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Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 307 records · Page 17Linked to original sources

Relationship between serum leptin and fatty liver in Japanese male adolescent university students.

OBJECTIVE: The aim of this study was to elucidate the relationship between serum leptin levels and fatty liver in male adolescents. METHODS: We investigated the relationship between the concentration of circulating leptin and fatty liver by measuring the serum concentration of leptin in 284 male students who received the matriculation health examination in Okayama University in 1996 (n = 197; age, 18-20 yr) or 1997 (n = 87; age, 18-20 yr). RESULTS: Serum leptin levels correlated positively with body mass index (BMI), percent body fat (%FAT), thickness of skin fold (TSF), and serum concentration of ALT in 197 subjects. Examination of serum leptin in 67 subjects with BMI > or = 24.2 but < 28.6 kg/m2 showed a progressively higher levels in subjects with high serum ALT. Serum leptin levels in subjects with abnormally high serum ALT (> or = 37 IU/L) were significantly higher (p < 0.05) than in subjects with normal serum ALT, independent of BMI, %FAT, and TSF. Serum leptin levels were also significantly higher in subjects with fatty liver (detected by abdominal ultrasonography), independent of BMI and %FAT, compared with subjects without fatty liver. Stepwise multiple regression analysis showed that serum leptin level was an independent risk factor for fatty liver. In addition, serum leptin levels correlated with serum ALT (r = 0.518; p < 0.0005) and cholinesterase (r = 0.511; p < 0.0005) levels in 48 subjects with fatty liver. CONCLUSIONS: Our results demonstrated that serum leptin concentrations are high in male adolescents with simple obesity and are associated with high serum ALT or fatty liver, independent of BMI and %FAT, suggesting that the concentration of circulating leptin correlates with fatty liver caused by accumulation of visceral fat.

Adipose Tissue↗

Characterization of binding sequences for butyrolactone autoregulator receptors in streptomycetes.

BarA of Streptomyces virginiae is a specific receptor protein for a member of butyrolactone autoregulators which binds to an upstream region of target genes to control transcription, leading to the production of the antibiotic virginiamycin M(1) and S. BarA-binding DNA sequences (BarA-responsive elements [BAREs]), to which BarA binds for transcriptional control, were restricted to 26 to 29-nucleotide (nt) sequences on barA and barB upstream regions by the surface plasmon resonance technique, gel shift assay, and DNase I footprint analysis. Two BAREs (BARE-1 and BARE-2) on the barB upstream region were located 57 to 29 bp (BARE-1) and 268 to 241 bp (BARE-2) upstream from the barB translational start codon. The BARE located on the barA upstream region (BARE-3) was found 101 to 76 bp upstream of the barA start codon. High-resolution S1 nuclease mapping analysis revealed that BARE-1 covered the barB transcription start site and BARE-3 covered an autoregulator-dependent transcription start site of the barA gene. Deletion and mutation analysis of BARE-2 demonstrated that at least a 19-nt sequence was required for sufficient BarA binding, and A or T residues at the edge as well as internal conserved nucleotides were indispensable. The identified binding sequences for autoregulator receptor proteins were found to be highly conserved among Streptomyces species.

Autoreceptors↗

Antibodies to human gastric epithelial cells and heat shock protein 60 in Helicobacter pylori positive mucosa associated lymphoid tissue lymphoma.

BACKGROUND: Development of gastric mucosa associated lymphoid tissue (MALT) lymphoma is thought to be closely associated with host immune reactions to Helicobacter pylori. AIM: To investigate humoral immune responses in patients with MALT lymphoma to antigens shared by H pylori and human gastric epithelial cells. METHODS: Sera were obtained from H pylori positive patients with MALT lymphoma (n = 11) or other gastroduodenal diseases (peptic ulcer, n = 40; non-ulcer dyspepsia, n = 20) and from H pylori negative healthy control subjects (n = 10). Antibodies to HGC-27 human gastric epithelial cells and human recombinant heat shock protein (Hsp) 60 were examined using an enzyme linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Antibody titres to HGC-27 cells were significantly elevated in H pylori positive patients with MALT lymphoma when compared with titres in patients with other gastroduodenal diseases and in healthy subjects. Immunoblotting of sera from patients with MALT lymphoma often detected a band with a molecular mass corresponding to Hsp60, and both ELISA and immunoblotting showed elevated antibody titres to the recombinant human Hsp60. Antigenic similarity between Hsp60 and H pylori HspB was documented by immunoblotting experiments. CONCLUSIONS: Autoantibodies reactive with host gastric epithelial cells are often increased in MALT lymphoma, and Hsp60 is a major target antigen. Immune responses induced by immunological cross reactivity between H pylori HspB and human Hsp60 in gastric epithelium may be involved in the development of MALT lymphoma.

