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M Shichiri

Publications and source records attributed to M Shichiri.

At least 19 recordsLinked to original sources
PubMed1995

Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the Maillard reaction.

Modification of proteins by long-term incubation with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological demonstration of the presence of AGE proteins in several human tissues suggests that they may be involved in aging, diabetic complications and atherosclerosis. AGE proteins are taken up by macrophages via the AGE receptor, which is similar to the macrophage scavenger receptor (MSR). In the present study, we examined whether MSR could mediate the endocytic uptake of AGE proteins by using Chinese hamster ovary (CHO) cells overexpressing bovine type II MSR (CHO-SRII). 125I-labelled AGE bovine serum albumin (125I-AGE-BSA) as well as 125I-acetylated low-density lipoprotein (125I-acetyl-LDL) underwent endocytic degradation by CHO-SRII cells, but not by control CHO cells. Endocytic degradation of 125I-acetyl-LDL and 125I-AGE-BSA by CHO-SRII cells was significantly inhibited by unlabeled AGE-BSA, as well as by acetyl-LDL. Immunoelectron microscopic studies using both AGE-BSA conjugated with gold particles and anti-(bovine MSR) antibody (D2) revealed co-localization of gold particles and the reactive sites for the antibody at coated pits of plasma membranes as well as in endosomes. These results clearly show that MSR mediates the endocytic uptake and degradation of AGE proteins, suggesting a new role of MSR in biological recognition of AGE in vivo.

Animals↗
PubMed1995

Beta-migrating very low density lipoproteins induce foam cell formation in mouse mesangial cells.

To elucidate whether beta-migrating very low density lipoproteins (beta-VLDL) induce foam cell formation in mesangial cells or not, surface binding and foam cell formation with beta-VLDL were studied in mouse mesangial cells. Specific binding kinetics for beta-VLDL and low density lipoproteins (LDL) on the mesangial cells were observed with Kd = 3.8 and 13.7 micrograms/ml, and Bmax = 65.9 and 71.9 ng/ml cell protein at 4 degrees C, respectively. The binding of beta-VLDL was inhibited by excess amounts of LDL or beta-VLDL, but not by acetyl-low density lipoproteins. Ligand blotting using beta-VLDL or LDL and immunoblotting using anti-human LDL receptor monoclonal antibody detected the same apparent single protein (approx. 130 kDa). Incorporation of [14C]oleate into cholesteryl ester in mouse mesangial cells was enhanced by beta-VLDL to 3-fold higher than that by LDL, and it was inhibited by chloroquine or anti-human LDL receptor monoclonal antibody. The light microscopic findings also demonstrated that cholesteryl ester deposition increased in these cells incubated with beta-VLDL, but not with LDL. In conclusion, beta-VLDL was specifically taken up by receptor-mediated endocytosis in mouse mesangial cells through LDL receptors, resulting in foam cell formation.

Animals↗
PubMed1995

Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study.

To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, we performed a prospective study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with multiple insulin injection treatment. A total of 110 patients with NIDDM was randomly assigned to multiple insulin injection treatment group (MIT group) or to conventional insulin injection treatment group (CIT group). Fifty-five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30 mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the other 55 NIDDM patients who showed simple retinopathy and urinary albumin excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The appearance and the progression of retinopathy, nephropathy and neuropathy were evaluated every 6 months over a 6-year period. The worsening of complications in this study was defined as an increase of 2 or more steps in the 19 stages of the modified ETDRS interim scale for retinopathy and an increase of one or more steps in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy. The cumulative percentages of the development and the progression in retinopathy after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT group in the secondary-intervention cohort (P = 0.049). The cumulative percentages of the development and the progression in nephropathy after 6 years were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups in the secondary-intervention cohort (P = 0.044). In neurological tests after 6 years, MIT group showed significant improvement in the nerve conduction velocities, while the CIT group showed significant deterioration in the median nerve conduction velocities and vibration threshold. Although both postural hypotension and the coefficient of variation of R-R interval tended to improve in the MIT group, they deteriorated in the CIT group. In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM. From this study, the glycemic threshold to prevent the onset and the progression of diabetic microangiopathy is indicated as follows; HbA1c < 6.5%, FBG < 110 mg/dl, and 2-h post-prandial blood glucose concentration < 180 mg/dl.

