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Biomedical subjects

M Yamaguchi

Publications and source records attributed to M Yamaguchi.

At least 469 records · Page 26Linked to original sources
PubMed1998

Secretory IgA induces degranulation of IL-3-primed basophils.

We examined whether secretory IgA (sIgA), known to mediate eosinophil stimulation, has an effect on basophil functions. An immobilized preparation of sIgA, but not of monomeric IgA, induced histamine release (approximately 15% of total histamine contents) from human basophils in vitro. sIgA-induced basophil histamine release was totally dependent on pretreatment with IL-3. IL-5 and granulocyte-macrophage CSF also primed basophils for sIgA-mediated release. Exogenous divalent ions, i.e., Ca2+ and Mg2+, were essential for sIgA-mediated basophil degranulation, and the degranulation was completed within 45 min. A newly synthesized lipid mediator, leukotriene C4, was also liberated from IL-3-primed, sIgA-stimulated basophils. Enzyme digestion experiments revealed that the (Fc)2 x secretory component portion of sIgA is important for sIgA-mediated basophil activation, but the functional binding sites of sIgA on basophils were surmised to be different from FcalphaR. These observations reveal the novel finding that sIgA is able to stimulate basophils as well as eosinophils. Since sIgA is the most abundant Ig isotype in the secretions from mucosal tissues, and basophils are active participants in allergic late-phase reactions, sIgA-mediated basophil mediator release is potentially involved in exacerbation of the inflammation associated with allergic disorders.

Basophils↗
PubMed1998

Increase of Ca2+-ATPase activity in the brain microsomes of rats with increasing ages: involvement of protein kinase C.

A possible mechanism of aging-induced increase in brain microsomal Ca2+-adenosine triphosphatase (ATPase) activity of rats was investigated. Calcium content in the brain tissues and Ca2+-ATPase activity in the brain microsomes of aging rats (50 weeks of age) increased significantly as compared with those of young rats (5 weeks of age). Brain microsomal Ca2+-ATPase activity in aging rats was decreased significantly by treatment of ethyleneglycol-bis-(aminoethylether) N,N,N',N'-tetraacetic acid (EGTA) (2.7 mM) or digitonin (10(-3)%), while such decrease was not seen in the enzyme activity of young rats. Microsomal Ca2+-ATPase activity in aging rats was markedly decreased by the presence of staurosporine (10(-8) and 10(-7) M), an inhibitor of protein kinase C, in the enzyme reaction mixture, although the enzyme activity of young rats was not inhibited. Meanwhile, dibucaine (10(-6) and 10(-5) M), an inhibitor of Ca2+/calmodulin-dependent protein kinase, did not have an effect on Ca2+-ATPase activity in the brain microsomes of young and aging rats. The addition of protein kinase C (100 and 200 mU/ml) in the reaction mixture caused a significant increase in brain microsomal Ca2+-ATPase activity of young rats. These results suggest that protein kinase C is partly involved in the elevation of brain microsomal Ca2+-ATPase activity in rats with increasing ages.

Aging↗
PubMed1998

Stimulatory effect of calcium-binding protein regucalcin on phosphatase activity in the brain cytosol of rats with different ages.

The effect of calcium-binding protein regucalcin on phosphatase activity in the brain cytosol of rats with different ages was investigated. The presence of regucalcin (10(-8) and 10(-7) M) in the enzyme reaction mixture caused a significant increase of neutral p-nitrophenylphosphatase activity in the brain cytosol obtained from 5- and 50-week-old rats. This increase was seen in the absence or presence of calmodulin (2 microg/mL) and calcium chloride (100 microM). Brain cytosolic phosphatase activity was not significantly altered by S-100A (10(-6) M) or calbindin (10(-7) M), which is a calcium-binding protein. Regucalcin-increased phosphatase activity was clearly decreased by N-ethylmaleimide, a modifying reagent of thiol(SH)-group, suggesting that regucalcin acts on the SH-group of the enzyme. Moreover, the presence of anti-regucalcin monoclonal antibody (50-200 ng/mL) in the reaction mixture caused a significant decrease of brain cytosolic phosphatase activity, suggesting that the endogenous regucalcin has a stimulatory effect on the enzyme activity. These results suggest that regucalcin plays a role in the regulation of protein phosphatase in rat brain cytosol.

