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Biomedical subjects

M Yamauchi

Publications and source records attributed to M Yamauchi.

At least 127 records · Page 7Linked to original sources
PubMed1998

Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes.

There is increasing evidence that insulin resistance may be causally related to atherosclerosis. The measurement of common carotid arterial intimal and medial complex thickness (IMT) by B-mode ultrasound technique has been recognized as a powerful and non-invasive method to evaluate early atherosclerotic lesions. We investigated the effect of treatment with troglitazone, an insulin sensitizer, on IMT in a total of 135 Japanese subjects with type 2 diabetes. Troglitazone (400 mg daily) was administered for 6 months in 57 patients. Compared to control group (n = 78), the group given troglitazone showed a significant decrease in IMT as early as 3 months after the administration (IMT change: -0.080[SE 0.016] mm vs. control 0.027[SE 0.007] mm, P < 0.001). The decrease in IMT was also found after 6 months, although further decrease was not observed. Both HbA1c and postprandial serum triglycerides were decreased after troglitazone, but there was no statistically significant relation between a decrease in IMT and those in HbA1c or postprandial triglycerides. These findings indicate that troglitazone has a potent inhibitory effect on progression of early atherosclerotic lesions probably through the decreased insulin resistance in type 2 diabetes.

Carotid Arteries↗
PubMed1998

Decreased type IV collagen of skin and serum in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To study type IV collagen of skin and serum in patients with ALS. BACKGROUND: Collagen abnormalities of skin have been reported in ALS patients. However, little is known concerning type IV collagen in ALS. METHODS: We studied type IV collagen immunoreactivity of skin and measured serum levels of the 7S fragment of the N-terminal domain of type IV collagen (7S collagen) in patients with ALS and control subjects. RESULTS: The basement membrane as well as blood vessels of skin in ALS patients was weakly positive for type IV collagen as compared with those of diseased control subjects. This weak immunostaining became more pronounced as ALS progressed. The optical density for type IV collagen immunoreactivity in ALS patients was significantly lower (p < 0.001) than in diseased control subjects and was significantly decreased with duration of illness (r = -0.85, p < 0.01). Serum 7S collagen levels in patients with ALS were significantly decreased (p < 0.01) as compared with those in diseased and healthy control subjects and were negatively and significantly associated with duration of illness (r = -0.81, p < 0.001). There was an appreciable positive correlation between concentrations of serum 7S collagen and the density for type IV collagen immunoreactivity in ALS patients (r = 0.81, p < 0.02). CONCLUSIONS: These data suggest that a metabolic alteration of type IV collagen may take place in the skin of ALS patients and that the decreased levels of serum 7S collagen may reflect a decreased type IV collagen immunoreactivity of skin in patients with ALS.

Aged↗
PubMed1998

Inhibitory effects of rolipram on partially purified phosphodiesterase 4 from rat brains.

Several previous studies have demonstrated that the phosphodiesterase 4 selective inhibitor rolipram affects cellular function at a much lower concentration than the reported Ki value for phosphodiesterase 4 inhibition. In this study, we examined the inhibitory effect of rolipram on rat brain phosphodiesterase 4 to determine the heterogeneity of the enzyme activity. Partial purification of various phosphodiesterases from the rat brain was performed by anion-exchange chromatography. The eluant was pooled into four fractions, two of which manifested cAMP-selective phosphodiesterase activity that was blocked by 10 microM of rolipram, indicating the presence of phosphodiesterase 4 in these fractions. The IC50 of rolipram (racemate) of these two fractions was 492 and 79 nM, respectively. The R-(-)-enantiomer of rolipram inhibited the cAMP-phosphodiesterase activity in the latter fraction 10 times more than did S-(+)-rolipram, and the inhibition of the former fraction was less stereospecific. Dixon plot analysis revealed that the rolipram enantiomers inhibited the cAMP-phosphodiesterase in the latter fraction in a multiphasic manner, with two Ki values, one at the micromolar level and the other at the sub-micromolar level, respectively, for both of the enantiomers. These results suggest that there is a heterogeneity for phosphodiesterase 4 in the rat brain, and some of the phosphodiesterase forms are sensitive to rolipram.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Normal human cementum-derived cells: isolation, clonal expansion, and in vitro and in vivo characterization.

