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S Horiuchi

Publications and source records attributed to S Horiuchi.

At least 163 records · Page 9Linked to original sources
PubMed1997

Photo-enhanced modification of human skin elastin in actinic elastosis by N(epsilon)-(carboxymethyl)lysine, one of the glycoxidation products of the Maillard reaction.

Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGEs), which are characterized by fluorescence, brown color, and cross-linking. Formation of AGEs in vitro requires oxygen and is dependent on transition metal-catalyzed oxidation of glucose or Amadori products. AGEs are thought to be involved in aging and age-enhanced diseases such as diabetic complications, atherosclerosis, dialysis-related amyloidosis, and Alzheimer's disease. Chronic exposure of the skin to sunlight induces hyperplasia of the elastic tissue in the upper dermis known as actinic elastosis. Herein we used a monoclonal anti-AGE antibody (6D12) whose epitope is N(epsilon)-(carboxymethyl)lysine (CML), one of the glycoxidation products of AGEs, and demonstrated that the lesions of actinic elastosis were modified by CML. Further immunohistochemical and immunoelectron microscopic examination with 6D12 demonstrated CML accumulates predominantly in elastic fibers especially in the amorphous electron-dense materials corresponding to photo-induced degenerated area rather than the electron-lucent region. Immunochemical analyses with enzyme-linked immunosorbent assay (ELISA) of elastase-soluble fractions demonstrated that the CML levels of the sun-exposed area were significantly higher than those of the sun-unexposed area. We conclude that ultraviolet-induced oxidation may accelerate CML formation in actinic elastosis of photoaged skin.

Adolescent↗
PubMed1997

Histological localization of advanced glycosylation end products in the progression of diabetic nephropathy.

We studied the immunohistochemical localization of advanced glycosylation end products (AGEs) in the progression of diabetic nephropathy. Fourteen NIDDM patients with diabetic nephropathy were evaluated: 2 patients with normoalbuminuria, 4 with microalbuminuria (MA) and 8 with overt proteinuria (OP). Three patients with minor glomerular abnormalities were used as nondiabetic controls. Immunoreactivity to a monoclonal anti-AGE antibody (6D12) was recognized on the internal elastic membranes of arterial walls in every diabetic group. Hyaline lesions of arterioles of the MA and OP groups demonstrated strong reactions with 6D12. A portion of the nodular and exudative lesions in glomeruli of OP group patients also revealed immunoreactivity to 6D12. No immunoreactivity to 6D12 was observed in nondiabetic control specimens. We confirm that the accumulation of AGEs began in arterial walls of the early stage and presented in glomerular lesions of the late stage of the progression of diabetic nephropathy.

Adult↗
PubMed1997

Two intracellular signaling pathways for activation of protein kinase C are involved in oxidized low-density lipoprotein-induced macrophage growth.

Recent studies demonstrated that oxidized LDL (Ox-LDL) induces macrophage growth in vitro. The present study was undertaken to elucidate the intracellular signaling pathways for macrophage growth. Ox-LDL initiated a rapid and transient rise in intracellular free calcium ion and induced activation of membrane protein kinase C (PKC). Pertussis toxin completely inhibited the Ox-LDL-induced rise in free calcium ion and significantly inhibited macrophage growth by 50%. Moreover, PKC inhibitors calphostin C and H-7 significantly inhibited Ox-LDL-induced macrophage growth by 80%. On the other hand, phospholipase A2-treated acetylated LDL did not induce a rise in calcium but significantly activated PKC and led to significant macrophage growth that was significantly inhibited by calphostin C by 90%. These results suggest the presence of two intracellular signaling pathways for activation of PKC, a rise in calcium that was mediated by pertussis toxin-sensitive G protein and the internalization of lysophosphatidylcholine through the scavenger receptors. These two pathways may play an important role in Ox-LDL-induced macrophage growth.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

The receptor for advanced glycation end products mediates the chemotaxis of rabbit smooth muscle cells.

