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S Horiuchi

Publications and source records attributed to S Horiuchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Immunohistochemical distribution and quantitative biochemical detection of advanced glycation end products in fetal to adult rats and in rats with streptozotocin-induced diabetes.

SUMMARY: We used immunohistochemical methods and four monoclonal antibodies for specific molecular structures of advanced glycation end products (AGE)-6D12, KNH-30, 1F6, and 2A2-to examine localization of AGE in fetal, young, and adult rats, and rats with streptozotocin-induced diabetes. 6D12 recognized N(epsilon)-(carboxymethyl)lysine (CML); KNH-30, N(epsilon)-(carboxyethyl)lysine (CEL); and 1F6, fluorolink. The epitope of 2A2 is as yet unknown. Immunoreactivities for these monoclonal antibodies were found in various organs and tissues in postnatal and adult rats, and accumulation increased with aging. In the fetuses, AGE structures were detected at 10 fetal days, and their accumulation increased during ontogeny. Reversed-phase high-performance liquid chromatography revealed CML in fetuses at 13 fetal days and in lungs of 28-week-old rats. In various organs and tissues of fetal, young, and adult rats, CML, CEL, 2A2-positive AGE, and fluorolink accumulated, in that order, which suggests that the accumulation of CML, a nonfluorescent/noncross-linked AGE, occurs earlier than accumulation of fluorolink, a fluorescent/cross-linked AGE. In diabetic rats, hepatocytes, splenic macrophages, renal glomerular endothelial and mesangial cells, testicular Leydig cells, and erythrocytes showed excessive accumulation of AGE, leading to the pathologic changes characteristic of diabetes mellitus. For the induction of these changes, persistent hyperglycemia and hyperketonemia might be important for acceleration of intracellular AGE accumulation in diabetic rats. Thus, AGE accumulation in tissues and cells occurs not only during aging and in diabetes mellitus but also from an early stage of ontogeny.

Aging↗
PubMed2001

Formation of advanced glycation end-product-modified superoxide dismutase-1 (SOD1) is one of the mechanisms responsible for inclusions common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutation, and transgenic mice expressing human SOD1 gene mutation.

Neuronal Lewy body-like hyaline inclusions (LBHI) and astrocytic hyaline inclusions (Ast-HI) are morphological hallmarks of certain familial amyotrophic lateral sclerosis (FALS) patients with superoxide dismutase-1 (SOD1) gene mutations, and transgenic mice expressing the human SOD1 gene mutation. The ultrastructure of inclusions in both diseases is identical: the essential common constituents are granule-coated fibrils approximately 15-25nm in diameter and granular materials. Detailed immunohistochemical analyses have shown that the essential common protein of the inclusions in both diseases is an SOD1 protein. This finding, together with the immunoelectron microscopy finding that the abnormal granule-coated fibrils comprising the inclusions are positive for SOD1, indicates that these granule-coated fibrils containing SOD1 are important evidence for mutant SOD1-linked disease in human and mouse. For immunoelectron microscopy, the granule-coated fibrils are modified by advanced glycation endproducts (AGE) such as N(epsilon)-carboxymethyl lysine, pyrraline and pentosidine (Maillard reaction). Based on the fact that AGE themselves are insoluble molecules with direct cytotoxic effects, the granule-coated fibrils and granular materials are not digested by the lysosomal and ubiquitin systems. The neurons and astrocytes of the normal individuals and non-transgenic mice show no significant immunoreactivity for AGE. Considered with the mutant-SOD1 aggregation toxicity, a portion of the SOD1 comprising both types of the inclusion is modified by the AGE, and the formation of the AGE-modified SOD1 (probably AGE-modified mutant SOD1) is one of the mechanisms responsible for the aggregation (i.e. granule-coated fibril formation).

Amyotrophic Lateral Sclerosis↗
PubMed2001

Comparisons of sleep patterns between mothers in post-partum from 9 to 12 weeks and non-pregnant women.

In order to evaluate two patterns of interrupted and non-interrupted sleep for the post-partum mothers from 9 to 12 weeks after delivery, we compared them with sleep patterns of non-pregnant women. Subjects were 10 primipara and 12 non-pregnant women. Their polysomnographic recordings were made using a Medilog recorder at home. In interrupted sleep, low sleep efficiency, decreased total sleep time, and a decreased percentage of stage 2 were significantly observed compared with non-pregnant women. Sleep parameters of non-interrupted sleep, except for increased percentage of stage 4, did not show any significant differences from non-pregnant women. Mothers' sleep fluctuated between interrupted sleep similar to the early post-partum sleep from 1 to 6 weeks and non-interrupted sleep with increased stage 4.

