Toxic shock-like syndrome caused by group G Streptococcus.
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Fatal Outcome↗
Biomedical subjects
K Handa
Publications and source records attributed to K Handa.
Assay of 222Rn in water samples by a modified integral counting method.
22Rn activity concentrations in water collected from 163 private wells and 14 springs in Tokyo were measured with a liquid scintillation spectrometer using a modified integral counting method. The activity concentrations of 222Rn range from 0.2 to 22.9 Bq/L and average 4.8 Bq/L. The errors due to the air luminescence counts and the interferences from 220Rn and 219Rn are discussed and evaluated. 222Rn samples of 0.2 Bq/L can be assayed within an overall uncertainty of 3.1%. The liquid scintillation method involving agitation of the sample water directly with a liquid scintillation cocktail was compared with the present method and evaluated.
Fresh Water↗
New insights in glycosphingolipid function: "glycosignaling domain," a cell surface assembly of glycosphingolipids with signal transducer molecules,involved in cell adhesion coupled with signaling.
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Animals↗
Use of temporary vena cava filters after catheter-directed fragmentation and thrombolysis in patients with acute pulmonary thromboembolism.
Acute pulmonary thromboembolism is a life-threatening disease and in almost all cases originates from deep venous thrombosis in the proximal deep venous system of the legs. In order to prevent further episodes of thromboembolism in 2 patients with acute pulmonary thromboembolism, we inserted an Antheor temporary vena cava filter after catheter-directed fragmentation and thrombolysis. No complications occurred during the insertion of the filters and our results suggest that this filter device may be clinically safe and effective for temporary protection against pulmonary thromboembolism.
Aged↗
[Successful treatment of an HB carrier developing severe hepatitis using lamivudine--case report].
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Adult↗
Sialosyl-fucosyl Poly-LacNAc without the sialosyl-Lex epitope as the physiological myeloid cell ligand in E-selectin-dependent adhesion: studies under static and dynamic flow conditions.
The majority of E- and P-selectin ligands in leukocytes and myelocytic or monocytic leukemia cells are carried by transmembrane glycoproteins having a tandem repeat mucin-like domain through which O-linked carbohydrate ligands are carried. However, determination of structure and adhesive function of carbohydrates in glycoproteins is extremely difficult because of the extensive structural heterogeneity and the scarcity of material for functional analysis. We have overcome this difficulty through use of poly-LacNAc gangliosides isolated from a large quantity of ( approximately 1.2 L packed) HL60 cells [Stroud, M. R., Handa, K., Salyan, M. E. K., Ito, K., Levery, S. B., Hakomori, S., Reinhold, B. B., & Reinhold, V. N. (1996) Biochemistry 35, 758-769, 770-778]. We identified two major types of poly-LacNAc gangliosides without the sialosyl-Lex epitope as being capable of binding to E-selectin: (i) those having a single alpha1-->3 fucosylation at internal GlcNAcs but not at the penultimate GlcNAc and (ii) those having double alpha1-->3 fucosylation at internal GlcNAcs, excluding the penultimate GlcNAc. Gangliosides from group i above did not show any adhesion under static conditions, but showed strong adhesion under dynamic flow conditions. Gangliosides from group ii above showed adhesion under both static and dynamic conditions, as did sialosyl-Lex (SLex)-containing structures in previous studies. However, SLex-containing poly-LacNAc gangliosides are virtually absent or present in only trace quantities in leukocytes and HL60 cells. Poly-LacNAc gangliosides from groups i and ii above, lacking SLex structure, are the major membrane components of leukocytes and HL60 cells. These carbohydrates, bound to lipid or to protein, may therefore be the physiological epitope for E-selectin-dependent binding of these cells, particularly under dynamic flow conditions.
Animals↗
Histo-blood group A/B versus H status of human carcinoma cells as correlated with haptotactic cell motility: approach with A and B gene transfection.
