Usefulness of accelerated diastolic reversed flow along the left ventricular posterior wall in aortic regurgitation for estimating left ventricular function.
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Adult↗
Biomedical subjects
S Handa
Publications and source records attributed to S Handa.
Isolation and structural characterization of a mono-sulfated isoglobotetraosylceramide, the first sulfoglycosphingolipid of the isoglobo-series, from rat kidney.
A novel sulfoglycosphingolipid based on the isoglobo-series core structure was isolated from rat kidney and purified by column chromatographies with DEAE-Sephadex and silica beads. The structure was characterized by solvolysis, compositional analysis, proton NMR spectroscopy, Fourier-transform infrared spectroscopy, methylation analysis and liquid secondary ion mass spectrometry (LSIMS). The characteristic fragment ions for a sulfate and a sulfated N-acetylhexosamine were observed in LSIMS spectra. The two-dimensional chemical-shift-correlated spectroscopy (COSY) and nuclear Overhauser enhancement spectroscopy experiments evidenced the presence of a 3-O-sulfated N-acetylgalactosamine and a Gal alpha 1-3Gal structure in the molecule. The major ceramide consisted of 4-hydroxysphinganine linked to a C24 nonhydroxy fatty acid, deduced from both compositional analysis and LSIMS. From the above results, the following structure was established for this glycolipid: HSO3-3GalNAc beta 1-3Gal alpha 1-3Gal beta 1-4Glc beta 1-1Cer, isoglobotetraosylceramide (iGb4Cer) IV3-sulfate. Rat kidney also contained globotetraosylceramide (Gb4Cer) IV3-sulfate which has a carbohydrate core identical to that from human kidney. The yields of iGb4Cer IV3-sulfate and Gb4Cer IV3-sulfate were 0.27 and 0.07 nmol/g wet tissue, respectively.
Animals↗
Human hepatoma gangliosides: occurrence of a novel I-type glycolipid with NeuAc alpha 2-6Gal structure.
Gangliosides with NeuAc alpha 2-6Gal structure have been studied in human hepatocellular carcinoma. The gangliosides were purified to homogeneity by a DEAE-Sephadex A-25 column chromatography and by repeated silica beads column chromatography. Three gangliosides containing NeuAc alpha 2-6Gal structure were isolated and were structurally characterized by using monoclonal antibodies, proton nuclear magnetic resonance, fast atom bombardment mass spectrometry, methylation analysis by gas chromatography-mass spectrometry, and exoglycosidase treatments. The first compound was identified as NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer. The structures of 2 other components were concluded to be as follows: [formula: see text] The first compound is a ganglioside that is characteristic of human meconium. The second compound has the same structure as a ganglioside recently found by us (Taki, T., Rokukawa, C., Kasama, T., Kon, K., Ando, S., Abe, T., and Handa, S., J. Biol. Chem., 267: 11811-11817, 1992) in meconium. The third compound is a novel type of ganglioside having blood group I-type structure as the core sequence. In addition to these gangliosides, 5 others were detected, and all except for GM3 were glycolipids with neolacto-series core structure. These results suggest that enzymes for the synthesis of neolacto type and NeuAc alpha 2-6Gal structure of glycolipids are activated in hepatoma.
Antibodies, Monoclonal↗
The strain-dependent constitutive expression of murine serum amyloid-P component is regulated at the transcriptional level.
The strain-dependent expression of murine serum amyloid P-component (SAP) has been known to be linked to the Sap locus. We have quantified the SAP mRNA in several inbred strains including DBA/2 and C57BL/6 mice which represent high and low producers of SAP at resting state, respectively, and found that the mRNA levels correlated well with the amount of SAP protein. Interestingly, the SAP mRNA level of F1 mouse between DBA/2 and C57BL/6 was low and similar to that of C57BL/6. Primer extension and ribonuclease (RNAase) protection analyses demonstrated that a single type of transcript was generated from the SAP gene and that the cap sites were identical regardless mouse strains tested under unstimulated and stimulated (by lipopolysaccharide (LPS) or interleukin-6 (IL-6)) conditions. To investigate possible structural difference of the SAP gene including 5' flanking region, we have cloned, sequenced and compared the SAP genes from DBA/2 and C57BL/6 mice. Sequence analyses revealed that the 5' flanking regulatory regions, as well as the coding regions, were well-conserved between the two strains. These results demonstrate that the strain-dependent SAP expression occurs at the transcriptional level but seems to be affected by neither different type of the transcripts nor structural difference of the 5' flanking and coding regions of the SAP gene. It was suggested that a possible transcription factor with suppressive activity, which is encoded by a gene linked to Sap, may be involved.