Aging↗
PubMed1998

Retardation of skeletal development and cervical abnormalities in transgenic mice expressing a dominant-negative retinoic acid receptor in chondrogenic cells.

Skeletal formation is a fundamental element of body patterning and is strictly regulated both temporally and spatially by a variety of molecules. Among these, retinoic acid (RA) has been shown to be involved in normal skeletal development. However, its pleiotropic effects have caused difficulty in identifying its crucial target cells and molecular mechanisms for each effect. Development of cartilage primordia is an important process in defining the skeletal structures. To address the role of RA in skeletal formation, we have generated mice expressing a dominant-negative retinoic acid receptor (RAR) in chondrogenic cells by using the type II collagen alpha1 promoter, and we have analyzed their phenotypes. These mice exhibited small cartilage primordia during development and retarded skeletal formation in both embryonic and postnatal periods. They also showed selective degeneration in their cervical vertebrae combined with homeotic transformations, but not in their extremities. The cervical phenotypes are reminiscent of phenotypes involving homeobox genes. We found that the expression of Hoxa-4 was indeed reduced in the cartilage primordia of cervical vertebrae of embryonic day 12.5 embryos. These observations demonstrate that endogenous RA acts directly on chondrogenic cells to promote skeletal growth in both embryonic and growing periods, and it regulates the proper formation of cervical vertebrae. Furthermore, RA apparently specifies the identities of the cervical vertebrae through the regulation of homeobox genes in the chondrogenic cells. Great similarities of the phenotypes between our mice and reported RAR knockout mice revealed that chondrogenic cells are a principal RA target during complex cascades of skeletal development.

Animals↗
PubMed1998

Neuromagnetic activity in the human left cerebral hemisphere concerning logical processing during auditory oddball stimulation.

The aim of this study was to examine the cortex during the logical processing of auditory information using a whole-cortex type dc-SQUID gradiometer. The task modified the normal auditory oddball paradigm to require the processing of simple logic before counting a rare stimulus mentally. Although the latency of P300 m did not change, a dipolar magnetic field pattern was observed over the left cerebral hemisphere at approximately 280 ms poststimulus before forming the field pattern of P300 m. The equivalent current dipole source was estimated to be medial to the N100 m source. It was suggested that the additional load of logic processing may activate Heschl's gyri in the left hemisphere.

Acoustic Stimulation↗
PubMed1998

MutS and MutL activate DNA helicase II in a mismatch-dependent manner.

MutS, MutL, and DNA helicase II are required for the mismatch-provoked excision step that occurs during Escherichia coli methyl-directed mismatch repair. In this study MutL is shown to enhance the unwinding activity of DNA helicase II more than 10-fold on a conventional helicase substrate in which a 35-residue oligonucleotide is annealed to a M13 circular single-stranded phage DNA under conditions where the two proteins are present at approximately molar stoichiometry with respect to the substrate. MutS- and MutL-dependent activation of DNA helicase II has also been demonstrated with a model substrate in which a 138-residue oligonucleotide was hybridized to a 138-nucleotide gap in an otherwise duplex 7,100-base pair circular DNA. Displacement of the oligonucleotide requires MutS, MutL, DNA helicase II, and ATP and is dependent on the presence of a mismatch within the hybrid region. Although DNA helicase II and Rep helicase share substantial sequence homology and features of mechanism, Rep helicase is inactive in this reaction.

Adenosine Triphosphatases↗
PubMed1998

Mitochondrial NADH-ubiquinone oxidoreductase (Complex I). Effect of substrates on the fragmentation of subunits by trypsin.

