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Biomedical subjects

S Horiuchi

Publications and source records attributed to S Horiuchi.

At least 217 records · Page 12Linked to original sources
PubMed1995

Recent trends and prospects in world population growth.

"This article assesses the causes of the stagnation in the declining trend in world population growth rates over the past decade. Three major factors have been identified as contributing to the stagnation: age structure, fertility trends in India and China, and the fact that although the number of developing countries with sustained declines in fertility levels rose sharply in the late 1960s and 1970s, it dropped off dramatically in the 1980s. Prospects for the growth rate in the 1990s favour a decline, owing to changes in the age structure and indications that China and India have resumed their fertility declines. However, there remain some populous developing countries that continue to have high levels of fertility. Fertility trends in those countries will have a certain influence on the world's growth rate."

Age Distribution↗
PubMed1995

Immunohistochemical and ultrastructural detection of advanced glycation end products in atherosclerotic lesions of human aorta with a novel specific monoclonal antibody.

To elucidate the deposition of advanced glycation end products (AGEs) in aortic atherosclerosis, aortic walls were obtained from 25 autopsy cases and examined immunohistochemically and immunoelectron microscopically with a monoclonal antibody specific for AGEs, 6D12. Among the autopsy cases, atherosclerotic lesions were found in the aortas of 22 cases and were composed of diffuse intimal thickening, fatty streaks, atherosclerotic plaques, and/or complicated lesions. In these cases, intracellular AGE accumulation was demonstrated in the intimal lesions of aortic atherosclerosis in 12 cases. Compared with the diffuse intimal thickening, intracellular AGE accumulation was marked in the fatty streaks and atherosclerotic plaques. Immunohistochemical double staining with 6D12 and monoclonal antibodies for macrophages or muscle actin or a polyclonal antibody for scavenger receptors demonstrated that the AGE accumulation in macrophages or their related foam cells was marked in the diffuse intimal thickening and fatty streak lesions and that almost all macrophages and macrophage-derived foam cells possessed scavenger receptors. Immunoelectron microscopic observation revealed the localization of 6D12-positive reaction in lysosomal lipid vacuoles or electron-dense granules of the foam cells. These results indicate that AGE accumulation occurs in macrophages, smooth muscle cells, and their related foam cells.

Adult↗
PubMed1995

Structural and functional differences of subspecies of apoA-I-containing lipoprotein in patients with plasma cholesteryl ester transfer protein deficiency.

ApoA-I-containing lipoproteins exist in plasma in two main forms: one contains only apoA-I (LpA-I) while the other contains both apoA-I and apoA-II (LpA-I/A-II). We characterized structural and functional changes of these lipoproteins in six patients with cholesteryl ester transfer protein (CETP) deficiency. In these patients, the amount of LpA-I and LpA-I/A-II had increased significantly. Sixty-five percent of plasma apoA-I was associated with LpA-I/A-II, which indicated that LpA-I/A-II was predominant. The chemical composition of both LpA-I and LpA-I/A-II was characterized by increased ratios of neutral to polar lipid, compared with findings in normal subjects. Particle sizes of these lipoproteins shifted to larger diameter ranges, as compared to the size seen in normal subjects. Incubation of patients' LpA-I and LpA-I/A-II with CETP markedly corrected the chemical and physical abnormalities in these lipoproteins. Cholesterol-reducing capacities of these lipoproteins from macrophage foam cells were significantly lower than in normal controls. Cholesterol esterification rates in LpA-I, LpA-I/A-II, and plasma were significantly lower in patients than in normal controls. We propose that the structure and function of LpA-I and LpA-I/A-II are severely affected in the presence of CETP deficiency.

Apolipoprotein A-I↗
PubMed1995

A new type of advanced third-stage larvae of the genus Gnathostoma in freshwater eels, Fluta alba, from Nakhon Nayok, central Thailand.

Five advanced third-stage larvae of a newly identified type of genus Gnathostoma were collected from freshwater eels, Fluta alba, which were purchased at a market in Nakhon Nayok, central Thailand. The most remarkable characteristic of the newly identified larvae was the larger body size compared with any other larva of Gnathostoma spp. They were also distinguishable from other species by the shape of their hooklets, which branched in a complex manner at the base: this had not been previously observed in any other larval Gnathostoma. The newly described larvae had an average number of 44.5, 45.0, 49.0 and 55.1 hooklets on the head-bulb from the first to the fourth rows, respectively, which were comparable to those of larval G. spinigerum. However, the average number of nuclei in each intestinal cell was 2.21 and fewer than those of the larvae of G. spinigerum. These results suggest that the new type of larvae belong to either G. vietnamicum, G. malaysiae, or constitute a new species of the genus Gnathostoma.