Animals↗
Human meconium gangliosides. Characterization of a novel I-type ganglioside with the NeuAc alpha 2-6Gal structure.
Three monosialogangliosides containing the NeuAc alpha 2-6Gal structure have been detected in human meconium by immunological analysis using a monoclonal antibody, MSG-15, and purified by repeated silica beads column chromatography. One was previously shown to be NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer. The remaining two were characterized by proton NMR, fast atom bombardment mass spectrometry, methylation analysis by gas chromatography-mass spectrometry, and immunological studies, and their structures were concluded to be as follows. [formula: see text] The second ganglioside has the same structure that was isolated from bovine buttermilk (Takamizawa, K., Iwamori, M., Mutai, M., and Nagai, Y. (1986) J. Biol. Chem. 261, 5625-5630), and this is the first description of the occurrence of the ganglioside with the branched structure with two N-acetyllactosamines linked to lactosylceramide via beta 1-6 and beta 1-3 in human linked to lactosylceramide via beta 1-6 and beta 1-3 in human tissues. The third ganglioside is a novel ganglioside with blood group I-type and a NeuAc alpha 2-6Gal structure.
Amino Sugars↗
Stimulation of anchorage-independent cell growth by endothelin in NRK 49F cells.
Endothelin (ET) is a vasoconstrictor peptide originally isolated from vascular endothelial cells. Recent studies have revealed that ET has many biological functions including growth factor-like activity. The present study aims to clarify whether ET-1 possesses the ability to stimulate anchorage-independent cellular growth, an indicator of factors with transforming activity. We found that NRK 49F cells possess a large number of high-affinity ET-1 receptors; labeled 125I-ET-1 binding was displaced by unlabeled ET-2 in a similar dose response, but in the case of ET-3, 100-fold more was required. Specific 125I-ET-3 binding was undetectable in NRK 49F cells, indicating that ET receptors in NRK 49F cells are ET-1/ET-2 selective. NRK 49F is a cell line which is most commonly used to assay for anchorage-independent cellular growth. Therefore, we explored whether ETs promote anchorage-independent cellular growth in this cell line. ET-1 and ET-2 stimulated NRK colony formation dose dependently in the presence of 1 nM epidermal growth factor (EGF). In contrast, ET-3 did not have colony-stimulating ability. In the presence of EGF, the maximal effect of ET-1 was approximately 90% of that of transforming growth factor-beta. Moreover, in the presence of maximal stimulating concentrations of EGF and transforming growth factor-beta, ET-1 additionally induced colony formation. These results indicate that ET-1 and -2 possess transforming growth factor-like activity for NRK 49F cells. Since ET-1 and -2 increased intracellular calcium levels, this ion may participate in signal transduction pathways by which ET-1 and -2 promote colony formation.
Animals↗
Elevation of 4 beta-galactosyltransferase activity for paragloboside synthesis in sera of patients with cancer.
