (n = 3522). Age-specific PSA levels were used to estimate the prevalences of undetected prostate cancer in the two populations. RESULTS: Age-specific mean PSA levels were significantly lower in Japanese-Americans than in native Japanese (two-sided P<.001). The prevalence of an elevated PSA level increased with age in both populations and exceeded 5% among men aged 60 years or more. Combined with data on prevalence of detected prostate cancer in the two populations, our data suggest that some 10.0% of Japanese-Americans aged 75 years have prostate cancer, with 31% of that fraction remaining undiagnosed. The corresponding estimates in Japan are a total cancer prevalence of 5.4%, of which 81% has not been detected clinically. CONCLUSIONS: The total cancer prevalence ratio 10.0/5.4 = 1.9 (95% confidence interval = 1.5-2.3) in Japanese-American men compared with Japanese men in Japan suggests an increased risk for Japanese-American men, but of less magnitude than the fourfold to sixfold increase indicated by the incidence data.
Adult↗
Na(+)-independent glucose utilization during Mn(2+)-induced contraction in ileal longitudinal smooth muscle.
In Ca(2+)- and Na(+)-deficient, isotonic 126 mM K+ medium, addition of 5 mM Mn2+ caused a tension about 2.5 x greater than the tonic response induced by 126 mM K+ medium (Ca2+ 2.5 mM, Na+ 0 mM) in ileal muscle. When glycogen was depleted by incubation in a glucose-free, hypertonic 60 mM K+ medium, addition of 5 mM Mn2+ induced only a very weak tension in Ca(2+)-free, isotonic 126 K+ medium. Phlorizin (10(-3) M), a blocker of Na(+)-coupled glucose cotransporter and ouabain (9 x 10(-5) M), an inhibitor of Na+, K(+)-ATPase, failed to inhibit the tension elicited by 5 mM Mn2+ in a Ca(2+)- and Na(+)-deficient, isotonic 126 mM K+ medium. Mn2+ was accumulated in the intracellular compartment in a Ca(2+)- and Na(+)-deficient, isotonic 126 mM K+ medium. The tissue ATP concentration was significantly reduced in a Na(+)-deficient 126 mM K+ medium. However, it recovered almost completely when 5 mM Mn2+ was added to the isotonic 126 mM K+ medium. These results suggest that the Mn(2+)-induced contraction in depolarized ileal longitudinal muscle in Na(+)-deficient medium may be maintained by a glucose transport which is not dependent on Na+ and insensitive to phlorizin.
Adenosine Triphosphate↗
Genetic predisposition to prostate cancer: possible explanations for ethnic differences in risk.
BACKGROUND: It seems unlikely that the large ethnic differences in prostate cancer risk can be explained completely by ethnic differences in diet or other lifestyle characteristics. Instead, the differences may be due to ethnic variation in endogenous factors, such as androgen metabolism or inherited susceptibility. METHODS: We have reviewed the literature for evidence and support of ethnic variation in genetic susceptibility to prostate cancer as a reason for the ethnic differences in rates. RESULTS: We distinguish two types of ethnic variation: 1) variation in the prevalence of certain alleles of specific genes that confer modestly increased risk. Such variation might be reflected in ethnic differences in serum levels of androgens, their metabolites, or indicators of metabolism in the prostate; 2) variation in the prevalence of rare germline mutations conferring substantially increased risk. Such variation would be reflected in ethnic differences in familial aggregation of prostate cancer. We discuss the evidence in support of each of these two possibilities. CONCLUSIONS: Ethnic variation in polymorphic alleles of genes associated with modest fluctuations in risk could explain a large proportion of the ethnic difference in cancer risk. In contrast, rare mutations associated with substantially increased risk are likely to account for a smaller fraction of these differences.
Asian↗
Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome.