Adult↗
PubMed2001

Need for sling surgery in patients with large cystoceles and masked stress urinary incontinence.

BACKGROUND: We studied the need for sling surgery in patients who suffered from large cystoceles and masked stress urinary incontinence. METHODS: Twenty patients who had large cystoceles but neither evidence nor history of stress incontinence were enrolled in this study. The cystocele was reduced using a reducing device. Masked urinary incontinence was identified by a 60 m pad weighing test and a stress test. The cystocele was reduced using a pessary ring in 14 patients, or a vaginal pack formed of two rolls of ordinary 28 x 28 cm gauze in six patients. Ten of 20 patients were diagnosed with masked stress urinary incontinence and were treated with anterior colporrhaphy and a suburethral sling procedure. The other 10 patients were continent after use of a cystocele reducing device and were treated with anterior colporrhaphy alone. Average follow-up periods of the patients with or without masked stress urinary incontinence were 51.2 months (range, 24.0-72.0 months) or 57.6 months (range, 27.0-70.0 months), respectively. RESULTS: One of the 10 patients diagnosed with masked stress incontinence had mild stress urinary incontinence postoperatively. None of the 10 continent patients had stress incontinence after anterior colporrhaphy alone. CONCLUSIONS: Reducing devices of protruding cystocele were clinically useful in the detection of masked stress incontinence. Sling surgery was effective to prevent emerging stress urinary incontinence for patients who suffered from cystocele and masked stress incontinence.

Aged↗
PubMed2001

Polytetrafluoroethylene patch sling for type 2 or type 3 stress urinary incontinence.

BACKGROUND: Surgical success rates and complications of anti-incontinence surgery were evaluated according to the type of stress incontinence and the type of surgery. METHODS: From 1989 to 1998, we treated 137 women for stress urinary incontinence with anti-incontinence surgery. Of the 137 patients, 110 had type 2 stress urinary incontinence and 27 had type 3 stress urinary incontinence. Of 110 patients with type 2 stress urinary incontinence, 57 underwent pubovaginal sling procedure and 53 were treated with the Gittes procedure. All of the patients with type 3 stress urinary incontinence underwent the pubovaginal sling procedure. RESULTS: Cure rates with the pubovaginal sling procedure were 82% in type 2 incontinence and 70% in type 3 incontinence. Cure rates with the Gittes procedure were 56%. The occurrence of de novo urge symptom and pelvic pain was low and bore no relation to either operative method or type of stress incontinence. CONCLUSIONS: The pubovaginal sling procedure using the polytetrafluoroethylene patch was effective for type 2 or 3 stress urinary incontinence.

Female↗
PubMed2001

Glycoxidation-modified macrophages and lipid peroxidation products are associated with the progression of human diabetic nephropathy.

The aim of this study is to investigate the role of glomerular macrophages activated by glycoxidation and lipid peroxidation products in the progression of glomerular lesions in diabetic nephropathy. Renal biopsy samples from 43 patients with diabetes (age, 54 +/- 14 years) and 10 control cases were immunohistochemically examined for the expression of carboxymethyllysine (CML), a representative glycoxidative product; oxidized phosphatidylcholine (Ox-PC), a representative lipid peroxidation product; leukocyte common antigen (LCA); CD68; and macrophage scavenger receptor (MSR) class A. The severity of the diffuse lesions in each glomerulus was histologically graded from 0 to IV. When grade II and III lesions had Kimmelstiel-Wilson (KW) nodules, they were placed in a new category called grade III with KW nodules. The number of cells positive for CML, Ox-PC, LCA, CD68, and MSR was compared in different grades. The number of macrophages per glomerulus increased with the glomerular lesion grade and was highest in grade III with KW nodules. Conversely, the number of lymphocytes did not parallel the grade of glomerular lesions. Almost 50% of macrophages contained CML, and more than 40% of those were observed in exudative lesions, tuft adhesions, and at the periphery of KW nodules. Ox-PC accumulated in 50% of CML-positive macrophages, which coexpress MSR. Macrophages positive for CML and Ox-PC increased with the grade. Glomerular macrophages may be activated by glycoxidative and lipid peroxidation products through MSR and may have a role in the development of human diabetic glomerulosclerosis.