Animals↗
PubMed1994

Lysophosphatidylcholine plays an essential role in the mitogenic effect of oxidized low density lipoprotein on murine macrophages.

We previously demonstrated that the growth of starch-induced murine macrophages was stimulated by modified low density lipoproteins, such as oxidized low density lipoprotein (Ox-LDL) and acetylated low density lipoprotein (acetyl-LDL), and that the mitogenic effect of Ox-LDL was much greater than that of acetyl-LDL (Yui, S., Sasaki, T., Miyazaki, A., Horiuchi, S., and Yamazaki, M. (1993) Arterioscler. Thromb. 13, 331-337). The present study was undertaken to elucidate the factor(s) that are involved in this growth-stimulating effect of Ox-LDL. The growth-stimulating effect of acetyl-LDL on murine resident macrophages was negligibly weak compared with that of Ox-LDL. However, the treatment of acetyl-LDL with phospholipase A2 led to an increase in lysophosphatidylcholine (lyso-PC) (75% of total phospholipids) and a concomitant increase in the mitogenic activity of acetyl-LDL. In contrast, cell-free incubation of Ox-LDL with high density lipoprotein resulted in a decrease in lyso-PC content and a concomitant loss of growth-stimulating activity. These results suggest that lyso-PC may play an essential role in the mitogenic activity of Ox-LDL.

Animals↗
PubMed1994

Evidence for impaired cellular cholesterol removal mediated by apo A-I containing lipoproteins in patients with familial lecithin: cholesterol acyltransferase deficiency.

We investigated the cholesterol reducing capacity of two species of lipoproteins containing apo A-I, one containing only apo A-I (LpA-I) and the other containing apo A-I and apo A-II (LpA-I/A-II), in 7 patients (4 homozygotes and 3 heterozygotes) with familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Interaction of normal LpA-I or LpA-I/A-II with macrophage foam cells induced a mass reduction in cholesterol from these cells and the cholesterol reducing capacity of LpA-I was greater than that of LpA-I/A-II. When foam cells were incubated with these lipoproteins from homozygotes or heterozygotes, the capacity of LpA-I and LpA-I/A-II particles to reduce cellular cholesterol was decreased by approx. 50% in the homozygotes but was increased by 25-50% in the heterozygotes. These results suggest that LpA-I and LpA-I/A-II isolated from homozygotes and from heterozygotes differ in their ability to accept cellular cholesterol. The former are poor and the latter good acceptors of intracellular cholesterol. We conclude that factors other than reverse cholesterol transport via apo A-I containing lipoproteins have to be considered to explain why homozygotes for LCAT deficiency are not at high risk for premature atherosclerosis.

Adult↗
PubMed1994

Acetylated low density lipoprotein reduces its ligand activity for the scavenger receptor after interaction with reconstituted high density lipoprotein.

Complexes of apolipoprotein A-I (apoA-I) with phospholipids are known to induce cholesterol efflux from cells. In a cholesteryl ester accumulation system in which rat peritoneal macrophages were incubated with acetylated low density lipoprotein (acetyl-LDL) and either dimyristoylphosphatidylcholine complexes (DMPC/apoA-I) or native high density lipoprotein (HDL), DMPC/apoA-I exhibited a much stronger effect than native HDL in preventing cholesteryl ester accumulation. The mechanism for this phenomenon was investigated in the present study. After 18 h incubation with DMPC/apoA-I in a cell-free system, acetyl-LDL was re-isolated from DMPC/apoA-I by Sephacryl S-300 gel filtration chromatography. Re-isolated acetyl-LDL exhibited an increase in its phospholipid content by 86% as well as a reduction in the electrophoretic mobility. Its endocytic degradation by macrophages was reduced by 60% when compared with control acetyl-LDL, suggesting a significant reduction in the ligand activity for the macrophage scavenger receptor. Transfer of apolipoproteins between acetyl-LDL and DMPC/apoA-I did not occur. These results indicate that transfer of DMPC from DMPC/apoA-I to acetyl-LDL weakens the ligand activity for the scavenger receptor due probably to a decrease in net negative charge. This study demonstrated for the first time that lipid modification (change in the lipid moiety) of acetyl-LDL can induce alteration in its apolipoprotein moiety, leading to a significant loss of its biological activity. Because discoidal HDLs are known to occur in vivo, this phenomenon may explain one of the anti-atherogenic functions of HDL in vivo.