Albuminuria↗
PubMed1995

Effects of early introduction of intensive insulin therapy on the clinical course in non-obese NIDDM patients.

In order to reconsider the extent of indication of insulin therapy in non-insulin dependent diabetes mellitus (NIDDM), we performed the following trial in a prospective fashion. At the beginning phase of treatment for diabetes, we introduced intensive insulin therapy in 22 non-obese (Body mass index approximately 24 kg/m2) NIDDM patients without proliferative retinopathy, who were selected in a standardized fashion, avoiding any arbitrary choice. None had received oral hypoglycemic agents (OHA) or insulin yet. By administering insulin 3 or 4 times a day, strict glycemic control was attained and maintained, and then the insulin dose was gradually lowered while keeping good glycemic control. In patients whose glycemic control was maintained at an excellent level for more than 7 days under an insulin dosage lower than 8 u/day, insulin therapy was discontinued. As a result, 15 patients (68%) attained good glycemic control both without insulin and OHA almost within a month and 6 patients (27%) shifted to OHA. It is recommended to introduce intensive insulin therapy in non-obese NIDDM patients without proliferative retinopathy and to aim at attaining good glycemic control both without insulin and OHA.

Blood Glucose↗
PubMed1995

Attenuation of atrial natriuretic peptide response to sodium loading after cardiac operation.

To evaluate the role of cardiac operation and the atrial appendage in secretion of atrial natriuretic peptide in response to sodium loading, we studied 44 patients who underwent heart operations with (28 patients; group I) or without (16 patients; group II) right atrial appendectomy and 16 patients who underwent lobectomy (group III). Before and after operation 1 ml/kg of 10% NaCl was infused for 15 minutes. Blood samples were taken before NaCl infusion and immediately after infusion and at 60 minutes after infusion. There were no significant changes in hemodynamics or hematocrit level throughout the study. Plasma and urine sodium levels and the fractional excretion of sodium were significantly increased by sodium loading. Before operation, plasma mean atrial natriuretic peptide levels increased markedly in response to sodium infusion in all groups. After operation, this atrial natriuretic peptide response disappeared in groups I and II, but remained present in group III. Elution profiles of plasma atrial natriuretic peptide showed that the major peak coincided with alpha-atrial natriuretic peptide before sodium loading, whereas a beta-atrial natriuretic peptide peak appeared 60 minutes after sodium loading in all groups both before and after operation. The mean plasma arginine vasopressin levels were significantly increased by sodium loading both before and after operation in all groups. Sodium loading decreased the mean plasma aldosterone levels in all groups before operation, but did not after operation in groups I and II. Plasma renin activity and angiotensin II concentrations were not changed by sodium loading. We conclude that atrial natriuretic peptide response to sodium loading is attenuated by cardiac operation irrespective of right appendectomy, but not by lobectomy. Sodium loading augments secretion of beta-atrial natriuretic peptide even in reduced atrial natriuretic peptide response states after heart operations.

Aged↗
PubMed1995

Ca2+/calmodulin-dependent protein kinase II and synapsin I-like protein in mouse insulinoma MIN6 cells.

Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) may play a key role in the regulation of insulin secretion. We obtained evidence for the presence of CaM kinase II and its substrate, a 84-kilodalton (kDa) protein, in mouse insulinoma MIN6 cells. CaM kinase II from MIN6 cells has one subunit of 55 kDa, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is autophosphorylated in a Ca2+/CaM-dependent manner, and phosphorylates several substrates that serve for rat brain CaM kinase II. In the membrane fraction of MIN6 cells, we identified a 84-kDa protein that was immunoreactive with the antirat brain synapsin I antibody. One-dimensional phosphopeptide mapping by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed the sites of the phosphorylation by cAMP-dependent protein kinase (cAMP kinase) and that by CaM kinase II to be site 1 (10 kDa) and site 2 (30 kDa), respectively, therefore, the same as for rat brain synapsin I. In this context, we tentatively termed it synapsin I-like protein. In 32P-labeled cells, nonfuel insulin secretagogues, such as ionomycin, KCl, and tolbutamide, and a fuel secretagogue, glucose, stimulated autophosphorylation of CaM kinase II and the phosphorylation of synapsin I-like protein. These secretagogues potentiated the Ca(2+)-independent activity of CaM kinase II and secretion of insulin from MIN6 cells. The 84-kDa protein is apparently a newly identified member of the synapsin family. We suggest that CaM kinase II regulates insulin secretion via phosphorylation of synapsin I-like protein.

Animals↗
PubMed1995

Development of a ferrocene-mediated needle-type glucose sensor covered with newly designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate.

To prepare the long-life and stable glucose sensor, we developed the ferrocene-mediated needle-type glucose sensor covered with newly designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate (MPC-co-BMA) membrane. In this membrane, the hydrophilic phosphorylcholine chains were grafted on the hydrophobic polymer surface. 1. The poly(MPC-co-BMA) membrane inhibited platelet activation and protein adhesion on the surface, showing excellent biocompatibility. These results suggested that the hydrophilic phospholipids chains might have the potential for suppressing activation and adsorption of biochemical molecules. 2. The ferrocene-mediated needle-type glucose sensor covered with poly(MPC-co-BMA) membrane achieved excellent results in vitro. Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to more than 16.7 mmol/l. The correlation between subcutaneous tissue (Y) and blood (X) glucose concentrations was Y = 1.04X + 0.12 (r = 0.98). The subcutaneous tissue glucose concentrations could be monitored precisely for 7 days without any in vivo calibrations, and for 14 days by introducing in vivo calibrations. We therefore conclude that this sensor is stable and reliable, as compared to any other glucose sensors we developed.

Adult↗
PubMed1995

Effects of a new calcium channel blocker, MPC-1304, on blood pressure, serum lipoproteins and serum carbohydrate metabolism in patients with essential hypertension.

The effects of MPC-1304, a new calcium channel blocker, on blood pressure, serum lipoproteins, and carbohydrate metabolism were compared with those of atenolol in a group of patients with mild to moderate essential hypertension. Systolic and diastolic pressures were significantly decreased by both MPC-1304 and atenolol administration. Serum levels of apolipoproteins A-I and A-II were significantly increased after 8-12 weeks of MPC-1304 treatment, but were unchanged during a similar period of atenolol treatment. Neither drug induced any significant change in other lipoprotein parameters, fasting blood sugar, immunoreactive insulin, C-peptide or HbA1c. No serious side-effects or abnormal laboratory values were observed during the course of administration of either drug. These findings indicated that MPC-1304 is as efficacious as an antihypertensive drug and is without adverse effect on lipoprotein or carbohydrate metabolism.

Adult↗
PubMed1995

Effects of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on serum lipids, lipoproteins and cholesterol ester transfer activity in primary hypercholesterolemic patients.