Adolescent↗
PubMed2001

Advanced glycation end products in Descemet's membrane and their effect on corneal endothelial cell.

PURPOSE: [corrected] The purpose of this study was to evaluate the effect of advanced glycation end products (AGEs) in Descemet's membrane on the attachment and spreading of the corneal endothelial cells. METHODS: An anti-AGEs monoclonal antibody (6D12), which recognizes a N(epsilon)-carboxymethyl lysine (CML)-protein adduct as an epitope, was used for immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Fresh bovine Descemet's membrane was incubated for 4 weeks in the buffered solution with 500 mM of glucose-6-phosphate (G-6-P). In the incubated Descemet's membrane, the immunohistochemical localization of CML was examined. Type I collagen-, type IV collagen-, fibronectin-, or laminin-coated 96-well plates were glycated by G-6-P. The amount of CML was determined by ELISA using 6D12. Cultured bovine corneal endothelial cells were seeded onto glycated or non-glycated extracellular matrix (ECM) in 96-well plates and allowed to attach for 3 hours. The number and the surface area of the attached cells were examined. RESULTS: Immunoreactivity to CML was detected in Descemet's membrane incubated in the buffered solution containing G-6-P. Glycation of fibronectin and laminin decreased the number and the surface area of the attached corneal endothelial cells. Aminoguanidine in the incubation mixture inhibited CML formation of ECM components and increased the number and the surface area of the attached corneal endothelial cells in a dose-dependent manner. CONCLUSIONS: AGE formation on fibronectin and laminin attenuated the attachment and spreading of the corneal endothelial cells. AGEs' formation in Descemet's membrane may be responsible for the corneal endothelial cell loss with aging and corneal endothelial abnormalities in diabetic patients

Animals↗
PubMed2001

Association of matrilysin mRNA expression with K-ras mutations and progression in pancreatic ductal adenocarcinomas.

The matrix metalloproteinase matrilysin has been implicated in the progression of gastrointestinal and other cancers. The aim of this study was to examine matrilysin mRNA expression and determine whether it is correlated with K-ras mutations and/or progression of pancreatic carcinoma. Using the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we analyzed 11 pancreatic cancer cell lines and 70 pancreatic adenocarcinoma tissues for matrilysin mRNA expression. The results were correlated with clinicopathological characteristics and K-ras mutations. Significant amounts of matrilysin mRNA were detected in six of the eight cell lines with K-ras mutations but not in the three cell lines with wild-type K-ras. Matrilysin mRNA was detected in 57 (81.4% ) of the 70 tumor tissues and in all of the eight liver metastases, but not in any of the adjacent non-tumorous tissues. Matrilysin expression was significantly correlated with the size of tumor, tumor spreading, lymph node metastasis, advanced pathologic tumor-node- metastasis stage and K-ras mutations. The relative amounts of matrilysin mRNA in tumor tissues increased with increase in tumor stage and were highest in liver metastatic tumor tissues. Our results suggest that matrilysin, the expression of which is correlated with K-ras mutations, plays a key role in tumor growth and progression of pancreatic carcinoma.

Adenocarcinoma↗
PubMed2001

The soluble interleukin 6 receptor: mechanisms of production and implications in disease.

Interleukin 6 (IL-6) performs a prominent role during disease and has been described as both a pro- and anti-inflammatory cytokine. A key feature in the regulation of IL-6 responses has been the identification of a soluble interleukin 6 receptor (sIL-6R), which forms a ligand-receptor complex with IL-6 that is capable of stimulating a variety of cellular responses including proliferation, differentiation and activation of inflammatory processes. Elevated sIL-6R levels have been documented in numerous clinical conditions indicating that its production is coordinated as part of a disease response. Thus, sIL-6R has the potential to regulate both local and systemic IL-6-mediated events. This review will outline the central role of sIL-6R in the coordination of IL-6 responses. Details relating to the mechanisms of sIL-6R production will be provided, while the potential significance of sIL-6R during the development of clinical conditions will be emphasized. We want to convey, therefore, that when thinking about the inflammatory capability of IL-6, it is essential to consider not only the action of IL-6 itself, but also the effect sIL-6R may have on cellular processes.

