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Biomedical subjects

Y Nagano

Publications and source records attributed to Y Nagano.

At least 55 records · Page 3Linked to original sources
PubMed1998

Identification of a highly encapsulated, genetically related group of invasive type III group B streptococci.

Type III group B streptococci (GBS) isolated from Tokyo and Salt Lake City were classified according to the similarity of HindIII and Sse83871 restriction digest patterns (RDPs) of bacterial DNA. The bacteria were clustered into three RDP types, with excellent correlation between subtyping based on the two enzymes. The majority (91%) of invasive isolates obtained from neonates were RDP type III-3. The mean sialic acid content of the III-3 strains was higher than that of other type III strains. Closely related isolates were concordant for expression of the bacterial enzyme C5a-ase, but invasive strains were no more likely to be C5a-ase positive than were strains isolated from the genitourinary tract of pregnant women. These data indicate that a group of genetically related organisms with increased capsule production causes the majority of invasive type III GBS disease.

Adult↗
PubMed1998

Co-stimulation of T cells with CD2 augments TCR-CD3-mediated activation of protein tyrosine kinase p72syk, resulting in increased tyrosine phosphorylation of adapter proteins, Shc and Cbl.

Complete T cell activation requires not only the first signal via TCR-CD3 engagement, but also a co-stimulatory signal through accessory receptors such as CD2, LFA-1 and CD28. However, the pathway of co-stimulatory signaling through accessory receptors is incompletely understood. We report here that CD2 provides a co-stimulus for activation of CD3-mediated syk/ZAP-70 family kinase, p72Syk (Syk), in Jurkat T cells. Although cross-linking of CD2 alone or any combination of CD2 with LFA-1alpha, LFA-1beta or CD28 did not induce tyrosine phosphorylation of Syk, co-cross-linking of CD2 with CD3 enhanced CD3-mediated tyrosine phosphorylation of Syk. Enhancement of tyrosine phosphorylation of Syk by CD2 co-stimulation was CD2 antibody concentration-dependent, and time course studies showed that CD2 co-stimulation enhanced Syk tyrosine phosphorylation by 30 s and through 5 min stimulation compared with the control. In vitro kinase assay revealed that co-cross-linking of CD2 with CD3 augmented Syk kinase activity using myelin basic protein as a substrate. Furthermore, CD2 co-stimulation with CD3 resulted in enhanced tyrosine phosphorylation of adapter proteins, such as Shc and Cbl, in an antibody concentration-dependent manner. Finally, CD2 provided a co-stimulatory signals for synthesis of IL-2 in Jurkat cells and phytohemagglutinin (PHA)-activated T cells and for proliferation of PHA-activated T cells. Taken together, these results indicate that CD2 is an important co-stimulatory receptor for CD3-mediated T cell activation and functions in concert with CD3.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Ventilatory control during exercise in normal children.

We investigated the relation between age and respiratory control during exercise in 80 children aged 6.4-17.6 y (42 male, age, 11.6 +/- 3.3 y; body weight, 41.3 +/- 14.7 kg; and 38 female, age, 12.6 +/- 2.7 y; body weight, 42.5 +/- 9.3 kg). Exercise tests were performed on a treadmill after a standard symptom-limited Bruce protocol. Data were analyzed separately for boys and girls. At rest and at peak exercise, the ratio of minute ventilation to carbon dioxide production (VE/VCO2), the ratio of effective alveolar ventilation to carbon dioxide production (VA/VCO2), the ratio of pulmonary dead space to tidal volume (Vd/Vt), and arterial PCO2 (PaCO2) were not correlated with age. At the exercise intensity of ventilatory anaerobic threshold, the PaCO2 increased, and the VA/VCO2 decreased, significantly with age, whereas the Vd/Vt was not related to age. Linear regression analysis demonstrated that the slope of the relationship between VE and VCO2 (deltaVE/deltaVCO2) and the slope of the relationship between VA and VCO2 (deltaVA/deltaVCO2) decreased with age. There were no gender differences in the regression slopes and the intercepts of the relationships. Results show that younger children breathe more during exercise to eliminate a given amount of CO2 to keep PaCO2 set point slightly but significantly lower than older children. This age dependence must be considered in investigating ventilatory control during exercise in children.

Adolescent↗
PubMed1998

Morphodifferentiation of skeletal muscle fiber ends at the myotendinous junction in the postnatal Chinese hamster: a scanning electron microscopic study.

