[Intracellular pH and PGI2 generation of human vascular endothelial cells].
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Calcium↗
Biomedical subjects
K Shirai
Publications and source records attributed to K Shirai.
Comparative studies of angiotensin converting enzyme inhibitors with and without the SH-radical.
This study was conducted to evaluate the effects of an SH-radical in an angiotensin converting enzyme (ACE) inhibitor on PGI2 generation, intracellular cGMP, and Ca2+ kinetics in vascular endothelial cells. In the cultured human umbilical vein endothelial cells, the non-SH containing ACE inhibitors, delapril and enalapril, did not result in significant changes in cGMP concentrations. By comparison, captopril significantly (P less than .01) increased cGMP concentrations. Only captopril showed a significant (P less than .01) effect on 45Ca kinetics in cultured human vascular endothelial cells. Captopril also decreased PGI2 generation in vascular endothelial cells. These effects were not seen with delapril or enalapril. The significance of the SH moiety in ACE inhibitors remains controversial. However, these results suggest that there could be differences in the vascular actions of ACE inhibitors related to the presence or absence of SH radical.
Angiotensin-Converting Enzyme Inhibitors↗
A testicular teratoma with rhabdomyosarcoma and seminoma.
A case of testicular mixed germ cell tumor with teratoma in a 36-year-old Japanese male is reported. Histologically, it was strongly suggested that the rhabdomyosarcoma had originated from the mesenchymal element of the teratoma. A review of the literature revealed six definitive and two possible previous cases of testicular rhabdomyosarcoma with teratoma, either with or without other germ cell malignancies. However, the present case associated with seminoma as a germ cell tumor is the first of its kind to be reported. In contrast to the poor prognosis observed in the previous cases, the present patient remains free of disease 3 years and 3 months after orchiectomy, chemotherapy and irradiation.
Adult↗
Pseudohomozygous type II hyperlipoproteinemia.
Nodular xanthomas on both elbows and a streak-like xanthoma on the intergluteal area developed in a 4-year-old girl with type IIa hyperlipoproteinemia. She had no disease associated with secondary hypercholesterolemia and no family history of hypercholesterolemia. Her xanthomas regressed under fat restriction diet and cholestyramine therapy. She was diagnosed as having pseudohomozygous type II hyperlipoproteinemia. The low-density lipoprotein (LDL) receptor activities of her cultured fibroblasts in terms of binding, internalization and degradation rate of LDL were normal. These results are consistent with a new syndrome of pseudohomozygous type II hyperlipoproteinemia and suggest that the mechanism of hypercholesterolemia, which induced xanthoma, differs from familial hypercholesterolemia.
Child, Preschool↗
Effect of cyclic GMP and sulfhydryl on prostacyclin production by human vascular endothelial cells.
The relationship between sulfhydryls and cGMP has been observed in several biological processes. Captopril is a sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor, that decreases PGI2 production in cultured human vascular endothelial cells. Enalapril does not appear to have this property. The role of cyclic GMP (cGMP) and sulfhydryls in the regulatory mechanisms in captopril-induced PGI2 production and Ca++ kinetics was investigated. Bradykinin and Ca ionophore A23187 enhanced PGI2 production, and increased the cytosolic free Ca++ concentration ([Ca++]i). It was observed that 8-bromo cGMP increased intracellular cGMP concentration ([Ca++]i), and decreased PGI2 production without changing [Ca++]i. Sulfhydryl containing compounds such as captopril, N-acetylcysteine and glutathione decreased PGI2 production via increased [cGMP]i. Enalapril, an ACE inhibitor without sulfhydryls, has no effect on PGI2 production, [Ca++]i and [cGMP]i. These results suggested that the presence of sulfhydryl groups is an important factor in the ability of vasoactive substances to induce PGI2 production.
Acetylcysteine↗
Endocrine disorders and body fat distribution.
To evaluate the role of hormones in formation of regional fat distribution, the ratios of visceral fat (V) to subcutaneous fat (S) in the abdomen of rats with various endocrine disorders were determined by computer tomography. Abdominal fat index (AFI), which was obtained by ultrasonography, correlated with V/S. In Cushing's syndrome, seven out of nine patients showed visceral type and V/S ratio positively correlated with cortisol levels. In acromegaly, three out of four patients showed visceral type and V/S ratio correlated not only with growth hormone level, but also with insulin level. All three insulinoma patients showed visceral type. During pregnancy, AFI decreased at the late stage of pregnancy. These results suggest that in visceral fat formation, insulin is the most important factor, and estrogen is an important factor for subcutaneous formation. In vitro experiments showed that visceral fat was much more sensitive to insulin in terms of glucose uptake and triglyceride synthesis than visceral fat. Fibroblast-like cells derived from adipose tissue were cultured. Estrone enhanced cell growth of fibroblast-like cells derived from subcutaneous fat tissue more than that from visceral fat tissue. The results suggested that hyperinsulinism primarily promotes visceral fat tissue enlargement and that estrogen might promote subcutaneous fat tissue enlargement.
