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Biomedical subjects

T Fujino

Publications and source records attributed to T Fujino.

At least 19 recordsLinked to original sources
PubMed2005

Menopausal status influences the relationship between serum ghrelin levels and fat mass in healthy women.

OBJECTIVE: To examine the relationships of fasting serum ghrelin levels to bone mass index (BMI) and body fat mass, focusing on the effects of menopausal status and changes in fat distribution in women after menopause. DESIGN: An observational study. PATIENTS: Fifty-nine pre-menopausal and 31 post-menopausal healthy Japanese women volunteers were enrolled in the present study. MEASUREMENTS: Total and regional body fat mass weight was measured by dual energy x-ray absorptiometry. Serum ghrelin was measured. Relationships of serum ghrelin levels to weight, BMI, total body and regional fat mass weight were separately examined in post-menopausal and pre-menopausal women. RESULTS: Serum ghrelin levels were significantly inversely correlated with weight (r = -0.377, p < 0.05, Pearson's correlation test), right arm fat mass (r = -0.408, p < 0.05), left arm fat mass (r = -0.386, p < 0.05), trunk fat mass (r = -0.361, p < 0.05) and total body fat mass (r = -0.383, p < 0.05) in the post-menopausal women but not in pre-menopausal women. CONCLUSIONS: Menopausal status may influence the relationship between serum ghrelin levels and fat mass in healthy women.

Adipose Tissue↗
PubMed2004

Bone mineral density of the lumbar spine is associated with TNF gene polymorphisms in early postmenopausal Japanese women.

We investigated the relationships between tumor necrosis factor (TNF) gene polymorphism, circulating TNF-alpha (TNF-alpha) concentrations, and bone mineral density (BMD) in the lumbar spine. TNF gene polymorphisms studied were the Nco I polymorphism within the first intron of TNF-beta (TNF-beta) and three single nucleotide polymorphisms in the promoter region of the TNF-alpha gene, at positions -857, -863, and -1031. Allelic variants of the TNF gene were identified using restriction fragment length polymorphism (RFLP) analysis in 177 postmenopausal Japanese women within 10 years after menopause, aged 56.4 +/- 4.5 years (mean +/- SD). A significantly higher prevalence of the alleles TNF-alpha-863A (20.3% versus 9.9%) and TNF-alpha-1031C (21.3% versus 12.4%) was seen in the low BMD group (Z-score < 0, n = 91) than in the high BMD group (0 < Z-score, n = 86). In genotype analysis, although difference did not reach a significant level, women with the rarest allelic variants, i.e., homozygous TNFbl, TNF-alpha-863A, and TNF-alpha-1031C, showed the lowest BMD Z-scores. Women with another rarest allelic variant, TNF-alpha-857T/T had significantly lower BMD Z-scores than did women with TNF-alpha-857C/T or -857C/C. The BMD Z-score decreased significantly with an increase in the total number of such rare alleles. Serum concentrations of TNF-alpha did not differ significantly among groups divided by genotypes. Multiple linear regression analysis revealed that the total number of rare alleles, in addition to the body mass index and the number of years since menopause, was an independent predictor of the BMD. These presumptive functional polymorphisms of the TNF gene may be associated with the lumbar spine BMD in early postmenopausal Japanese women.

Absorptiometry, Photon↗
PubMed2004

Improvement of scopolamine-induced memory impairment by Z-ajoene in the water maze in mice.

Z-ajoene, a major compound containing sulfur in oil-macerated garlic products, exhibited inhibitory effects against scopolamine-induced memory impairment in mice using the Morris water maze test. The effects of Z-ajoene were observed dose-dependently (0.25-25 mg/kg). At the highest dosage, the memory performance of mice was improved compared to normal mice. The acetylcholinesterase (AChE) activity in the brain was reduced by administration of Z-ajoene dose-dependently. However, alliin and diallyl disulfide, organosulfur compounds from garlic, did not improve memory performance nor AChE inhibitory effect. These results suggest that Z-ajoene may act on the cholinergic system and on memory impairment caused by excess activity of AChE.

Acetylcholinesterase↗
PubMed2004

The leptin receptor in human osteoblasts and the direct effect of leptin on bone metabolism.