The postnatal morphodifferentiation of muscle fiber ends at the myotendinous junction was examined by scanning electron microscopy in gastrocnemius muscles of the Chinese hamster. Muscle fiber ends during the first week were simply conical or slightly complex, having a few pit-like invaginations and longitudinal and narrow clefts. By the second week, fiber ends gradually became complicated with an increased number of clefts and finger-like processes. Pits and short clefts linearly arranged towards the fiber tip were visible until the second week. This possibly indicates the linear elongation of the clefts by the fusion of adjacent pits to one another and to preexisting clefts. By the fourth week, the fiber ends had almost fully matured and displayed numerous cytoplasmic processes and lateral grooves.

Animals↗
PubMed1998

Structure and activation of the large latent transforming growth factor-Beta complex.

BACKGROUND: Many cytokines regulate processes involved in the pathogenesis of proliferative vitreoretinopathy. Transforming growth factor-beta (TGF-beta) is an example of a pluripotent growth factor that regulates cell proliferation, extracellular matrix (ECM) deposition, cell migration, and differentiation--all biological activities involved in the formation and progression of proliferative vitreoretinopathies. METHODS: A review of experimental results that demonstrate how vascular cells generate biologically active TGF-beta is presented. Most cell types--including endothelial cells and pericytes, which form the retinal microvasculature--express TGF-beta as a large latent TGF-beta complex. Mature TGF-beta, the biologically active form, must be generated from the large latent complex before it can signal by binding to its high affinity cell surface receptors. RESULTS: A critical step in regulating TGF-beta effects may be the activation of the large latent TGF-beta complex. Activation of the complex can be achieved by chemical and enzymatic treatments, or by various cell systems. We have identified that co-culturing bovine smooth muscle cells or pericytes and endothelial cells generates active TGF-beta. CONCLUSION: The mechanism of latent TGF-beta activation self-regulates through effectors of plasmin generation. Studying TGF-beta generation by co-cultures of pericytes and endothelial cells can provide us with insights into how disruption of latent TGF-beta activation may lead to unregulated endothelial proliferation, ECM deposition, and cellular infiltration, as observed clinically in neovascular- and fibrotic-related pathologies.

Animals↗
PubMed1997

Induction of endothelial platelet-derived growth factor-B-chain and intercellular adhesion molecule-1 by lysophosphatidylcholine.

Lysophosphatidylcholine (lyso-PC) is a major phospholipid component of atherogenic lipoproteins. Lyso-PC has been shown to differentially upregulate the adhesion molecules, such as VCAM-1 and ICAM-1, as well as smooth muscle growth factors, such as PDGF-A, B chains and HB-EGF gene expression in various cultured endothelial cells. In this paper, we demonstrate increased expression of cell- and matrix-associated forms of PDGF-B protein elicited by lyso-PC and further characterized potential signal transduction mechanisms responsible for lyso-PC-induced human umbilical vein endothelial cell. Cycloheximide inhibited PDGF-B but not ICAM-1 mRNA induction by lyso-PC, suggesting the dependence on de novo protein synthesis for PDGF-B, but not ICAM-1. A protein kinase C (PKC) inhibitor did not block lyso-PC-induced increases in PDGF-B or ICAM-1 mRNA. The elevated level of cAMP blocked both PDGF-B and ICAM-1 upregulation by lyso-PC. However cAMP-elevating agents did not suppress ICAM-1 upregulation by PMA. Taken together, PDGF-B and ICAM-1 gene induction by lyso-PC may involve different signaling mechanisms; however, both appear to be independent of PMA-regulatable PKC activation but are suppressed by increased levels of intracellular cAMP.

Blotting, Northern↗
PubMed1997

Analysis of heart rate variability demonstrates effects of development on vagal modulation of heart rate in healthy children.

OBJECTIVES: Analysis of heart rate variability (HRV) has been found to be a useful method of assessing cardiovascular autonomic control, but normal values for standard HRV measures in children have not been established. We analyzed HRV in 60 healthy children aged 3 to 15 years to determine normal values and to assess the effects of development on cardiac autonomic control with the use of ambulatory electrocardiographic monitoring. RESULTS: The high-frequency (HF) component, an index of cardiac autonomic tone, increased significantly with age from 3 to 6 years (p < 0.01) and decreased with age from 6 to 15 years (p < 0.01), and the magnitude of HF correlated significantly with the R-R intervals. Thus the changes in cardiac autonomic tone could be described as a simple equation using age and heart rate. CONCLUSIONS: We present normal values and changes in the cardiac autonomic system during childhood after HRV analysis, which could lead to a better understanding and treatment of cardiac disease in children.

Adolescent↗
PubMed1997

Long lasting smooth muscle relaxation by a novel PACAP analogue in guinea-pig and primate airways in vitro.

