Biomedical subjects

K Handa

Publications and source records attributed to K Handa.

At least 19 recordsLinked to original sources

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1995

Myeloglycan, a series of E-selectin-binding polylactosaminolipids found in normal human leukocytes and myelocytic leukemia HL60 cells.

Sialosyl-Lex (SLex) is assumed to be the binding epitope of E- and P-selectin in normal human neutrophils and myelocytic leukemia HL60 cells. Glycosphingolipid (GSL) fractions from large quantities of normal human neutrophils and HL60 cell extract did not contain SLex GSLs having 6-10 sugar residues, as commonly found in solid tumor cells and tissues. Instead, the binding target of E-selectin was revealed to be a series of long-chain, unbranched polylactosamine GSLs with terminally sialylated, internally alpha 1-->3 polyfucosylated structure as the major component, or having SLex at the terminus and internally polyfucosylated structure as a minor component. These GSLs are hereby collectively termed "myeloglycan." Regardless of the site of fucosylation, all myeloglycans cross-react strongly with "anti-SLex" monoclonal antibodies such as CSLEX, FH6, SNH3, and SNH4.

Acetylglucosamine↗

PubMed1995

Serum glycoproteins and severity of coronary atherosclerosis.

The relation of serum glycoproteins and C-reactive protein (CRP) to severity of coronary atherosclerosis was examined in 133 men and 92 women undergoing coronary angiography. The following serum glycoproteins were determined: alpha 1-antitrypsin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, ceruloplasmin, haptoglobin, fibrinogen, C4b binding protein, and lipoprotein (a) [Lp(a)]. Sex- and age-adjusted levels of alpha 1-antitrypsin, alpha 1-acid glycoproteins, alpha 2-macroglobulin, ceruloplasmin, Lp(a) and CRP were significantly associated with the severity of coronary atherosclerosis as determined by the Gensini score; these associations remained significant even after adjustment for body-mass index, smoking history, hypertension, and total cholesterol, except for Lp(a) (p = 0.075). These findings suggest that certain serum glycoproteins and CRP can serve as independent indicators for the progression of coronary atherosclerosis.

Aged↗

PubMed1995

Relationship of cigarette smoking to the severity of coronary and thoracic aortic atherosclerosis.

We studied the relationship of cigarette smoking to the severity of coronary and thoracic aortic atherosclerosis in 116 men who received coronary angiography and transesophageal echocardiography. Severity of coronary atherosclerosis was assessed in terms of Gensini's score (GS), and that of thoracic aortic atherosclerosis was assessed by the average sclerotic length (ASL) and average sclerotic area (ASA). The plasma fibrinogen levels were significantly positively correlated with smoking, and fasting blood sugar levels tended to be positively associated with smoking. GS was inversely associated with serum levels of high density lipoprotein (HDL) cholesterol. ASL and ASA were positively associated with age, fasting blood sugar levels and plasma fibrinogen levels, and these associations were statistically significant. Analysis of covariance was used to examine the net association between cigarette smoking and GS, ASL or ASA controlling for age, total cholesterol, HDL cholesterol, fasting blood sugar and plasma fibrinogen. We found that GS, ASL, and ASA were all significantly increased with increasing number of cigarette years. Additional adjustment for other risk factors (triglyceride, uric acid, body mass index, alcohol use and hypertension) also showed a strong independent contribution of smoking to GS, ASL and ASA. We concluded that the cumulative exposure to cigarette smoking was an independent indicator of the severity of coronary atherosclerosis as well as thoracic aortic atherosclerosis.

Adult↗

PubMed1994

Species-specific expression of sialosyl-Le(x) on polymorphonuclear leukocytes (PMN), in relation to selectin-dependent PMN responses.

Sialosyl-Le(x) (SLex) and its positional isomer sialosyl-Le(a) are the epitopes recognized by the lectin domain of E- and P-selectins. Expression of SLex in polymorphonuclear leukocytes (PMN) plays an important role in recruitment of these cells at sites of inflammation through activation of selectins. We studied expression of SLex in PMN of seven mammalian species in comparison with that in humans. Only PMN of humans (no other species) expressed SLex or other lacto-series epitopes such as Le(x) or Le(y). The observed absence of these epitopes in rat PMN seems inconsistent with recent reports that the lung inflammation process in a rat model is inhibited by perfusion of SLex oligosaccharide (Mulligan MS, et al. (1993a) Nature 364:149; (1993b) J Exp Med 178:623). Rat selectins may be able to recognize SLex, even though this epitope is absent in rat PMN.

Animals↗

PubMed1994

A characteristics protein highly expressed in guinea pig inner ear, defined by monoclonal antibody WH-1.