Adult↗

Decreased amplitude of left ventricular posterior wall motion with notch movement to determine the left posterior septal accessory pathway in Wolff-Parkinson-White syndrome.

OBJECTIVE: To determine preoperatively, by analysing asynchronous left ventricular wall motion, whether to approach through the right ventricle or the left ventricle when carrying out catheter ablation of the accessory pathway in Wolff-Parkinson-White syndrome, especially in patients with the pathway located on the septum. METHODS: 73 patients with manifest Wolff-Parkinson-White syndrome who underwent successful catheter ablation were studied. Location of accessory pathway was classified as right ventricular side: right anterior paraseptum, right anterior, right lateral, right posterior, anterior septum, midseptum, right posterior septum; left ventricular side: left posterior septum, left posterior, left lateral, left anterior. Asynchronous systolic wall motion was analysed by cross sectional echocardiography. RESULTS: Echocardiography showed that the amplitude of left ventricular posterior systolic wall motion was reduced when the pathway was located on the left ventricular side as opposed to the right ventricular side (mean (SD), 11.1 (1.7) v 12.9 (1.1) mm, p < 0.001), especially in patients with left posterior septal accessory pathway (9.7 (0.8) mm). There were no overlapping values between the left posterior septal accessory pathway and the right ventricular side accessory pathway. Posterior wall notch motion was observed in all patients with a left posterior septal accessory pathway (9/9), but not at all in patients with pathways located on the right ventricular side of the septum. In patients with a septal accessory pathway, an ECG algorithm provided poor information (relatively low sensitivity, specificity, and predictive value) for determining whether the subsite faced either the left (left posterior septum) or the right ventricle (anterior septum, midseptum, right posterior septum). CONCLUSIONS: Decreased amplitude of left ventricular posterior wall motion with notch movement is an important finding for accessory pathways located on the left posterior septum. These findings provided clinically useful information for determining whether to approach catheter ablation from the right or the left ventricle.

Adolescent↗

Suppressive effect of norzoanthamine hydrochloride on experimental osteoporosis in ovariectomized mice.

Norzoanthamine is an alkaloid isolated from a colonial zoanthid. We examined the effects of norzoanthamine hydrochloride on bone weight, strength and morphology in ovariectomized mice, a postmenopausal osteoporosis model. Norzoanthamine hydrochloride significantly suppressed the decrease in femoral weight and bone biomechanical parameters caused by ovariectomy without an increase in uterine weight. This means that norzoanthamine hydrochloride does not have an estrogen-like effect on reproductive organs. Morphological observations of longitudinally ground sections of the humeri showed that norzoanthamine hydrochloride administration (2 mg/kg/d, p.o.) completely suppressed the loss of trabecular bone. Furthermore, norzoanthamine hydrochloride thickened the cortical bone. Based on these results, norzoanthamine hydrochloride may act as both a suppressor of bone resorption and an enhancer of bone formation in vivo.

Alkaloids↗

Steady-state inhibitory kinetic studies on the ligand binding modes of Aspergillus niger glucoamylase.

Inhibitory activities of 1-deoxynojirimycin and gluconolactone on Aspergillus niger glucoamylase were studied in relation to the subsite structure of the enzyme. Although both of these inhibitors are considered to bind at subsite 1 of the enzyme active site, 1-deoxynojirimycin showed competitive type inhibition but gluconolactone was a mixed type (or noncompetitive type) inhibitor for the hydrolysis of p-nitrophenyl alpha-D-glucoside. The former type of inhibition suggested that the main binding mode of the substrate was productive, but the latter, nonproductive. A possible way of explaining these apparent inconsistent results is to assume that the main binding mode of the substrate is productive and gluconolactone forms a nonproductive ternary complex with the enzyme and the substrate.

1-Deoxynojirimycin↗

(2E,6R)-8-hydroxy-2,6-dimethyl-2-octenoic acid, a novel anti-osteoporotic monoterpene, isolated from Cistanche salsa.

(2E,6R)-8-Hydroxy-2,6-dimethyl-2-octenoic acid [(R)-HDOA], a novel monoterpene from Cistanche salsa, a Chinese herb, was found to be an anti-osteoporotic compound. The extract of Cistanche salsa significantly suppressed the bone weight loss in ovariectomized mice, a postmenopausal osteoporosis model. The active substance was then purified by using this osteoporotic model and the chemical structure was determined. The active compound from Cistanche salsa, (R)-HDOA, suppressed the decrease of bone weight and the mechanical strength in the ovariectomized mice. Furthermore, (R)- and (S)-HDOA were synthesized and the activity of each was evaluated. (R)-HDOA suppressed the bone weight loss, although (S)-HDOA did not showed any activity.