Galactosyltransferase activities in sera of cancer patients were determined by assaying the formation of paragloboside from UDP-galactose and lactotriaosylceramide immobilized on microtiter plates by means of the enzyme-linked immunosorbent assay using a monoclonal antibody, H-11, directed to paragloboside. Enzyme properties were as follows. Optimum pH was 6.8 in cacodylate buffer, and Km values were 2 microM for lactotriaosylceramide and 29 microM for UDP-galactose. The enzyme activity was inhibited by the addition of alpha-lactalbumin. Glucose (20 mM) inhibited the enzyme activity in the presence of alpha-lactalbumin (0.1 mg/ml) but not in its absence. These enzyme properties are similar to those of bovine milk galactosyltransferase, indicating that the enzyme in the sera might be lactose synthetase. The enzyme activities in sera from patients with cancer, patients with benign disease, or a reference sample group were assayed. The activity was below the limit of detection (5.5 pmol/25 microliters serum/2 h) in the reference sample group. Remarkable elevations of the enzyme activity were observed with high incidence in patients with cancer, especially those with blood cancer (100%). A high incidence was observed in the progressive stage, and the enzyme activity was detected at stage 1 in lung, esophagus, stomach, colorectal, and testis cancer. The enzyme activity in sera from patients with benign disease was elevated in 22% of the patients. After effective therapies, the enzyme activity decreased to below the limit of detection. Release of the galactosyltransferase into culture medium of cancer cells could be demonstrated. These observations suggest that the galactosyltransferase is released from cancer tissue into the circulation. The present method for the assay of galactosyltransferase may be useful for the detection of patients with cancer and for monitoring neoplastic recurrence after therapy.
Antibodies, Monoclonal↗
Left ventricular ejection performance in mitral stenosis, and effects of successful percutaneous transvenous mitral commissurotomy.
Impaired left ventricular ejection performance was reported in pure mitral stenosis. The speculative mechanisms included insufficient preload, increased wall stress, high right ventricular pressure and unknown myocardial factors, but no definitive mechanism has been established. Fifteen patients with tight mitral stenosis who underwent successful percutaneous transvenous mitral commissurotomy were studied to ascertain whether ejection performance would improve with sufficient blood filling. The indexes of preload (end-diastolic volume) and ejection performance (stroke volume, ejection fraction, and mean systolic and mean normalized ejection rates) were calculated angiographically before and immediately after mitral commissurotomy. Improved blood filling (the result of successful mitral commissurotomy) produced an increase in end-diastolic volume (mean +/- SD 99.0 +/- 30.2 to 112.1 +/- 30.1 ml/m2; p less than 0.05). All 4 indexes of ejection performance also improved. There was good correlation between end-diastolic and stroke volumes before intervention (stroke volume = 0.476 x end-diastolic volume + 16.77; r = 0.76), and the relation between them showed no change even after mitral commissurotomy. It is concluded that both left ventricular preload and ejection performance improved after successful percutaneous transvenous mitral commissurotomy. Insufficient preload could affect ejection performance in patients with tight mitral stenosis.
Adult↗
Expression and structure of serum gp70 as an acute phase protein in NZB mice.
A cDNA corresponding to a serum gp70 synthesized as an acute phase protein in mouse hepatocytes was cloned and analyzed. This cloned cDNA had the characteristics of an endogenous xenotropic murine leukemia virus. Synthesized oligo-DNA specific for this cDNA reacted strongly with liver RNA derived from NZB mice injected with LPS as a trigger of an acute phase inflammatory response. There was also low level of gp70 in the kidney in response to LPS injection. The LTR structure of the cDNA showed that this clone is the immediate precursor of an infectious xenotropic virus in the proposed evolutionary scheme of murine leukemia virus.
Acute-Phase Proteins↗
Postischaemic hypercontraction is enhanced in ischaemically injured canine myocardium.
OBJECTIVE: The aim was to identify the role of calcium flux in the pathogenesis of transient overshoot of regional myocardial contraction after brief ischaemia, ie, postischaemic hypercontraction. METHODS: Ten anaesthetised mongrel dogs were examined under open chest conditions. The left anterior descending coronary artery was initially occluded for 2 min and reperfused for 10 min. A further period of coronary occlusion of 15 min duration was followed by 15 min reperfusion to produce postischaemic regional dysfunction. A third occlusion of 2 min duration was followed by 10 min reperfusion to induce postischaemic hypercontraction. Coronary blood flow was measured using an ultrasonic transit time flow meter. Segment length was measured by ultrasonic microcrystals. RESULTS: Postischaemic hypercontraction after 2 min coronary occlusion was exaggerated in ischaemically injured myocardium. The 10 dogs were divided into two groups, a control group (n = 5) and a verapamil treated group (n = 5), and were exposed to a final 2 min period of coronary occlusion with or without verapamil in the ischaemically injured myocardium. Postischaemic hypercontraction was attenuated in the verapamil treated group compared with the control group. CONCLUSIONS: Exaggeration of postischaemic hypercontraction in ischaemically injured myocardium may be mediated by a trans-sarcolemmal calcium flux. Changes in calcium flux may play a role in the pathogenesis of this phenomenon in the normal myocardium.