Cultures of primary human cementum-derived cells (HCDCs) were established from healthy premolar teeth extracted for orthodontic reasons. Cementum was manually dissected, fragmented, and digested twice with collagenase. Following a thorough wash to remove liberated cells, the remaining cementum fragments were plated in Dulbecco's modified Eagle's medium/F12 medium containing 10% fetal bovine serum. Discrete colonies that contained cells exhibiting fibroblast-like morphology were visible after 14-21 days of culture. When the colonies became sufficiently large, cells from individual colonies were isolated and subcultured. Cementum-derived cells exhibited low levels or no alkaline phosphatase activity and mineralized in vitro to a lesser degree than human periodontal ligament (PDL) cells and human bone marrow stromal cell (BMSC) cultures. To study differentiation capacities of HCDCs, cells were attached to hydroxyapatite/tricalcium phosphate ceramic and transplanted subcutaneously into immunodeficient mice. The transplants were harvested 3, 6, and 8 weeks after transplantation and evaluated histologically. In human BMSC transplants, new bone tissue was formed with a prominent osteoblastic layer and osteocytes embedded in mineralized bone matrix. No osseous tissue was formed by PDL cells. Of six single colony-derived strains of HCDCs tested, three formed a bone-like tissue that featured osteocyte/cementocyte-like cells embedded within a mineralized matrix and which was lined with a layer of cells, although they were somewhat more elongated than osteoblasts. These results show that cells from normal human cementum can be isolated and expanded in vitro. Furthermore, these cells are capable of differentiating and forming mineralized tissue when transplanted into immunodeficient mice.

Adolescent↗
PubMed1998

Apatite induction by insoluble dentin collagen.

Phosphoproteins are thought to play a role in mineral formation in dentin. A portion of this phosphoprotein is bound to collagen. We have investigated the requirement for bound phosphate in mineral induction by isolated dentin collagen. Insoluble bovine dentin collagen obtained by ethylene-diamino-tetra-acetic acid (EDTA) demineralization had 19.5 mol of P/mol of collagen that could not be extracted with 0.5 M EDTA in 4 M guanidine HCl. When this collagen was incubated in supersaturated solutions that did not spontaneously precipitate, apatite was induced. With progressive enzymatic dephosphorylation, induction times for mineral formation became progressively longer. The dentin did not induce mineral formation when 90% of the ester phosphate was removed. Insoluble bone collagen, which had even less phosphate, also did not induce mineral formation. Mineral induction times by dentin collagen increased with decreasing solution saturations. Using these data, the interfacial tension for mineral induction was determined to be 90 ergs/cm2. This value approximated that of phosphatidic acid liposomes and of phosvitin cross-linked to agarose beads, and it might reflect the energetics of heterogeneous nucleation on a highly phosphorylated surface. Sequestering of calcium-phosphate clusters on the phosphoprotein probably accounts for the observed calcium binding by dentin collagen in excess of that required to neutralize the phosphate esters of the collagen. Because the phosphoprotein is immobilized at a low density on the collagen, it cannot self-associate in calcium-phosphate solutions as it does when it is free in solution. This immobilized phosphoprotein allows the mineral clusters formed on its surface to grow into a crystalline order.

Animals↗
PubMed1998

Low bone mineral density in a case of mosaicism Klinefelter syndrome: rapid response to testosterone therapy.

Male hypogonadism has been recognized as one of the major causes of secondary osteoporosis, but most cases seem to be left undiagnosed. We report a 54-year-old case of mosaicism Klinefelter syndrome lacking typical clinical features such as tall stature or low intelligence, who was found to have marked decrease in lumbar bone mineral density (BMD: 0.686 g/cm2) during treatment of diabetes mellitus. In investigation for etiologies of secondary osteoporosis, he was diagnosed as having mosaicism Klinefelter syndrome (XXY/XY/XX). Although he was infertile, he lacked typical clinical features of Klinefelter syndrome. Testosterone replacement was started, which resulted in an increase in BMD up to 0.712 g/cm2 two months after the initiation of therapy. The fact that BMD increased shortly after the initiation of testosterone replacement therapy in the present case supported a beneficial effect of testosterone on BMD, as recently suggested in idiopathic hypogonadotropic hypogonadism. Although the present case was diagnosed as having mosaicism Klinefelter syndrome by investigating etiologies for osteoporosis, it may be stressed that male hypogonadism, in general, should be adequately suspected in the presence of infertility and from the findings of physical examination.

Bone Density↗
PubMed1998

A case of aldosterone-producing adenoma with severe postoperative hyperkalemia.

