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Biomedical subjects

K Handa

Publications and source records attributed to K Handa.

At least 91 records · Page 5Linked to original sources
PubMed1992

Multi-recognition capability of E-selectin in a dynamic flow system, as evidenced by differential effects of sialidases and anti-carbohydrate antibodies on selectin-mediated cell adhesion at low vs. high wall shear stress: a preliminary note.

E-selectin has a "multi-recognition" capability in terms of epitope binding specificity, depending on adhesion conditions (static vs. low- or high-shear stress dynamic systems). Specifically, (i) adhesion based on expression of alpha 2-->3 sialylated Le(x) (SLe(x)) is prominent under static or low shear stress dynamic conditions; (ii) adhesion under high shear stress dynamic conditions does not depend on the known SLe(x) species, but rather on Lex with an adjacent unidentified sialosyl substitution, which shows different susceptibility to sialidases and antibodies compared to known SLe(x).

Antibodies, Monoclonal↗
PubMed1992

Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells.

Initial adhesion of B16 melanoma variants to non-activated endothelial cells is mediated through specific interaction between GM3 (NeuAc alpha 2----3Gal beta 1----4Glc beta 1----Cer) expressed on melanoma cells and lactosylceramide (LacCer, Gal beta 1----4Glc beta 1----Cer) expressed on endothelial cells. This adhesion is predominant over integrin- or lectin-mediated adhesion in a dynamic flow experimental system employing a parallel plate laminar flow chamber (Lawrence, M. B., Smith, C. W., Eskin, S. G., and McIntire, L. V. (1990) Blood 75, 227-237). In this system, a tumor cell suspension flows over a glass plate coated with glycosphingolipid, lectin, or fibronectin, and adhesion is recorded on videotape. These conditions were designed to mimic the microvascular environment in which tumor metastatic deposition takes place. In contrast, lectin- and fibronectin-based mechanisms are predominant in previously used static adhesion systems. Under static conditions, the relative degree of adhesion of the four B16 variants to endothelial cells or to LacCer-coated plates was the same as their relative degree of GM3 expression (i.e. BL6 approximately F10 greater than F1 greater than WA4), and adhesion was inhibited in the presence of methyl-beta-lactoside, or liposomes containing LacCer or GM3. Adhesion was also inhibited by pretreatment of B16 cells with anti-GM3 antibody DH2 or sialidase and by pretreatment of endothelial cells with anti-LacCer antibody T5A7. Under dynamic flow conditions, WA4 cells did not adhere to mouse endothelial cells at high shear stress (greater than 2.5 dynes/cm2) but did adhere at lower shear stress. In contrast, BL6 and F10 cells adhered strongly at both low and high shear stress. BL6 cell adhesion to endothelial cells at both low and high shear stress was inhibited in the presence of antibody DH2, ethyl-beta-lactoside, or lactose, as well as by pretreatment of BL6 cells with sialidase. Thus, some clear differences, as well as similarities, in cell adhesion under static versus dynamic conditions are demonstrated. These findings suggest that melanoma cell adhesion to endothelial cells, based on GM3/LacCer interaction, initiates metastatic deposition, which may trigger a series of "cascade" reactions leading to activation of endothelial cells and expression of Ig family or selectin receptors, thereby promoting adhesion and migration of tumor cells.

Animals↗
PubMed1992

Inhibition of selectin-dependent tumor cell adhesion to endothelial cells and platelets by blocking O-glycosylation of these cells.

Expression of sialosyl-Le(x) (SLe(x)) and sialosyl-Le(a) (SLe(a)) on tumor cell lines HL60, Colo205, and U937 was greatly suppressed by application of benzyl-alpha-GalNAc for inhibition of O-linked carbohydrate chain extension, which resulted in reduced adhesion of tumor cells to activated endothelial cells or platelets mediated by ELAM-1 (E-selectin) or GMP-140 (P-selectin). Inhibitors or modifiers of N-glycosylation had no effect on expression of SLe(x) or SLe(a) in these tumor cells. These findings suggest the possibility that targeting of O-glycosylation inhibitors or modifiers to tumor cells may effectively suppress metastatic potential.

