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Biomedical subjects

S Fujii

Publications and source records attributed to S Fujii.

At least 217 records · Page 12Linked to original sources
PubMed1999

Conformational classification of functional nucleic acids.

The kink parameters would provide the tolerant aspect for irregular helical structure of nucleic acid. Using these kink parameters, the classification of conformation space was carried for the functional nucleic acid molecules. The kink parameters could afford us the simple structural aspects about the constructive parts of functional molecules. Local elastic kink phenomena can be classified by rod like models with the combination of kink parameters. The constructive parts, such as the stable tetra nucleotides loop, U-turn conformation and adenosine platform, were selected and the statistical analyses were carried on the parameters calculated by program BIOCON.

Base Sequence↗
PubMed1999

Roles of asp126 and asp156 in the enzyme function of sphingomyelinase from Bacillus cereus.

To elucidate the roles of conserved Asp residues of Bacillus cereus sphingomyelinase (SMase) in the kinetic and binding properties of the enzyme toward various substrates and Mg2+, the kinetic data on mutant SMases (D126G and D156G) were compared with those of wild type (WT) enzyme. The stereoselectivity of the enzyme in the hydrolysis of monodispersed short-chain sphingomyelin (SM) analogs and the binding of Mg2+ to the enzyme were not affected by the replacement of Asp126 or Asp156. The pH-dependence curves of kinetic parameters (1/Km and kcat) for D156G-catalyzed hydrolysis of micellar SM mixed with Triton X-100 (1:10) and of micellar 2-hexadecanoylamino-4-nitrophenylphosphocholine (HNP) were similar in shape to those for WT enzyme-catalyzed hydrolysis. On the other hand, the curves for D126G lacked the transition observed for D156G and WT enzymes. Comparison of the values and the shape of pH-dependence curves of kinetic parameters indicated that Asp126 of WT SMase enhances the enzyme's catalytic activity toward both substrates and its binding of HNP but not SM. The deprotonation of Asp126 enhances the substrate binding and slightly suppresses the catalytic activity toward both substrates. Asp156 of WT SMase acts to decrease the binding of both substrates and the catalytic activity to HNP but not SM. From the present study and the predicted three-dimensional structure of B. cereus SMase, Asp126 was thought to be located close to the active site, and its ionization was shown to affect the catalytic activity and substrate binding.

Aspartic Acid↗
PubMed1999

Expression of steroid receptors, Ki-67, and p53 in uterine leiomyosarcomas.

The expression of estrogen receptor (ER), progesterone receptor (PR), tumor suppressor oncogene p53, and Ki-67 was compared in uterine smooth muscle tumors, including leiomyosarcoma (LMS), tumor of uncertain malignant potential (UMP), cellular leiomyoma (CL), bizarre leiomyoma (BL), and usual leiomyoma (UL). ER and PR were expressed in all ULs. PR was expressed in UL irrespective of the phase of the menstrual cycle; this staining was also observed in CL, UMP, and BL, although BL showed variable staining for ER. Compared to these tumors, the expression of both ER and PR was markedly reduced in LMS. The results of ER and PR transcripts by reverse transcription-polymerase chain reaction were compatible with those of immunohistochemistry. The number of Ki-67 positive cells in LMS was significantly higher than in UMP, BL, CL, and UL. p53 immunoreactivity was seen in 10 of 14 LMSs, and missense mutation in the p53 gene was found in 4 of 10 LMSs. These results suggest that abnormal expression of ovarian steroid receptors, p53, and Ki-67 is frequently associated with LMS of the uterus.

Adult↗
PubMed1999

Infrequent occurrence of high-risk human papillomavirus and of p53 mutation in minimal deviation adenocarcinoma of the cervix.

To assess the occurrence of high-risk human papillomavirus (HPV) infection and p53 alterations in minimal deviation adenocarcinoma (MDA) of the uterine cervix, paraffin sections were used to investigate the presence of HPVs 16 and 18 and p53 expression and mutation in six cases of MDA. By polymerase chain reaction, only one case was positive for HPV 16 and none was positive for HPV 18. By in situ polymerase chain reaction in the case positive for HPV 16, HPV 16 was detected in a low-grade squamous intraepithelial lesion overlying the MDA but not in the MDA itself. All of the MDAs were negative or only focally positive for p53 by immunohistochemistry. Our polymerase chain reaction DNA sequencing study failed to detect p53 mutation in exons 5 to 8 in those cases focally positive for p53 expression. These results suggest that MDA may be associated only occasionally with the high-risk HPVs or with p53 gene alterations.

