Severe orthostatic hypotension with diabetic autonomic neuropathy successfully treated with a beta(1)-blocker: a case report.
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Adrenergic Fibers↗
Biomedical subjects
J Ishikawa
Publications and source records attributed to J Ishikawa.
Surgical efficacy of carpal tunnel release for carpal tunnel syndrome in acromegaly: report of four patients.
Although carpal tunnel syndrome is frequent in acromegaly, few acromegalics will be encountered by most hand surgeons. This paper considers the treatment of four cases of acromegaly in whom carpal tunnel syndrome arose, to discuss aspects of management of carpal tunnel syndrome in this patient group.
Acromegaly↗
Nocardial infections in Japan from 1992 to 2001, including the first report of infection by Nocardia transvalensis.
In the period from 1992 to 2001, 303 cases of nocardioses were diagnosed in Japan, with the corresponding etiological agents isolated and characterized. Taxonomic analyses of these 303 strains showed that most nocardial infections were caused by members of the Nocardia asteroides group (72.3%). Speciation showed that 72 strains were N. asteroides, 31 strains were N. cyriacigeorgica, 2 strains were N. beijingensis, 81 strains were N. farcinica, and 33 strains were N. nova. Sixty-six strains of N. brasiliensis were the next most prevalent species of the total Nocardia isolates, followed by 14 strains of N. otitidiscaviarum. Infections by N. transvalensis (3 strains) and N. pseudobrasiliensis (1 strain) were also confirmed. The infections due to N. transvalensis, N. cyriacigeorgica, and N. beijingensis were the first reported in Japan. The most common factor that predisposed individuals to nocardial infection in Japan was therapy by immunosuppressive agents (22.4%), including SLE therapy (3.6%), followed by cancer (6.6%), diabetes (3.6%) and AIDS (2.0%). Nocardial infections occurred more commonly in the elderly, with most of the patients between the ages of 61 and 80 years of age. No significant difference regarding infectivity levels between the sexes was observed.
Adolescent↗
Phagocytosis of Dictyostelium discoideum studied by the particle-tracking method.
Single phagocytic events of cellular slime mold Dictyostelium discoideum were studied by the method of particle tracking. A 2-microm polystyrene bead, which had been covalently coated with folate, was attached to the advancing edge of a Dictyostelium ameba with the aid of an optical trap. The bead was transported backward on the cell surface. Forty-five percent of the transported beads were internalized. The bead motion was analyzed by determining every 33 ms the x-y coordinate of the centroid of the phase-contrast image of the bead. The x(t) and y(t) traces were smoothed over 1 s and the difference between the smoothed (x(t) and y(t)) and the original traces, delta(x) identical with x(t) - x(t) and delta(y) identical with y(t) - y(t), were calculated, which represented relatively rapid components of the bead motion. The plot of delta(2) = (delta(x)(2) + delta(y)(2)) against time could be divided into three phases on the basis of the variance of delta(2). Comparison of the plot with the video sequence indicated that the first phase corresponded to the transport, the second phase to the internalization, and the third phase to the postinternalization process (intracellular movement). Cytochalasin A at 5 microM completely inhibited phagocytosis without affecting the binding of bead to the cell surface, indicating the importance of actin cytoskeleton in all the phases. At 1 microM cytochalasin A the variance of the postinternalization process decreased, and the duration of the transport phase increased. At 0.25 microM cytochalasin A the duration of the internalization phase exhibited a significant increase, but other parameters did not change appreciably. The complex and differential effects of cytochalasin A on the parameters characterizing the three phases in the phagocytic process indicate that various aspects of actin dynamics are involved in the individual process of phagocytosis.
Animals↗
Successful second allogeneic peripheral blood stem cell transplantation and donor lymphocyte infusion in patients with relapsed acute leukemia using the same donors as for the initial allogeneic bone marrow transplantation.
We report the successful treatment of two acute lympho- blastic leukemia (ALL) patients who relapsed following allogeneic bone marrow transplantation (allo-BMT) with allogeneic peripheral blood sem cell transplantation(allo-PBSCT) and donor lymphocyte infusion (DLI) from the same HLA-identical related donors as those used for the first allo-BMT. The patients relapsed on days 154 and 351 from the initial allo-BMT, respectively. Since conventional reinduction chemotherapy failed, allo-PBSCT was undertaken while the patients were still myelosuppressed immediately after reinduction chemotherapy. To induce and/or enhance GVL effects following allo-PBSCT, we performed rapid tapering of CsA and added DLI. After allo-PBSCT and DLI, the patients maintained their complete remission at 55 and 48 months post allo-PBSCT, respectively. From these findings, allo-PBSCT and DLI may be a useful treatment strategy for acute leukemia relapsing after allo-BMT.