Animals↗
PubMed1994

Induction of macrophage growth by advanced glycation end products of the Maillard reaction.

We previously showed that negatively-charged phospholipids, acetylated low density lipoprotein (LDL) and oxidized LDL, which are known to be taken up by macrophages via the scavenger receptor for modified LDLs, were able to induce the growth of peripheral macrophages in vitro. The present study demonstrated the macrophage growth-stimulating activity of the ligands for another macrophage receptor for advanced glycation end products (AGE) of the Maillard reaction. Experiments with murine macrophages showed that significant cell growth was induced by AGE-modified proteins such as bovine serum albumin (AGE-BSA) and AGE-human hemoglobin. The capacity of AGE-BSA to induce macrophage growth was completely blocked when cells were cultured with the mAb against granulocyte/macrophage CSF (GM-CSF). Moreover, PCR analysis revealed that AGE-BSA induced the expression of mRNA of GM-CSF. These data suggest that the macrophage AGE receptor may play an active role not only in phagocytic elimination of AGE-proteins but also induction of the growth of macrophages.

Animals↗
PubMed1994

Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism.

To detect transcripts encoding the interleukin-6 receptor (IL-6R) molecule lacking the transmembrane (TM) domain, in various cell lines and peripheral blood mononuclear cells (PBMC), we used the polymerase chain reaction (PCR) with primer pairs that flank the TM domain and which were selected to generate a 398-bp fragment. We detected 398-bp and 304-bp DNA molecules in the PCR products of the U1, J22HL60, MT-2, MT-4, U937 and HL60 cell lines and of PBMC isolated from several individuals. The sequencing analysis of both DNA molecules showed that a 94-bp region consisting of the TM domain of IL-6R was deleted in the 304-bp molecule. Moreover, we detected a soluble (s) IL-6R protein of 45 kDa in culture supernatants of the MT-2, MT-4 and U937 cell lines by radioimmunoprecipitation using specific antibodies against sIL-6R. Our results indicate that active deletion of the TM domain by alternative splicing of mRNA represents one mechanism for release of sIL-6R into the culture supernatants of cells, or into serum or urine.

Alternative Splicing↗
PubMed1994

Purification and characterization of cathepsin E type acid proteinase from gastric mucosa of bullfrog, Rana catesbeiana.

An acid proteinase different from pepsin was purified from bullfrog (Rana catesbeiana) gastric mucosa by chromatography on hydroxyapatite, Q-Sepharose, Con A-Sepharose 4B, and Mono Q columns. Its molecular weight after purification was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be 45 kDa under reducing conditions and about 90 kDa under nonreducing conditions. Thus, it is a dimer of two identical subunits. On acid treatment, the molecular weight of the subunit decreased from 45 to 42 kDa, showing a similar change to that of pepsinogen in its activation under acidic conditions. Therefore, the enzyme was thought to have both a proform and a mature form. It preferred hemoglobin to other protein substrates examined and showed broad optimal activity in the range of pH 2.0 to 3.5 towards hemoglobin. Its proteolytic activity, like that of porcine pepsin, was strongly inhibited by pepstatin. Its amino acid composition was similar to those of other aspartic proteinases. From these results, the enzyme was identified as a cathepsin E type acid proteinase of bullfrog, and cathepsin E type enzyme was purified from anuran for the first time.

Amino Acids↗
PubMed1994

Advanced glycation end products of the Maillard reaction and their relation to aging.

Long-term incubation of proteins with glucose leads to advanced glycation end products (AGE). Demonstration of AGE in vivo as well as determination of its main structure are crucial to elucidate its potential link to aging processes and diabetic complications. We prepared polyclonal and monoclonal anti-AGE antibodies and used them to identify and quantitate AGE in human lens proteins. Results suggest that there occurs a common AGE structure and provide the direct evidence for the presence of AGE in human lens crystallins and its age-related increase.