Acromegaly↗
[The evaluation of the effect of Estracyt on prostatic cancer].
The clinical effect of Estracyt on untreated prostatic carcinoma was evaluated. The subjects consisted of 51 of 71 patients with prostatic carcinoma who were observed for 6 months or more after oral administration of 560 mg of estramustine phosphate. This drug was effective in all patients: markedly effective in 34 (66.6%), moderately effective in 13 (25.5%), and slightly effective in 4 (7.8%). During the observation period varying from 6 months to 2 years and 6 months, 7 patients had recurrence of progression. The interval between the drug administration and recurrence of progression varied from 6 months to 1 year and 10 months (mean, 15.8 months). Prostate acid phosphatase and gamma-seminoprotein remained normal between 3 and 15 months after the administration but became elevated due to recurrence of progression after 18 months or more in some patients. Blood testosterone, luteinizing hormone, and follicle stimulating hormone decreased while blood cortisol increased. Therefore, estrogen was acting effectively. Side effects were observed in 56.9% of the patients, the most frequent being mazoplasia in 33 patients (45.8%), and cardiovascular complications and apoplexy in 11 patients (15.3%). Estracyt was effective for untreated prostatic carcinoma but the problems such as recurrence of progression and side effects require further examination.
Adenocarcinoma↗
Effect of nifedipine administration on pulse wave velocity (PWV) of chronic hemodialysis patients--2-year trial.
Pulse wave velocity (PWV) is known to reflect the stiffness of the aorta, one of the major features of atherosclerosis. To clarify the severity and progression mechanism of atherosclerosis in hemodialysis patients and the preventive effect of nifedipine, PWV was annually measured for 2 years, and the change of PWV and contributory factors were analyzed. PWV in hemodialysis patients was faster than in age-matched normal controls. PWV was correlated with the duration of hemodialysis. delta PWV, which is obtained from the difference in PWV over 1 year, was positively correlated with age, high blood pressure, and serum cholesterol levels and was negatively correlated with HDL levels. The Ca x Pi value was also positively correlated with delta PWV. Nifedipine was administered to 47 patients for 2 years, and the change of PWV was compared with age-matched control hemodialysis patients. The PWV of the control group was gradually increased by 10%. The PWV of the group given nifedipine decreased by 2%. These results suggested that administration of nifedipine may prevent the progression of PWV in hemodialysis patients and may decrease the progression of atherosclerosis.
Adult↗
Frequency and role of apo E phenotype in familial hypercholesterolemia and non-familial hyperlipidemia in the Japanese.
The frequencies of the major apolipoprotein E(apo E) phenotypes in 65 normal, 426 hyperlipidemics, and 92 familial hypercholesterolemic Japanese subjects (FH) were studied, and features of hyperlipidemia compared between non-FH hyperlipidemia and FH. The frequencies of apo E phenotypes 3/3, 4/3, 3/2, 4/4 were almost the same in normal, non-FH hyperlipidemic, and FH subjects. The incidence of apo E7 was about 0.5% of total subjects. In type IV and V hyperlipidemias, incidence of E4/3 was higher than in any other hyperlipidemia. Incidence of E3/2 was also high in types III and V. In type II non-FH hyperlipidemia, incidence of E3/2 in type IIb was higher than in type IIa. VLDL-triglyceride, VLDL-cholesterol, apo C-II, apo C-III, and apo E levels were higher in E3/2 than in E3/3. But, in type IIa FH and type IIb FH, the incidence of E3/2 was the same, and lipid and apolipoprotein levels between 3/2 and 3/3 in FH were the same. These results indicate that allele epsilon 2 may be involved in the retention of VLDL or IDL, but not in FH.
Apolipoproteins E↗
Incidence of childhood obesity over the last 10 years in Japan.
1. Childhood obesity has been increasing for the last ten years in Tateyama City. Obesity in boys between the ages of 11 to 13 years was especially prominent. 2. Childhood obesity hardly improved especially in middle and morbid obesity. Eighty-five percent of light obesity in children lead to adult obesity. 3. Complications such as hypertension, serum lipid disorder and fatty liver were also observed in childhood obesity. Considering that Tateyama City is a typical Japanese country city, the above results could be representative of Japanese childhood obesity. Recent increases in childhood obesity might be due to the westernized dietary habit.
Adolescent↗
Contractile and relaxant responses of the canine isolated spinal artery to vasoactive substances.