BACKGROUND: Familial long-QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur due to ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far. We investigated mutations of these genes in LQTS families. METHODS AND RESULTS: Thirty-two Japanese families with LQTS were brought together for screening for mutations. Genomic DNA from each proband was examined by the polymerase chain reaction-single-strand conformation polymorphism technique followed by direct DNA sequencing. In four of the families, comprising 16 patients, mutations were identified in KVLQT1; five other families (9 patients) segregated mutant alleles of HERG. All 25 of these patients carried the specific mutations present in their respective families, and none of 80 normal individuals carried these alleles. Mutations were confirmed by endonuclease digestion or hybridization of mutant allele-specific oligonucleotides. No mutation in SCN5A was found in any family. CONCLUSIONS: We identified nine different mutations among 32 families with LQTS. Eight of these were novel and account for 25% of all types of mutations reported to date. Such a variety of mutations makes it difficult to screen high-risk groups using simple methods such as endonuclease digestion or mutant allele-specific amplification.
Alleles↗
Characterization of cytokine and iNOS mRNA expression in situ during the course of experimental autoimmune myocarditis in rats.
Ribonuclease protection assay was used to demonstrate mRNA expression of several cytokines as well as inducible NO synthase (iNOS), constitutive endothelial NO synthase (cNOS) and perforin in the myocardium during the course of experimental autoimmune myocarditis (EAM) in rats. Interleukin 2 (IL-2) appeared in the initial inflammatory phase (day 14), subsided in the maximum inflammatory phase (day 19) and disappeared by the recovery phase (day 25). mRNA of IL-3 beta, interferon gamma INF-gamma and tumor necrosis factor alpha (TNF-alpha) were detected only in the maximum inflammatory phase and iNOS also appeared for several days at this time. In contrast. IL-10 mRNA was detected after the maximum inflammatory stage and persisted into the recovery phase (days 25-36). Although transforming growth factor beta 1 (TGF-beta 1) could be detected in all phases, the expression was markedly enhanced in the maximum inflammatory phase and gradually diminished (around day 36) to basal levels. Perforin mRNA was not detected at any point in the disease. Besides macrophages and CD4 T cells, a number of neutrophils were found in the myocardium especially at peak inflammatory stage. We suggest that antigen (Ag) primed Ag presenting cells or macrophages interact with T cells (Th1) to produce IL-2 and subsequent IFN-gamma, which further activates macrophages in the myocardium. Consequently, TNF-alpha and iNOS may inflict tissue damage to myocardium. It is also suggested that TGF-beta) and one representative Th2 cytokine, IL-10, help inhibit inflammation. These findings suggest that Th1 and Th2 cytokines are produced at different stages of EAM and modulate the inflammation and the course of EAM.
Animals↗
Novel analysis of minimal residual disease in leukemia with TCR beta rearrangement--detection of monoclonality by single strand conformation polymorphism and PCR using a clonotype primer of leukemic T cell receptor beta-chain RNA.
Several means of analyzing minimal residual disease (MRD) in leukemia involving the rearranged T cell receptor (TCR) gene have been described. We investigated MRD in leukemia with TCR beta rearrangement by examining TCR beta-chain RNA. A complementary DNA (cDNA) corresponding to the variable region of the TCR beta-chains originating from the peripheral blood or bone marrow from four patients was amplified. Single strand conformation polymorphism (SSCP) analysis of amplified cDNA showed that all four patients had monoclonal leukemia with TCR beta rearrangement; two patients had Vbeta2+ leukemia, another patient had Vbeta14+ leukemia and the other had Vbeta9+ leukemia. Flow cytometry supported this finding. Sequencing of the Vbeta2-complementarity determining region 3 (CDR3), Vbeta9-CDR3 and Vbeta14-CDR3 revealed monoclonality. To investigate MRD using TCR beta-chain RNA, cDNA from each patient was diluted with the cDNA of a healthy person and amplified using a specific CDR3 clonotype primer. A band in the ethidium bromide-stained agarose gel was detected from samples diluted 10,000-fold. SSCP analysis determined which V region gene was utilized in monoclonal leukemic cells. The leukemic cell specific TCR, determined in such a manner, may be a target for immunotherapy. Because the MRD of T cell malignancy can be easily examined once the CDR3 clonotype primer is made, this novel analysis is considered to be a useful method.