Acetylgalactosamine↗
PubMed1992

Administration of slow-release nifedipine does not affect lactate threshold, hormone release during exercise, and quality of life in normal subjects.

In a double-blind crossover study of 10 normal healthy subjects, we examined the effects of slow-release nifedipine (nifedipine-SR, 10 mg b.i.d) administration on exercise capacity, hormone levels during exercise, and quality of life (QOL) after a 2-week treatment. Two exercise tests, a progressive exercise test and a constant work-rate exercise test, were performed. Maximal oxygen uptake (VO2max) and blood lactate concentration were measured during the progressive exercise test and the exercise intensity corresponding to half lactate threshold (LT), LT, and 4 mmol/l of lactate concentration was determined. Subjects underwent 20 minutes of constant work-rate exercise at each work load, and blood lactate, plasma epinephrine, plasma norepinephrine, plasma renin activity, plasma aldosterone, atrial natriuretic peptide, plasma beta-endorphin, and met-enkephalin were measured. Taking nifedipine-SR had no effect on the responses of blood pressure, heart rate, VO2max, maximal work load, and LT compared to taking placebo. Blood lactate, plasma catecholamine, plasma renin activity, aldosterone, atrial natriuretic peptide, and beta-endorphin levels increased during exercise, and there was no difference between nifedipine-SR and placebo. Met-enkephalin did not increase with either treatment. In the QOL questionnaires, no differences were noted between the two treatments. These findings suggest nifedipine-SR to be a potentially useful drug in view of the lack of effect on exercise capacity, hormone release, and QOL.

Adolescent↗
PubMed1992

Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects.

A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO2 max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO2 max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.

Adrenergic beta-Antagonists↗
PubMed1992

A multicenter comparison of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in patients with ischemic heart disease.

The effects of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in 37 patients with ischemic heart disease were examined in a randomized, multicenter study. Nicorandil (n = 20, 10-40 mg/day, b.i.d.) and diltiazem (n = 17, 60-240 mg/day, b.i.d.) were administered for 12 weeks. Both nicorandil and diltiazem administration showed an effective antianginal effect. Diltiazem administration showed a significant hypotensive action. There were no significant changes in serum lipids, apolipoproteins, and lipoproteins for both nicorandil and diltiazem. There were no significant changes in body weight, uric acid, and fasting blood sugar levels during the test period for both drugs. These data show that nicorandil, like diltiazem, does not have any adverse effects on lipid metabolism and that it is a favorable drug to use as an agent for treating arteriosclerotic heart disease.

Aged↗
PubMed1992

Effects of niceritrol on levels of serum lipids, lipoprotein(a), and fibrinogen in patients with primary hypercholesterolemia.

Thirty-three consecutive unselected patients with primary hypercholesterolemia received niceritrol 1.5 g daily for 12 weeks, with the effect of administering divided dose (twice daily (b.i.d.) and three times daily (t.i.d.)) evaluated. The serum concentrations of lipoprotein(a) (Lp(a)), lipids, the major apolipoproteins (apo), cholesteryl ester transfer activity and fibrinogen were determined before and after treatment. The b.i.d. and t.i.d. regimens each significantly reduced the serum levels of total cholesterol and triglyceride. The mean changes in serum lipids and lipoproteins did not differ significantly between the two groups. After 12 weeks of treatment, there was a significant decrease in total plasma cholesterol, triglyceride, low density lipoprotein cholesterol, apo A-II, apo B and fibrinogen and an increase in the high density lipoprotein cholesterol levels. Although the serum level of Lp(a) did not change in every patient, niceritrol significantly reduced the serum Lp(a) level in those with an initially high level of Lp(a) (greater than or equal to 20 mg/dl).