Long-term incubation of proteins with glucose leads to advanced glycation end products (AGEs) with fluorescence and a brown color. We recently demonstrated immunologically the intracellular AGE accumulation in smooth muscle cell (SMC)-derived foam cells in advanced atherosclerotic lesions. To understand the mechanism of AGE accumulation in these foam cells, we have now characterized the interaction of AGE proteins with rabbit-cultured arterial SMCs. In experiments at 4 degrees C, 125I-labeled AGE-bovine serum albumin (AGE-BSA) showed a dose-dependent saturable binding to SMCs with an apparent dissociation constant (Kd) of 4.0 microg/ml. In experiments at 37 degrees C, AGE-BSA underwent receptor-mediated endocytosis and subsequent lysosomal degradation. The endocytic uptake of 125I-AGE-BSA was effectively inhibited by unlabeled AGE proteins such as AGE-BSA and AGE-hemoglobin, but not by acetylated LDL and oxidized LDL, well-known ligands for the macrophage scavenger receptor (MSR). Moreover, the binding of 125I-AGE-BSA to SMCs was affected neither by amphoterin, a ligand for one type of the AGE receptor, named RAGE, nor by 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole-hexanoic acid-BSA, a ligand for the other AGE receptors, p60 and p90. This indicates that the endocytic uptake of AGE proteins by SMCs is mediated by an AGE receptor distinct from MSR, RAGE, p60, and p90. To examine the functional role of this AGE receptor, the migratory effects of AGE-BSA on these SMCs were tested. Incubation with 1-50 microg/ml of AGE-BSA for 14 h resulted in significant dose-dependent cell migration. The AGE-BSA-induced SMC migration was chemotactic in nature and was significantly inhibited (approximately 80%) by an antibody against transforming growth factor-beta (TGF-beta), and the amount of TGF-beta secreted into the culture medium from SMC by AGE-BSA was sevenfold higher than that of control, indicating that TGF-beta is involved in the AGE-induced SMC chemotaxis. These data suggest that AGE may play a role in SMC migration in advanced atherosclerotic lesions.

Animals↗
PubMed1997

The multiple roles of macrophage scavenger receptors (MSR) in vivo: resistance to atherosclerosis and susceptibility to infection in MSR knockout mice.

Both type I and type II MSRs are integral membrane proteins containing a collagenous domain and elicit an extraordinarily wide range of ligand binding capability. They were found during the search for the molecule(s) responsible for the accumulation of modified LDL during atherogenesis. However, all prior the evidence relating to their physiological and pathophysiological roles in vivo had been indirect. Targeted disruption of the MSR gene results in a reduction in the size of atherosclerotic lesions in an apo E deficient animal. Macrophages from MSR deficient mice exhibit a marked decrease in modified LDL uptake in vitro, whereas modified LDL clearance from plasma remains normal, suggesting that there are alternative mechanisms for the uptake of modified LDL from the circulation. In addition, MSR knockout mice are more susceptible to L. monocytogenes and HSV-1 infection, indicating a role for MSR in host defense against various pathogens.

Animals↗
PubMed1997

[AGE receptor].

Explore the source record for details and available documents.

Animals↗
PubMed1997

[An experiment in a new method of nursing education--the problem-based learning for prenatal nursing].

At the opening of lectures in 1995 on the Science of maternity Nursing in the Special Subjects of Nursing, a problem-based learning was tried as a new educating method in the unit of "Prenatal Nursing." In the present paper, reviewing the introduction/implementation of the method, subjects in the future are described. This process contained two major flows, one was the training of tutors in problem-based learning, including participating the workshop held at McMaster University, and the other was the preparation for the class at the introduction of the new educational method, such as the overall subject composition and the development of teaching materials of prenatal nursing and resources, etc. according to the procedures of the problem-based learning. As the results of the actual implementation, various different reactions in comparison with the lecture method were observed both in tutors and students. As the subjects hereafter, the following three points have been clearly elucidated, that is, in order to proceed the problem-based learning under the present condition that it is not in the comprehensive curriculum, to prevent the overload and conflict in the student learning, considering and adjusting the relationship with contents and methods of concurrent subjects and units, to establish the system for tutorial assessment and evaluation, and to insure tutors and fulfill their training system.

Curriculum↗
PubMed1997

[A study of nursing systems in transition in developed countries].