It is important to elucidate whether the leptin receptor, especially the long signal-transducing form of the leptin receptor (OB-Rb) is expressed in human osteoblasts. We detected the expression of human OB-Rb in cultured commercially available human osteoblasts (NHOst cells) using real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). After confirming the expression of OB-Rb, we investigated the effect of leptin on NHOst cells. Leptin enhanced cell proliferation of the cells shown by the MTT assay. Furthermore, leptin changed the copy numbers of Bax and Bcl-2 mRNAs in the cultured cells as shown by real-time quantitative RT-PCR, although the effect was not consistent. Leptin did not change the production of osteocalcin and osteopontin by the cells. Leptin did not change the expression of OB-Rb mRNA in the cells. In conclusion, OB-Rb mRNA is expressed in cultured commercially available human osteoblasts. Leptin may have some effects on bone metabolism by directly modulating cell proliferation and apoptosis of osteoblasts in humans.

Apoptosis↗
PubMed2003

A gene for a Class II DNA photolyase from Oryza sativa: cloning of the cDNA by dilution-amplification.

Ultraviolet radiation induces the formation of two classes of photoproducts in DNA-the cyclobutane pyrimidine dimer (CPD) and the pyrimidine [6-4] pyrimidone photoproduct (6-4 product). Many organisms produce enzymes, termed photolyases, which specifically bind to these lesions and split them via a UV-A/blue light-dependent mechanism, thereby reversing the damage. These photolyases are specific for either CPDs or 6-4 products. Two classes of photolyases (class I and class II) repair CPDs. A gene that encodes a protein with class II CPD photolyase activity in vitro has been cloned from several plants including Arabidopsis thaliana, Cucumis sativus and Chlamydomonas reinhardtii. We report here the isolation of a homolog of this gene from rice (Oryza sativa), which was cloned on the basis of sequence similarity and PCR-based dilution-amplification. The cDNA comprises a very GC-rich (75%) 5; region, while the 3; portion has a GC content of 50%. This gene encodes a protein with CPD photolyase activity when expressed in E. coli. The CPD photolyase gene encodes at least two types of mRNA, formed by alternative splicing of exon 5. One of the mRNAs encodes an ORF for 506 amino acid residues, while the other is predicted to code for 364 amino acid residues. The two RNAs occur in about equal amounts in O. sativa cells.

Amino Acid Sequence↗
PubMed2003

Tegumentary papillae of Echinostoma caproni cercariae (Trematoda: Echinostomatidae).

Argentophilic staining and scanning electron microscopy were used to study the tegumentary papillae of Echinostoma caproni cercariae. The most abundant tegumentary papillae were uniciliate, but multiciliate papillae were also found, mainly on the ventral aspect of the oral collar. The distribution pattern of the papillae on the body and tail was in general similar to that seen in the cercariae of other 37-collar-spined Echinostoma species. Some differences were noted between E. caproni and the allopatric species, E. trivolvis. E. caproni has a greater number of papillae associated with the collar spines than does E. trivolvis. E. caproni has uniciliate papillae on the acetabulum, whereas E. trivolvis does not. Chaetotaxy is useful to distinguish subtle morphological differences in cercarial species in the 37-collar-spined Echinostoma complex.

Animals↗
PubMed2001

Genomic organization and transcription units of the human acyl-CoA synthetase 3 gene.

Acyl-CoA synthetases (ACSs) play an essential role in fatty acid metabolism. ACS3 is an arachidonate-preferring enzyme expressed in a wide range of human tissues including brain, heart, placenta, prostate, skeletal muscle, testis and thymus. As an initial step to understanding the transcriptional regulation of the human ACS3 gene, we analyzed the genomic organization and transcription units of the human ACS3 gene. Sequence analysis of genomic clones demonstrates that the human ACS3 gene spans at least 80.6 kb and contains 17 exons. The human ACS3 gene was mapped between the sequence-tagged site markers D2S360 and WI-21901. Sequence inspection of the 5'-flanking region revealed potential DNA elements including CCAAT, AP-1, Oct-1, GATAs, SRY, CdxA, Nkx-2.5, c-Myb, HSF2, NF-AT, AP-2, NF-Y, and p300. A minimal promoter region required for the expression of the human ACS3 gene in melanoma G361 cells was determined.

5' Flanking Region↗
PubMed2001

Roles of prostaglandin I(2) and thromboxane A(2) in cardiac ischemia-reperfusion injury: a study using mice lacking their respective receptors.