Alternative Splicing↗
PubMed2001

The application of magnetic cell sorter (MACS) to detect fetal cells in maternal peripheral blood.

OBJECTIVES: The aim of the present study was to investigate the effectiveness of sorting fetal nucleated red blood cells (FNRBC) from maternal peripheral blood, particularly during early gestation periods, by a combination of specific gravity centrifugation and magnetic cell sorter (MACS). METHODS: Without prior knowledge of the gender of the fetus, we determined gender by analyzing a Y-chromosome specific sequence by nested-PCR, using 10 ml of the peripheral blood of healthy primigravida women at different stages of gestation (first trimester: n = 17, second trimester: n = 13, and third trimester: n = 19). The results of this prenatal sex determination were compared to the sex of newborns. RESULTS: The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of the present method during the first trimester were 100, 81.8, 100, and 75%, respectively; during the second trimester, 80, 50, 80, and 50%, respectively; and during the third trimester, 25, 63.6, 53.8, and 33.3%, respectively. CONCLUSION: The results show that this prenatal sex determination method has a highly accurate diagnostic rate during the first trimester, suggesting that it could be developed as a practical, non-invasive prenatal diagnostic technique for use during early gestation periods.

Cell Separation↗
PubMed2001

CD36, a member of class B scavenger receptor family, is a receptor for advanced glycation end products.

Interaction of advanced glycation end products (AGE) with AGE-receptors induces several cellular phenomena relating potentially to diabetic complications. Five AGE-receptors identified so far are RAGE (receptor for AGE), 80 K-H, OST-48, galectin-3, and SR-A (macrophage scavenger receptor type I and II). Since SR-A belongs to the class A scavenger receptor family and the scavenger receptor collectively represents a family of multiligand lipoprotein receptors, it is possible that CD36 belonging to the class B scavenger receptor family (SR-B) can recognize AGE-proteins as a ligand. This was tested in the present study at the cellular level using CHO (Chinese hamster ovary) cells overexpressing human CD36 (CHO-CD36 cells). 125I-AGE-BSA (bovine serum albumin) was endocytosed in a dose-dependent fashion and underwent lysosomal degradation by CHO-CD36 but not wild-type CHO cells. Endocytic uptake of 125I-AGE-BSA by these cells was inhibited 50% by oxidized LDL (Ox-LDL) and 60% by FA6-152, an anti-CD36 antibody inhibiting cellular binding of Ox-LDL. Our results indicate that CD36 expressed by these cells mediates endocytic uptake and subsequent intracellular degradation of AGE-proteins. Because CD36 is one of the major Ox-LDL receptors and is upregulated in macrophage- and smooth muscle cell-derived foam cells in human atherosclerotic lesions, the present results suggest that, like Ox-LDL, AGE-proteins generated in situ are recognized by CD36, which might contribute to the pathogenesis of diabetic macrovascular complications.

Animals↗
PubMed2001

Advanced glycation end products in human optic nerve head.

AIMS: To localise advanced glycation end products (AGEs) in human optic nerve head. METHODS: Optic nerve samples from 13 elderly individuals (seven diabetics and six non-diabetics) were obtained at necropsy. Pyrraline, an advanced glycation end product, was immunohistochemically localised in the optic nerve heads. RESULTS: In the diabetic subjects, moderate to intense immunoreactivity for pyrraline was detected in sclera, pia mater, cribriform plates, connective tissues in the optic nerve, and around vessels in the optic nerve and pia mater. Immunoreactivity for pyrraline was also detected around retinal vessels. In the non-diabetic subjects, slight or no immunoreactivity for pyrraline was found in cribriform plates and around the optic nerve vessels. CONCLUSION: Accumulation of AGEs in cribriform plates and around vessels in the optic nerve may contribute to the development of optic neuropathy in diabetic patients.

Aged↗
PubMed2001

Carboxymethyllysine in dermal tissues of diabetic and nondiabetic patients with chronic renal failure: relevance to glycoxidation damage.

