Biomedical subjects

Kenji Fukuzawa

Publications and source records attributed to Kenji Fukuzawa.

23 records · Page 2Linked to original sources

PubMed2002

Lack of significant differences in the corrected activity of lysophospholipase D, producer of phospholipid mediator lysophosphatidic acid, in incubated serum from women with and without ovarian tumors.

BACKGROUND: Several studies have shown that lysophosphatidic acid (LPA), a phospholipidic chemical mediator, is relevant to the pathogenesis of ovarian carcinoma. Higher plasma levels of LPA have been reported in patients with ovarian carcinoma than in healthy patients, and LPA is known to activate ovarian carcinoma cells. To determine the reason for the increased plasma LPA levels in ovarian carcinoma patients, we compared the activities of serum lysophospholipase D, a novel LPA-producing metallo-enzyme, in healthy volunteers, patients with benign ovarian tumor, and patients with ovarian carcinoma. METHODS: Lysophospholipase D activity was assessed by measuring the percentage conversion of [14C]palmitoyl-lysophosphatidylcholine (LPC) added to human serum. The apparent enzyme activities were corrected based on the serum levels of palmitoyl-LPC determined by gas-liquid chromatography after its purification and conversion to fatty acid methyl esters. RESULTS: The apparent activity of lysophospholipase D in serum preparations from four patients with ovarian carcinoma at Stage IV was significantly higher than those from five healthy subjects, five patients with benign ovarian tumors, and fourteen patients with ovarian carcinoma at Stages I (n = 5), II (n = 4), and III (n = 5). The serum levels of LPC, an endogenous substrate of lysophospholipase D, in ovarian carcinoma patients were less than those in patients with benign ovarian tumors. There were no significant differences in the corrected lysophospholipase D activity for the LPC levels in healthy women, patients with benign ovarian tumors, and patients with ovarian carcinoma at various stages. CONCLUSIONS: The current results suggest that lysophospholipase D is not associated with the elevated plasma levels of LPA in ovarian carcinoma patients previously reported, although only a limited number of patients were analyzed.

Adult↗

PubMed2002

Clinicopathological significance of lipid peroxidation in carotid plaques.

Several reports have suggested an association between lipid peroxidation and human carotid atherosclerosis, but few reports have demonstrated a link between lipid peroxidation and carotid plaques in humans. In this study, we investigated the relationship between clinical features, histopathological characteristics and lipid peroxidation in patients undergoing carotid endarterectomy (CEA). Forty-one carotid plaques were obtained. A portion of the most severe lesions was subjected to histopathologic examination, and the remainder of the plaques examined for lipid peroxidation. Thiobarbituric acid-reactive substances (TBARS) values were determined as a marker for lipid peroxidation. The lipid-rich core (LC) and macrophage infiltration (Mphi) component as a percentage of total plaque area were measured morphometrically. Based on the results, all plaques were classified into four groups. Group I (GI): LC <10%; Group IIa (GIIa): LC 10-30%, Mphi <5%; Group IIb (GIIb): LC 10-30%, Mphi < or = 5%, and Group III (GIII): LC < or =30%. The plaque TBARS values of GIII were significantly higher than those of GI, GIIa, and GIIb. The TBARS values of GIIb were one-and-a-half times higher than those of GIIa. Our results show that lipid peroxidation in carotid plaques is significantly associated with carotid atherosclerosis, especially plaque instability. These findings provide direct evidence of an association between lipid peroxidation and human atherosclerosis.

Aged↗

PubMed2002

Enhancement by alpha-tocopheryl hemisuccinate of nitric oxide production induced by lypopolysaccharide and interferon-gamma through the upregulation of protein kinase C in rat vascular smooth muscle cells.

The effect of alpha-tocopheryl hemisuccinate (TS) on lipopolysaccharide (LPS)/interferon-gamma (IFN)-induced nitric oxide production in rat vascular smooth muscle cells (VSMC) was examined. The LPS/IFN-induced NO production was enhanced by TS but not by the other alpha-tocopherol (alpha-T) derivatives alpha-tocopheryl acetate (TA) and alpha-tocopheryl nicotinate (TN), or alpha-T itself. alpha-T, TA and TN inhibited the enhancement by TS of LPS/IFN-induced NO production. The enhancing effect of TS was observed in the presence of LPS, but not IFN, suggesting that TS participates in the LPS-stimulated signal pathway leading to NO production. Protein kinase C (PKC) inhibitors, but not protein kinase A inhibitors, inhibited the enhancing effect of TS on LPS/IFN-induced NO production. Furthermore, TS enhanced the amount of PKCalpha in VSMC. From these results, we concluded that the enhancing effect of LPS/IFN-induced NO production was caused by upregulation of PKC in VSMC.

Animals↗

PubMed2002

Increased production of bioactive lysophosphatidic acid by serum lysophospholipase D in human pregnancy.

Lysophosphatidic acid (LPA) is a prototype of the lysophospholipid mediator family and has multiple effects in the female reproductive system. Although several metabolic routes have been reported for intracellular formation of LPA, a unique route involving lysophospholipase D, an extracellular enzyme that produces LPA in blood and body fluids, is particularly intriguing for its agonistic role. In this study, using an assay with radioactive palmitoyl-lysophosphatidylcholine, we found that lysophospholipase D activity producing palmitoyl-LPA in human serum gradually increased during pregnancy. Elevated activity of lysophospholipase D was not caused by changes in levels of their precursors, lysophosphatidylcholines, in nonpregnant women or in pregnant women at different gestational periods. With increasing length of gestation, the elevated activity in pregnant women was found to produce increasing proportions of LPA with a palmitoyl group versus other LPAs. These results suggest that LPA formed by increased activity of lysophospholipase D in blood might participate in maintenance of pregnancy.

Adult↗

PubMed2002

Increased formation of lysophosphatidic acids by lysophospholipase D in serum of hypercholesterolemic rabbits.

Lysophosphatidic acid (LPA) is a biologically active phospholipid that has been identified as a vasoactive principle in incubated plasma and serum of mammals. Previously, we found that mammalian plasma and serum contain a lysophospholipase D, which hydrolyzes lysophosphatidylcholines (LPCs) with different fatty acyl groups to the corresponding LPAs during its incubation at 37 degree C. In this study, we examined whether lysophospholipase D activity and levels of LPCs in rabbit serum were modulated by feeding rabbits a high cholesterol diet. Results showed that the serum levels of LPCs increased gradually in animals fed a high cholesterol diet for 12 weeks. We found that the levels of individual LPAs formed on incubation of serum for 24 h increased with an increase in the period of feeding of rabbits a high cholesterol diet. LPA with a linoleate residue was the most abundant LPA, followed in order by 16:0-, 18:1- and 18:0-LPAs. LPA was found to increase attachment of the monocytic cell line THP-1 to vascular endothelial cells pre-stimulated with tumor necrosis factor-alpha. These results indicated that increases in the levels of LPAs generated by lysophospholipase D in the blood of hypercholesterolemic rabbits may be relevant to attachment of monocytes to vascular walls, a key phenomenon observed at an early stage of atherosclerosis.

Animals↗