Adult↗
Changing prevalent T serotypes and emm genotypes of Streptococcus pyogenes isolates from streptococcal toxic shock-like syndrome (TSLS) patients in Japan.
We surveyed T serotypes and emm genotypes of Streptococcus pyogenes isolates from streptococcal toxic shock-like syndrome (TSLS) patients. T1 (emm1) remained dominant through 1992 to 2000, but the dominant T3 (emm3.1) strains from 1992 to 1995 disappeared during 1996-2000. Strains of several emm genotypes emerged during 1996-2000, indicating alterations in the prevalent strains causing TSLS.
Antigens, Bacterial↗
Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites.
Streptomyces avermitilis is a soil bacterium that carries out not only a complex morphological differentiation but also the production of secondary metabolites, one of which, avermectin, is commercially important in human and veterinary medicine. The major interest in this genus Streptomyces is the diversity of its production of secondary metabolites as an industrial microorganism. A major factor in its prominence as a producer of the variety of secondary metabolites is its possession of several metabolic pathways for biosynthesis. Here we report sequence analysis of S. avermitilis, covering 99% of its genome. At least 8.7 million base pairs exist in the linear chromosome; this is the largest bacterial genome sequence, and it provides insights into the intrinsic diversity of the production of the secondary metabolites of Streptomyces. Twenty-five kinds of secondary metabolite gene clusters were found in the genome of S. avermitilis. Four of them are concerned with the biosyntheses of melanin pigments, in which two clusters encode tyrosinase and its cofactor, another two encode an ochronotic pigment derived from homogentiginic acid, and another polyketide-derived melanin. The gene clusters for carotenoid and siderophore biosyntheses are composed of seven and five genes, respectively. There are eight kinds of gene clusters for type-I polyketide compound biosyntheses, and two clusters are involved in the biosyntheses of type-II polyketide-derived compounds. Furthermore, a polyketide synthase that resembles phloroglucinol synthase was detected. Eight clusters are involved in the biosyntheses of peptide compounds that are synthesized by nonribosomal peptide synthetases. These secondary metabolite clusters are widely located in the genome but half of them are near both ends of the genome. The total length of these clusters occupies about 6.4% of the genome.
Base Sequence↗
A new IFN-like cytokine, limitin, modulates the immune response without influencing thymocyte development.
A novel IFN-like molecule, limitin, was recently identified and revealed to suppress B lymphopoiesis through the IFN-alphabeta receptor, although it lacked growth suppression on myeloid and erythroid progenitors. Here we have studied diverse effects of limitin on T lymphocytes and compared limitin with previously known IFNs. Like IFN-alpha and -beta, limitin modified immunity in the following responses. It suppressed mitogen- and Ag-induced T cell proliferation through inhibiting the responsiveness to exogenous IL-2 rather than suppressing the production of IL-2. In contrast, limitin enhanced cytotoxic T lymphocyte activity associated with the perforin-granzyme pathway. To evaluate the effect of limitin in vivo, a lethal graft-versus-host disease assay was established. Limitin-treatment of host mice resulted in the enhancement of graft-versus-host disease. Limitin did not influence thymocyte development either in fetal thymus organ cultures or in newborn mice injected with limitin-Ig, suggesting that limitin is distinguishable from IFN-alpha and -beta. From these findings, it can be speculated that the human homolog of limitin may be applicable for clinical usage because of its IFN-like activities with low adverse effects on, for example, T lymphopoiesis, erythropoiesis, and myelopoiesis.
Adjuvants, Immunologic↗
Tolerance induction across Mls and minor histocompatibility complex by inhibiting activation of T helper type 1 in early period.