Adolescent↗
Characterization and sensitivity to interleukin 2 and interferon alpha of leukemic cells from a patient with large granular lymphocytic leukemia associated with chronic active Epstein-Barr virus infection.
A patient presented with chronic large granular lymphocyte leukemia associated with chronic active Epstein-Barr virus infection (CAEBV). Cell cycle analysis revealed a minimal growth compatible with chronic lymphocytic leukemia After 5 months of treatment, the patient died from acute transformation of the leukemia. Cell harvested during chronic phase were analyzed for sensitivity to interleukin 2 (IL-2) and interferon alpha (IFN alpha) in vitro by means of surface phenotyping and cell cycle assay. IL-2 induced remarkable growth of the cells, whereas IFN alpha did not confer a growth advantage. Since IFN alpha was expected to have no growth induction effect on the leukemia cells, it was administered to the patient to treat the CAEBV.
Antineoplastic Agents↗
Characterization of internal DNA-binding and C-terminal dimerization domains of human centromere/kinetochore autoantigen CENP-C in vitro: role of DNA-binding and self-associating activities in kinetochore organization.
Human centromere protein C (CENP-C), a chromosomal component of the inner plate of kinetochores, was originally identified as one of the centromere autoantigens. In a previous study, we showed that it possesses DNA-binding activity in vitro. Recently, centromere-binding activity was suggested at the C-terminal region in vivo. However, little is known about the role of CENP-C in kinetochore organization. Here, to characterize its biochemical properties, three separate antigenic regions of human CENP-C were expressed in Escherichia coli, affinity purified and used in South-western blotting and chemical cross-linking analyses. We found that the internal DNA-binding domain was composed of two kinds of elements: the 'core' and two flanking 'stabilizing' elements that support the activity. When cross-linked with disuccinimidyl suberate (DSS), the N-terminal region produced the ladder bands of dimer and tetramer: the C-terminal region exclusively produced the dimer band, whereas the internal region was not affected at all. Dimer formation at the C-terminus in the native state was also indicated by gel filtration and the presence of conformation-specific autoantibodies in the patient's sera. These results suggest that human CENP-C consists of three functional units required for 'kinetochore assembly': a putative N-terminal oligomerization domain, an internal DNA-binding domain and a C-terminal dimerization domain.
Autoantigens↗
Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes.
To assess the consequence of second BMT (BMT2) for leukemia relapse after allogeneic BMT, we analyzed the clinical course of 66 recipients who were treated by BMT2 in Japan. Diagnoses included 29 ANLL, 27 ALL, six CML and four MDS. Durations between the first BMT (BMT1) to relapse and BMT1 to BMT2 were 13.5 +/- 13.7 months and 17.4 +/- 13.9 months, respectively. Donors for BMT2 were replaced in 11 cases. Thirty-one patients were in CR (or CP) at BMT2. Earlier deaths were observed in those who received BMT2 within 12 months after BMT1, mostly caused by regimen-related toxicity and infections. Overall leukemia-free survival rate was 28% at 2 years and 16% at 4 years. Factors influencing the poor prognosis after BMT2 were early (<6 months) relapse, early (<12 months) BMT2, not in remission at BMT2, and ALL. Intensified conditioning did not affect either remission duration or LFS. Among the 39 cases observed for more than 100 days, 18 developed chronic GVHD (cGVHD) and showed longer remission duration than those without cGVHD. Our analysis indicates that BMT2 as treatment for leukemia relapse is effective in selected cases, and exploration of pre-BMT treatment and post-BMT immunotherapy is warranted.