Animals↗

Molecular cloning and expression of the gene encoding a phospholipase A1 from Aspergillus oryzae.

Phospholipase A1 (PLA1) is a hydrolytic enzyme that catalyzes removal of the acyl group from position 1 of lecithin to form lysolecithin. The genomic DNA and cDNA encoding PLA1 from Aspergillus oryzae were cloned with the mixed deoxyribonucleotide-primed polymerase chain reaction. The PLA1 gene is composed of 1,056 bp and has four exons and three short introns (63, 54, and 51 bp). The deduced amino acid sequence of PLA1 contained the N-terminal sequence of the mature PLA1 analyzed by Edman degradation. PLA1 cDNA has an open reading frame of 885 bp encoding the PLA1 precursor of 295 amino acid residues. The mature PLA1 is composed of 269 amino acid residues, and a prepro-sequence of 26 amino acid residues is at the N-terminal region of the PLA1 precursor. PLA1 has two possible N-glycosylation sites (Asn27 and Asn55). PLA1 has a consensus pentapeptide (-Gly-His-Ser-Xaa-Gly-), which is conserved in lipases. The amino acid sequence of PLA1 showed 47% identity with that of mono- and diacylglycerol lipase from Penicillium camembertii. The PLA1 cDNA was expressed in Saccharomyces cerevisiae KS58-2D, indicating the cloned gene to be functional.

Amino Acid Sequence↗

Clinical implication of left precordial T wave inversions in the presence of complete right bundle branch block.

This study was designed to elucidate whether left precordial negative T waves are electrocardiographic indicators for the diagnosis of hypertrophic cardiomyopathy (HCM) even in the presence of complete right bundle branch block (CRBBB). In 7 consecutive patients with CRBBB accompanied by negative T waves in at least one of the left precordial leads (V4, V5, V6, maximal negativity; 1.06 +/- 0.40 mVol) (left precordial negative T wave group) and in 15 randomly selected CRBBB patients without left precordial T wave inversions (control group), echocardiography was performed to rule out underlying diseases causing left ventricular overload and to identify candidates for magnetic resonance (MR) imaging. None had anginal pain indicating ischemic heart disease. When 2-dimensional echocardiography indicated left ventricular hypertrophy with wall thickness > or = 15 mm, the magnitude and distribution of hypertrophy were scrutinized on contiguous left ventricular MR short-axis images. The diagnostic criterion of HCM was the demonstration of hypertrophy with a wall thickness of 20 mm or more on the left ventricular MR short-axis images. All patients in the left precordial negative T wave group had negative T waves in both I (negativity; 0.27 +/- 0.17 mVol) and aVL (negativity; 0.23 +/- 0.14 mVol), whereas none in the control group did. The diagnostic criterion for HCM was fulfilled in six patients in the left precordial negative T wave group. However there were no patients who fulfilled the criterion in the control group. Negative T waves were recorded in the I (negativity; 0.30 +/- 0.17 mVol), aVL (negativity; 0.25 +/- 0.14 mVol), V4 (negativity; 1.03 +/- 0.46 mVol), V5 (negativity; 0.83 +/- 0.37 mVol) and V6 leads (negativity; 0.31 +/- 0.31 mVol) in all patients with HCM, while they were recorded in only 6% of the patients without HCM. In conclusion, the existence of left precordial negative T waves in the presence of CRBBB strongly indicates HCM.

Bundle-Branch Block↗

Molecular forms of circulating adrenomedullin in patients with congestive heart failure.

In the biosynthesis of adrenomedullin (AM), an intermediate form, AM(1-52)-glycine-COOH (iAM), is cleaved from proAM and subsequently processed to a biologically active mature form, AM(1-52)-NH2 (mAM), by enzymatic amidation. We recently reported that immunoreactive AM in human plasma consists of mAM and iAM. To clarify the pathophysiological roles of mAM and iAM in heart failure, we established an assay method to specifically detect mAM, and we determined the plasma concentrations of mAM and iAM in 68 patients with congestive heart failure (CHF). The plasma mAM concentrations of the CHF patients classified as being class I or II of New York Heart Association (NYHA) functional classification were significantly greater than those of the 28 healthy controls, and a further increase was noted in the class III or IV patients. Similar increases in plasma iAM were also observed in these patients compared with controls. The increased plasma mAM and iAM in 12 patients with exacerbated CHF were significantly reduced by treatment of their CHF for 7 days. In addition, the plasma concentrations of both mAM and iAM were significantly correlated with pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, cardiothoracic ratio, heart rate, and the plasma concentrations of atrial and brain natriuretic peptides in the CHF patients. Thus the plasma concentrations of both mAM and iAM were increased progressively in proportion to the severity of CHF. These results suggest that, though the role of iAM remains to be clarified, mAM acts against the further deterioration of heart failure in patients with CHF.