Adult↗
PubMed1992

[Evaluation of school dental health activities in Hiraizumi primary school, Iwate prefecture].

The purpose of this study was to evaluate the health activities in Hiraizumi primary school, Iwate prefecture. As a result of intensive dental health activities from 1978 to 1990, which consisted of tooth brushing instruction by class, dental education for the schoolchildren and their guardians, utilization of fluoride mouth rinsing (once a week), and, by following a model school of caries prevention designated by the Ministry of Education et al., the oral health status of the Hiraizumi primary schoolchildren improved significantly compared with those of the Ohya primary schoolchildren who followed the routine school dental health activities. The results of questionnaires, taken from both primary schoolchildren in 1986 and 1989, show that the oral health behavior of the Hiraizumi primary schoolchildren also improved.

Age Factors↗
PubMed1992

[Clinical significance of scintigraphy in pulmonary aspergilloma].

In order to study the scintigraphic findings related to the pathophysiology of pulmonary aspergilloma, chest scintigraphy with T1-201 chloride and perfusion lung scintigraphy were performed in 18 and 19 patients with pulmonary aspergilloma, respectively. In T1-201 scintigraphy, accumulation of T1-201 in the diseased areas related to Aspergillus infection was observed in 18 of 19 foci. Roentgenographic findings related to the accumulation of T1-201 in the lesion were thickness of the cavity wall and pleural thickening adjacent to the cavity, but they showed no relation to the size of the fungus ball, and 2 cases without fungus ball showed positive results. Moreover, in T1-201 single photon emission computed tomography, accumulation of T1-201 was demonstrated in the area surrounding fungus ball. In addition, findings of inflammation such as leukocytosis, elevated erythrocyte sedimentation rate, positive CRP and fever were observed in more than 50% of all cases. These results suggest that tissues surrounding the fungus ball, including the cavity wall and thickened pleura undergo inflammatory process secondary to infection by Aspergillus. Perfusion lung scintigrams showed decreased perfusion in all of 19 cases, which was more marked than that expected from the chest radiograph in many cases. In T1-201 myocardial scintigraphy, visualization of the right ventricle was observed in 15 of 18 cases. T1-201 chest scintigraphy and perfusion lung scintigraphy are useful for evaluation of the activity of the disease process, right ventricular overloading, and regional perfusion in pulmonary aspergilloma.

Adult↗
PubMed1992

Lifestyles, glucose tolerance and blood pressure in male self-defence officials in northern Kyushu, Japan.

Evidence on determinants of BP is mostly derived from studies in western populations. The relationship of BP with lifestyle variables and glucose tolerance was studied in 1,302 male self-defence officials aged 49-56 years who received a health examination before retirement at the Self-Defense Forces Fukuoka Hospital from October 1986 to December 1988. Those with treated hypertension or diabetes mellitus and those with conditions affecting BP levels were excluded from the study. In multiple regression analysis, alcohol use, body mass index and glucose intolerance were strongly associated with elevated BP while there was an inverse relation between cigarette smoking and BP. Physical activity expressed as the time spent in vigorous exercise was not associated with either systolic or diastolic BP. These findings indicate that alcohol use, obesity and glucose intolerance are also important determinants of BP in male Japanese, and that cigarette smoking is a potential covariate in the study of BP.

Alcohol Drinking↗
PubMed1991

Selectin GMP-140 (CD62; PADGEM) binds to sialosyl-Le(a) and sialosyl-Le(x), and sulfated glycans modulate this binding.

GMP-140 (CD62; PADGEM) is a member of the selectin family expressed highly at the surface of platelets and endothelial cells by agonists such as thrombin or phorbol esters. Previous studies indicate that the lectin domain of GMP-140 recognizes sialosyl-Le(x) (SLex) and to a lesser extent Le(x) (Polley MJ, et al., Proc Natl Acad Sci USA 88:6224, 1991). We now report that GMP-140 binds to sialosyl Lea (SLea) and to SLex, and that degree of binding to SLea is greater than that to SLex under our experimental conditions. Binding of activated platelets to SLea or SLex was inhibited to various degrees in the presence of sulfated glycans, suggesting that sulfated glycans induce conformational change in the lectin domain of GMP-140 and modulates its binding affinity to SLea and SLex.