In a search for the molecular basis of ABH status of tumors as correlated with malignancy, we studied various malignancy-related phenotypes of high H/Le(y)-expressing tumor cell lines in comparison with phenotypes of the same lines transfected with histo-blood group A or B genes. A and B gene transfectants, prepared independently from different H-active parental cells, showed A or B activity and abolition of H activity. All A and B gene transfectants, regardless of source, were characterized by significantly reduced Matrigel-dependent haptotactic motility. The level of haptotaxis of all transfectants was similar to that of parental cells in the presence of antibodies against human integrin subunits alpha3, alpha6, or beta1. These subunits showed high expression of A or B epitope in the A and B gene transfectants. Enhancement versus reduction of malignancy, associated with deletion versus induction of A/B epitopes, may be due in part to enhanced haptotaxis sustained by alpha3, alpha6, and beta1 integrin receptors, the activities of which are regulated by H or A/B glycosylation. These phenotypic changes provide a rationale for the deletion of A and B epitopes as one criterion defining human tumor malignancy.
ABO Blood-Group System↗
A close association of GM3 with c-Src and Rho in GM3-enriched microdomains at the B16 melanoma cell surface membrane: a preliminary note.
B16 melanoma is characterized by high content of GM3 ganglioside, which has been recognized as a melanoma-associated antigen defined by specific monoclonal antibodies. We report now that GM3 is present predominantly (>90%) in the 1% Triton X-100-insoluble, low-density microvesicular fraction ("detergent-insoluble glycosphingolipid-enriched microdomain"; DIGEM) separated on sucrose density-gradient centrifugation. Associated with DIGEM, many signal transducer molecules such as c-Src, FAK, and the low-molecular-weight G-proteins Rho A and H-Ras were also found. Rho A and FAK were found in part, and PLC-beta2 and G alphas were found exclusively, in the high-density fraction. Immunoprecipitation of GM3 present in DIGEM by anti-GM3 antibody DH2, followed by Western blotting, revealed co-precipitation of Rho A and c-Src with GM3. These findings suggest (i) a specific organization of GM3 in close association with Rho A and c-Src within DIGEM at the melanoma cell surface; and (ii) such organizational units may be directly involved in signal transduction, in which glycosphingolipids receive signals which are subsequently transduced by associated transducer molecules.
Animals↗
Behavioral correlates of plasma sex hormones and their relationships with plasma lipids and lipoproteins in Japanese men.
In contrast to the hypothesis that endogenous testosterone decreases plasma high-density lipoprotein (HDL) cholesterol levels, many, but not all, studies have reported a positive correlation between plasma total testosterone and HDL cholesterol. We examined behavioral correlates of plasma testosterone and estradiol and the relationships between these sex hormones and plasma lipoproteins, in middle-aged Japanese men. Plasma, lipids, including HDL subfractions, total and free testosterone, and total estradiol were determined with 313 men aged 50-54 years who received a preretirement health examination at the Self-Defence Forces Fukuoka Hospital from January to June in 1992. Body mass index and waist-hip ratio were also measured. Smoking habit, alcohol use, and physical activity were ascertained by a self-administered questionnaire. Obesity, especially waist-hip ratio, was a strong correlate of both total and free testosterone, but not of estradiol. Smoking was associated with elevated levels of testosterone without a dose-effect relation. Neither alcohol use nor physical activity was associated with total or free testosterone, but plasma estradiol levels were higher among current alcohol drinkers. HDL and HDL2 cholesterol were unrelated to either total or free testosterone in the univariate analysis, but negatively associated with free, not total, testosterone after adjustment for obesity. HDL and HDL2 cholesterol also were positively associated with estradiol regardless of adjustment for obesity and other covariates. These findings add to evidence for a hypothesis that high levels of endogenous testosterone and low estradiol levels may cause a decrease in plasma HDL cholesterol, thereby being linked with atherosclerosis in middle aged men.
Alcohol Drinking↗
A new procedure for establishing functional monoclonal antibodies capable of inhibiting E- or P-selectin-dependent cell adhesion.
Employing a new procedure, we established many monoclonal antibodies (mAbs) which inhibit E- or P-selectin-dependent cell adhesion. One of these mAbs is capable of staining selectin in paraffin-embedded histological sections. The procedure is based on immunization of BALB/c mice with irradiated mouse myeloma NS-1 cells (syngeneic HAT-sensitive fusion partner cells) transfected with cDNA encoding human E- or P-selectin. Resulting NS-1 transfectant cells permanently express human E- or P-selectin as immunogen. The mAbs are useful for detecting selectins by flow cytometric and immunohistological methods, and for inhibiting selectin-dependent adhesion in experimental models. In contrast, the majority of anti-selectin mAbs previously established do not have these capabilities.