BACKGROUND: Prostaglandin (PG) I(2) and thromboxane (TX) A(2), the most common prostanoids in the cardiovascular system, are produced abundantly during cardiac ischemia/reperfusion (I/R); their roles in I/R injury, however, remain undetermined. We intended to clarify these roles of PGI(2) and TXA(2) using mice lacking the PGI(2) receptor, IP(-/-) mice, or the TXA(2) receptor, TP(-/-) mice. METHODS AND RESULTS: The left anterior descending coronary artery was occluded for 1 hour and then reperfused for 24 hours. The size of myocardial infarct in IP(-/-) mice was significantly larger than that in wild-type mice, although the size of the area at risk was similar between the 2 groups of mice. In contrast, there was no such difference between TP(-/-) and wild-type mice. To further determine whether PGI(2) and TXA(2) act directly on the cardiac tissue or indirectly through their action on blood constituents, we perfused excised heart according to the Langendorff technique. The isolated heart was then subjected to global ischemia followed by reperfusion. In IP(-/-) mice, developed tension and coronary flow rate during reperfusion were significantly lower and release of creatine kinase was significantly higher than those in wild-type mice. There were no such differences, however, between TP(-/-) and wild-type mice. CONCLUSIONS: PGI(2), which was produced endogenously during cardiac I/R, exerts a protective effect on cardiomyocytes independent of its effects on platelets and neutrophils. In contrast, TXA(2) has little role in the cardiac I/R injury.

Adenosine Triphosphate↗
PubMed2001

Exon/intron organization and transcription units of the human acyl-CoA synthetase 4 gene.

Acyl-CoA synthetase 4 (ACS4) is an arachidonate-preferring isozyme of ACS family predominantly expressed in steroidogenic tissues. Isolation and characterization of genomic clones encoding human ACS4 revealed that the genomic organization of the gene. The human ACS4 gene spans approximately 90 kb and consists of 16 exons. Sequence inspection of the 5'-flanking region revealed potential DNA elements including GATAs, p300, AP-4, SRY, CREB and MyoD. A minimal promoter region required for the expression of ACS4 in HeLa S3 cells was determined. The human ACS4 gene was mapped between the STS markers, WI-17685 and CHLC.GATA81B07 on Xq22-23 region.

Amino Acid Sequence↗
PubMed2001

Molecular identification and characterization of two medium-chain acyl-CoA synthetases, MACS1 and the Sa gene product.

In this study, we identified and characterized two murine cDNAs encoding medium-chain acyl-CoA synthetase (MACS). One, designated MACS1, is a novel protein and the other the product of the Sa gene (Sa protein), which is preferentially expressed in spontaneously hypertensive rats. Based on the murine MACS1 sequence, we also identified the location and organization of the human MACS1 gene, showing that the human MACS1 and Sa genes are located in the opposite transcriptional direction within a 150-kilobase region on chromosome 16p13.1. Murine MACS1 and Sa protein were overexpressed in COS cells, purified to homogeneity, and characterized. Among C4-C16 fatty acids, MACS1 preferentially utilizes octanoate, whereas isobutyrate is the most preferred fatty acid among C2-C6 fatty acids for Sa protein. Like Sa gene transcript, MACS1 mRNA was detected mainly in the liver and kidney. Subcellular fractionation revealed that both MACS1 and Sa protein are localized in the mitochondrial matrix. (14)C-Fatty acid incorporation studies indicated that acyl-CoAs produced by MACS1 and Sa protein are utilized mainly for oxidation.

Amino Acid Sequence↗
PubMed2001

Transcriptional regulation of the murine acetyl-CoA synthetase 1 gene through multiple clustered binding sites for sterol regulatory element-binding proteins and a single neighboring site for Sp1.

Cytosolic acetyl-CoA synthetase (AceCS1) activates acetate to supply the cells with acetyl-CoA for lipid synthesis. The cDNA for the mammalian AceCS1 has been isolated recently, and the mRNA was shown to be negatively regulated by sterols in cultured cells. In the current study, we describe the molecular mechanisms directing the sterol-regulated expression of murine AceCS1 by cloning and functional studies of the 5'-flanking region of the AceCS1 gene. An AceCS1 promoter-reporter gene (approximately 2.1 kilobase pairs) was negatively regulated when sterols were added to the medium of cultured cells, and the promoter was markedly induced by co-transfection of a plasmid that expresses the transcriptionally active nuclear form of either sterol regulatory element-binding protein (SREBP)-1a or -2 in HepG2 cells. Sequence analysis suggested that the AceCS1 promoter contains an E-box, two putative CCAAT-boxes, eight sterol regulatory element (SRE) motifs, and six GC-boxes. Gel shift assays demonstrated that all eight SRE motifs bound purified SREBP-1a in vitro with similar affinity. Luciferase reporter gene assays revealed that sterol regulation was critically dependent on three closely spaced SRE motifs and an adjacent GC-box. However, mutation of two putative upstream CCAAT-boxes did not affect SREBP dependent activation. Electrophoretic mobility "supershift" analyses confirmed that both Sp1 and Sp3 bound to the critical GC-box. In addition, transfection studies in Drosophila SL2 cells demonstrated that SREBP synergistically activated the AceCS1 promoter along with Sp1 or Sp3 but not with nuclear factor-Y.