Antibodies, Monoclonal↗
PubMed1991

Downregulation of GMP-140 (CD62 or PADGEM) expression on platelets by N,N-dimethyl and N,N,N-trimethyl derivatives of sphingosine.

GMP-140 (CD62 or PADGEM), a member of the selectin family, is a membrane glycoprotein in secretory granules of platelets and endothelial cells. When these cells are activated by agonists such as thrombin or AMP, GMP-140 is rapidly redistributed to the cell surface. The carbohydrate epitope defined by GMP-140 was identified as sialosyl-Le(x) (as for ELAM-1), which may play an essential role in adhesion of leukocytes or tumor cells on endothelial cells, through aggregation with platelets. Redistribution of GMP-140 from alpha-granules of platelets to the cell surface, induced by thrombin and PMA, was strongly inhibited by preincubation of platelets with N,N-dimethylsphingosine (DMS) or N,N,N-trimethylsphingosine (TMS) at 10-20 microM concentration for a brief period (5 min). Inhibition of GMP-140 redistribution to the cell surface by DMS or TMS was also detected by a cell adhesion assay using HL60 cells, which highly express sialosyl-Le(x); i.e., HL60 cells adhered on platelets activated by thrombin or PMA but not on platelets which were briefly preincubated with DMS or TMS followed by activation. The inhibitory effect of DMS or TMS on GMP-140 redistribution is not due to cytotoxicity, since the TMS-treated platelets were fully capable of aggregating in the presence of ristocetin. Sphingosine (SPN) and protein kinase C inhibitors such as H-7 and calphostin C showed weaker inhibitory activity than DMS and TMS. Our results indicate that both DMS and TMS could be useful reagents to inhibit cell surface expression of crucial selectins which promote adhesion of Le(x-) or sialosyl-Le(x)-expressing cells with platelets and endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1991

Alcohol intake and nonfatal acute myocardial infarction in Japan.

The relation between alcohol and nonfatal acute myocardial infarction (AMI) was examined in a case-control study of 89 male patients and 271 control subjects in Fukuoka, Japan. Patients admitted for the first AMI at 2 hospitals in Fukuoka City were aged 40 to 69 years, and control subjects were recruited based on the telephone directory of the city. Information on alcohol drinking and potential coronary risk factors was obtained by using a self-administered questionnaire, and past drinkers were separated from lifelong abstainers in the analysis. After adjustment for age, occupation, cigarette smoking, strenuous exercise, body mass index, hypertension, diabetes mellitus and parental heart disease, the risk of AMI was progressively less with increasing levels of alcohol consumption. With those who never drank as a referent, adjusted odds ratios for current drinkers consuming less than 30, 30 to 59, and greater than or equal to 60 ml/day of alcohol were 1.11 (95% confidence interval 0.51 to 2.42), 0.31 (0.11 to 0.83), and 0.13 (0.05 to 0.36), respectively. These findings add to the body of data showing that alcohol drinkers are less likely to have AMI.

Adult↗
PubMed1991

Effects of captopril on opioid peptides during exercise and quality of life in normal subjects.