Aging↗
PubMed1994

Species difference in cholesteryl ester cycle and HDL-induced cholesterol efflux from macrophage foam cells.

The species difference in the turnover rates of the cholesteryl ester (CE) cycle in macrophage foam cells (MFC) was examined in mice and rats. MFC were induced by acetyl-LDL and pulsed with [3H]oleate, followed by a chase with [14C]oleate. The replacement of the initial amount of cholesteryl [3H]oleate by cholesteryl [14C]oleate within 24 hours was 63% in mouse MFC, whereas it was 33% in rat MFC. The corresponding replacement in rabbit MFC was < 10%. In addition, HDL removed 41% of the CE mass from mouse MFC but only 22% from rat MFC. HDL-induced CE reduction from mouse MFC was enhanced by 40% by the inhibitor for acyl-coenzyme A:cholesterol acyltransferase (58-035), whereas the enhancing effect was not observed with rat MFC. These results indicate that the rate of CE turnover may serve as a critical factor to determine the capacity of MFC to respond to HDL-induced CE reduction, suggesting the possibility that the species difference in the turnover rates of the CE cycle in MFC might explain, in part, the species difference in susceptibility to experimental atherosclerosis.

Acyl Coenzyme A↗
PubMed1994

Characterization of subspecies of apolipoprotein A-I-containing lipoprotein in homozygotes for familial lecithin:cholesterol acyltransferase deficiency.

We characterized the two species of lipoproteins containing apolipoprotein A-I (apoA-I), one containing only apoA-I (LpA-I) and the other containing apoA-I and apoA-II (LpA-I/A-II), in four homozygotes for familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Two homozygotes lacked both LCAT mass and activity, whereas the other two had some residual LCAT mass and activity. In these patients, the amount of all apoA-I-containing lipoproteins was one fourth that of normal control subjects, and > 60% was LpA-I. The chemical composition of both LpA-I and LpA-I/A-II is characterized by markedly decreased ratios of neutral to polar lipids compared with those of normals and the sizes of LpA-I and LpA-I/A-II particles are shifted to smaller and larger diameter ranges when compared with those of normal particles. Changes in particle diameter are also reflected in slower electrophoretic mobilities of both LpA-I and LpA-I/A-II particles. All of these abnormalities were more evident in the two homozygotes who lacked LCAT activity. Incubation of LCAT-deficient plasma with LCAT markedly corrected the chemical and physical abnormalities in both LpA-I and LpA-I/A-II particles. These data, taken together, emphasize the importance of LCAT in modifying the chemical composition, size, and shape of LpA-I and LpA-I/A-II particles.

Adult↗
PubMed1994

[Changes in sleep parameters of young women from late pregnancy to postpartum].

Mothers in postpartum periods are forced to be awake at night in order to take care of their babies. It is important to investigate relationships between the sleep patterns of postpartum mothers and their babies' activities under conditions in daily life to determine effects on their health. In this study, changes in sleep parameters of young women from late pregnancy to the 6th postpartum week were studied using the ambulatory EEG monitoring system. Subjects were 10 primiparae, aged 23-31 yrs (mean age of 26.8 yrs), who had a normal course of pregnancy and delivery. EEG, EMG, EOG and ECG of the mothers and their babies' actigrams from legs during sleep were simultaneously recorded using Medilog 9000 at home at four points: during late pregnancy (36 weeks), and the 1st, 3rd and 6th postpartum weeks. In the late pregnancy period, mean sleep efficiency for the 10 subjects was 94.5%, and mean total sleep time was 368.8 min. We compared the sleep parameters of four points using a two-way analysis of variance (point x subject). Total sleep time showed no significant differences among the four points (postpartum 1st week: 336.8 min, 3rd: 314.2 min, 6th:312.6 min.). Percent of waking time after sleep onset in the 1st postpartum week (21.1%) significantly increased compared with late pregnancy (5.4%), but did not change through the 3rd (19.7%) and 6th week (20.7%). The percent of stage 3 + 4 and stage REM did not change across the four points, but the percent of stage 2 in the postpartum period (1st week: 39.7%, 3rd: 41.2%, 6th: 41.0%) significantly decreased compared with late pregnancy (59.6%). There were no significant differences in the number of awakening among the four points. In conclusion, wakefulness after sleep onset during postpartum period increased compared with late pregnancy. The mothers' sleep pattern did not change through the 1st, 3rd and 6th postpartum weeks. These findings suggested strongly that their sleep was interrupted by their babies' activities, as shown in another abstract.