1. Effects of vasoactive substances were investigated in the canine isolated spinal branch of the intercostal artery (SBICA). 2. Addition of angiotensin II (AII), vasopressin, noradrenaline (NA), adrenaline, 5-hydroxytryptamine (5-HT), and dopamine each produced concentration-dependent contraction in the SBICA, whereas prostaglandin F2 alpha, histamine, and tyramine caused only slight contraction. The decreasing order of the potency of contractile agents was AII much greater than vasopressin = NA greater than 5-HT greater than adrenaline much greater than dopamine. 3. Although the pD2 value for phenylephrine (5.31 +/- 0.36) was smaller than that for NA (6.48 +/- 0.13), there was no significant difference in Emax value between these two agonists in the SBICA. On the other hand, xylazine produced only a slight contraction, the pD2 value being 3.59 +/- 0.08. Phentolamine (10(-8)-10(-6) M) and prazosin (10(-8)-10(-6) M) competitively inhibited the NA-induced contraction, while yohimbine (10(-8)-10(-6) M) did not. 4. Acetylcholine (ACh), sodium nitroprusside (SNP), ATP, ADP, and adenosine caused concentration-dependent relaxations in SBICA following contraction with NA. On the other hand, isoprenaline up to 10(-4) M did not produce any relaxation. The decreasing order of potency of the relaxant agents was ACh greater than SNP much greater than ATP = ADP = adenosine. 5. The ACh-induced relaxation was competitively inhibited by atropine and was abolished by mechanical removal of the endothelium. Aspirin (5 x 10(-5) M) did not affect the relaxant response to ACh, while oxyhaemoglobin (10(-5) M) and methylene blue (10(-5) M) produced significant attenuation. 6. These results suggest that NA produces contraction of the isolated canine SBICA which is mainly mediated via alpha 1-adrenoceptors and that ACh causes a relaxation of the SBICA due to release of endothelium-derived relaxing factor (EDRF) from the endothelial cells.
Acetylcholine↗
Effects of long-term treatment with probucol on serum lipoproteins in cases of familial hypercholesterolemia in the elderly.
The effect of probucol in lowering serum lipoprotein in young and middle-aged (YM) and elderly (E) patients with familial hypercholesterolemia were compared. Probucol at 1000 mg/day was administered orally to 37 YM patients and 14 E patients for an average of 10 months. Probucol treatment for this period caused significant reductions in the serum levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, and apoprotein AI, AII, B, and CIII in both groups. The decreases in the levels of total cholesterol, LDL-C, and apoprotein B were greater in the E group than in the YM group (total cholesterol: YM, -19.3%, E, -31.3% [P less than .001]; LDL-C: YM, -17.0%, E, -35.4% [P less than .001]; apoprotein B: YM, -12.3%, E, -28.1% [P less than .01]). The decreases in other parameters in the two groups were not significantly different. The serum probucol concentrations in the YM and E groups were not significantly different. No significant side effects were observed in any patient. Thus probucol reduced the serum level of LDL more in the E group than in the YM group, and did so without any increase in the serum concentration of the drug or in side effects, suggesting that probucol is safe and beneficial for use in elderly patients.
Administration, Oral↗
Effect of alanine-producing bacteria on the growth of chicks.
The effects of alanine-producing bacteria administered orally on the growth of chicks was investigated. The chicks were given diets containing adequate amounts of only the essential amino acids as sources of nitrogen: a basal diet (BD); a BD plus 40 g of urea per kilogram of diet (UD); a UD with bacteria named AR-8-3; a UD with bacteria named AB-605; and a BD plus 59.4 g and plus 118.7 g of L-alanine per kg of diet, respectively, from Day 8 to Day 15. The growth of chicks fed diets containing urea or alanine was significantly faster than that of the BD controls; no significant difference in growth was detected among the groups given the UD and bacteria. Since viable bacteria could not be detected from the intestinal content or from excreta for both groups given the bacteria, the establishment and achievement of alanine-producing activity by the bacteria in the gastrointestinal tract were considered doubtful. The supplement with 59.4 g of alanine per kg of diet improved the growth rate, but the higher inclusion (118.7 g of alanine per kg of diet) resulted in no further improvement.
Alanine↗
Relationship between lipase and esterase.
There are at least two sites on the lipase which are concerned with catalysis: the catalytic site and the hydrophobic recognition site (lipid-binding site). The recognition site may be destroyed by mild proteolytic digestion, but the catalytic site may not be changed by this treatment. Mild treatment with trypsin caused change in the catalytic properties of hepatic triglyceride lipase; the water-insoluble ester-hydrolyzing activity of hepatic triglyceride lipase decreased, whereas the water-soluble ester-hydrolyzing activity did not change. After proteolytic digestion, hepatic triglyceride lipase resembles esterase since it hydrolyzes the water-soluble substrate better than the water-insoluble substrate. Conversely, esterase was converted to lipase by treatment with phospholipid. Cardiolipin in a concentration-dependent fashion enhanced triolein-hydrolysis of human serum carboxylesterase and this effect was associated with a dose-dependent decrease in water-soluble tributyrin hydrolysis. Based on these results, we propose the hypothesis that lipase and esterase have similar catalytic sites and that addition of a hydrophobic recognition site to esterase causes conversion of esterase to lipase (Fig. 9).