It has been shown that treatment of bovine mitochondrial complex I (NADH-ubiquinone oxidoreductase) with NADH or NADPH, but not with NAD or NADP, increases the susceptibility of a number of subunits to tryptic degradation. This increased susceptibility involved subunits that contain electron carriers, such as FMN and iron-sulfur clusters, as well as subunits that lack electron carriers. Results shown elsewhere on changes in the cross-linking pattern of complex I subunits when the enzyme was pretreated with NADH or NADPH (Belogrudov, G., and Hatefi, Y. (1994) Biochemistry 33, 4571-4576) also indicated that complex I undergoes extensive conformation changes when reduced by substrate. Furthermore, we had previously shown that in submitochondrial particles the affinity of complex I for NAD increases by >/=20-fold in electron transfer from succinate to NAD when the particles are energized by ATP hydrolysis. Together, these results suggest that energy coupling in complex I may involve protein conformation changes as a key step. In addition, it has been shown here that treatment of complex I with trypsin in the presence of NADPH, but not NADH or NAD(P), produced from the 39-kDa subunit a 33-kDa degradation product that resisted further hydrolysis. Like the 39-kDa subunit, the 33-kDa product bound to a NADP-agarose affinity column, and could be eluted with a buffer containing NADPH. It is possible that together with the acyl carrier protein of complex I the NADP(H)-binding 39-kDa subunit is involved in intramitochondrial fatty acid synthesis.

Animals↗
PubMed1998

Autocrine inhibition of leptin production by tumor necrosis factor-alpha (TNF-alpha) through TNF-alpha type-I receptor in vitro.

The aim of this study was to find factors which regulate m-leptin secretion during pregnancy. Mouse parametrial adipocytes from day 13 of pregnancy were cultured with or without mouse placental lactogen (mPL)-I, mPL-II, or mouse tumor necrosis factor-alpha (mTNF-alpha) and mouse-leptin (m-leptin) concentration in the medium was assessed by RIA. Up to four days of mPL-I or mPL-II treatment did not affect m-leptin secretion. However, mTNF-alpha, which is produced by adipocytes, significantly inhibited m-leptin secretion in a dose- and time-dependent manner. Antibody to mTNF-alpha completely blocked the inhibitory effect of mTNF-alpha on m-leptin secretion. mTNF-alpha significantly inhibited the expression of m-leptin messenger RNA. Agonistic polyclonal antibody directed against the mTNF-type-I receptor (mTNF-RI) significantly inhibited m-leptin secretion, but the anti-mTNF-RII antibody did not change m-leptin secretion. Moreover, human TNF-alpha (h-TNF-alpha) also inhibited human-leptin (h-leptin) secretion by cultured human adipocytes collected from the subcutaneous fat of pregnant women. These results suggest that TNF-alpha, which is secreted by adipocytes, inhibits m-leptin secretion through mTNF-RI and suggest the presence of an autocrine or paracrine regulation of leptin secretion in human and mouse adipose tissue in vivo.

Adipocytes↗
PubMed1998

De novo CD5+ diffuse large B-cell lymphomas express VH genes with somatic mutation.

To clarify the cellular origin of de novo CD5+ diffuse large B-cell lymphoma (CD5+ DLBL), particularly in comparison with other CD5+ B-cell neoplasms such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), we analyzed the nucleotide sequence of the Ig heavy chain variable region (IgVH) genes of de novo CD5+ DLBL cases. All 4 cases examined had extensive somatic mutations in contrast with CLL or MCL. The VH gene sequences of de novo CD5+ DLBL displayed 86.9% to 95.2% homology with the corresponding germlines, whereas those of simultaneously analyzed CLL and MCL displayed 97.6% to 100% homology. The VH family used was VH3 in 1 case, VH4 in 2 cases, and VH5 in 1 case. In 2 of 4 examined cases, the distribution of replacement and silent mutations over the complementarity determining region and framework region in the VH genes was compatible with the pattern resulting from the antigen selection. Clinically, CD5+ DLBL frequently involved a variety of extranodal sites (12/13) and lymph node (11/13). Immunophenotypically, CD5+ DLBL scarcely expressed CD21 and CD23 (3/13 and 2/13, respectively). These findings indicate that de novo CD5+ DLBL cells are derived from a B-1 subset distinct from those of CLL or MCL.

Aged↗
PubMed1998

Dose-Response Effect of Dietary Docosahexaenoic Acid on Fatty Acid Profiles of Serum and Tissue Lipids in Rats.