The present study was designed to investigate nursing systems in other countries in comparison with the current system in Japan, and thereby assess how nursing personnel should be in order to improve the quality of nursing. The study focused on the actual situation of the nursing system and licensed practical nurses (LPNs) or second-level nurses similar to LPNs in other countries. The survey was conducted in regard to six countries considered to be advanced in the development of nursing activities and likely to provide useful suggestions for the future direction of nursing in Japan: Australia, Canada, France, Sweden, the United Kingdom and the United States. Questionnaires were sent to the heads or staff of a total of 29 organizations, including WHO Collaborating Centers and professional organizations for nursing, in these countries. Nineteen organizations responded (response rate: 65.5%), and an effective response with completed questionnaire forms was obtained from 15 organizations. In addition, an interview survey was conducted on three nursing administration and education experts in the United States in order to acquire clear understanding of the actual state of nursing in health care practice. The results were as follows: 1. Six countries (Japan included) excluding France had LPNs. Educational preparation for LPNs has been discontinued in the United Kingdom. 2. The number of nurses per 1,000 population was lowest in Japan: the total number of registered nurses (RNs) and LPNs in Japan was less than the number of RNs in the United Kingdom. Only in Japan the proportions of LPNs and RNs were similar, while in other countries of number of LPNs was one-third to one-fourth of the number of RNs. 3. In the five other countries having LPNs, the nurse's competency or scope of practice was clearly defined for both LPNs and RNs. In contrast, no clear line was drawn between the two in Japan. 4. The length of education required for LPNs ranged from 11 to 14 years (including the period of compulsory education) and was shortest in Japan (11 years). The educational requirement for admission to LPN school in Japan was 9 years of compulsory education (graduation from junior high school), whereas in other countries it was at the level of senior high school graduation. 5. Four countries had conversion programs for LPNs to become RNs, and the conversion courses were positioned within the framework of higher education comparable to the university level. 6. In the United Kingdom, where the educational preparation for LPNs has been discontinued, nurses are included in a single higher level profession. At the same time there was found to be a need to train and educate auxiliary personnel in order to maintain multi-level care services. Because of the increasing tendency toward advanced medical technology and highly specialized medical care associated with the rapidly increasing care needs in the community, the current educational preparation for LPNs in Japan in unsatisfactory as a training and educational system for nursing manpower to cope with the current situation. The above findings suggest that the education system for LPNs be reviewed with a view to discontinuing it and consolidating nursing education in Japan.

Australia↗
PubMed1997

[Participation in the IEC Workshop on Adolescent Sexual Health--a challenge to protect reproductive health/right in Latin America and Caribbean Region].

In order to explore the possibility of new global activity in nursing/midwifery to be performed by the WHO Collaborating Center for Nursing Development in Primary Health Care at St. Luke's College of Nursing, the center sent two faculty members to attend the IEC Workshop on Adolescent Sexual Health held in November 1996 in Mexico. The two representatives took part as resource persons and reported to the workshop on the activities of nurses and midwives for adolescent sexual health in Japan. During the session, they obtained information on the actual situation of adolescent sexual health in Latin America and Caribbean region and the novel strategies which were carried out in cooperation between governmental and non governmental organizations. The workshop also provided a good opportunity for international communication and information exchange with health workers in the region about adolescent sexual health. By participating in the workshop, we obtained first-hand information on various aspects of cooperation in international health.

Adolescent↗
PubMed1997

Relationship of epidermal growth factor binding capacity to histopathologic features and prognosis in human renal cell carcinoma.

We studied the association between epidermal growth factor (EGF) binding capacity and histopathologic features or prognosis in human renal cell carcinoma (RCC) by Scatchard analysis in 67 patients. EGF binding capacity was significantly greater in metastatic than in nonmetastatic tumors, and in nuclear grade 3 than nuclear grade 1 tumors. Multivariate analysis revealed that tumor stage, nuclear grade, EGF binding capacity, and tumor size significantly correlated with overall survival. These results suggest that EGF binding may be an important determinant of prognosis in patients with RCC.

Adult↗
PubMed1996

Identification of advanced glycation end products of the Maillard reaction in Pick's disease.