We have previously succeeded in inducing persistent donor-specific tolerance across Mls plus multiple minor histocompatibility barriers by portal venous (p.v.) injection of donor spleen or bone marrow cells plus cyclophosphamide (CY) treatment. Microchimerism was established in the lymph-hemopoietic organs of the tolerant recipients. However, the mechanisms, particularly the roles of CY in the tolerance induction, have not been clarified. We examined the tolerance induction using other anti-mitotic agents and evaluated the in vitro proliferative responses and cytokine expression of T cells from the recipients after stimulation with donor alloantigens. The administration of not only CY but also mitomycin C (MMC) and cytosin arabinoside (Ara C) elicited a prolongation of skin graft survival. CY induced tolerance when it was administered 2 days after the p.v. injection, but not immediately or 4 days after the p.v. injection. T cells collected from the tolerant recipients showed no proliferative responses as a result of stimulation with donor alloantigens whereas the responses of T cells from non-tolerant recipients were significantly enhanced. Interferon-gamma (IFNgamma) was extensively expressed in the non-tolerant T cells from 24 to 48 h after the stimulation with donor alloantigens. In contrast, the expression of IFNgamma was observed in the tolerant T cells from 72 h after the stimulation. Also, the tolerant T cells showed the expression of interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-beta1) from 72 h after the stimulation whereas the non-tolerant T cells did not. These data suggest that CY, when administered 2 days after the p.v. injection, induces persistent tolerance by inhibiting T helper type 1 (Th1) activity in the early period but not the Th1 activity in the later periods.
Animals↗
Relationships among the physical parameters required to give a linear relation between slope and intercept of Fowler-Nordheim plots.
For field emitters with a given surface condition, but different apex radii, there exists an empirical linear relationship between the slopes and intercepts of their Fowler-Nordheim plots. This behavior is quite different from that predicted by the theory with the assumption of a smooth surface. We have already characterized the possible reasons for this discrepancy; one possibility is that the emission area rapidly increases with increase in the apex radius. The previous report (Jpn. J. Appl. Phys. Part II 32 (1993) L342), however, showed a curved relation between the slope and the intercept of Fowler-Nordheim plots. In the present article, we try to extract the relationship between the emission area and the apex radius needed in order to give a linear relationship between slope and intercept of the F-N plots. As an additional result of the present analysis, the change in work function of the field emitting surface is demonstrated.
Journal Article↗
On the increase of the intensity ratio of doubly charged ions to singly charged ions for liquid gold and copper ion sources.
The reason for the increase of R21 which is defined by the intensity ratio of the doubly charged ions to the singly charged ions, was studied. Based on the conventional field evaporation theory, an increase in the electric field and/or the source temperature is considered to be attributable. We took the fact that R21 turned to decrease at the higher current regime into consideration and examined whether the change of R21 due to change in the field or temperature would finally meet the criterion for the decrease of R21. It was concluded that an increase of the source temperature may be a possible reason for the increase of R21.
Journal Article↗
Major histocompatibility complex restriction between hematopoietic stem cells and stromal cells in vitro.
We have previously found that a significant number of hematopoietic progenitors accumulate in engrafted bones with the same major histocompatibility complex (MHC) as the transplanted bone marrow cells. In the present study, to further clarify the MHC restriction between hematopoietic stem cells (HSC) and microenvironment, we carried out cobblestone colony formation assays by culturing HSCs with MHC-matched or -mismatched stromal cell monolayers. The formation of cobblestone colonies under MHC-mismatched stromal cells significantly decreased in comparison with MHC-matched stromal cells. However, the decrease in cobblestone colony formation under MHC-mismatched stromal cells was not significant when using MHC class I-deficient HSC or stromal cells. Taken together with the results using B10 congenic strains, it is suggested that the MHC preference is restricted by MHC class Ia molecules. Treatment with monoclonal antibodies (mAbs) against MHC class Ia molecules of stromal cell phenotypes significantly enhanced the cobblestone colony formation, whereas treatment with mAbs against HSC phenotypes significantly inhibited it. The expression of cytokines to promote hematopoiesis was enhanced by the mAbs against stromal cell phenotypes. The enhancement of cytokine expression was also observed when stromal cells and HSCs were MHC-matched. These results suggest that signaling via the MHC molecules augments stromal cell activity and elicits the MHC restriction.
Animals↗
[Efficacy and toxicity of lenograstim (glycosylated recombinant human granulocyte-colony stimulating factor) on peripheral blood stem cell harvest in healthy donors].
Peripheral blood stem cell harvest with lenograstim (glycosylated rhG-CSF) was performed 12 times from 10 normal donors. Five micrograms/kg of lenograstim was administered subcutaneously twice a day (10 micrograms/kg/day) for 4 to 6 days, and apheresis was performed on day 5 to 7 depending on the collected CD 34+ cell counts. We collected a sufficient number of CD 34+ cells in 9 mobilizations from 7 donors less than 50 years of age, with a total number of collected CD 34+ cells in each mobilization of 22.1 +/- 6.5 x 10(7). In contrast, we could not obtain a sufficient number of CD 34+ cells in 2 mobilizations from 3 donors above 50 years of age, with a total number of collected CD 34+ cells of 9.8 +/- 3.3 x 10(7). Although all donors had adverse events in response to lenograstim administration, all of them were grade 2 or less toxicity. These results indicate that peripheral blood stem cell mobilization and apheresis by lenograstim is safe and well tolerated, but the risk of poor mobilization may become higher in donors more than 50 years of age.