Adolescent↗
Plasma levels of thrombomodulin and lipoprotein (a) in patients with cerebral thrombosis.
To evaluate the clinical implications of soluble thrombomodulin and lipoprotein (a) [Lp(a)] in patients with cerebral thrombosis, these parameters were measured in the plasma of 28 patients with cerebral thrombosis within 3 days of onset, 36 with cerebral thrombosis more than 1 month after onset, six with cerebral hemorrhage more than 3 months after onset and 37 healthy volunteers. In the patients with chronic-phase cerebral thrombosis, the thrombomodulin and Lp(a) levels were significantly higher and the total cholesterol level was significantly lower than in the normal group, while the patients with acute-phase cerebral thrombosis had significantly lower total cholesterol levels. The plasma level of Lp(a) in acute-phase cerebral thrombosis, but not that of thrombomodulin, was significantly higher in thromboses located in the cortex area and in patients with recurrent attacks than in the normal controls. There were no significant differences in thrombomodulin, Lp(a) or total cholesterol levels between the chronic-phase cerebral hemorrhage and normal groups. These findings support the hypothesis that Lp(a) plays a part as a risk factor in cerebral thrombosis, especially in patients with a cortex area thrombosis and in patients with a recurrent attack. The high levels of thrombomodulin in the chronic-phase cerebral thrombosis group suggests the presence of continuous endothelial cell damage.
Adult↗
Clockwise and counter-clockwise circulation of wavefronts around an anatomical obstacle as one mechanism of two morphologies of sustained ventricular tachycardia in patients after a corrective operation of tetralogy of Fallot.
Two different monomorphic VTs were observed in two patients after a corrective operation for tetralogy of Fallot. The activation pattern of the wavefronts of the two VTs were different: in a counter-clockwise direction around the anatomical obstacle due to a ventriculotomy of the right ventricle in one VT; and in a clockwise direction around the same obstacle in the other VT. The different revolutions of the wavefronts could be the mechanism for the different morphologies of VT.
Adolescent↗
Procainamide induced change of the width of the zone of entrainment and its relation to the inducibility of reentrant ventricular tachycardia.
Procainamide depresses conduction velocity and prolongs refractoriness in myocardium responsible for reentrant VT, but the mechanism by which the induction of VT is suppressed after procainamide administration remains to be determined. In the present study, the relationship between electrophysiological parameters and the noninducibility of VT was assessed during procainamide therapy with a special reference to the change of an excitable gap. Clinically documented monomorphic sustained VT was induced in 30 patients and, utilizing the phenomenon of transient entrainment, the zone of entrainment was measured as the difference between the cycle length of VT and the longest paced cycle length interrupting VT (block cycle length) which was determined as the paced cycle length decreased in steps of 10 ms, and used as an index of the excitable gap. The effective refractory period was measured at the pacing site and the paced QRS duration was used as an index of the global conduction time in the ventricle. The cycle length of VT, the block cycle length, and the width of the zone of entrainment were determined and compared between the responders and nonresponders. In 15 patients, these parameters were determined at the intermediate dose and related to subsequent noninducibility at the final dose. At the final doses of procainamide, VT was suppressed in 8 (26.7%) of 30 patients. However, the cycle length of VT, the block cycle length, and the width of the zone of entrainment were unable to predict the drug efficacy, i.e., noninducibility. The change in the effective refractory period at the pacing site or the width of the paced QRS duration was not different between the responders and nonresponders. Among the variables, only the width of the zone of entrainment showed a significant narrowing in the responders at the intermediate dose of procainamide, and it was smaller than that of the nonresponders. The significant narrowing of the width of the zone of entrainment was associated with the subsequent noninducibility of VT at the final dose. The present study showed that the baseline cycle length of VT, the block cycle length, the drug induced change of the effective refractory period, or the paced QRS duration was not a predictor of the noninducibility after procainamide administration. However, a significant narrowing of the width of the zone of entrainment at the intermediate dose was associated with the noninducibility of VT at the final dose.