The recent identification of advanced glycation end products (AGEs) of the Maillard reaction in the central nervous system suggests their potential involvement in the aging process. Other studies have also suggested a possible link between AGEs and Alzheimer's disease. To investigate the role of AGEs in Pick's disease, another neurodegenerative disease associated with dementia, we examined the AGE-immunoreaction in Pick's bodies and ballooned neurons, two characteristic neuropathological features of Pick's disease, using antibodies against identified AGE-structures, N epsilon-(carboxymethyl)lysine and pentosidine. These two structures were observed immunohistochemically in Pick's bodies and ballooned neurons of brain tissues obtained at autopsy from three elderly patients diagnosed with Pick's disease. These immunoreactions were further confirmed by absorption experiments and double-immunostaining. The present findings suggest that AGEs are involved in the pathology of Pick's disease.

Aged↗
PubMed1996

Rapid formation of advanced glycation end products by intermediate metabolites of glycolytic pathway and polyol pathway.

To clarify roles of intermediate metabolites of the glycolytic pathway and the polyol pathway in nonenzymatic glycation under physiological conditions, we incubated bovine serum albumin with intermediates of both pathways in the micromolar range as well as with 20 mmol/l glucose, and observed the formation of advanced glycation end products (AGEs). We found that triose phosphates, glyceraldehyde, and a novel polyol pathway-related metabolite, fructose 3-phosphate along with its breakdown product, 3-deoxyglucosone were extremely potent glycating agents that at nearly physiological concentrations on incubation with albumin produced substantial amounts of AGEs as early as 24 hours, while 20 mmol/l glucose afforded trace amounts of AGEs after two week incubation. The results along with the previous evidence of the increased level of intermediates in diabetic states may suggest that the intermediate metabolites rather than glucose contribute to enhanced glycation in diabetic tissues, inspite of the much lower concentrations compared with glucose.

Animals↗
PubMed1996

The scavenger receptor serves as a route for internalization of lysophosphatidylcholine in oxidized low density lipoprotein-induced macrophage proliferation.

We have recently demonstrated that the growth of murine macrophages is induced by oxidized low density lipoprotein (Ox-LDL) and that lysophosphatidylcholine (lyso-PC), a major phospholipid component of Ox-LDL, plays an essential role in its mitogenic effect. The present study was undertaken to further characterize the role of the macrophage scavenger receptor (MSR) in Ox-LDL-induced macrophage growth. The growth-stimulating effect of Ox-LDL on murine resident peritoneal macrophages was inhibited by maleylated bovine serum albumin (maleyl-BSA), a non-lipoprotein ligand for MSR but a poor carrier of lyso-PC, while maleyl-BSA itself failed to induce macrophage growth even in the presence of lyso-PC. Moreover, it competitively inhibited the endocytic uptake of 125I-Ox-LDL and the specific uptake of lyso-PC by MSR, whereas nonspecific lyso-PC transfer to cells was not affected. Furthermore, the Ox-LDL-induced cell growth of peritoneal macrophages obtained from MSR knockout mice was significantly weaker than that of macrophages obtained from their wild-type littermates. Our results suggest that the MSR is an important and efficient internalization pathway for lyso-PC in Ox-LDL-induced macrophage growth.

Albumins↗
PubMed1996

Lipoprotein(a) induces cell growth in rat peritoneal macrophages through inhibition of transforming growth factor-beta activation.

To elucidate the atherogenicity of lipoprotein(a) (Lp(a)), we examined its growth-stimulating activity in rat resident peritoneal macrophages. When macrophages were incubated with Lp(a), cell numbers were increased 1.5-fold as compared with control macrophages. Furthermore, apolipoprotein(a) (apo(a)), a plasminogen-like glycoprotein which is covalently attached to a low density lipoprotein-like particle (Lp(a)), also induced macrophage growth, while the growth-stimulating effect of Lp(a-) was negligible. These results suggest that apo(a) plays an active role in the mitogenic activity of Lp(a). Lp(a)-induced macrophage growth was inhibited by exogenously added active transforming growth factor-beta (TGF-beta) dose-dependently, and also by the addition of plasmin, which converts latent TGF-beta to an active form. Moreover, the amounts of endogenous active TGF-beta in the medium were significantly reduced by the incubation with Lp(a). It is evident from these results that Lp(a) induces macrophage growth by inhibiting TGF-beta activation. The capacity of Lp(a) to stimulate macrophage growth shown here could be novel atherogenic function of Lp(a).