Animals↗
13C-nuclear magnetic resonance of glycosphingolipids.
Spectra of 125 MHz 13C-nuclear magnetic resonance (NMR) of glycosphingolipids, GlcCer, GalCer, sulfatide, LacCer, and nLc4Cer have been studied, and the following results were obtained. (i) Signals of ring carbons of each sugar component are distributed in a wide field (50-110 ppm) and clearly separated. (ii) Chemical shifts of anomeric carbon (C1) and methylene carbon (C6) of sugars are far from those of other methine carbons of sugars and characteristic of sugar components, which makes it possible to identify each sugar component and its molar raito. (iii) The downfield shifts (about 6-9 ppm) of alpha-carbon signals involved in the glycosidic linkages and upfield shifts (about 1.5-2 ppm) of the neighboring beta-carbons, which are known as glycosylation shifts, could be observed. (iv) Characteristic shifts of aglycon signals caused by the presence of an OH group at the alpha-position of fatty acid were assigned. These observations are useful for the characterization of glycosphingolipid structures.
Carbohydrate Conformation↗
Augmented plasma protein C activity after coronary thrombolysis with urokinase in patients with acute myocardial infarction.
Coronary thrombolysis reduces morbidity and mortality in patients with acute myocardial infarction, however, the exact effects of thrombolytic agents on the status of intrinsic hemostases are not fully understood. In the present study, we examined serial changes in plasma thrombin and protein C activities of 6 patients with acute myocardial infarction treated with urokinase. Fibrinolysis occurred immediately after urokinase injection with an increase in the plasma thrombin-antithrombin III complex, suggesting a subsequent procoagulant state due to thrombin generation. Correspondent increases in plasma protein C activity were observed, however, protein S levels did not change at all. Our findings suggest that urokinase administration for coronary thrombolysis not only causes fibrinolysis, but also induces thrombin activity, which may be antagonized by augmented intrinsic protein C activity.
Aged↗
Progression of systolic dysfunction correlated with the ultrasonographically assessed myocardial tissue damage in patients with dilated cardiomyopathy.
An echocardiographic follow-up study was performed in 59 patients with dilated cardiomyopathy to characterize the relationship between left ventricular systolic dysfunction and the myocardial tissue character assessed by echocardiographic myocardial gray level distributions. All the selected patients were divided into two groups; those with (group A) and those without (group B) progressive systolic dysfunction. In group A, the ejection fraction decreased from 47 +/- 5 to 23 +/- 4% (p < 0.05) during the follow-up period. The histogram of the myocardial gray level distribution became wider, less peaked and more right-sided in those patients. The relative echo intensity of the myocardium increased from 1.29 +/- 0.19 to 1.60 +/- 0.18 (p < 0.01). In group B, however, neither the shape of the gray level distribution nor ejection fraction changed during the same follow-up period. The relative echo intensity did also not change. Our present results suggested that some of the patients with dilated cardiomyopathy showed progressive systolic dysfunction with extensive myocardial tissue damage.
Adult↗
Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation.
BACKGROUND: Shear-induced platelet aggregation (SIPA) is an important mechanism in thrombogenesis. von Willebrand factor (vWF) binding to platelet glycoprotein Ib (GP Ib) has been found to be crucial for platelet aggregation under the high shear force probably generated in stenosed coronary artery. The physiological significance of vWF-dependent SIPA has not been clarified. METHODS AND RESULTS: Blood samples were collected from 23 normal volunteers. SIPA was continuously monitored using a modified cone-plate viscometer adapted for measuring the transmitted light intensity of the material. The effects of low concentrations of epinephrine, ADP, and collagen on SIPA under both low shear (12 dyne/cm2) and high shear (108 dyne/cm2) force were investigated. All agonists tested enhanced SIPA under low shear force, whereas only epinephrine augmented SIPA under high shear force. The maximum extents of SIPA under high shear force in the absence and presence of epinephrine (10 ng/ml) were 37.9 +/- 11.5% and 59.7 +/- 13.9%, respectively. The antagonist of the alpha 2-adrenergic receptor yohimbine (1 microgram/ml) antagonized the effects of epinephrine. The monoclonal antibody NMC-4 against vWF, which was shown to inhibit its binding to GP Ib, completely abolished SIPA under high shear force, even in the presence of epinephrine. However, this antibody only partially inhibited SIPA under low shear force. CONCLUSIONS: Our findings suggest that epinephrine is the agonist that enhances SIPA mediated by vWF through its specific receptor. This may be clinically important because occlusion of the coronary artery often occurs in stenosed atherosclerotic vessels under sympathetic stimulation.