Animals↗
Effects of an angiotensin II antagonist on reperfusion arrhythmias in dogs.
Losartan, an angiotensin II receptor antagonist with no bradykinin potentiating property, provides the opportunity to study the consequences of blocking angiotensin II. The objective of this study was to evaluate the antiarrhythmic responses of reperfusion arrhythmia to losartan in dogs. The effects of losartan on ventricular tachyarrhythmias induced during occlusion and reperfusion of the left anterior descending coronary artery were investigated in 30 dogs. The animals were randomized to receive either losartan (n = 15) or saline (n = 15). The VF inducing threshold was measured before occlusion and after reperfusion. Losartan (50 micrograms/kg per min) or saline was intravenously administered 5 minutes before occlusion and continued throughout the entire study period. The incidence of ventricular tachyarrhythmias during reperfusion was lower in the losartan group than in the control group (4/15 vs 6/15). There was no significant change in VF inducing threshold between the period before occlusion and during reperfusion in the losartan group [10.9 +/- 5.7 vs 11.1 +/- 5.7 mA, P = NS), whereas there was a significant decrease in the control group (15.5 +/- 4.4 vs 7.7 +/- 3.9 mA, P < 0.01). Blockade of the angiotensin II receptor has beneficial effects on reperfusion arrhythmias.
Aldosterone↗
Syncope in the presence of newly developed bundle branch block: bradycardia or tachycardia related.
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Adult↗
Thrombomodulin levels in patients with coronary artery disease.
We investigated the association between the serum level of thrombomodulin and known coronary risk factors in 119 men who underwent coronary angiography. Total cholesterol level was significantly higher in patients with coronary atherosclerosis than in those without. Significantly higher frequency of hypertension was noted in patients with coronary atherosclerosis. Uric acid level and frequency of smoking tended to be higher in patients with coronary atherosclerosis but the differences were short short of the significant level. The serum level of thrombomodulin between patients with coronary atherosclerosis and those without was not statistically significant. Age, blood urea nitrogen, and creatinine were positively correlated and creatinine clearance was inversely correlated with the serum level of thrombomodulin. Serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, uric acid, and fasting blood sugar, plasma level of fibrinogen, and body mass index were not related to the serum level of thrombomodulin. There was no significant correlation between the severity of coronary atherosclerosis, hypertension, alcohol use, or smoking and the serum level of thrombomodulin. Restenosis was present in 8 of 16 patients who underwent percutaneous transluminal coronary angioplasty and had a follow-up angiogram at 6.0 +/- 3.0 months. Univariate analysis revealed no significant difference in the thrombomodulin level with and without restenosis. The present findings suggest that elevated thrombomodulin levels in patients with coronary artery disease may reflect retention of thrombomodulin due to decrease in thrombomodulin clearance in the kidney.
Adult↗
Disialosyl galactosylgloboside as an adhesion molecule expressed on renal cell carcinoma and its relationship to metastatic potential.
Aberrant glycosylation expressed in specific types of human cancer may define stage, direction, and fate of tumor progression. Well-studied examples are expression of sialosyl-Lewis(x) or sialosyl-Lewis(a) in colorectal carcinoma and histo-blood group A and H/Le(y) in lung cancer. In renal cell carcinoma (RCC), expression of sialosyl-Lewis(x) has no correlation with metastatic potential. Clinicopathological studies have revealed that the degree of expression of disialosyl galactosylgloboside (DSGG) and monosialosyl galactosylgloboside is correlated with metastatic potential (to lung and lymph nodes) of RCC and inversely correlated with patient survival. In the present study, we compared the adhesion of RCC lines to sections of various tissues measured by Stamper-Woodruff assay and other similar assays under dynamic flow conditions. Of the eight RCC lines tested, only TOS-1 (which expresses DSGG) bound strongly to lung tissue sections. TOS-1 did not bind to sections of liver, kidney, or lymph nodes. In the same eight RCC lines, we also compared expression of DSGG and monosialosyl galactosylgloboside (reflected by reactivity with RM1 and RM2), overall ganglioside patterns, and correlation with lung tissue-binding ability. Under both static and dynamic flow conditions, the binding of TOS-1 cells to lung alveolar tissue was correlated with their DSGG expression, i.e., the binding was inhibited by RM2 but not by RM1. This binding was also inhibited by sialidase but not by EDTA (i.e., it was CA 2+ independent). The other seven cell lines (TOS-2, TOS-M, SMKT-R1, -R2, -R3, and -R4, and ACHN), which do not express DSGG, showed much weaker adhesion to lung tissue. None of the eight cell lines showed E- or P-selectin-dependent adhesion. These results suggest the existence of a yet-uncharacterized sialoadhesive receptor++ that specifically recognizes DSGG. This receptor could be the binding target in RCC metastasis to lung.