1. We compared the relaxant effect of pituitary adenylate cyclase activating peptide (PACAP) 1-27 with that of a newly developed PACAP 1-27 analogue, [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2, in the guinea-pig trachea and primate bronchi in vitro (n = 4-5). 2. In the guinea-pig trachea precontracted by a submaximally effective carbachol concentration (0.1 microM), cumulative administration of PACAP 1-27 and the beta 2-adrenoceptor agonist salbutamol (3 nM-3 microM) caused significant and concentration-dependent smooth muscle relaxation, with salbutamol being approximately one log-step more potent in this model. However, in primate bronchi precontracted by carbachol (0.1 microM), cumulative administration of PACAP 1-27 and salbutamol caused concentration-dependent smooth muscle relaxation with very similar potencies and maximum relaxant effects. 3. In the guinea-pig trachea, non-cumulative administration of the PACAP 1-27 analogue and the original PACAP 1-27 (0.3-3 microM) caused concentration-dependent relaxation with a very similar maximum relaxant effect and potency. However, the onset and offset of action was markedly slower for the PACAP 1-27 analogue than for the original PACAP 1-27 (< 90% versus < 10% of peak relaxation remaining 6 h after administration). Separate experiments confirmed that the PACAP 1-27 analogue also caused significant relaxation with slower onset and offset of action than did the original PACAP 1-27 in primate bronchi. 4. Peptidase inhibition by captopril (10 microM) and phosphoramidon (1 microM) significantly increased the maximum relaxant effect and duration of action of PACAP 1-27 but not of the PACAP 1-27 analogue, during the 3 h of observation in the guinea-pig trachea. 5. We conclude that [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2 produces significant, concentration-dependent and sustained airway smooth muscle relaxation in vitro. The sustained relaxant effect is due, at least in part, to the PACAP 1-27 analogue being less susceptible to cleavage by peptidases than the original peptide PACAP 1-27.

Albuterol↗
PubMed1997

Topographic comparison of subneural apparatuses at neuromuscular junctions in normal and dystrophic (mdx) mice: a scanning electron microscope study.

The differences in the morphodifferentiation of subneural apparatuses (SNAs) at neuromuscular junctions (NMJs) in the extensor digitorum longus muscle of normal and dystrophic (mdx) mice were examined by scanning electron microscopy. In normal mice, primitive shallow cup-like synaptic troughs present at birth had developed to anastomosing grooves containing both pit-like and slit-like junctional folds (JFs) during the 2nd postnatal week. At the 35th day, the SNAs had developed to almost the adult forms, consisting of labyrinthine synaptic grooves with exclusively slit-like JFs. In the mdx mice, the SNAs showed transformation similar to those in the normal mice until the 35th postnatal day. After this period, SNAs with a number of cup-like depressions occurred and increased in number. These morphological changes seemed to be found on regenerating muscle fibers after necrosis, probably indicating the remodelling of their NMJs.

Animals↗
PubMed1997

Resistance to herpes simplex virus type 1 and its latent infection of human T cell lymphotropic virus type I-transformed T cell lines of rabbits.

Fourteen T cell lines of rabbits were infected with herpes simplex virus type 1 (HSV-1) and examined for their susceptibility to lytic infection and ability to support virus replication. T cell lines of CD4+ 8- phenotype were more vulnerable to lysis and supported higher levels of virus replication than those of other phenotypes. Cell lines of CD4+ 8+ and CD4- 8+ phenotypes continued to proliferate, while remaining productively infected, for more than a month. These latently infected cell lines could be established by treatment with anti-HSV-1 serum and complement. Viral genes were only partially expressed and the CD8 membrane antigen was down-regulated. Infected cell lines, as well as peripheral blood lymphocytes, were shown to induce meningoencephalitis when inoculated intravenously into syngeneic hosts, suggesting a possible role for infected lymphocytes in HSV-1 transport in vivo.

Animals↗
PubMed1996

Oxygen uptake efficiency slope: a new index of cardiorespiratory functional reserve derived from the relation between oxygen uptake and minute ventilation during incremental exercise.