Adrenergic alpha-Antagonists↗
Mechanisms of transient augmentation of myocardial contraction after a brief coronary occlusion.
The purpose of this study was 1) to clarify whether augmented myocardial contraction after a brief coronary occlusion, i.e. post-ischemic hypercontraction, depends on a transient increase in coronary blood flow or preceding myocardial ischemia, and 2) to identify the role of catecholamines or calcium flux in this phenomenon. Sixteen mongrel dogs were examined in open-chest anesthetized condition. One-minute reperfusion after two-minute total coronary occlusion of the left anterior descending artery resulted in a transient increase in segment shortening. Intracoronary administration of adenosine caused hyperemia without any changes in segment shortening. Two minutes of total coronary occlusion with adenosine caused post-ischemic hypercontraction to the same degree, but without any additional hyperemia. Two minutes of partial occlusion with 75% flow reduction caused less post-ischemic hypercontraction. Post-ischemic hypercontraction did not occur after partial occlusion with 50% flow reduction, irrespective of hyperemia with adenosine during reperfusion. Propranolol or verapamil did not prevent this phenomenon. Thus, post-ischemic hypercontraction is not dependent on the transient increase in coronary blood flow, but is related to the preceding myocardial ischemia. Local release of catecholamines is not likely to be the cause. A calcium antagonist, verapamil, did not modify this phenomenon. The precise mechanism of this phenomenon is still uncertain, although some alterations in cellular hemostasis, such as ionic changes, are likely to be the cause.
Animals↗
[Clinical significance of the use-dependent sodium channel block and reverse use-dependent potassium channel block of class I and class III antiarrhythmic agents and their values to predict drug efficacy].
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Anti-Arrhythmia Agents↗
Mitral stenosis in pseudoxanthoma elasticum.
A 54-year-old woman with pseudoxanthoma elasticum presented with tight mitral stenosis with thickened and restricted mitral valve leaflets. She initially revealed systemic hypertension and moderate mitral regurgitation due to mitral valve prolapse. One year after the start of treatment for hypertension, thickening of the mitral valve gradually progressed and she showed tight mitral stenosis without regurgitation. It was considered that another differential diagnosis must be added to the uncommon causes of mitral stenosis.
Biopsy↗
Concentrations of interleukin-1 beta, interleukin-6, interleukin-8 and TNF-alpha in cerebrospinal fluid from children with septic or aseptic meningitis.
Cytokines at an inflammatory site may be a better indicator of the clinical severity of an infectious disease than the serum levels of the cytokines. Concentrations of interleukin-1 beta (IL-1 beta) in paired samples of cerebrospinal fluid (CSF) from 10 rabbits with experimental bacterial meningitis caused by H. influenzae type b, were measured, and compared to the concentrations of four cytokines; IL-1 beta, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in CSF samples from 45 children with or without meningitis. The IL-1 beta concentrations in the CSF from rabbits with experimental meningitis were significantly higher than the concentrations in control animals without meningitis (p < 0.001). The mean CSF concentrations of IL-8 from meningitic children were significantly higher than in the control group without meningitis (p < 0.005). TNF-alpha was only detected in septic meningitis. Assays of IL-6, however, were not significantly different in the septic meningitis group, the aseptic meningitis group and the non-meningitis group. These data indicate a possible role of IL-1 beta, IL-8 and TNF-alpha as mediators in the meningeal inflammatory process in patients with meningitis and TNF-alpha, in particular, may play a role in the pathogenesis of septic meningitis.
Adolescent↗