Animals↗
PubMed1996

N (epsilon)-(carboxymethyl)lysine protein adduct is a major immunological epitope in proteins modified with advanced glycation end products of the Maillard reaction.

Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological studies have suggested the potential role of AGE in atherosclerosis, aging, and diabetic complications. We previously prepared a monoclonal (6D12) as well as a polyclonal anti-AGE antibody and proposed the presence of a common AGE structure(s) that may act as a major immunochemical epitope [Horiuchi, S., Araki, N., & Morino, Y. (1991) J. Biol. Chem. 266, 7329-7332]. The purpose of the present study was to determine the major epitope. Amino acid analysis of AGE-proteins indicated that N(epsilon)-(carboxymethyl)lysine (CML) was a major modified lysine residue. Immunologic studies demonstrated the positive reaction of 6D12 not only to all CML-modified proteins tested, but also to BSA modified with several aldehydes known to generate a CML-protein adduct, and a linear correlation between the CML contents of CML-BSA and their immunoreactivity to 6D12 up to approximately 8 mol/mol of protein. Further experiments with CML analogs revealed that the epitope of 6D12 is a CML-protein adduct with an important carbonyl group. In contrast to 6D12, our polyclonal anti-AGE antibody showed a significant but much weaker immunoreactivity to CML-BSA, suggesting that the polyclonal antibody contains two populations, one reactive to CML (CML-PA) and the other unreactive to CML (Non-CML-PA). Non-CML-PA separated from CML-PA by CML-BSA affinity chromatography did not react with all CML-modified preparations, but retained its property to react commonly with AGE preparations obtained from proteins, lysine derivatives, and monoaminocarboxylic acids. Therefore, it is clear that a CML-protein adduct is a major immunological epitope in AGE structures, but there still exist other major epitope(s) expressed commonly in AGE-proteins.

Animals↗
PubMed1996

Vitamin B6 deficiency accelerates metabolic turnover of cystathionase in rat liver.

Although most of cystathionase was found to exist as an inactive apoenzyme in the liver of vitamin B6-deficient rats, the concentrations of the immunoreactive enzyme protein were virtually the same for control and vitamin B6-deficient livers. Under vitamin B6 deficiency, however, the rate of synthesis of cystathionase, measured by incorporation of labeled amino acid into the immunoprecipitated enzyme, was increased severalfold due to an increased level of cystathionase mRNA. Western blot analysis of lysosomal proteins showed that the amount of cystathionase in the lysosomes from the liver of vitamin B6-deficient rats was also increased severalfold. This observation suggests that lysosomes specifically recognize the apocystathionase for sequestration in preference to the holoenzyme. The present study provides the molecular basis for dual roles of vitamin B6 in controlling the metabolic turnover of cystathionase; it regulates synthesis of the enzyme by modulating the expression of cystathionase gene, and it regulates degradation of the enzyme by different susceptibilities of apo- and holoenzymes to lysosomal proteolysis.

Animals↗
PubMed1996

Activation of acyl-coenzyme A:cholesterol acyltransferase activity by cholesterol is not due to altered mRNA levels in HepG2 cells.

Many studies have shown that sterols can stimulate acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in cells. To elucidate this mechanism, effects of sterol-mediated induction on both the enzyme activity of ACAT and its mRNA levels were studied in human hepatoblastoma cell line, HepG2 cells. When HepG2 cells were loaded with cholesterol and 25-hydroxycholesterol, both the whole-cell ACAT activity and the microsomal ACAT activity were increased by 85.1% and 41.3%. In contrast, cholesterol depletion of HepG2 cells with compactin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, resulted in a decrease in both the whole-cell and the microsomal ACAT activity by 46.4% and 58.3%. Under identical conditions, RT-PCR and Northern blotting analyses revealed that neither cholesterol loading nor cholesterol depletion of HepG2 cells altered the amounts of ACAT mRNA. Moreover, these treatments had no effect on the enzymatic ACAT activity determined by the reconstituted assay in which HepG2 cell homogenate had been supplemented in vitro with a saturating level of exogenous cholesterol. These results indicate that cholesterol-induced up-regulation of ACAT activity in HepG2 cells does not occur at the level of transcription, but rather at a posttranscriptional level.

Base Sequence↗