Adrenomedullin↗

Tuberous sclerosis associated with multiple hepatic lipomatous tumors and hemorrhagic renal angiomyolipoma.

We report a case of tuberous sclerosis associated with hepatic lipomatous tumors and renal angiomyolipomas. Abdominal ultrasonography revealed a high echoic large tumor in the left kidney. A provisional diagnosis of angiomyolipomas of the kidney was made based on computed tomography. Subsequent laparotomy revealed that the extracted tumor was renal angiomyolipoma. It was also revealed that there was an association with hepatic lipomatous tumors thought to be lipomas or angiomyolipomas by liver biopsy. Nearly half of all cases of angiomyolipoma in the kidney are reported as occasional association with tuberous sclerosis complex, but lipomatous tumors in the liver are rare.

Adult↗

New index for oxygen cost of contractility from curved end-systolic pressure-volume relations in cross-circulated rat hearts.

We have already reported the linear oxygen consumption per beat (VO(2))-systolic pressure-volume area (PVA) relation from the curved left ventricular (LV) end-systolic pressure-volume relation (ESPVR) in the cross-circulated rat heart. The VO(2) intercept (PVA-independent VO(2)) is primarily composed of VO(2) for Ca(2+) handling in excitation-contraction (E-C) coupling and basal metabolism. The aim of the present study was to obtain the oxygen cost of LV contractility that indicates VO(2) for Ca(2+) handling in E-C coupling per unit LV contractility change in the rat heart. Oxygen cost of LV contractility is obtainable as a slope of a linear relation between PVA-independent VO(2) and LV contractility. We obtained a composite VO(2)-PVA relation line at a mid-range LV volume (mLVV) under gradually enhanced LV contractility by stepwise increased Ca(2+) infusion and thus the gradually increased PVA-independent VO(2) values. As a LV contractility index, we could not use E(max) (ESP-V ratio; ESP/ESV) for the linear ESPVR because of the curved ESPVR in the rat LV. A PVA at a mLVV (PVA(mLVV)) has been proposed as a good index for assessing rat LV mechanoenergetics. Since the experimentally obtained PVA(mLVV) was not triangular due to the curved ESPVR, we propose an equivalent ESP-V ratio at a mLVV, (eESP/ESV)(mLVV), as a LV contractility index. This index was calculated as an ESP-V ratio of the specific virtual triangular PVA(mLVV) that is energetically equivalent to the real PVA(mLVV). The present approach enabled us to obtain a linear relation between PVA-independent VO(2) and (eESP/ESV)(mLVV) and the oxygen cost of LV contractility as the slope of this relation.

Animals↗

Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion.

Leptin is an adipocyte-derived blood-borne satiety factor that acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. We have demonstrated that the hypothalamic arcuate nucleus (Arc) is a primary site of the satiety effect of leptin (Neurosci Lett 224:149-152, 1997). To explore the hypothalamic pathway of sympathetic activation of leptin, we examined the effects of a single intravenous or intracerebroventricular injection of recombinant human leptin on catecholamine secretion in rats. We also examined the effects of direct microinjection of leptin into the ventromedial hypothalamus (VMH), Arc, paraventricular nucleus (PVN), and dorsomedial hypothalamus (DMH) in rats. To further assess whether sympathetic activation of leptin is mediated via the VMH, we also examined the effects of a single intravenous injection of leptin in VMH-lesioned rats. A single injection of leptin (0.25-1.0 mg i.v./rat or 0.5-2.0 pg i.c.v./rat) increased plasma norepinephrine (NE) and epinephrine (EPI) concentrations in a dose-dependent manner. Plasma NE and EPI concentrations were increased significantly when leptin was injected directly into the VMH but were unchanged when injected into the Arc, PVN, and DMH. Plasma NE and EPI concentrations were unchanged in VMH-lesioned rats that received a single intravenous injection of leptin. The present study provides evidence that a leptin-induced increase in catecholamine secretion is mediated primarily via the VMH and suggests the presence of distinct hypothalamic pathways mediating the satiety effect and sympathetic activation of leptin.