Carbohydrate Conformation↗
Monosialogangliosides of human myelogenous leukemia HL60 cells and normal human leukocytes. 1. Separation of E-selectin binding from nonbinding gangliosides, and absence of sialosyl-Le(x) having tetraosyl to octaosyl core.
Previous studies suggested that sialosyl-Le(x) (SLex) is a ligand expressed in human neutrophils and myelogenous leukemia HL60 cells which binds to E-selectin and possibly P-selectin. However, clear data on structures of carbohydrate epitopes in these cells were lacking. A systematic study was therefore initiated, employing a large quantity of HL60 cells (> or = 1200 mL packed) and human leukocytes (approximately 100 mL packed). Gangliosides were extracted, followed by extensive fractionation and examination of the E- and P-selectin binding ability of each fraction. The following results were of particular interest: (i) Only monosialogangliosides having a polylactosamine core with > 10 monosaccharide units (or > 4 N-acetyllactosamine units) showed E-selectin binding under static conditions with thin-layer chromatography overlay technique employing 32P-labeled E-selectin-expressing CHO cells. (ii) Sulfate groups were not detectable in the binding fractions, and di- and trisialoganglioside fractions did not show E-selectin binding under these conditions. (iii) None of the fractions showed P-selectin binding under a similar assay system using 32P-labeled P-selectin-expressing CHO cells. (iv) Major gangliosides of HL60 cells were structures I-XI (shown in Table 1 of text), none of which showed E-selectin binding under the above conditions. (v) SLex gangliosides having tetraosyl to octaosyl ceramide core, which are the major gangliosides of epithelial tumors (shown in Table 2), were completely absent from HL60 cells and neutrophils. Isolation and chemical characterization of ganglioside structures I-XI are described in this paper.
Animals↗
Monosialogangliosides of human myelogenous leukemia HL60 cells and normal human leukocytes. 2. Characterization of E-selectin binding fractions, and structural requirements for physiological binding to E-selectin.
E-selectin binding gangliosides were isolated from myelogenous leukemia HL60 cells, and the E-selectin binding pattern was compared with that of human neutrophils as described in the preceding paper in this issue. The binding fractions were identified as monosialogangliosides having a series of unbranched polylactosamine cores. Structures of fractions 12-3, 13-1, 13-2, and 14, which showed clear binding to E-selectin under the conditions described in the preceding paper, were characterized by functional group analysis by application of monoclonal antibodies, 1H-NMR, FAB-MS, and electrospray mass spectrometry with collision-induced dissociation of permethylated fractions. Fractions 12-3, 13-1, and 13-2 were characterized by the presence of a major ganglioside with the following structure: NeuAc alpha 2-->3Gal beta 1-->4 GlcNAc beta 1-->3Gal beta 1-->4(Fuc alpha 1-->3) GlcNAc beta 1-->3Gal beta 1-->4(Fuc alpha 1-->3)-GlcNAc beta 1-->3Gal beta 1-->4GlcNAc beta 1-->3 Gal beta 1-->4 Glc beta Cer. Fractions 12-3 and 13-2 contained, in addition, small quantities (10-15%) of extended SLex with internally fucosylated structures: NeuAc alpha 2-->3 Gal beta 1-->4-(Fuc alpha 1-->3) GlcNAc beta 1-->3 Gal beta 1-->4(Fuc alpha 1-->3) GlcNAc beta 1-->3 Gal beta 1-->4 (+/- Fuc alpha 1-->3)GlcNA c beta 1-->3 Gal beta beta 1-->4GlcNAc beta 1-->3 Gal beta 1-->Glc Beta Cer. Fraction 13-1, showing stronger E-selectin binding activity than 12-3 and 13-2, contained only a trace quantity (< 1%) of SLex. Fraction 14, which also showed clear binding to E-selectin, was characterized by the presence of the following structures, in addition to two internally monofucosylated structures (XX and XXI, Table 2, text): NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc beta 1-->3 Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc beta 1-->3Gal beta 1-->4 GlcNAc beta 1-->3 Gal beta 1-->4 GlcNAc beta 1-->3 Gal beta 1-->4 Glc beta Cer; andNeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->3 Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc beta 1-->3Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4 (Fuc alpha 1--3)-GlcNAc beta 1-->3Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1--4Glc beta Cer. SLex determinant was completely absent. Thus, the E-selectin binding epitope in HL60 cells is carried by unbranched terminally alpha 2-->3 sialylated polylactosamine having at least 10 monosaccharide units (4 N-acetyllactosamine units) with internal multiple fucosylation at GlcNAc. These structures are hereby collectively called "myeloglycan". Monosialogangliosides from normal human neutrophils showed an essentially identical pattern of gangliosides with selectin binding property. Myeloglycan, rather than SLex, provides a major physiological epitope in E-selectin-dependent binding of leukocytes and HL60 cells.
Binding Sites↗
Evaluation of the coagulation and fibrinolytic systems in men with intermittent claudication.
The authors evaluated elements of the coagulation and fibrinolytic systems in 18 male patients with intermittent claudication vs 19 men matched for risk factors who served as controls. Prothrombin time and activated partial thromboplastin time did not significantly differ in the patients and the controls. The plasminogen level in the two groups was not significantly different. The level of lipoprotein(a) was significantly higher in the patients than in the controls. The levels of antigen and the activity of protein C did not differ significantly between the two groups. The thrombomodulin level was significantly higher in the patients than in the controls. There were no significant differences between the two groups in the levels of alpha 2-macroglobulin, C1-inactivator, or antithrombin III. The levels of fibrinogen and alpha 1-antitrypsin were significantly higher in the patients vs the controls. Significantly lower levels of alpha 2-plasmin inhibitor and higher levels of alpha 2-plasmin inhibitor/plasmin complex and thrombin/antithrombin III complex were found in the patients vs the controls. These findings suggest that the levels of thrombin/antithrombin III complex, alpha 2-plasmin inhibitor/plasmin complex, and thrombomodulin may perhaps serve as indicators for injury to the peripheral endothelium and that the coagulation and fibrinolytic systems may be activated in patients with intermittent claudication.
Aged↗
Relation of C4b-binding protein to athero-sclerosis of the descending thoracic aorta.
C4b binding protein (C4bp) is a regulator of the classical pathway of the complementing system. It forms a complex with protein S which serves as a cofactor of coagulation inhibitor, protein C. We have reported that C4bp is an acute phase reactant and associated with total cholesterol and triglyceride concentrations (Biochim. Biophys. Acta 963 (1988) 98-108). This suggests a possible association of C4bp with athero-sclerosis. We examined the relation of C4bp levels and the severity of atherosclerosis of the descending thoracic aorta in 98 Japanese men. The severity of aortic atherosclerosis was assessed by average sclerotic length (ASL) and average sclerotic area (ASA), using transesophageal echocardiography. After adjustment for age, C4bp levels increased significantly with increasing ASL and ASA. The association remained significant even after adjusting for total cholesterol, hypertension, smoking, drinking, body mass index, fasting blood sugar, and uric acid. Immunohistochemical analysis of specimens of the descending thoracic aorta from autopsies, demonstrated the presence of C4bp in the foamy macrophages of fatty streaks and the necrotic core of atheromatous plaque. These findings indicate that the serum level of C4bp can serve as an independent indicator of aortic athero-sclerosis.
Adult↗