The dose-response effects of dietary docosahexaenoic acid (22:6n-3, DHA) on the fatty acid profiles of total lipids of rat serum and tissues were investigated. Rats were fed diets containing graded levels of purified DHA at 0, 1.0, 3.4, and 8.7% of total energy in the diets for 2 weeks. It was found that each tissue had its own peculiar composition of fatty acids which differed markedly from that of circulating serum lipid. This composition was basically influenced dose-dependently by the dietary lipids with graded levels of DHA, but to different degrees in different tissues. Those of brain were most resistant and of heart most susceptible to dietary DHA.

Journal Article↗
PubMed1998

Inhibitory effect of genistein on bone resorption in tissue culture.

The effect of genistein on bone resorption in vitro was investigated. Femoral-metaphyseal tissues obtained from elderly female rats were cultured for 48 hr in Dulbecco's modified Eagle's medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained 10(-7) to 10(-3) M genistein. The bone-resorbing factors parathyroid hormone (1-34) (PTH; 10(-7) M), prostaglandin E2 (PGE2; 10(-5) M), and lipopolysaccharide ( 10 microg/mL) caused a significant decrease in bone calcium content. The decrease in bone calcium content induced by bone-resorbing factors was inhibited completely by genistein (10(-7) to 10(-5) M). In addition, this isoflavonoid (10(-5) M) completely inhibited the PTH (10(-7) M)- or PGE2 (10(-5) M)-induced increase in medium glucose consumption and lactic acid production by bone tissues. Moreover, genistein (10(-5) M) blocked both PTH (10(-7) M)-increased acid phosphatase and -decreased alkaline phosphatase activities of bone tissues. The inhibitory effect of genistein (10(-5) M) on PTH (10(-7) M)-stimulated bone resorption was clearly prevented by the presence of 10(-6) M tamoxifen, an anti-estrogen reagent. Genistein (10(-5) M) did not further enhance the inhibitory effect of estrogen (10(-9) M) on PTH-stimulated bone resorption. These findings indicate that genistein has a direct inhibitory effect on bone resorption in tissue culture in vitro.

Acid Phosphatase↗
PubMed1998

Ca2+ administration stimulates the binding of AP-1 factor to the 5'-flanking region of the rat gene for the Ca2+-binding protein regucalcin.

mRNA of the Ca2+-binding protein, regucalcin, is mainly expressed in the liver and only to a small extent in the kidney, and the expression of hepatic regucalcin mRNA is markedly stimulated by Ca2+ administration [Shimokawa and Yamaguchi (1992) FEBS Lett. 305, 151-154]. The existence of nuclear factors that bind to the 5'-flanking region of the rat regucalcin gene was investigated. When nuclear proteins obtained from various rat tissues were used in gel mobility-shift assays, tissue-specific formation of a protein-DNA complex was found in the liver and kidney. An additional novel protein-DNA complex was formed when liver nuclear extracts obtained from Ca2+-administered rats (10mg of Ca2+/100g body weight) were used. Competition gel mobility-shift experiments using consensus and mutant oligonucleotides for AP-1 factor showed that the additional novel complex was formed from binding of the AP-1 factor to the regucalcin gene. Ca2+-induced binding of the AP-1 factor to the regucalcin gene was completely inhibited by simultaneous administration of trifluoperazine, an antagonist of calmodulin, suggesting that the activation of nuclear AP-1 protein is partly mediated through a Ca2+/calmodulin-dependent pathway. Moreover, the 5'-flanking region of the rat regucalcin gene ligated to a luciferase reporter gene possessed the promoter activity in H4-II-E hepatoma cells. This promoter activity was enhanced by treatment with Bay K 8644, a Ca2+-channel agonist. The present study demonstrates that the Ca2+-response sequences are located within the 5'-flanking region of the rat regucalcin gene.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Immunochemical quantification of crossline as a fluorescent advanced glycation endproduct in erythrocyte membrane proteins from diabetic patients with or without retinopathy.