A new monoclonal antibody (termed WH-1; isotype IgG2b) was established using a homogenate of dissected guinea pig cochleas (N = 60) as immunogen. Western blotting and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) identified the WH-1 antigen as a protein or glycoprotein with M(r) approximately 40 kDa. Immunoperoxidase treatment of histologic cryosections of guinea pig cochlea, followed by light microscopic examination, revealed strong positive staining at three sites: (i) parts of Hensen's stripe, marginal band, covering net, and Kimura's membrane (within the tectorial membrane [TM]); (ii) Deiters' cells, pillar cells, Hensen's cells, and stereocilia of outer hair cells (within the organ of Corti); (iii) interdental cells, inner and outer sulcus cells, Reissner's membrane, and surface membrane of stria vascularis epithelium. Similar staining patterns were observed for cryosections of rat and mouse cochleas. Only a trace quantity of cross-reacting protein was detectable in brainstem. The protein was not detectable in tongue extract by Western blotting. However, sections of brainstem and tongue did show positive immunohistological staining with WH-1. Localization of WH-1 antigen was further examined by electron microscopy. WH-1 positivity on outer hair cell stereocilia, certain sites on the TM, interdental cell surface, Reissner's membrane epithelia, and inner and outer sulcus cells was confirmed. WH-1 antigen was not detected on inner hair cell stereocilia by light or electron microscopy. The localization of WH-1 antigen on outer hair cell stereocilia and TM suggests that it may play some role in adhesion between these structures.

Animals↗

PubMed1994

Mapping local and systemic symptom determinants of cucumber mosaic cucumovirus in tobacco.

Cucumber mosaic cucumovirus (CMV) can be divided into two subgroups, I and II. LS-CMV and most other subgroup II strains cause a mild, systemic mottle on tobacco and can induce a necrotic etching (necrotic rings) symptom on inoculated tobacco leaves. In contrast, Fny-CMV and most other subgroup I strains cause severe, systemic mosaic symptoms on tobacco, but do not induce the necrotic etching symptom. Full-length cDNA clones of all three genomic RNAs of LS-CMV were constructed and infectious RNAs were generated from these clones. Using pseudorecombinants constructed from the infectious transcripts of LS-CMV and Fny-CMV, we found that both RNAs 1 and 2 of Fny-CMV are involved in determining the severity of systemic symptom on tobacco, and that LS-CMV RNA 3 contains the determinant for the necrotic etching symptom. Chimeras formed between Fny- and LS-CMV RNA 3 were used to demonstrate that the inducer of the necrotic etching symptoms mapped to the 5' 618 nucleotides of LS-CMV RNA 3, and required sequences in both the 5' non-translated region, as well as the 3a gene of CMV.

Amino Acid Sequence↗

PubMed1994

Relationship of alcohol consumption and smoking to plasma cortisol and blood pressure.

The role of plasma cortisol in the relationship of alcohol consumption and smoking with BP was investigated in a study of 297 Japanese men, aged 50-54 years, who were not receiving antihypertensive agents. They were admitted to the Self-Defense Forces Fukuoka Hospital between January and June 1992 for a detailed pre-retirement health examination. A history of alcohol consumption and cigarette smoking were determined from a self-administered questionnaire. The plasma level of cortisol and BP were determined in the morning of the first admission day. While the plasma level of cortisol was positively related to systolic and diastolic BP, cortisol levels did not vary substantially with alcohol consumption. Both BP and plasma cortisol levels were lower among current smokers than nonsmokers. The lower BP observed among current smokers was ascribed in part (about 20-30%) to the plasma cortisol levels. While the cortisol levels may contribute the lower BP among current smokers, the data did not support its role in mediating the alcohol-BP relationship.

Alcohol Drinking↗

PubMed1993

Plasmin and thrombin inhibitors in essentially untreated patients with coronary artery spasm.

We examined activities or levels of plasmin and thrombin inhibitors in essentially untreated patients with angiographically documented coronary artery spasm. The patients received the ergonovine malate provocation test and were classified into two groups: (a) those with significant coronary artery spasm that produced reduction of the internal luminal diameter of 50% or greater with chest pain and change of electrocardiography (n = 18), and (b) those without coronary artery spasm (n = 17). There was no significant differences in alpha 1-antitrypsin and alpha 2-macroglobulin levels, and C1-inactivator activity between the control and patients with coronary artery spasm. On the other hand, the lower antithrombin III and alpha 2-plasmin inhibitor activities were noted in patients with coronary artery spasm than the control. Thrombin/antithrombin III complex and alpha 2-plasmin inhibitor/plasmin complex levels were significantly higher in coronary artery spasm patients. These results suggest that the coagulation and fibrinolytic systems may maintain their equilibrium in untreated patients with coronary artery spasm.

Antifibrinolytic Agents↗

PubMed1993

Detection of a point mutation in cholesteryl ester transfer protein gene by polymerase chain reaction-mediated site-directed mutagenesis.

We describe a method for the rapid and non-radioactive examination of DNA samples for a mutation of cholesteryl ester transfer protein using a polymerase chain reaction-mediated site-directed mutagenesis. CETP deficiencies were studied in 554 Japanese subjects (370 men, 184 women) aged between 18 and 91 (mean 48.3 years). By this method, we detected one homozygote and 3 heterozygotes of the CETP deficiency.