Animals↗

A murine stromal cell line promotes the expansion of CD34high+-primitive progenitor cells isolated from human umbilical cord blood in combination with human cytokines.

The in vitro expansion of CD34+ cells is important for clinical applications such as transplantation and gene therapy with CD34+ cells isolated from human umbilical cord blood. In the present study, we developed a xenogenic coculture system involving HUCB-CD34+ cells and a murine stromal cell line, HESS-5 cells, in the presence of recombinant human (rh) cytokines. We examined the effects of combinations of cytokines, such as rh-IL-3, rh-SCF, rh-granulocyte colony-stimulating factor (G-CSF), rh-granulocyte-macrophage-CSF and h-erythropoietin (EPO), on the expansion of CD34high+ cells and colony-forming progenitor cells (CFCs). The proliferation of CD34high+ cells and CFCs was dramatically promoted on coculture with HESS-5 cells, and the expansion ratio of the CD34high+ cells showed good correlation with that of high-proliferative potential colony-forming cells (HPP-CFCs). The most potent combination of cytokines in this xenogenic coculture system for the expansion of CD34high+ cells and HPP-CFCs was rh-IL-3 and rh-SCF. The proliferation of CD34high+ cells was supported in the presence of HESS-5 cells with direct cell contact, but not observed in the indirect coculture involving a microporous membrane. Furthermore, we developed a unique coculture method, designated as the bilayer coculture method, involving CD34+ cells and HESS-5 cells using a microporous membrane. This expansion system will be applicable to the expansion of the primitive progenitor cells of HUCB-CD34+ cells and is worthy of consideration for the clinical application of HUCB-CD34+ cells.

Animals↗

Maintenance of near-diploid karyotype of PA-1 human ovarian teratocarcinoma cells due to death of polyploid cells by chromosome fragmentation/pulverization.

Chromosome instability (polyploidy or aneuploidy) is one of the characteristics of malignant tumors. Human teratocarcinoma cell line PA-1, which was established more than 10 years ago, consists of a majority of near-diploid cells and a minority of polyploid cells, indicating that it is karyologically very stable. In the present study we investigated this genomic stability from the view point of cytogenetics. Cleavages and breaks in the chromosome were found in the metaphase of PA-1 polyploid cells, accompanied by the formation of polynucleosomal DNA fragments. These findings were absent in the near-diploid cells. In addition, polyploid cells did not show colony-formation ability by in situ analysis of cytogenetics in each colony. Thus, the maintenance of the near-diploid karyotype in PA-1 cells may be due to a blockage in the M-phase of the polyploid cells by functional mitotic checkpoints, if any, leading to cell death due to inability to enter the next cell cycle.

Chromosome Banding↗

Cytogenetic characteristics and p53 gene status of human teratocarcinoma PA-1 cells in 407-445 passages.

To study why the human teratocarcinoma cell line PA-1 maintains a stable near-diploid karyotype even after it has been cultured for more than twenty years, p53 gene status of the cell line in 407-445 passages were investigated in detail by DNA sequence analysis and a yeast function status assay. Direct sequence analysis of RT-PCR products showed both wild and mutated bands (p53 codon 239 mutation). Consistent with the above results, the functional assay showed that one allele of the p53 gene was active (wild), while the other was inactive (mutant). In addition, the PA-1 cells expressed the p21 protein to a lesser extent than normal human fibroblasts. Though many lines of evidence have shown that mutant p53 works dominant-negatively, our results suggest that mutation in a p53 allele alone can not induce cytogenetic instability.

Aneuploidy↗

[Eustachian tube function of adhesive tympanum--pre and post operative evaluation].

We examined the eustachian tube function of 48 patients with adhesive tympanum who had undergone operations. Preoperative tubal openings were observed and determined in 57% of these cases by the dynamic movement of the tympanic membrane, 35% by the impedance method, and 74% by the sonotubometry and was found to be lower than in healthy subject. Furthermore the tubal opening duration in sonotubometry was significantly shortened in patients with adhesive tympanum as compared to healthy subjects. However, in a few cases of adhesive tympanum, tubal opening was prolonged remarkably, and indicated a mixed tendency of stenotic and patulous types. Postoperative tubal opening was not seen in 90.9% of the cases as determined by the inflation-deflation test. Mucociliary function was poor in 81.3% of the cases. No remarkable differences were seen between cases of total adhesion and those of posterosuperior quadrant adhesion by any method. The condition of the tympanic membrane and the tympanic cavity after operation, and the eustachian tube function were not correlated in some cases and indicated possible involvement of other factors.

Adolescent↗