Effects of a combination therapy of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on lipid metabolism were investigated measuring a wide range of parameters in 42 patients with primary hypercholesterolemia. After a wash-out period patients were randomly allocated to 1 of the 2 groups, the fluvastatin-preceding group (G-1) and the niceritrol-preceding group (G-2). In G-1 fluvastatin monotherapy (30 mg/day) significantly decreased total cholesterol (TC) and LDL-cholesterol (LDL-C). There was no significant change in HDL-cholesterol (HDL-C), triglyceride (TG) and lipoprotein (a) (Lp(a)). Further effect in HDL-C and TG was observed after the addition of niceritrol (750 mg/day). On the other hand, in G-2, while niceritrol alone (750 mg/day) produced no significant change in TC, LDL-C, HDL-C, TG and Lp(a), the addition of fluvastatin (30 mg/day) reduced TC and LDL-C levels significantly. Cholesterol ester transfer (CET) activity was significantly reduced by niceritrol monotherapy. After the concomitant use of the 2 drugs CET activity was significantly reduced only in G-2. No significant change in lipoprotein lipase and hepatic triglyceride lipase activities were observed in the 2 groups at either point in time. No serious adverse effect was observed in this study. It is concluded that fluvastatin is an effective drug for lowering LDL-cholesterol and causes no adverse alteration in lipid metabolism. Combination with niceritrol at a dose of 750 mg/day dose not appear to augment or attenuate beneficial effects of fluvastatin.

Anticholesteremic Agents↗
PubMed1995

[Familial hyperparathyroidism].

Recently, not only the multiple endocrine adenomatosis (MEN)-associated type but also the type which can be isolated from MEN syndrome have been widely accepted in the classification of familial hyperparathyroidism. Analysis of gene markers specific to MEN syndrome contributed markedly to the establishment of isolated familial hyperparathyroidism. We attempted an analysis of 15 pedigrees in the report of familial hyperparathyroidism in which MEN syndrome was actively ruled out. In 7 pedigrees, adenoma alone was seen while in 2 pedigrees was hyperplasia alone seen. In 6 pedigrees parathyroid carcinoma was also admitted (other members of the pedigree were affected with parathyroid adenoma or hyperplasia). There were 5 pedigrees in which cementifying fibroma or ossifying fibroma of the jaw was associated with familial hyperparathyroidism. The association of parathyroid carcinomas or benign jaw tumors should be paid attention.

Fibroma↗
PubMed1993

Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes.

BACKGROUND: Cardiac hypertrophy is commonly observed in acromegalic patients, in whom serum insulin-like growth factor-I (IGF-I) levels are elevated. In the present study, we examined whether IGF-I induces hypertrophy in cultured neonatal rat cardiomyocytes through its specific receptor and whether IGF binding protein-3 (IGFBP-3), which is a major circulating carrier protein for IGF-I, inhibits IGF-I-induced cardiac hypertrophy in vitro. METHODS AND RESULTS: Because the response of cardiac hypertrophy is characterized by the induction of expression for muscle-specific genes, the effect of IGF-I on steady-state levels of mRNA for myosin light chain-2 (MLC-2) and troponin I and for skeletal and cardiac alpha-actin isoforms was evaluated by Northern blot analysis. IGF-I (10(-7) M) increased mRNA levels for MLC-2 and troponin I as early as 60 minutes with maximum levels by 6 hours, which were maintained for as long as 24 hours. IGF-I (10(-7) M) also increased transcripts for skeletal alpha-actin but not for cardiac alpha-actin. The cell size as evaluated morphometrically was almost doubled after 48-hour treatment with IGF-I. IGF-I induction of protein synthesis was dose dependent (10(-10) to 10(-7) M) with a maximal 2.2-fold increase seen at 10(-8) M. In contrast to the hypertrophic effect of IGF-I, growth hormone affected neither protein synthesis nor expression for muscle-specific genes. Binding study using 125I-IGF-I revealed the presence of specific binding sites for IGF-I in rat cardiomyocytes. IGFBP-3 induced a dose-dependent inhibition of protein synthesis stimulated by IGF-I; IGFBP-3 (10(-7) M) completely inhibited the [3H]leucine uptake stimulated by IGF-I (10(-8) M). IGFBP-3 similarly inhibited the IGF-I-stimulated gene expressions for MLC-2 and troponin I. CONCLUSIONS: These results suggest that IGF-I directly causes cardiac hypertrophy and that its effect can be blocked by IGFBP-3.

Actins↗
PubMed1992

Cross-linking of apolipoproteins is involved in a loss of the ligand activity of high density lipoprotein upon Cu(2+)-mediated oxidation.