Adjuvants, Immunologic↗
Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.
We investigated the functions of adiponectin, an adipocyte-specific secretory protein and a new member of the family of soluble defense collagens, in hematopoiesis and immune responses. Adiponectin suppressed colony formation from colony-forming units (CFU)-granulocyte-macrophage, CFU-macrophage, and CFU-granulocyte, whereas it had no effect on that of burst-forming units-erythroid or mixed erythroid-myeloid CFU. In addition, adiponectin inhibited proliferation of 4 of 9 myeloid cell lines but did not suppress proliferation of erythroid or lymphoid cell lines except for one cell line. These results suggest that adiponectin predominantly inhibits proliferation of myelomonocytic lineage cells. At least one mechanism of the growth inhibition is induction of apoptosis because treatment of acute myelomonocytic leukemia lines with adiponectin induced the appearance of subdiploid peaks and oligonucleosomal DNA fragmentation. Aside from inhibiting growth of myelomonocytic progenitors, adiponectin suppressed mature macrophage functions. Treatment of cultured macrophages with adiponectin significantly inhibited their phagocytic activity and their lipopolysaccharide-induced production of tumor necrosis factor alpha. Suppression of phagocytosis by adiponectin is mediated by one of the complement C1q receptors, C1qRp, because this function was completely abrogated by the addition of an anti-C1qRp monoclonal antibody. These observations suggest that adiponectin is an important negative regulator in hematopoiesis and immune systems and raise the possibility that it may be involved in ending inflammatory responses through its inhibitory functions. (Blood. 2000;96:1723-1732)
Adiponectin↗
Cytokines prevent dexamethasone-induced apoptosis via the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways in a new multiple myeloma cell line.
A new human myeloma cell line, OPM-6, was established from the peripheral blood of a patient with advanced IgG-kappa plasma cell leukemia. Cytogenetic and phenotypic analysis confirmed that the cells were derived from the patient's leukemic cells. Insulin-like growth factor-1 (IGF-1) acts as an autocrine growth factor in these cells. In addition, OPM-6 cells were particularly sensitive to dexamethasone (DEX), when endogenous IGF-1 was blocked. Under these conditions, >95% of the DEX-treated cells died within 36 h. Therefore, OPM-6 represents a potentially powerful tool for the analysis of the molecular mechanisms of DEX-induced apoptosis, because it is possible to easily analyze the direct effects of DEX using this system. Using this culture system of OPM-6, we demonstrated that the treatment with DEX plus a monoclonal antibody to the human IGF-1 receptor (alphaIGF-1R) leads to the down-regulation of the gene expression of Bcl-xL, an antiapoptotic gene, and the activation of CPP32 during this apoptotic process. IFN-alpha as well as IL-6 prevented DEX plus alphaIGF-1R-induced apoptosis, and this prevention was blocked by the mitogen-activated protein kinase kinase inhibitor, PD098059, or the phosphatidylinositol 3-kinase inhibitor, wortmannin. Therefore, both IL-6 and IFN-alpha blocked DEX plus alphaIGF-1R-induced apoptosis through activation of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways.
Aged↗
Integrin-associated protein/CD47 regulates motile activity in human B-cell lines through CDC42.
Cell migration requires a dynamic interaction between the cell, its substrate, and the cytoskeleton-associated motile apparatus. Integrin-associated protein (IAP)/CD47 is a 50-kd cell surface protein that is physically associated with beta3 integrins and that modulates the functions of beta3 integrins in various cells. However, in B-lymphocytes that express beta1 integrins but few beta3 integrins, the roles of IAP/CD47 remain to be determined. Cross-linking of IAP/CD47 by the immobilized anti-IAP/CD47 monoclonal antibody (mAb) B6H12, but not 2D3, produced signals to promote polarization with lamellipodia, a characteristic morphology during leukocyte migration, in pre-B and mature B-cell lines (BALL, Nalm6, ONHL-1, Daudi), but not in myeloma cell lines (RPMI8226, OPM-2). In the presence of the immobilized fibronectin (FN), soluble B6H12 could increase the rate of the polarization and activate migratory activity of BALL cells to FN in a transwell filter assay. Furthermore, the dominant-negative form of CDC42 completely blocked B6H12-induced morphologic and functional changes without inhibiting phorbol 12-myristate 13-acetate-induced spreading on FN in BALL cells, whereas the dominant-negative form of Rac1 inhibited all these changes. These findings demonstrate that in B-lymphocytes, IAP/CD47 may transduce the signals to activate the migratory activity, in which CDC42 may be specifically involved, and that IAP/CD47 shows synergistic effect with alpha4beta1 on B-cell migration. These findings would provide new insight into the role of IAP/CD47 on B-cell function.