Adult↗

PubMed1993

Prediction of protein secondary structure by the hidden Markov model.

The purpose of this paper is to introduce a new method for analyzing the amino acid sequences of proteins using the hidden Markov model (HMM), which is a type of stochastic model. Secondary structures such as helix, sheet and turn are learned by HMMs, and these HMMs are applied to new sequences whose structures are unknown. The output probabilities from the HMMs are used to predict the secondary structures of the sequences. The authors tested this prediction system on approximately 100 sequences from a public database (Brookhaven PDB). Although the implementation is 'without grammar' (no rule for the appearance patterns of secondary structure) the result was reasonable.

Algorithms↗

PubMed1993

[Population-based comparative study on dietary habits and serum fatty acid compositions].

Appropriate dietary instruction on fat intake is required for Japanese to prevent coronary heart disease because there has been a consistent increase in fat intake during the past two decades. To gain fundamental information for dietary instruction, we examined the relation between dietary habits related to fat and serum fatty acid compositions in women aged 40-69 of four Japanese populations (fishing, coastal farming, inland farming and urban populations) and a Caucasian population in which different dietary habits have been reported. Among Japanese, dietary intake of monounsaturated and polyunsaturated fatty acids (in particular omega 6-polyunsaturated fatty acid) were higher in the urban population than in the other populations. Intake of omega 3-polyunsaturated fatty acids did not vary among the Japanese populations, but intakes of eicosapentaenoic acid and docosahexaenoic acid were higher in fishing and coastal farming populations than in the other two populations. Serum concentrations and compositions of omega 6-polyunsaturated fatty acids (mostly linoleic acid) were higher in the urban and inland farming populations than in the other two populations whereas those of omega 3-polyunsaturated fatty acids (in particular eicosapentaenoic acid) showed the opposite trend. The proportion of omega 6-polyunsaturated fatty acids was higher and that of omega 3-polyunsaturated fatty acids was lower in Caucasian women than in the Japanese populations. The ratio of omega 3 (polyunsaturated fatty acids) to omega 6 was highest in the fishing population (ratio = 0.38), intermediate in coastal farming (0.35), urban (0.27) and inland farming (0.24) populations, and lowest in Caucasians (0.07). Within populations, the percentage of serum omega 6-polyunsaturated fatty acids increased with the increase of frequency of meat intake and oil intake. The percentage of serum omega 3-polyunsaturated fatty acids increased with the increase in frequency of fish intake. Because there are evident associations between the frequency of fish, meat and oil intake and serum fatty acid compositions, a frequency questionnaire on these foods would be useful for dietary instruction in the prevention of coronary heart disease.

Adult↗

PubMed1993

[Study on the oral health status of schoolchildren in Korea].

In 1992, dental health examination was conducted in three areas in Korea; Seoul (large city), Cheonan (rural city) and Cheongju (water fluoridated rural city). We also examined the children of Tokyo in Japan. The subjects were the schoolchildren in the 6th grade of primary school and the 3rd grade of junior high school, and the number of the subjects was 202 in Seoul, 191 in Cheonan, 164 in Cheongju and 152 in Tokyo. We compared the oral health status among these four areas using many indices such as the prevalence rate of dental caries and malocclusion, DMFT, DMFS, DI-S and P-M-A index. In Korea the children in Seoul showed the highest caries prevalence rate, DMFT and DMFS. The Cheonan children were average. The children in Cheongju had the lowest caries experience. The children in Tokyo had more dental caries than the Korean children in both school grades. The children in Tokyo had more gingivitis and malocclusion than the Korean children in the three areas. It was revealed that the oral health status of the Korean schoolchildren was much better than the Japanese children. And water fluoridation project in Cheongju was effective to prevent the dental caries especially in the 6th grade children.

Adolescent↗

PubMed1993

[Study of pathophysiology of pulmonary circulation in polycythemia using scintigraphy].

In order to evaluate the pathophysiology of pulmonary circulation in polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with 99m-Tc MAA were performed in 19 cases with polycythemia including polycythemia rubra vera and in 11 cases with secondary polycythemia due to pulmonary diseases. Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all cases and 54.5% of them showed moderate lung uptake. The grade of right ventricular visualization was moderate in one case and slight in 16 cases; right ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy, only one of which showed right ventricular hypertrophy on electrocardiography. Abnormalities of lung perfusion consisted of scattered small areas of hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related to decrease in FEV1.0%, V25 and PaO2 and increase in circulating blood volume and peripheral red blood cell counts. Abnormalities of pulmonary function consisted of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in 36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of secondary polycythemia due to pulmonary diseases showed more marked right ventricular visualization, pulmonary perfusion impairment and abnormalities of various kinds of pulmonary function than polycythemia rubra vera cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