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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 145 records · Page 8Linked to original sources
PubMed2000

Reversal of intra-amniotic Chlamydia trachomatis antigen status.

Chlamydia trachomatis (CT) infection in pregnant women is related to unfavorable obstetric outcomes such as prematurity, intrauterine growth retardation, and stillbirth. A 22-year-old woman underwent transabdominal amniocentesis at 16 weeks of gestation (GW). A CT antigen test using polymerase chain reaction in the amniotic fluid was found to be positive, though the patient had no symptom of infection. Beginning at 20 GW, clarithromycin was orally administered at a dose of 400 mg/day for 2 weeks. The CT antigen test in amniotic fluid at 28 GW turned to a negative result. A female baby was vaginally born at 38 GW by spontaneous labor. The CT antigen test of her gastric contents showed a negative result and anti-CT IgM in umbilical cord blood was negative. Neither respiratory distress, pneumonia, nor conjunctivitis was detected. To the best of our knowledge, this case is the first report showing the reversal of the intra-amniotic CT antigen status by antibiotic treatment.

Adult↗
PubMed2000

Prediction of respiratory distress syndrome by the level of pulmonary surfactant protein A in cord blood sera.

The purpose of this study was to determine the utility of measuring the level of pulmonary surfactant protein A (SP-A) in cord blood sera to predict for respiratory distress syndrome (RDS). SP-A levels in cord blood sera from 48 infants born at gestational ages < 32 weeks were measured by a sandwich ELISA system. Mean value of SP-A in cord blood was 5.8 ng/ml in cases with RDS and 15.1 ng/ml in those without RDS (p = 0.002). The best cut-off point of cord blood SP-A to predict RDS was determined as 10 ng/ml. The sensitivity and the specificity of the cut-off point for predicting RDS were 81 and 76%, respectively. Multivariate regression analysis showed that high SP-A level in cord blood, premature rupture of the membranes longer than 24 h and heavy birth weight were all significantly related to the non-RDS outcome.

Birth Weight↗
PubMed2000

Plasma concentration of uroguanylin in patients on maintenance dialysis therapy.

BACKGROUND: Uroguanylin, originally isolated from urine, is a new natriuretic peptide. Its plasma level is increased in association with renal impairment and fluid retention in patients with renal diseases. METHODS: Uroguanylin concentrations were measured in patients on hemodialysis (HD, n = 76) and those on continuous ambulatory peritoneal dialysis (CAPD, n = 10) using a sensitive ra- dioimmunoassay for human uroguanylin. RESULTS: Plasma concentrations of immunoreactive (ir)-uroguanylin in the patients on HD and CAPD (212.0 +/- 17.4 and 245.3 +/- 39.5 fmol/ml) were significantly higher than the value for the normal controls (5.0 +/- 0.3 fmol/ml). Plasma ir-uroguanylin levels before the start of regular HD were correlated with predialysis excess weight based on their dry weights (r = 0.33, p < 0.01) and with dialysis duration (r = 0.26, p < 0.05). The plasma levels in patients with HD, for whom high-flux membranes were used, were decreased at the end of regular HD as compared with the prior levels (p < 0.05), but not in those who underwent HD with conventional membranes. CONCLUSION: These findings suggest that the plasma ir-uroguanylin level is related to the patient's volume status as well as renal impairment. Whether the accumulation of uroguanylin has a pathological effect has yet to be determined.

Adult↗
PubMed2000

Increased plasma levels of mature adrenomedullin in chronic glomerulonephritis.

Adrenomedullin (AM) is a potent vasodilative and natriuretic peptide that is processed from its precursor as the intermediate form, AM-glycine-COOH (iAM). Subsequently, iAM is converted to the biologically active mature form, AM(1-52)-CONH(2) (mAM), by enzymatic amidation. Using immunoradiometric assays that recognize total AM (tAM) and only mAM, we determined the plasma and urinary levels of mAM and iAM in patients with chronic glomerulonephritis (CGN). The plasma mAM concentration was significantly higher in the patients than in the controls (1.8 +/- 0.1 vs. 1.3 +/- 0.1 fmol/ml, p < 0.01), whereas the plasma iAM concentration of the CGN patients did not significantly differ from that of the controls (9.4 +/- 0.5 vs. 8.9 +/- 0.5 fmol/ml). Levels of urinary mAM excretion in the patients did not statistically differ from those of the controls (1. 6 +/- 0.4 vs. 2.0 +/- 0.3 fmol/mg creatinine), whereas urinary iAM excretion was significantly lower in the CGN patients (3.7 +/- 0.7 vs. 5.6 +/- 0.8 fmol/mg creatinine, p < 0.05). Urinary excretion levels of mAM significantly correlated with those of sodium (r = 0. 47, p < 0.05), whereas those of iAM did not. In conclusion, the plasma ratio of mAM to iAM is augmented in CGN patients, and mAM appears to be involved in the regulation of sodium. Therefore, determination of the mAM in addition to the tAM concentration is essential in CGN patients.