Antibodies, Monoclonal↗
Antigen dose defines T helper 1 and T helper 2 responses in the lungs of C57BL/6 and BALB/c mice independently of splenic responses.
To investigate the effect of antigen dose on immune response, C57BL/6 and BALB/c mice were sensitized with aluminum hydroxide gel (alum)-precipitated ovalbumin (OVA) then challenged with aerosolized OVA. Low-dose sensitization (less than 8 microg of OVA) elicited T helper 2 (Th2)-type immunoglobulins (Igs) secretion from C57BL/6 mice, including high levels of serum IgE, IgG1 and low levels of IgG2a, while BALB/c mice secreted T helper 1 (Th1)-type Igs, including low levels of IgE, IgG1 and high levels of IgG2a. In contrast, high-dose sensitization (more than 50 microgram) elicited Th1-type Igs secretion in C57BL/6mice, while BALB/c mice exhibited Th2-type Igs secretion. Furthermore, the number of eosinophils infiltrating into the lungs of low-dose OVA-sensitized C57BL/6 mice was significantly greater than in BALB/c mice sensitized with the same amount of OVA. Only a very high dose of OVA (1 mg) could induce greater eosinophil infiltration into the lungs of BALB/c mice compared with C57BL/6 mice. Additionally, low-dose sensitization generated Th2-type cytokines, including high levels of interleukin (IL) -4, IL-5 and a low level of interferon-gamma (IFN-gamma) in the lungs of C57BL/6 mice, while BALB/c mice generated Th1-type cytokines in their lungs, including low levels of IL-4, IL-5 and a high level of IFN-gamma. In contrast, high-dose sensitization elicited Th1-type cytokines production in the lungs of C57BL/6 mice, while BALB/c mice generated Th2-type cytokines in their lungs. Interestingly, splenocyte cultures from C57BL/6 mice produced Th1-type cytokines, while cultures from BALB/c mice produced Th2-type cytokines regardless of OVA sensitization dose (100 ng-1 mg). These results indicate that C57BL/6 and BALB/c mice have different susceptibilities to OVA-sensitization and OVA-induced pulmonary eosinophilia regulated by Th1- and Th2-type cytokines, independent of splenic Th1- and Th2-type cytokines production.
Animals↗
Cardiac sympathetic dysfunction contributes to left ventricular remodeling after acute myocardial infarction.
To investigate the role of the cardiac sympathetic nervous system in left ventricular remodelling, 50 patients with first-time acute myocardial infarction (AMI) and patency of the infarct-related artery after reperfusion underwent quantitative iodine-123 metaiodobenzylguanidine (MIBG) imaging at 4 days and 4 weeks (n=42), and quantitative technetium-99m tetrofosmin imaging at 2 days after AMI. They also underwent both ventriculography and coronary angiography on admission and about 4 weeks after AMI. On the basis of left ventricular end-systolic volume (LVESV), patients were divided into two groups. Patients with LVESV dilatation (n=20) had a significantly lower ejection fraction (P<0.003) and a significantly higher severity score of 99mTc-tetrofosmin (P<0.04), and total severity (P<0.01), delta extent (P<0.007) and delta severity (P<0.0008) scores of MIBG than patients without LVESV dilatation (n=30). delta severity score of MIBG was directly correlated with change in LVESV at 4 weeks (r=0.63, P<0.0001). Stepwise linear discriminant function analysis showed that delta severity score of MIBG (P<0.0002) was the only discriminator of LVESV dilatation. Patients with LVESV dilatation had higher regional washout rates in both the infarct and the non-infarct zones than patients without such dilatation. Furthermore, no MIBG parameters changed significantly between 4 days and 4 weeks after AMI. In reperfused AMI, delta severity score of MIBG was related to the degree of ventricular dilatation and was the only powerful discriminator of ventricular dilatation. These results suggest that cardiac sympathetic nervous abnormality might contribute to left ventricular remodelling in reperfused AMI. MIBG imaging may allow identification of reperfused AMI patients at high risk for left ventricular remodelling.
3-Iodobenzylguanidine↗