Crossline is a novel advanced glycation endproduct (AGE) which has both a crosslink and fluorescence similar to AGE-protein in vivo. To assess the association of AGEs to the development of diabetic retinopathy we developed a sensitive and specific enzyme-linked immunosorbent assay (ELISA) for crossline in blood samples and investigated the association of the development of retinopathy and erythrocyte membrane protein (EMP)-crossline concentrations in patients with Type 2 diabetes mellitus (Type 2 DM). Crossline formation in EMP exceeded that in haemoglobin and was detectable in normal EMP samples without pretreatment by this ELISA system. Mean (+/-SE) EMP crossline levels were elevated 1.6-fold in diabetic patients without retinopathy (7.6 +/- 0.5 pmol mg(-1), p < 0.005), 2.2-fold in diabetic patients with non-proliferative retinopathy (10.5 +/- 0.6 pmol mg(-1), p < 0.001) and 2.6-fold in diabetic patients with proliferative retinopathy (12.0 +/- 0.6 pmol mg(-1), p < 0.001) compared with healthy control subjects (4.7 +/- 0.5 pmol mg(-1)). Type 2 DM patients with retinopathy had significantly higher EMP-crossline levels than those without retinopathy (p < 0.005). Our data suggest that elevated EMP-crossline concentrations are associated with the presence of retinopathy in patients with Type 2 DM and EMP-crossline measured by our ELISA may provide a useful marker for assessing the role of glycation in the development of diabetic retinopathy.

Aged↗
PubMed1998

Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver.

As in other tumors, the assessment of microvessel density (MVD) in hepatocellular carcinoma (HCC) may be essential to perform an effective anti-angiogenic therapy for this tumor. The relationship between vascular endothelial growth factor (VEGF) and MVD of HCC as well as the surrounding liver remains to be elucidated. In 71 patients who had undergone curative hepatic resection for HCC, MVD and VEGF expressions were evaluated for HCC and the liver by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and/or immunostaining. The intensity and extent of VEGF immunoreactivity were evaluated using a computer image analyzer-cell analysis system (CAS). Angiographic data were re-evaluated and compared with MVD in 50 tumors. Tumoral MVD was significantly correlated with tumor capsule formation (t test, P = .0016). Small HCCs (< or = 2 cm) had a significantly lower MVD compared with moderate-sized HCCs (2-5 cm) (t test, P = .016), and the MVD of large HCCs was relatively lower than that of moderate tumors. Tumor vascularity on angiography was not correlated with the MVD. Neither VEGF mRNA levels nor protein expression in HCC were correlated with the tumoral MVD or any histopathological features of the tumor. However, cirrhotic livers had significantly higher MVD and VEGF expressions compared with noncirrhotic livers (t test, P = .0015 and P = .047, respectively). Only the MVD of tumor was significantly correlated with intrahepatic recurrence (t test, P = .0048) and disease-free survival (DFS) rates (log rank test, P = .0035). Moreover, the MVD was an independent predictor for DFS by multivariate analysis (chi2 test, P = .03). In conclusion, the MVD in HCC may be involved in the dismal prognosis of this tumor, and VEGF may be associated with the angiogenic process of the cirrhotic liver, but not with the angiogenesis of HCC.

Adult↗
PubMed1998

Successful methotrexate therapy for adult Still's disease with marked thrombocytopenia.

A 34-year-old Japanese woman developed spiking fever, splenomegaly, arthritis, neutrophilia, hyperferritinaemia (22517 ng/ml), elevated C-reactive protein (9.1 mg/ml) and severe thrombocytopenia (1.7 x 10(4)/microl). The patient had depressed antithrombin III activity and abnormally high concentrations of both fibrin degradation products and thrombin-antithrombin complexes. This condition was resistant to high-dose prednisolone therapy (120 mg/day) and non-steroidal anti-inflammatory drugs. We initiated oral methotrexate therapy (7.5 mg/week, orally) with a favourable outcome. The patient's spiking fever subsided on the first day of methotrexate administration. Elevated levels of ferritin and C-reactive protein in the sera rapidly normalised. Methotrexate rapidly improved the disease state which suggested that methotrexate act via modulation of cytokine production or secretion.

Administration, Oral↗
PubMed1998

Estimation of left ventricular contractile performance in atrial fibrillation: experimental and clinical studies.