It is known that some patients with primary aldosteronism show postoperative hyperkalemia, which is due to inability of the adrenal gland to secrete sufficient amounts of aldosterone. However, hyperkalemia is generally neither severe nor prolonged, in which replacement therapy with mineralocorticoid is seldom necessary. We report a case of a 46-year-old woman with an aldosterone-producing adenoma associated with severe postoperative hyperkalemia. After unilateral adrenalectomy, the patient showed episodes of severe hyperkalemia for four months, which required not only cation-exchange resin, but also mineralocorticoid replacement. Plasma aldosterone concentration (PAC) was low, although PAC was increased after rapid ACTH test. Histological examination indicated the presence of adrenocortical tumor and paradoxical hyperplasia of zona glomerulosa in the adjacent adrenal. Immunohistochemistry demonstrated that the enzymes involved in aldosterone synthesis, such as cholesterol side chain cleavage (P-450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), and 21-hydroxylase (P-450c21), or the enzyme involved in glucocorticoid synthesis, 11beta-hydroxylase (P-450c11beta), were expressed in the tumor, but they were completely absent in zona glomerulosa of the adjacent adrenal. These findings were consistent with the patterns of primary aldosteronism. Serum potassium level was gradually decreased with concomitant increase in PAC. These results suggest that severe postoperative hyperkalemia of the present case was attributable to severe suppression of aldosterone synthesis in the adjacent and contralateral adrenal, which resulted in slow recovery of aldosterone secretion. It is plausible that aldosterone synthesis of adjacent and contralateral adrenal glands is severely impaired in some cases with primary aldosteronism, as glucocorticoid synthesis in Cushing syndrome.

Adenoma↗
PubMed1998

Lateral difference in the reproduction of arm positioning movement: an examination of the hypothesis on the levels of psychological processes.

The purpose of this study was to determine whether the hypothesis on the levels of psychological processes (Hatta, 1977, 1978) accounts for lateral differences in arm positioning movement (a spatial localization task). Fifteen right-handed male subjects were asked to perform a constrained criterion movement, 12 cm in length, with the left or right arm. Then, after a 10-sec retention interval, they were asked to perform the movement with the same arm, estimating lengths of 6, 12 or 24 cm. Different levels of psychological processes were assumed to be involved in estimating these various movement lengths--half, the same, or double that of the original. All possible combinations of the arm (left/right) and three movement length were tested. The CE scores were lower (more accurate) for the left arm (half; 1.5 +/- 8.1 mm, same; 4.3 +/- 6.2mm, double; 5.9 +/- 20.3 mm) than those for the right arm (half; 5.9 +/- 7.6 mm, same; 10.6 +/- 10.6 mm, double; 11.8 +/- 23.6 mm) in all conditions, indicating a lateral difference (the right hemisphere dominance) in arm positioning tasks. This typical lateral difference, which displayed no significant difference among conditions, is supposed to be mediated by complex or high-level psychological processes. These psychological processes are required by the subjects in the estimation of the various movement lengths. This study suggests that the level of psychological processes is a crucial factor in the manifestation of lateral differences in the performance of arm positioning movements.

Adult↗
PubMed1998

A cartilage matrix deficiency experimentally induced by vitamin B6 deficiency.

A vitamin B6-deficiency-induced disorder in avian articular cartilage resembling osteoarthritis has been further characterized. We measured several parameters of proteoglycan (PG) metabolism, i.e., fixed charge density and sulfated glycosaminoglycans (S-GAG) content in PN-deficient versus control articular cartilage and synovial fluid from the knee joint. Statistically significant changes were: 1) decreased content and increased extractability of total sulfated PGs from articular cartilage with guanidine HCl; 2) elevation of S-GAG concentration in synovial fluid; 3) increased plasma cystathionine (sulfur amino acid) levels. PG synthesis as assessed by 35SO4 incorporation into S-GAGs was not impaired. A lack of cartilage swelling in 0.15 M saline and the normal water content indicated that although disturbed, the collagen network was not disrupted. This finding was in agreement with a previous microscopic study that revealed no fissures in the articular cartilage. Previous findings of a normal aggregating PG size-distribution and absence of elevated metalloproteases made a disturbance of aggregating PG metabolism unlikely. Escape into the synovial fluid of small PGs, normally bound to articular collagen, was believed to result from an alteration in collagen molecular organization that could be secondary to elevated circulating SH-compounds.