Acetate-CoA Ligase↗
PubMed2001

Abnormal uterus with polycysts, accumulation of uterine prostaglandins, and reduced fertility in mice heterozygous for acyl-CoA synthetase 4 deficiency.

Arachidonate released by various stimuli is rapidly reesterified into membrane phospholipids initiated by acyl-CoA synthetase (ACS) and subsequent acyl-transfer reactions. ACS4 is an arachidonate-preferring enzyme abundant in steroidogenic tissues and postulated to modulate eicosanoid production. Female mice heterozygous for ACS4 deficiency become pregnant less frequently and produce small litters with extremely low transmission of the disrupted alleles. Striking morphological changes, including extremely enlarged uteri and lumina filled with numerous proliferative cysts of various sizes, were detected in ACS4+/- females. Furthermore, marked accumulation of prostaglandins was seen in the uterus of the heterozygous females. These results indicate that ACS4 modulates female fertility and uterine prostaglandin production.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Prognostic significance of combined conventional and immunocytochemical cytology for peritoneal washings in endometrial carcinoma.

BACKGROUND: Noncancerous cells simulating adenocarcinoma cells may interfere with the analysis of peritoneal cytology (PC) in patients with endometrial carcinoma. Immunocytochemistry (ICC) may improve the diagnosis of PC. METHODS: PC slides from 115 patients with endometrial carcinoma were reviewed. Suspicious or positive cell clusters were recovered with a cell transfer method and were subjected to ICC for MOC-31, cytokeratin 5/6, and p53. Conventional Papanicolaou staining and ICC results were compared directly on the same cells. RESULTS: By combined conventional and immunocytochemical PC (CONV-ICC-PC), cytodiagnosis was positive in 18 of 115 patients (15.7%) and suspicious in 3 of 115 patients (2.6%). According to a multivariate Cox regression analysis of patients with tumors confined to the uterus that included grade, myometrial invasion, cervical involvement, and CONV-ICC-PC, only CONV-ICC-PC was an independent prognostic factor (P < 0.05). A multivariate analysis for all of the patients studied that compared CONV-ICC-PC with staging variables revealed that only peritoneal metastasis (P < 0.0001) and lymph node metastasis (P < 0.01) were independent prognostic factors. When peritoneal metastases were excluded, CONV-ICC-PC (P < 0.01) and lymph node metastasis (P < 0.0025) were the independent prognostic factors. By cell transfer and p53 immunostaining in samples from 14 patients with malignant cells in their peritoneal washings, no deaths occurred among 5 patients with negative p53, whereas 5 of 9 patients with positive p53 died of disease at the time of data analysis. CONCLUSIONS: MOC-31 immunostaining improves the diagnosis of PC in endometrial carcinoma. Positive PC is an important prognostic factor for patients with endometrial carcinoma confined to the uterus. The p53 positive cells in PC have possible prognostic significance.

Adult↗
PubMed2001

Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate.

Using peptide sequences derived from bovine cardiac acetyl-CoA synthetase (AceCS), we isolated and characterized cDNAs for a bovine and murine cardiac enzyme designated AceCS2. We also isolated a murine cDNA encoding a hepatic type enzyme, designated AceCS1, identical to one reported recently (Luong, A., Hannah, V. C., Brown, M. S., and Goldstein, J. L. (2000) J. Biol. Chem. 275, 26458-26466). Murine AceCS1 and AceCS2 were purified to homogeneity and characterized. Among C2-C5 short and medium chain fatty acids, both enzymes preferentially utilize acetate with similar affinity. The AceCS2 transcripts are expressed in a wide range of tissues, with the highest levels in heart, and are apparently absent from the liver. The levels of AceCS2 mRNA in skeletal muscle were increased markedly under ketogenic conditions. Subcellular fractionation revealed that AceCS2 is a mitochondrial matrix enzyme. [(14)C]Acetate incorporation indicated that acetyl-CoAs produced by AceCS2 are utilized mainly for oxidation.