There are few studies regarding the assessment of left ventricular contractile function in patients with atrial fibrillation (AF). The aim of this study was to assess the left ventricular (LV) contractile function, i.e., the end-systolic pressure-volume relation (Ees) and a recently developed LV systolic myocardial stiffness constant (Ksm), without load manipulation in AF. In an experimental study of acute AF in dogs (n = 5), we were able to assess these indexes of the LV contractile function during acute AF, and found that the values were similar to those obtained during occlusion of the inferior vena cava (IVC) at the baseline state. During rapid ventricular pacing (140 or 160 bpm), the indices of LV contractile function increased due to the force-frequency relation (4.56 +/- 1.85, Ees baseline; 6.42 +/- 2.54*+, Ees pacing; 5.15 +/- 2.01 mmHg/ml, Ees AF; *P < 0.05 vs baseline, +P < 0.05 vs. AF)(4.73 +/- 0.48, Ksm baseline; 6.24 +/- 1.12*+, Ksm pacing; 3.99 +/- 1.14, Ksm AF; *P < 0.05 vs baseline, +P < 0.05 vs AF). In a study of chronic clinical AF in patients without heart disease (lone AF, n = 7), the indexes of LV contractile function were preserved compared with those of control patients (CTL, n = 10) obtained during IVC occlusion; the values were decreased in patients with both AF and dilated cardiomyopathy (AFDCM, n = 5)(2.5 +/- 1.1, Ees CTL; 2.4 +/- 0.4, Ees lone AF; 1.1 +/- 0.3 mmHg/ml*+, Ees AFDCM; *P < 0.05 vs CTL, +P < 0.05 vs lone AF)(5.3 +/- 1.8, Ksm CTL; 4.9 +/- 1.6, Ksm lone AF; 2.7 +/- 0.2*+, Ksm AFDCM; *P < 0.05 vs CTL, +P < 0.05 vs lone AF). Thus, during acute AF in dogs and in chronic AF patients, LV contractile function was assessed without load manipulation. In both the acute AF dogs and the chronic lone AF patients, LV contractile function was preserved, and in the AFDCM patients it was depressed.

Acute Disease↗
PubMed1998

[Pulmonary artery sling with tracheal stenosis--primary repair in infancy].

Between 1984 and 1996 five infants underwent surgical repair of pulmonary artery sling associated with severe congenital tracheal stenosis. All infants had symptoms of severe respiratory distress and three of them required ventilator support preoperatively ages ranged from 2 to 11 months (mean age 6 months). Complete tracheal rings were present in all patients as an associated lesion and right upper lobe tracheal bronchus in 3 patients. The length of tracheal stenosis ranged from 18 to 45 mm (median 40 mm). Three had associated intracardiac anomalies (Scimitar syndrome (1), VSD (1), double-outlet right ventricle with VSD (1), double-outlet right ventricle with pulmonary hypertension (1)). Surgical intervention was carried out through a right thoracotomy (1) or median sternotomy (4). Cardiopulmonary bypass (CPB) was used in 3 patients and extracorporeal membrane oxgenator (ECMO). In 1. All infants had reimplantation of the left pulmonary artery into the main pulmonary artery left anterior to the trachea. Four patients underwent simultaneous tracheoplasty using costal cartilage grafts and one had complete resection of obstructed trachea between the right upper lobe tracheal bronchus and carina. The length of resected trachea was about 30% of the entire length of the trachea. Three infants underwent simultaneous intracardiac repair. There was no hospital death. All were weaned from ventilatory support and extubated on 1 to 16 months (mean 4, 5 months) postoperatively. AS an additional procedure, aortopexy, removal of granulation tissue or balloon dilatation of the trachea were carried out in one patient each following tracheoplasty using cartilage grafts. There was one late death at 1 year postoperatively. Three of 4 survivors are doing well with no stridor. We adonostridor. We adovocate 1) early aggressive primary repair of pulmonary artery sling with tracheal stenosis, 2) concomitant repair of tracheal lesion and intracardiac anomalies whenever possible, 3) application of CPB or ECMO to avoid cumbersome intubation technique, and 4) utmost effort to perform tracheal resection and end-to-end anastomosis.

Anastomosis, Surgical↗