Animals↗
PubMed1998

[Mitral regurgitation due to mitral valve prolapse associated with epidermolysis bullosa: case report].

Mitral valve prolapse (MVP) has been associated with several connective tissue disorders, including Marfan's syndrome, Ehlers-Danlos syndrome, and pseudoxanthoma elasticum. We present a case of MVP in a patient with epidermolysis bullosa. The authors are aware of only one previously reported case of this association. A 49-year-old man with a history of epidermolysis bullosa since childhood was admitted to our institution due to dyspnea on effort. On general examination he was observed to have alopecia, deformities in his nails, and fusions of his fingers. Transesophageal echocardiography confirmed the presence of MVP. In addition, coronary angiography showed three-vessel disease. Mitral valve replacement (ATS valve 25 mm) and coronary artery bypass grafting (left internal thoracic artery-LAD) were performed. The resected mitral valve (anterior leaflet) contained the area of the myxomatous lesion histologically. The pathological mechanism of epidermolysis bullosa is thought to be the destruction of collagen fibers due to increased levels of enzyme collagenase. Therefore there may be a common cause of MVP and epidermolysis bullosa based upon an abnormality of collagen metabolism.

Coronary Artery Bypass↗
PubMed1998

[A case of traumatic lung cyst].

Traumatic lung cyst is an uncommon lung injury due to closed chest trauma. A 5-year-old boy was admitted to our hospital after being run over by motor vehicle. Computed tomography of the chest demonstrated multiple cystic lesions. This case was diagnosed as traumatic lung cysts. Computed tomography taken 37 days after initial injury showed complete resolution of the cysts. Computed tomography was useful in diagnosing traumatic lung cyst and following its clinical course.

Accidents, Traffic↗
PubMed1998

[Preventive effect of fluid warmer system on hypothermia induced by rapid intravenous infusion].

The changes in body temperature induced by rapid intravenous infusion of lactated Ringer solution and the effect of a fluid warmer system (HOT LINE, Level 1 Technologies, Inc., Rockland, MD) were investigated in 35 patients undergoing cardiovascular surgery. The patients were divided into 5 groups by categories of the fluid temperature (-19 or -38 degrees C), infusion route (radial or right subclavian vein), and infusion rate of lactated Ringer solution (1000 or 250 ml for 30 min). Pulmonary arterial, esophageal, bladder, and forehead deep temperatures, which reflect core temperature, were significantly decreased by the rapid infusion of unwarmed solution (0.8-1.0 degree C, P < 0.05). In contrast, these temperatures were maintained in the warmed solution groups as well as in the group of slow infusion rate. With regard to the infusion route, there was no significant difference in the temperature between the radial vein and subclavian vein groups. Plantar deep temperature showed no significant change during this study. In conclusion, infusion of warmed solution using HOT LINE could prevent hypothermia induced by rapid intravenous infusion, and this effect is not greatly influenced by route of venous infusion.

Adult↗
PubMed1997

Phosphodiesterase type 4 that regulates cAMP level in cortical neurons shows high sensitivity to rolipram.

To characterize the role of phosphodiesterase type 4 (a cAMP-specific and rolipram-sensitive phosphodiesterase) among phosphodiesterases in the regulation of the intracellular cAMP level in cortical neurons, we investigated the effects of phosphodiesterase inhibitors on the intracellular cAMP levels in primary cultured rat cortical neurons. Selective inhibitors of phosphodiesterase type 4 and type 2 significantly enhanced beta-adrenoceptor-mediated cAMP increase. Selective inhibitors of phosphodiesterase type 1, type 3 and type 5/6 had no effect on the cAMP level. Rolipram enhanced the beta-adrenoceptor-mediated cAMP increase in cortical neurons, astrocytes and vascular smooth muscle cells at different minimum effective concentrations (10, 100 and 1000 nM, respectively). These findings indicate that phosphodiesterase type 4, showing a high-sensitivity to rolipram, plays a major role in regulating cAMP in the cortical neurons, and that rolipram at low doses enhances the intracellular cAMP increase in the cortical neurons selectively.

Adenylyl Cyclases↗
PubMed1997

Molecular cloning and expression of a rat cDNA encoding 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase.