In a placebo-controlled, randomized, crossover, double-blind study of 17 normal volunteers, we examined the effects of captopril on the concentration of opioid peptides during bicycle exercise and on quality of life after a 2-week treatment period. Two exercise tests (progressive exercise and constant work rate exercise) were performed. Maximum oxygen uptake and blood lactate concentrations were measured in progressive exercise tests. The exercise intensities corresponding to a 1/2 lactate threshold, a lactate threshold, and a 4 mmol/L lactate concentration were determined. Constant work rate exercise at selected work loads for 20 minutes was carried out to measure the concentrations of opioid peptides and other hormones. Quality of life was assessed after the 2-week treatment period. Captopril treatment had no effect on the exercise response of blood pressure, heart rate, maximum VO2, and maximum work loads. The plasma concentrations of lactate, epinephrine, norepinephrine, and aldosterone increased during exercise and captopril did not change them. Beta-endorphin levels and plasma renin activity also increased during exercise, and the increases were greater with captopril treatment. Met-enkephalin and leu-enkephalin concentrations did not increase during exercise. According to responses in the quality of life questionnaires, administration of captopril improved the physiologic state more than the placebo did. These findings suggest that captopril may act on the central nervous system involving an increase in the beta-endorphin level.

Captopril↗
PubMed1991

[Effect of careful tooth-brushing instruction by teachers on incipient gingivitis in school children].

At the Hiraizumi Primary School in Iwate Prefecture, 84 children with incipient gingivitis were selected at the annual dental examination in May. And the teachers instructed these children individually how to remove the remaining dental plaque. Moreover, the children were checked for the cleanliness of the teeth and inflammation of the gingiva by the teacher or their parents three times a day during the one week just before the second examination. In July the second examination was held and it was revealed that in sixty-three of eighty-four selected children the incipient inflammation of gingiva had improved.

Age Factors↗
PubMed1991

[A case of polyarteritis nodosa with bilateral hilar lymphadenopathy].

A 55-year-old male was admitted with non productive cough and fever which had continued for 6 weeks. The patient had symptoms of peripheral neuralgia. Chest X-ray revealed bilateral hilar lymphadenopathy (BHL) and reticular shadows in both lung fields. Other laboratory abnormalities included hematuria, RBC cast, high BUN, leukocytosis and thrombocytosis. Destruction of the internal membrane of arterioles was observed in a livedo reticularis on the right lower extremity. Renal angiography showed irregularity in the diameter, discontinuation and narrowing of peripheral arteries of both kidneys. These findings suggested the existence of "angiitis". These data were compatible with the diagnosis of polyarteritis nodosa (PN). Prednisolone (60 mg/day) administration resulted in the improvement of his symptoms and laboratory findings. A case of PN with lymph node swelling has been reported, however PN with BHL has not yet been reported. This is the first report of PN with BHL.

Humans↗
PubMed1991

[The relationship between ventilatory lung motion and pulmonary perfusion shown by ventilatory lung motion imaging].

Using ventilatory lung motion imaging, which was obtained from two perfusion lung scintigrams with 99mTc-macroaggregated albumin taken in maximal inspiration and maximal expiration, the lung motion [E-I)/I) of the each unilateral lung was studied in various cardiopulmonary diseases. The sum of (E-I)/I(+) of the unilateral lung showed a decrease in the diseased lung of localized pleuropulmonary diseases, including primary lung cancer and pleural thickening, and in both lungs in cases of heart diseases, diffuse pulmonary diseases including diffuse interstitial pneumonia and diffuse panbronchiolitis. The sum of (E-I)/I(+) of the both lungs, which correlated with vital capacity and PaO2, showed a decrease in diffuse interstitial pneumonia, pulmonary emphysema, diffuse panbronchiolitis, primary lung cancer, pleural diseases and so on. (E-I)/I(+), correlated with pulmonary perfusion (n = 49, r = 0.51, p less than 0.001), but not a few cases showed mismatch, which was observed in primary lung cancer, pleural diseases, pulmonary emphysema, diffuse panbronchiolitis and so on. (E-I)/I(+) better correlated with pulmonary ventilation by ventilation scintigraphy with 81mKr or 133Xe (n = 49, r = 0.61, p less than 0.001) than pulmonary perfusion. The ventilatory lung motion imaging, which demonstrates the motion of the intra-pulmonary areas and lung edges, appears useful for estimating pulmonary ventilation of the perfused area as well as pulmonary perfusion.

Heart Diseases↗