Adolescent↗
PubMed2000

Analyses of matrix metalloproteinases and their inhibitors in cyst fluid of serous ovarian tumors.

OBJECTIVES: Expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in serous tumors of the ovary was investigated to determine whether and how these proteolytic enzymes are associated with the progression of these tumors. METHODS: Cyst fluid of 24 serous ovarian tumors (8 adenocarcinomas, 2 borderline tumors and 14 adenomas) was analyzed using gelatin/casein zymography and enzyme-linked immunosorbent assay. RESULTS: Concentrations of MMP-9 and MMP-2 were statistically higher in serous adenocarcinomas than in serous adenomas (p < 0.01, p < 0.05, respectively), while the concentrations of TIMP-1 and TIMP-2 showed no significant difference between adenocarcinomas and adenomas. The molar ratio of TIMP-2/MMP-2 was lower in adenocarcinomas than in adenomas (p < 0.05). With gelatin zymography, the MMP-9 band was detected in all serous adenocarcinomas, but only in 8 of 14 serous adenomas (p = 0.05). Using casein zymography, MMP-7 was more frequently detected in serous adenocarcinomas (7/8) than in serous adenomas (4/14; p < 0.05). CONCLUSIONS: These observations indicate that matriolytic enzymes such as MMP-2, MMP-7 and MMP-9 are secreted into cyst fluid from serous adenocarcinoma tissues. In part, the aggressive invasion of serous carcinoma cells may be explained by the expression of matriolytic enzymes.

Adenoma↗
PubMed2000

Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression.

Steroidogenic acute regulatory (StAR) protein plays a critical role in the movement of cholesterol from the outer to the inner mitochondrial membrane. Steroidogenic factor 1 (SF-1) controls basal and cAMP-stimulated transcription of the StAR gene. The 1.3-kb StAR promoter has three SF-1 binding sites, and two consensus transcription factor Spl binding sequences near the two most distal SF-1 binding sites. Spl mediates cAMP-dependent transcription of steroidogenic P450 enzyme genes, raising the possibility of Sp1 involvement in cAMP regulation of the StAR gene. However, the mechanism of Spl-mediated, cAMP-stimulated responsiveness is not known. In this study, we elucidated the roles of Sp1 and SF-1 in the regulation of the human StAR gene promoter. We found that there was negligible promoter activity in a pGL2 StAR construct (-235 to +39) in which Spl and SF-1 binding sites were mutated in Y-1 adrenal tumor cells. An Sp1 binding site mutation (pGL2Sp1M) did not support promoter activity, suggesting that Spl cooperates with SF-1 in regulating StAR promoter function. In gel shift assays, the SF-1 binding site formed a complex with an SF-1-GST fusion protein and Spl. Coimmunoprecipitation cross-linking experiments indicated that SF-1 physically interacts with Sp1 in vitro. Finally, a mammalian two-hybrid system was employed to demonstrate that Spl and SF-1 associate in vivo. In conclusion, our data indicate that Spl and SF-1 physically interact and cooperate in the regulation of human StAR promoter activity.

Adrenal Cortex Neoplasms↗
PubMed2000

Phorbor myristate acetate induces NADPH oxidase activity of cytochalasin B-primed neutrophils through the protein kinase C-independent pathway.

We examined the effect of cytochalasin B (CB) or granulocyte colony stimulating factor (GCSF) on superoxide radical (O2-) production of neutrophils by phorbor myristate acetate (PMA)-stimulation. It was observed that O2- generation of intact and GCSF-treated neutrophils by PMA-stimulation showed a lag during the early stage, and was largely inhibited by 1-(5-isoquinoline-sulfonyl)-3-methyl-piperazine (200 microm) or GF109203X (GFX) (0.2 microM), but not by ethanol (1%) and wortmannin (100 nM). In contrast, O2- generation of CB-pretreated neutrophils by PMA-stimulation did not show a lag, but was less than that of intact cells, and was only minimally depressed by the above inhibitors, but was markedly depressed by the simultaneous addition of GFX and ethanol or GFX and wortmannin. Although translocation of p47phox and p67phox to the membrane fraction by PMA-stimulation of intact and GCSF-treated neutrophils occurred in parallel with O2- production, that of CB-treated neutrophils by PMA-stimulation was not always proportional to O2- production. These findings suggest that pretreatment of neutrophils with CB dramatically alters the PMA response of the cells; that is, the protein kinase C-dependent pathway is largely depressed, and a phospholipase D-dependent one for NADPH oxidase activation appears in CB-treated cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Screening for pyrimidine metabolism disorders using dried filter-paper urine samples: method development and a pilot study in Nagoya City, Japan.