Acetate-CoA Ligase↗
PubMed2001

Relationship between serum lipoprotein(a) level and thrombin generation to the circadian variation in onset of acute myocardial infarction.

A high incidence of acute myocardial infarction (AMI) has been reported between 06:00 and 12:00 h. This may be related to an abnormality in hemostasis. An association has been founded between the serum lipid level and coronary atherosclerosis, as well as the serum lipid level and a hemostatic abnormality. We investigated the association between the time of AMI, the level of serum lipid, and of hemostatic factor. Of the 42 subjects evaluated retrospectively, 20 had experienced an AMI between 06:00 and 12:00 h (group A), while 22 had developed an AMI during some other period (group B). All patients received emergency coronary angiography, which identified a total occlusion of coronary artery in the proximal portion of the left antecedent branch. The serum level of several lipid factors and of hemostatic factors were compared between the two groups. Characteristics of patients were similar in both groups. The serum levels of lipoprotein(a) (Lp(a)) and of thrombin-antithrombin III complex (TAT) were higher in group A than in group B, respectively. The level of other factors were similar in both groups. Group A showed a significant correlation between the level of Lp(a) and TAT, with a tendency (not statistically significant), toward a positive correlation between Lp(a) and PAI-1, and a negative correlation between Lp(a) and t-PA. In a subgroup that experienced AMI in the early morning, a higher level of Lp(a) was associated with an elevation of TAT, a marker for thrombin generation, and with the level of fibrinolytic factor. This suggests that Lp(a) is closely related to the increase in the early morning incidence of AMI via a change in the prothrombotic state.

Antithrombin III↗
PubMed2001

Inhibition of myeloid differentiation by Hoxa9, Hoxb8, and Meis homeobox genes.

OBJECTIVE: The homeobox gene Hoxb8 is activated in the murine myelomonocytic cell line WEHI-3B as a result of intracisternal A particle integration. Cooperative activation between Hoxa9 and Meis1 is induced by retroviral integration in BXH2 murine myeloid leukemias and the myeloid leukemia cell line M1. The present study was conducted to examine possible Meis gene activation and cooperative DNA binding of homeobox proteins in WEHI-3B and to reveal the specific role of Hox and Meis genes in myeloid differentiation. MATERIALS AND METHODS: Northern blot analysis and reverse transcriptase polymerase chain reaction were performed to examine homeobox genes expression. Electrophoretic mobility shift assay was performed to evaluate DNA binding of homeobox proteins. Myeloid differentiation of 32Dcl3 was induced by granulocyte colony-stimulating factor. RESULTS: Meis2 was coactivated with Hoxb8 in WEHI-3B cells. DNA-protein complexes including Hox, Meis, and Pbx were observed in WEHI-3B and 32Dcl3. Expression and the DNA-binding complex of Hoxa9, Hoxb8, Meis1, and Meis2 were down-regulated during myeloid differentiation of 32Dcl3 cells. Enforced expression of Hox or Meis genes inhibited myeloid differentiation of 32Dcl3. CONCLUSION: The results indicate that Meis2 is an important Meis gene for myeloid leukemogenesis and that Hox and Meis are important genes for myeloid leukemogenesis through differentiation block.

Animals↗
PubMed2001

Histopathological prognostic factors of adult granulosa cell tumors of the ovary.

BACKGROUND: The prognostic factors of adult granulosa cell tumor (AGCT) have not been well defined. METHODS: In 27 AGCT patients, we examined clinical stage, microscopic patterns, mitotic index (MI), and lymph-vascular space invasion (LVSI) to determine whether these factors were related to disease-free survival (DFS) of patients with AGCT. We also performed immunohistochemical examination for p53. RESULTS: Seventeen cases represented stage I tumors, four stage II, five stage III, and one stage IV. Patients with stage I disease had more favorable prognosis than those with stage II to IV disease (p=0.034). There was no relation between the microscopic patterns and the DFS. The MI, which was categorized into < or =3/10 high power field (HPF) and > or =4/10 HPF, was significantly related to patients DFS (p<0.0005). The DFS time for patients with moderate or prominent LVSI was significantly shorter than that for patients with no or minimal LVSI (p<0.0001). By multivariate analysis, MI and LVSI were shown to be independent prognostic factors. Five of seven patients with recurrent tumor had extrapelvic spread; two in the abdominal cavity and three in the liver. CONCLUSION: The results of this study suggest that prognosis for patients with AGCT depends on the MI and LVSI. During the follow-up period of patients, they need to be examined for distant metastasis including liver.

Adolescent↗