Adolescent↗
Morphological variation of nonreentrant idiopathic ventricular tachycardia originating from the right ventricular outflow tract and effect of radiofrequency lesion.
RF catheter ablation was performed in 16 patients with nonreentrant idiopathic VT originating from the RVOT. All documented VT was monomorphic, but subtle morphological variation in the VT-QRS complex was observed in 10 (63%) of 16 patients. Through endocardial mapping, VT origin was determined within a narrow site (< 0.5 x 0.5 cm) in 4 of the 10 patients with the morphological variation. In the other 6 of 10 patients, the origin extended to an area of > 0.5 x 0.5 cm. In VT with morphological variation, the local electrogram at the site of VT origin also showed variation in morphology and activation sequence. For VT of narrow origin, RF application to the site eliminated the VT. However, in VT from a wide arrhythmogenic area, RF current had to be delivered to 3-7 distinct sites to cover the possible origin, and specific QRS configuration of VT and/or PVC was ablated at each of the earliest activation site. All but one VT were successfully ablated by RF current. Subtle morphological variation was frequent in this type of VT, and about half were associated with a wide arrhythmogenic area. Precise mapping and analysis of the efficacy of each RF application might be helpful to better understand the relationship between subtle changes of VT-QRS morphology and their origins.
Adult↗
Radiofrequency catheter ablation for idiopathic right ventricular tachycardia with special reference to morphological variation and long-term outcome.
OBJECTIVE: To assess the long term outcome of radiofrequency (RF) catheter ablation for idiopathic ventricular tachycardia (VT) originating from the outflow tract of the right ventricle, with special reference to the morphological variation in the VT-QRS complexes. PATIENTS: 13 patients whose ventricular tachycardia was treated with RF ablation were followed up more than 18 months after RF ablation. RESULTS: Endocardial mapping revealed the various extensions of ventricular tachycardia origin (from 0.5 x 0.5 cm to 2.0 x 2.0 cm) in which the earliest local electrogram was recorded during ventricular tachycardia. In all five tachycardias from a relatively wider origin (more than 0.5 x 0.5 cm) and in four of eight from a narrow origin (< 0.5 x 0.5 cm), subtle morphological variation in the VT-QRS complexes was observed. In tachycardias with morphological variation, the local electrogram at the tachycardia origin also showed concomitant variation in morphology and activation sequence. Ventricular tachycardia from a narrow site was eliminated by RF ablation to the confined site, but a larger number of RF applications was required in tachycardias from a wider origin. All 13 tachycardias were successfully ablated by RF current, and during the follow up period of 28.2 (SD 7.2) months, recurrence was observed in only one patient who had a wider origin. CONCLUSIONS: Long term efficacy of RF ablation was excellent in idiopathic ventricular tachycardia originating from the outflow tract of the right ventricle. Subtle morphological variations were frequently observed in this type of ventricular tachycardia, and about half of them represented a relatively wider arrhythmogenic area.
Adult↗
Acquired immune thrombocytopenia caused by IgG antiglycoprotein Ib antibody in a patient with Hodgkin's disease.
We studied a patient with thrombocytopenia associated with Hodgkin's disease (HD). The megakaryocyte number in the bone marrow and the level of platelet-associated IgG were both increased in the patient. Intravenous gamma-globulin therapy and chemotherapy for HD dramatically normalized the platelet count, suggesting that antibody produced by lymphoma cells is likely to account for the thrombocytopenia. Antigen-captured ELISA and Western blotting showed that the patient's serum had an IgG autoantibody against platelet membrane glycoprotein Ib. The patient's plasma had no inhibitory effect on normal platelet aggregation induced by ristocetin. These findings suggest that the autoantibody found in the patient had a pathogenetic role in the thrombocytopenia, but not in platelet dysfunction.
Adolescent↗