A screening system for pyrimidine metabolism disorders by measurement with high-performance liquid chromatography using dried filter-paper urine samples is presented. This system permits the simultaneous determination of dihydrouracil, uracil, orotic acid and pseudouridine. The coefficient of variations for the four compounds on the filter-paper urine samples were 0.010 approximately 0.069 and the recoveries were 98.5 approximately 107.1%. The detection limits of the four compounds were 2 approximately 20 micromol/liter. The correlation between the filter-paper urine samples and liquid urine samples was excellent (0.938-0.988). We supeculated that this method could be used to detect pyrimidine metabolism disorders, such as dihydropyrimidinuria, dihydropyrimidine dehydrogenase deficiency and hereditary orotic aciduria. As a pilot study, we have analyzed dried filter-paper urine samples from 34, 200 healthy Japanese, and found three cases of dihydropyrimidinuria without clinical symptoms.

Drug Stability↗
PubMed2000

Unique electroencephalographic change of acute encephalopathy in glutaric aciduria type 1.

We report the peculiar serial electroencephalographic (EEG) findings in a 7-year-old boy with glutaric aciduria type 1 during an episode of acute encephalopathy. The patient developed Reye-like syndrome triggered by cellulitis. Cranial magnetic resonance imaging demonstrated diffuse softening of cerebral hemisphere. The EEG on the day following onset of acute encephalopathy showed suppression burst pattern including continuous 14-15 Hz rhythmic waves at first. Then, periodic synchronous discharge appeared and lasted for about 40 minutes. Periodic synchronous discharge finally disappeared and nearly total electrocerebral silence continued. There have been no reports indicating such a change of EEG in a short period. The serial EEG changes probably reflect the process of electrical death of neurons in cerebral hemispheres.

Acute Disease↗
PubMed2000

Catastrophic antiphospholipid antibody syndrome in systemic lupus erythematosus: an autopsy case report of a young woman.

Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of antiphospholipid syndrome (APS) characterized by disseminated microangiopathy that results in multiorgan failure. CAPS mainly occurs in association with systemic lupus erythematosus (SLE). Clinically, CAPS mimics disseminated SLE vasculitis, intravascular coagulation (DIC), and particularly thrombotic thrombocytopenic purpura (TTP). We describe an autopsy case of young woman with CAPS in SLE, which is difficult to differentiate from TTP secondary to SLE.

Adult↗
PubMed2000

Aneuploidy of sex chromosomes in basal cell carcinoma: its clonality and involvement in the development of carcinogenesis.

Although basal cell carcinoma (BCC) is a major skin cancer, the mechanism of carcinogenesis with regard to cytogenetic abnormalities has not been fully investigated. In the present study, we carried out cytogenetic analyses of 18 patients (9 male and 9 female) with BCC. Aneuploidy was seen by Q-banding method in more than half of the cases and was mostly loss of the sex chromosome. We also performed FISH to the interphase nuclei of various tissues and short-term cultured BCC cells. The frequency of sex chromosomal aneuploidy was significantly higher in all samples from BCC patients (peripheral blood lymphocytes, non-lesional tissues, BCC tumor tissues and cultured BCC cells) than in age-matched normal controls. In addition, we analyzed clonality of BCC tissues using a human androgen receptor gene assay and found uniparental pattern of inactive X-chromosomes. This indicates that BCC cells were monoclonal in origin and the development of BCC might be correlated with sex chromosomal aneuploidy, which acquired accumulation of genetic mutations.

Adult↗
PubMed2000

A phase III randomized study comparing oral doxifluridine and oral 5-fluorouracil after curative resection of gastric cancer.

To investigate the usefulness of oral doxifluridine (5'-DFUR), an active intermediate metabolite of capecitabine (XELODA), in gastric cancer patients after curative resection, we conducted a phase III randomized controlled study to compare oral 5'-DFUR and oral 5-fluorouracil (5-FU). 485 gastric cancer patients with Stage II or III operative findings at curative resection were registered and administered 5'-DFUR (460 mg/m2/day, daily, for two years) or 5-FU (115 mg/m2/day, daily, for the same period). Although no differences in overall survival or disease-free survival were detected, subset analysis showed 5'-DFUR was more effective in reducing peritoneal recurrence than 5-FU (p = 0.047), and in patients with Stage III or stage IIIb (histologic findings) in the 5'-DFUR group had more favorable disease-free survival curves and survival curves than the 5-FU group with similar stages.