The cDNA of a 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (AICARFT/IMPCHase) was isolated from rat liver RNA by reverse transcription and the polymerase chain reaction (PCR). The rat AICARFT/IMPCHase cDNA included 1928 bp containing a coding region of 1779 bp for a 592-amino acid polypeptide (Mr = 64 200). Rat and human AICARFT/IMPCHase cDNAs show 84 and 91% homology at the nucleotide and amino acid sequence level, respectively. The protein produced by the rat cDNA using pET-expression system catalysed the penultimate and final steps of de novo purine biosynthesis. Northern analysis identified a 2.8-kb AICARFT/IMPCHase mRNA and the level of the AICARFT/IMPCHase transcripts increased markedly at 24 h after partial (70%) hepatectomy.

Amino Acid Sequence↗
PubMed1997

The structure and organization of the human NPAT gene.

Ataxia telangiectasia (AT) is an autosomal recessive gene disorder, and ATM, a housekeeping gene, has been identified as the gene responsible for AT. Recently we found that another housekeeping gene, NPAT, is located upstream of ATM on human chromosome 11. The two housekeeping genes are transcribed in opposite directions and share a 0.5-kb 5' flanking sequence. The structure and organization of NPAT were determined by direct sequencing of cosmid clones carrying the gene and by application of the long and accurate (LA)-PCR method to amplify regions encompassing the exon/intron boundaries and all of the exons. The gene spans at least 44 kb and consists of 18 exons and 17 introns. It has been suggested that AT heterozygotes have an increased risk of developing cancer, especially breast cancer in women. Frequently, loss of heterozygosity at loci on 11q22-q24 has been observed in DNA isolated from tumors of the breast, uterine cervix, and colon, perhaps suggesting the location of a tumor suppressor gene in 11q22-q24. For investigation of the role of NPAT in AT and these tumors with allelic loss of 11q22-q24, appropriate primer sequences and PCR conditions for amplification of all the NPAT exons from genomic DNA were determined. We previously reported that no recombinations are found among Atm, Npat, and Acat1 (acetoacetyl-CoA thiolase) loci as determined by fine genetic linkage mapping of the mouse AT region. The results of the LA-PCR analysis using NPAT- and ACAT-specific primers and human genomic DNA allowed us to map ACAT 12 kb centromeric to NPAT.

Animals↗
PubMed1997

ClpX and MuB interact with overlapping regions of Mu transposase: implications for control of the transposition pathway.

Transposition of phage Mu is catalyzed by an extremely stable transposase-DNA complex. Once recombination is complete, the Escherichia coli ClpX protein, a member of the Clp/Hsp100 chaperone family, initiates disassembly of the complex for phage DNA replication to commence. To understand how the transition between recombination and replication is controlled, we investigated how transposase-DNA complexes are recognized by ClpX. We find that a 10-amino-acid peptide from the carboxy-terminal domain of transposase is required for its recognition by ClpX. This short, positively charged peptide is also sufficient to convert a heterologous protein into a ClpX substrate. The region of transposase that interacts with the transposition activator, MuB protein, is also defined further and found to overlap with that recognized by ClpX. As a consequence, MuB inhibits disassembly of several transposase-DNA complexes that are intermediates in recombination. This ability of MuB to block access to transposase suggests a mechanism for restricting ClpX-mediated remodeling to the proper stage during replicative transposition. We propose that overlap of sequences involved in subunit interactions and those that target a protein for remodeling or destruction may be a useful design for proteins that function in pathways where remodeling or degradation must be regulated.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1997

The protein composition of normal and developmentally defective enamel.

The development of human enamel involves a complex series of events including the secretion and degradation of a unique extracellular matrix. Ameloblasts progress through a succession of cellular phenotypes executing specialized secretory and regulatory functions. When performing optimally, ameloblasts produce a highly structured and mineralized tissue. Given the elaborate developmental events required for normal enamel formation, it is not surprising that a variety of enamel malformations arise from defects in matrix synthesis, secretion and extracellular processing. Normal matrix secretion and post-secretory processing by ameloblasts can be affected by a variety of hereditary and environmental conditions. These disturbances can result in an abnormal amount and/or composition of matrix proteins, and subsequently, an altered enamel structure and/or mineral content. For example, abnormal matrix removal during enamel maturation apparently contributes to hypomineralization associated with dental fluorosis. Incomplete matrix removal can also occur in several different forms of the hereditary condition amelogenesis imperfects. Specific types of this condition can have retention of substantial enamel protein (e.g. 5% by weight) that is, at least in part, composed of amelogenin and/or its breakdown products. Characterization of the enamel proteins in teeth affected by developmental disturbances can provide insight into the pathogenesis and normal formation of this highly specialized tissue.

Adult↗