Carboxymethyllysine (CML) is currently recognized as a major advanced glycation end product and a marker for glycoxidation. Plasma CML levels are increased in patients with chronic renal failure (CRF). However, significance and mechanism of CML accumulation in these patients are poorly understood. The objective of the present study was to analyze CML in soluble and collagen-binding fractions of the dermis to investigate CML deposition and formation and collagen damage related to CML accumulation in patients with CRF. Skin samples (among them autopsy samples) were obtained from 33 subjects: 8 nondiabetic CRF patients, 7 diabetic predialysis patients with CRF (CRF-DM), 7 hemodialysis patients, and 11 control subjects without either CRF or DM. The dermal samples were extracted sequentially by phosphate-buffered normal saline, pepsin, and collagenase. The extracts were referred to as the soluble fraction and the proteinase-extracted fraction (including pepsin-extracted and collagenase-extracted fractions). Our ELISA assay for CML in dermal collagen from predialysis patients with CRF (CRF and CRF-DM groups) demonstrated that the levels of CML in both the soluble fraction (containing soluble CML which was mainly determined by serum clearance) and the structural collagen-binding proteinase-extracted fraction (in which high CML levels could be a strong indication of in situ formation) were increased and could not be completely reduced after hemodialysis in CRF-DM and CRF groups. These results suggest that accumulation of CML may be due to both a low serum clearance and/or increased in situ CML formation in CRF. CML contents in the proteinase extracted fraction inversely correlated with the susceptibility of collagen to extraction by proteinases (n = 33, r = -0.59, p < 0.001). Our results provide the first biochemical evidence that CML level is increased in both the soluble and collagen-binding fractions and that increased CML level resulted in increased fractions of proteinase-resistant collagen in dermal extracts of patients with CRF.

Aged↗
PubMed2001

Effects of mechanical stimulation on gene expression of articular chondrocytes in polylayer culture.

Mechanical loads are constantly being applied to articular cartilage. However, comparatively few studies have investigated the effects of mechanical stress on the gene expression of chondrocytes. Hence, the objective of the present study was to clarify the effects of mechanical stress on cultured chondrocytes. Articular chondrocytes of rabbits were isolated and placed in minimun essential medium eagle a modification containing 10% fetal bovine serum. The chondrocytes were cultured in polylayer in polypropylene tubes. After 48 hours, centrifugal stress (2.7 MJ) was applied once every 24 hours for 28 consecutive days. The mRNA expression of insulin-like growth factor-I (IGF-I) and cartilage-specific genes (type II collagen and aggrecan) in chondrocytes, cell count, wet tissue mass and protein content were subsequently measured. The results showed that the mRNA expression of the IGF-I gene for the stress groups was significantly greater than that of the control group from days 3 to 5 of incubation, as was the mRNA expression of the type II collagen gene from days 7 to 14 of incubation. However, there were no significant differences in the mRNA expression of the aggrecan gene between the control and stress groups. The cell count for the stress groups was significantly higher from days 7 to 28 of incubation, and the wet tissue mass and protein content were significantly higher from days 14 to 28 of incubation. These findings suggest that one of the mechanisms by which mechanical stress increases the number of cultured chondrocytes and the volume of extracellular matrix is to increase IGF-I expression at the early stage of incubation.

Aggrecans↗
PubMed2001

Induction of acyl-coenzyme A:cholesterol acyltransferase-1 by 1,25-dihydroxyvitamin D(3) or 9-cis-retinoic acid in undifferentiated THP-1 cells.

We have previously shown that acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) protein content increases significantly during the human monocyte-macrophage differentiation process. To gain further insight, we used undifferentiated human monocytic THP-1 cells as a model system with which to examine whether ACAT-1 mRNA and protein content can be increased by treating cells with 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] or with 9-cis-retinoic acid (9-cis-RA), two agents known to upregulate the expression of various genes during the monocyte-macrophage differentiation process. Immunoblot analysis with anti-human ACAT-1 antibodies revealed that ACAT-1 protein was increased by 2.6-fold, using 1,25-(OH)(2)D(3) at a physiological concentration (100 pM). ACAT-1 protein was also increased when using 9-cis-RA, but only at relatively high concentrations (0.1;-1 microM). Northern blot analysis revealed that among the four ACAT-1 mRNA transcripts (2.8, 3.6, 4.2, and 7.0 kb) examined, only the 2.8- and 3.6-kb transcripts were selectively increased. On the basis of enzyme assays in vitro, ACAT activity was increased 3.0-fold by using 100 nM 1,25-(OH)(2)D(3), and 1.8-fold by using 1 microM 9-cis-RA. Together, our results suggest that 1,25-(OH)(3) participates in ACAT-1 gene expression during the monocyte-macrophage differentiation process.

Alitretinoin↗