OBJECTIVES: We investigated the usefulness of a new variable, oxygen uptake efficiency slope (OUES), as a submaximal measure of cardiorespiratory functional reserve. The OUES is derived from the relation between oxygen uptake (Vo2 [ml/min]) and minute ventilation (VE [liters/min]) during incremental exercise and is determined by VO2 = a log VE + b, where a = OUES, which shows the effectiveness of Vo2. BACKGROUND: Maximal oxygen uptake (VO2max) is effort dependent. There is no standard submaximal measurement of cardiorespiratory reserve that provides generally acceptable results. METHODS: Exercise tests, following a standard Bruce protocol, were performed on a treadmill by 108 patients with heart disease and 36 normal volunteers. Expired gas was continuously analyzed. The OUES was calculated from data of the first 75%, 90% and 100% of exercise duration. We also determined the following submaximal variables: the ventilatory anaerobic threshold (VAT), the slope of the regression line of the minute ventilation-carbon dioxide production relation (VE-VCO2 slope) and the extrapolated maximal oxygen consumption (EMOC). We analyzed the relation of OUES and other submaximal variables against VO2max and examined the effects of submaximal exercise on OUES. RESULTS: The correlation coefficient of the logarithmic curve-fitting model was 0.978 +/- 0.016 (mean +/- SD). The OUES and VO2max had a significant correlation (r = 0.941, p < 0.0001). The correlation between VO2max and OUES was stronger than that between VO2max and VAT, the VE-VCO2 slope or EMOC. The OUES values for 100% and 90% of exercise were not different from each other (at an alpha value of 0.05 and treatment effect of 170, the power of the test [1-beta] was 0.90); OUES for 75% of exercise was slightly lower (3.5%). CONCLUSIONS: Our results suggest that OUES may provide an objective, effort-independent estimation of cardiorespiratory functional reserve that is related both to pulmonary dead space and to metabolic acidosis.

Adolescent↗
PubMed1996

Exercise-induced ventricular tachycardia without demonstrable heart disease in childhood.

Exercise-induced ventricular tachycardia (VT) without demonstrable heart disease was studied in pediatric patients. The study population consisted of 17 patients aged 5-14 years (average 9.1 years), who demonstrated reproducible VT during or immediately after exercise testing using a treadmill. The main reasons for the exercise testing were episodes of exercise-related syncope in two patients, exercise-related palpitation in seven and evaluation of sporadic ventricular premature contraction (VPC) in eight. Of the eight patients in the asymptomatic group, two developed sustained VT and the other six had non-sustained VT. Of the nine patients in the symptomatic group, six developed sustained VT. Verapamil produced a good response in seven of 14 patients, and propranolol in six. None of the patients died during the follow-up period, an average of 59.6 months. In four patients, both VT and VPC disappeared, not only on exercise testing, but also on Holter electro-cardiograms, so the anti-arrhythmic agents were discontinued. One patient had syncope and convulsion caused by rapid bidirectional VT in the follow-up period. It was concluded that the prognosis of exercise-induced VT without demonstrable heart disease in children is relatively benign, but careful follow-up is required.

Adolescent↗
PubMed1996

Improved production of phenomycin by a genetically engineered Escherichia coli.

We established an improved production of an antitumor polypeptide anti biotic, phenomycin (PHM), by using a genetically engineered Escherichia coli. Phenomycin consists of 89 natural amino acids without intramolecular disulfide bridge. PHM gene was synthesized as a fusion gene in which PHM at the C-terminus and the residues 1 approximately 20 of Hirudin variant 1 (HV1) at the N-terminus connected by a factor Xa recognition sequence (Ile-Glu-Gly-Arg). E coli JM 109 transformed with a plasmid containing the synthesized gene expressed a fusion protein and the trypsinization of the fusion protein purified by ultrafiltration and ion-exchange chromatography gave efficiently recombinant PHM at a final yield of 50 mg/liter of culture. This PHM yield was six times higher than that obtained by a natural PHM producing strain of Streptoverticillium baldacci. Recombinant PHM was not distinguishable from natural PHM in all aspects observed.

Anti-Bacterial Agents↗
PubMed1996

Structure and activation of the large latent transforming growth factor-beta complex.

Most cell types express transforming growth factor-beta (TGF-beta) as a large latent TGF-beta complex that must be converted to an active form before TGF-beta can interact with cell surface TGF-beta receptors. This conversion involves the release of mature TGF-beta from the complex by disrupting noncovalent interactions between mature TGF-beta and its propeptide, latency associated peptide. A critical step in regulating TGF-beta effects may be the activation of the large latent TGF-beta complex. Activation of the complex can be achieved by chemical and enzymatic treatments, or by various cell systems. We have identified that coculturing bovine endothelial and smooth muscle cells generates active TGF-beta. Coculture activation of the large latent TGF-beta complex occurs through a plasmin-dependent mechanism that requires concentration of reactants on the cell surface and/or extracellular matrix. The mechanism of latent TGF-beta activation self-regulates through effectors of plasmin generation.

Animals↗