A recent study demonstrated that Cu(2+)-mediated oxidation of high density lipoprotein (HDL) resulted in a loss of the capacity to reduce cholesterol from macrophage foam cells [(1991) Proc. Natl. Acad. Sci. USA 88, 6457-6461]. In the present study we characterized the physicochemical properties of oxidized HDL and correlated them with the ligand activity toward the HDL receptor. Among them, the cross-linking of apolipoproteins and an increase in lipid peroxides were characteristic and closely similar to those of tetranitromethane-treated HDL, an abortive ligand for the HDL receptor. Cellular experiments with murine peritoneal macrophages revealed that both the cellular binding activity of HDL and its capacity to enhance cholesterol efflux from macrophage foam cells were markedly reduced upon oxidation. These results suggest that cross-linking of HDL apolipoproteins is involved in the loss of the ligand activity of oxidized HDL.

Animals↗
PubMed1992

Exposure of rat peritoneal macrophages to acetylated low density lipoprotein results in release of plasma membrane cholesterol. An efficient substrate for esterification by acyl-CoA:cholesterol acyltransferase.

In J774 macrophages and murine macrophages stimulated with acetylated low density lipoprotein (acetyl-LDL), the plasma membrane free cholesterol (FC) became accessible to acyl-CoA:cholesterol acyltransferase (ACAT) as substrate, the result being an accumulation of cholesteryl esters (CE) (Tabas, I., Rosoff, W. J., and Boykow, G. C (1988) J. Biol. Chem. 263, 1266-1272). As the route of delivery of FC to ACAT was not well characterized, we examined this route in the present study. In foam cells derived from rat peritoneal macrophages by preincubation with acetyl-LDL, esterification of the exogenously labeled [3H]FC was low (1.3% of total labeled cholesterol). In contrast, when cells were first labeled with exogenous [3H]FC and then chased with acetyl-LDL, the esterification was more extensive (9.2% of the total labeled cholesterol). During this experiment a significant portion of cellular [3H]FC was released into the medium (up to 33.4% of the total labeled cholesterol). In experiments using a two-compartment chamber in which cells in the lower and upper chambers were separated by filter paper yet the cells in both compartments could communicate without direct contact, [3H]FC released into the medium was biologically active and could serve as an efficient substrate for ACAT. Thus, when acetyl-LDL is not included in culture medium, FC delivery from the macrophage plasma membrane to ACAT is not enhanced, whereas in the presence of acetyl-LDL, plasma membrane FC released and bound to acetyl-LDL may re-enter the cells, possibly through the scavenger receptor. This would provide a significant route for CE synthesis in macrophages.

Animals↗
PubMed1992

Increased production of endothelin-1 in patients with inflammatory arthritides.

OBJECTIVE: Endothelin-1 (ET-1) is a potent vasoconstrictive peptide, but its precise mechanism of action in vivo has remained unknown. METHODS: We measured ET-1 activity by radioimmunoassay, in both plasma and synovial fluid from patients with inflammatory arthritides. RESULTS: ET-1-like immunoreactivity was found in synovial fluid, at levels severalfold higher than those in plasma. Reverse-phase high-performance liquid chromatography showed an elution profile corresponding to actual ET-1. A single class of high-affinity binding sites for ET-1 in cultured synovial cells was also detected. Furthermore, ET-1 induced mild DNA synthesis in synovial cells. CONCLUSION: Taken together, these results indicate that ET-1 might contribute to the synovial proliferation seen in inflammatory arthritides, in an autocrine/paracrine manner.

Adult↗
PubMed1992

Normoglycemia per se but not normoinsulinemia is responsible for suppressing endogenous insulin secretion after oral glucose load in NIDDM.