Adult↗
PubMed1994

Endocytic pathway of scavenger receptors via trans-Golgi system in bovine alveolar macrophages.

BACKGROUND: The scavenger receptors are trimeric membrane glycoproteins present on the surface membrane of macrophages and macrophage-derived foam cells and are implicated in the deposition of cholesterol in the arterial walls during atherogenesis. This receptor mediates endocytosis of a diverse alley of negatively charged macromolecules including modified low density lipoproteins. EXPERIMENTAL DESIGN: We tried biochemical and morphologic approaches to elucidate in more detail the endocytic and intracellular pathway of the scavenger receptors during endocytosis of acetylated low density lipoproteins (AcLDL) and oxidized LDL (OxLDL) by bovine alveolar macrophages. Biochemically, cell interaction and subsequent intracellular degradation of AcLDL and OxLDL were examined using [125I]AcLDL or [125I]OxLDL. At the ultramorphologic level, the scavenger receptors were detected by a mouse monoclonal antibody against bovine macrophages, D2, with colloidal gold particles (AcLDL-Au or OxLDL-Au particles) as tracer of ligands. RESULTS: The biochemical studies demonstrated that after binding of AcLDL and OxLDL to the cell surface, these ligands were internalized and degraded intracellularly. Immunoelectron microscopy revealed that after a 2-hour incubation at 4 degrees C AcLDL-Au or OxLDL-Au particles were bound to the scavenger receptors present on the cell surfaces. Upon a temperature shift from 4 to 37 degrees C, these particles were concentrated in coated pits and internalized in endosomes. After subsequent dissociation of the particles from the receptors within the endosomes, the ligands were transported to secondary lysosomes, the receptors were transported to a trans-Golgi system. In the Golgi complex, the receptors were packed in secretory vesicles and recycled to the cell surface membrane. The transport and recycling of the receptors via the trans-Golgi system were completely inhibited by incubation below 18 degrees C or pretreatment with monensin. CONCLUSIONS: These results suggest that during endocytosis of modified low density lipoprotein, the Golgi complex plays a crucial role in sorting and recycling of the scavenger receptors in macrophages.

Animals↗
PubMed1993

Two independent macrophage receptors for acetylated high-density lipoprotein.

We previously demonstrated that acetylated human high-density lipoprotein (acetyl-HDL) was recognized by a scavenger receptor of rat sinusoidal liver cells (Murakami, M., Horiuchi, S., Takata, K. and Morino, Y. (1987) J. Biochem. (Tokyo) 101, 729-741). The present study describes the interaction of acetyl-HDL with rat peritoneal macrophages in vitro. Acetylation of HDL enhanced its cell-association by 2-fold and cellular degradation by > 25-fold. The cell-association of [125I]acetyl-HDL was effectively inhibited by unlabeled acetyl-HDL (> 85%), whereas the inhibition by HDL or acetylated human low-density lipoprotein (acetyl-LDL) was partial (60% and 50%, respectively). However, when both HDL and acetyl-LDL were present, the cell-association of [125I]acetyl-HDL was effectively inhibited by > 80%, a level identical or closely similar to that by acetyl-HDL. The cellular degradation of [125I]acetyl-HDL was effectively suppressed by acetyl-LDL whereas the effect of HDL was much weaker. These findings indicate that acetyl-HDL is endocytosed by both the HDL receptor and the scavenger receptor for acetyl-LDL in which the ligands bound to the latter might be subjected to lysosomal degradation.

Acetylation↗
PubMed1993

Angiogenic effects of advanced glycation end products of the Maillard reaction on cultured human umbilical cord vein endothelial cells.

The effects of advanced glycation end products (AGE) of the Maillard reaction on proliferation, migration and angiogenesis of cultured human umbilical vein endothelial cells (HUVEC) were studied. In an in vitro angiogenesis system, tube formation of HUVEC was dose-dependently stimulated by AGE at 0.5-50 micrograms/ml. Migration of HUVEC was also stimulated by AGE in a similar concentration range, and checkerboard analysis revealed that AGE were chemotactic but not chemokinetic. Proliferation of HUVEC was not affected by AGE. These data provide evidence that AGE are angiogenic.

Cell Movement↗