Animals↗
[The enzymes related to lipoprotein metabolism (LpL, H-TGL, LCAT, ACAT, HMG-CoA reductase, 7 alpha-hydroxylase)].
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Cholesterol↗
Effects of chloroquine on the metabolism of phosphatidylcholine associated with low density lipoprotein in arterial smooth muscle cells.
Phospholipid associated with LDL (LDL-phospholipid) has been suggested to affect metabolism of LDL in arterial smooth muscle cells. However, the metabolism of LDL-phosphatidylcholine in these cells has not been well clarified. We compared the metabolic pathway of LDL-phosphatidylcholine with that of cholesteryl ester associated with LDL (LDL-cholesteryl ester) in rabbit arterial smooth muscle cells by incubating the cells in the absence or presence of chloroquine, an inhibitor of lysosomal function. When the cells were incubated with LDL-[3H]cholesterol linoleate in the absence of chloroquine, 26.6 and 51.4% of incorporated radioactivity was found as cholesteryl ester in the lysosome-rich and microsome-rich fractions, respectively. When the cells were incubated in the presence of 50 microM chloroquine, the radioactivity found as cholesteryl ester in the lysosome-rich fraction increased to 45.5% while that in microsome-rich fraction decreased to 21.4%, indicating that LDL-cholesteryl ester accumulated in lysosomes as a consequence of inhibition of lysosomal function. When the cells were incubated with LDL-[14C]linoleoyl phosphatidylcholine in the absence of chloroquine, 25.1% of incorporated radioactivity was found as phosphatidylcholine in the lysosome-rich fraction and 24.8% in the cytosol-rich fraction. When the cells were incubated in the presence of chloroquine, phosphatidylcholine-associated radioactivity found in the lysosome-rich and cytosol-rich fractions changed only to 28.8% and 26.1%, respectively, showing that LDL-phosphatidylcholine did not accumulate in lysosomes when lysosomal function was inhibited. In conclusion, these data indicate that LDL-phosphatidylcholine, in contrast to LDL-cholesteryl ester, is not only hydrolyzed in lysosomes, but also at other subcellular sites.
Animals↗
Lipoprotein lipase with a defect in lipid interface recognition in a case with type I hyperlipidaemia.
Defective lipoprotein lipase (LpL) was found in the postheparin plasma (PHP) of a patient with severe hypertriglyceridaemia. The patient was a 14-year-old girl with a maximum plasma triglyceride (TG) level of 3600 mg d-1 who had been suffering from recurrent pancreatitis. The patient's LpL purified from the PHP by heparin-Sepharose and phenyl-Sepharose chromatographies hydrolysed tributryrin, but not triolein emulsified with Triton X-100 and phosphatidylcholine (PC), or in chylomicrons, whereas normal LpL hydrolysed these substrates. Moreover, unlike normal LpL, LpL from the patient did not associate with VLDL, as shown by Sepharose 4B column chromatography. The patient's LpL hydrolysed triolein emulsified with lysophospholipid at a normal rate in the presence of apolipoprotein CII. These findings suggest that this patient has LpL with a normal catalytic site for tributyrin but with a defect in lipid interface recognition resulting in loss of ability to recognize VLDL or chylomicrons, but not of triolein emulsified with lysophospholipid.
Adolescent↗
Application of thrombin-antithrombin III complex for detecting a latent hypercoagulable state in patients with coronary artery disease.
It is thought that a hypercoagulable state contributes to the pathogenesis of coronary artery disease (CAD), but few sensitive markers have been available for detecting the state. In the present study the plasma level of thrombin-antithrombin III complex (TAT), a specific indicator of thrombin generation in blood, was investigated before and after a submaximal exercise test in 18 patients with CAD and in 12 healthy controls. The mean (+/- SEM) value of plasma TAT before the exercise was 3.30 (0.81) ng/ml in the patient group and 1.49 (0.08) ng/ml in controls, and its level increased to 29.22 (5.74) ng/ml and 12.07 (2.89) ng/ml after the exercise, respectively. Thus, the TAT value in the patient group was higher than that in the controls both before and after the exercise. However, no differences could be found between the groups in the following parameters; prothrombin time, activated partial thromboplastin time, antithrombin III, fibrinogen, FDP, plasminogen, alpha 2-plasmin inhibitor, and alpha 2-macroglobulin. Through these results it was concluded that plasma TAT level could be a sensitive marker for latent activation of blood coagulation, and also that the results of these experiments showed that patients with CAD were in a latent hypercoagulable state.
Adolescent↗