It is well known that intensive insulin treatment of non-insulin-dependent diabetics (NIDDM) suppresses endogenous insulin secretion and thereafter improves it. To determine whether 'peripheral normo-insulinemia' or 'normoglycemia' established by the treatment is responsible for this suppression, the following five experiments were conducted on 15 well-controlled non-obese NIDDM patients. Experiment 1: a 100 g oral glucose load (OGL) was performed and blood glucose was monitored by an artificial endocrine pancreas (AP). Experiment 2: a 100 g OGL was done and blood glucose was normalized by AP-controlled insulin infusion. Experiments 3 and 4: a 100 g OGL was conducted while 'hyperglycemia' seen in experiment 1 was mimicked by AP-controlled glucose infusion with pre-programmed insulin infusion at the same rates as those in experiment 2 ('normoinsulinemia') or at rates 1.5 times higher than those in experiment 2 ('relative hyperinsulinemia'), respectively. Experiment 5: a 40 g OGL was conducted while AP-controlled insulin and glucose infusions were administered to make the plasma insulin level lower than in experiment 2 ('hypoinsulinemia') and to mimic the normoglycemic profile observed in experiment 2, respectively. In experiments 3 and 4, neither 'normoinsulinemia' nor 'relative hyperinsulinemia' suppressed the increase in plasma C-peptide after a 100 g OGL. In experiment 5, where the plasma insulin level showed a significantly (P less than 0.05) lower level than in experiment 2 and glycemia was normalized, C-peptide did not show a significant rise after OGL. These results indicate that 'normoglycemia' rather than 'normoinsulinemia' attained during exogenous insulin therapy, is responsible for suppressing endogenous insulin secretion against orally administered glucose.

Blood Glucose↗
PubMed1992

Alpha-oxidation of fatty acids in fasted or diabetic rats.

Induction of alpha-oxidation, a possible gluconeogenic process, which should produce odd-chain fatty acids from even-chain fatty acids, was studied in rats fasted or made diabetic with streptozotocin. When a omega-phenylated even-chain fatty acid, phenylbutyric acid (1.2 mmol/kg), was administered to rats under these conditions, a significant increase in the urinary excretion of benzoic acid, the metabolic end-product of omega-phenylated odd-chain fatty acids, was observed in fasted (3.54 +/- 0.46 mumol/day) and diabetic (6.73 +/- 2.10) rats (control, 0.58 +/- 0.43; P less than 0.001). Phenylated longer chain fatty acids, phenylhexanoic and phenyldecanoic acid, did not produce significantly more benzoic acid than did phenylbutyric acid. Although the rate of alpha-oxidation was very low compared to that of beta-oxidation, these results suggested that alpha-oxidation of fatty acids was induced under fasting or diabetic conditions, and that alpha-oxidation might take place at the butyric acid stage.

Animals↗
PubMed1992

Thyroxine-binding globulin variant (TBG-Kumamoto): identification of a point mutation and genotype analysis of its family.

Thyroxine-binding globulin (TBG) is the major thyroid hormone transport protein. Several inherited TBG variants resulting in partial or complete TBG deficiencies have been shown to be caused by either one or two nucleotide substitutions, or one nucleotide deletion in the coding regions of the TBG gene. In this report, a Japanese female patient (proband) with hyperthyroid state, whose lower TBG levels did not return to normal under the euthyroid state after treatment was examined. Genomic DNA samples from the proband with thyroxine-binding globulin deficiency (termed TBG-Kumamoto) and her family were subjected to the polymerase chain reaction, and the generated DNA fragments were sequenced. A single nucleotide substitution in the codon for the amino acid 363 of native TBG molecule (CCT to CTT) was found, resulting in the replacement of proline by leucine. It was revealed that the proband was a heterozygote and her father was a hemizygote. The mutation was confirmed by the allele-specific amplification of genomic DNAs from the proband and her father using oligonucleotide primers of normal or mutant residues at the 3' position in the polymerase chain reaction. These results indicate that the abnormality of TBG-Kumamoto is the consequence of this mutation. Genetically, this point mutation observed in TBG-Kumamoto might be classified as a new type of TBG deficiency.

Adult↗