Administration, Oral↗
PubMed2000

Alteration of CDKN2/p16 in human astrocytic tumors is related with increased susceptibility to antimetabolite anticancer agents.

A slowly proliferating cell fraction in tumors shows reduced sensitivity to cell cycle-dependent anticancer agents. To understand the molecular basis of drug resistance observed in brain tumors, we examined the relationship between alteration of p16, a cyclin dependent kinase inhibitor whose functions are frequently lost in many human gliomas, and chemosensitivity of tumor cells to various kinds of anticancer agents. Alterations of the p16 gene that include mutation(s) and homozygous deletion as well as p16 protein expression level, were examined in 56 specimens of astrocytic tumors. Their in vitro chemosensitivities to 30 kinds of anticancer agents were analyzed with flow cytometry which detects drug-induced cell death. We found that the alterations were correlated with increased sensitivity to antimetabolite anticancer agents but not with other kinds of agents, including alkylating agents, antibiotics, topoisomerase inhibitors and antimicrotubule agents. The present results suggest that p16 plays a role in determining chemosensitivity of brain tumors, depending on pharmacological mechanisms of anticancer agents. Proper understanding of the molecular machinery which regulates the chemosensitivity may contribute to the choice of anticancer agents for individual patients.

Antimetabolites, Antineoplastic↗
PubMed2000

Cancer regression induced by modified CTL therapy is regulated by HLA class II and class I antigens in Japanese patients with advanced cancer.

Autologous cancer-specific bulk CTLs are unlikely to be induced by in vitro CTL generation (ivtCTLG) using peripheral blood mononuclear cells (PBMCs) of cancer patients when autologous cancer cells are used as in vitro stimulators. However, autologous cancer-specific bulk CTLs are frequently activated when allogeneic cancer cells are used as in vitro stimulators, regardless of the type of cancer cell. We have developed a cancer-specific immunotherapy called modified CTL therapy, which involves adoptive immunotherapy of autologous cancer-specific bulk CTLs after active immunization of autologous or allogeneic cancer cells screened as in vitro stimulators according to their ability to induce autologous cancer-specific CTLs (ACS. CTLs). Cancer did not regress in patients in whom ACS.CTLs were not induced by ivtCTLG using the patients' PBMCs in therapy. Cancer regression, albeit temporary, occurred solely in patients under the immunological condition that ACS.CTLs were induced by ivtCTLG using PBMCs through the therapy. The induction of ACS.CTLs by ivtCTLG using patient PBMCs in therapy was related to patients' HLA class II antigens. HLA DR8 was seen more frequently in ACS.CTL-inducible patients than in ACS.CTL-uninducible patients (P=0.051). On the contrary, HLA DQ3 was seen more frequently in ACS.CTL-uninducible patients (P=0.055). On the other hand, the success in therapy, albeit temporary, was related mainly to patients' HLA class I antigens. HLA B61 was seen more frequently in patients whose therapy proved effective than in patients whose therapy proved ineffective (P=0.018). HLA Cw7 was seen more frequently in therapy-ineffective patients (P=0.040).

Adult↗
PubMed2000

The expansion of the CAG repeat in exon 1 of the human androgen receptor gene is associated with uterine endometrial carcinoma.

Uterine endometrial carcinoma is common among women. Several reports indicated that this cancer is influenced by androgens mediated through their receptors. The human androgen receptor gene contains a polymorphic CAG repeat in the coding region of exon 1. Other studies suggested a possible association between the CAG repeat of this gene and the development of several cancers. DNA samples isolated from 29 patients with sporadic endometrial cancer were analyzed for allelic changes in 12 highly polymorphic microsatellite loci on nine chromosomes, containing CAG repeat in the exon 1 of the androgen receptor gene. A significantly high rate of allelic change in the CAG repeat was observed (51.7%) in these patients, although the frequencies of additional loci were similar to those reported by others (0-22.2%). The changed alleles of the tumor tissue were always longer than that of normal tissue except in only one case. Since only one allele on the X chromosome is commonly active in female cells, a differential methylation assay was carried out by using genomic DNA cut with HpaII. In 14 of 15 cases, we found that the activated allele was longer in these samples from tumor tissues than those from normal tissue; in the remaining case, the length of this repeat was unchanged. The expression assays were done by using poly(A+) RNA from tumor and normal uterine tissues, revealing that an activated allele in these tumor tissues was longer than that in the normal tissues in all the cases examined. These findings suggest that expansions of the CAG repeat in the androgen receptor gene may play an important role in the carcinogenesis of uterine endometrial cells.

Alleles↗