Adenocarcinoma↗
PubMed1999

Direct evidence of in vivo nitric oxide production and inducible nitric oxide synthase mRNA expression in the brain of living rat during experimental meningitis.

To detect endogenous nitric oxide (NO) produced in a rat bacterial meningitis model, the authors applied an electron paramagnetic resonance (EPR) NO-trapping technique. Iron complex with N,N-diethyldithiocarbamate were used as a trapping agent. Experimental meningitis was induced by a mixture of lipopolysaccharide and interferon-gamma. Sequential changes of NO formation under meningitis were observed in rat brain tissue by using X-band (9 GHz) EPR spectroscopy, and endogenous NO was detected in the head of a living rat with a 700-MHz EPR system. Inducible NO synthase mRNA expression in the brain tissues also was proven by using a reverse transcriptase-polymerase chain reaction technique.

Animals↗
PubMed1999

Biochemical properties potentially rendering human brain microvasculature vulnerable to proteolytic injury associated with the use of fibrinolytic drugs.

BACKGROUND: Determinants of predisposition to intracranial bleeding in response to the administration of thrombolytic drugs have not yet been well characterized. OBJECTIVE: To delineate factors involved, by characterizing susceptibility of human cerebral microvascular endothelium (HCME) to injury associated with inflammatory cytokines, levels of which are typically elevated in blood in patients who have suffered a myocardial infarction or stroke and been treated with thrombolytic drugs. METHODS: Elaboration of fibrinolytic system proteins by HCME exposed either to interleukin-1 beta or to tumor necrosis factor-alpha (TNF) in serum-free medium for 24 h was characterized. Cell-conditioned medium was assayed for tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor type 1--(PAI-1) by enzyme-linked immunosorbent assay. To determine whether the induction of u-PA was mediated by oxygen-centered radicals, the following were added to media: superoxide dismutase (a scavenger of O2-.), catalase (a scavenger of O2-. and H2O2) and dimethylthiourea (a scavenger of OH.). RESULTS: Interleukin-1 beta had no effect upon elaboration of fibrinolytic system proteins by HCME. By contrast, TNF selectively increased elaboration of u-PA. Accumulation of t-PA and PAI-1 remained unchanged. Accumulation of u-PA was inhibited by cycloheximide, implying that there was a requirement for protein synthesis. Dimethylthiourea abolished the increase elaboration of u-PA induced by TNF completely, catalase did so partially, and SOD did not do so at all. CONCLUSION: The propensity of HCME to elaborate u-PA rather than PAI-1 appears to render cerebral microvasculature particularly vulnerable to proteolytic attack in settings in which inflammatory cytokines are elaborated locally or in which their concentrations in blood are elevated.

Brain↗
PubMed1999

Analysis of a chronic myelogenous leukemia patient vaccinated with leukemic dendritic cells following autologous peripheral blood stem cell transplantation.

Dendritic cells (DCs) are believed to be the most potent antigen-presenting cells and may be important in the induction of anti-leukemia specific T cell responses. In this preliminary clinical study, a patient with chronic phase chronic myelogenous leukemia (CML) was vaccinated with autologous leukemic DCs following autologous peripheral blood stem cell transplantation (PBSCT). In an in vitro study, leukemic DCs were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha, and interleukin-4 from granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC fraction of this patient, and were found to be Ph1+, and to possess the morphologic and phenotypic characteristics of mature DCs. These cells could also elicit antigen specific immune responses, including a vigorous cytotoxicity specific to CML cells. In the clinical experiment, we obtained evidence that infused leukemic DCs could induce T cell clones expressing the same T cell receptor usage as a cytotoxic T cell line, suggesting that the immune repertoire includes tumor-reactive T cells. These cytotoxic T lymphocytes are activated in vivo. The vaccination of leukemic DC caused a decrease in the number of Ph1+ cells in the peripheral blood and bone marrow. These results indicate that the activity is an immunologically mediated phenomenon and vaccination therapy with leukemic DC following autologous PBSCT may be effective in treating CML.

Amino Acid Sequence↗
PubMed1999

Natural killer cell subpopulations and cytotoxicity for infertile patients undergoing in vitro fertilization.

PROBLEM: We evaluated the participation of the lymphocyte subpopulations in the endometrium and peripheral blood on in vitro fertilization and embryo transfer (IVF-ET) outcomes. METHOD OF STUDY: Peripheral blood samples were analyzed for the expression of CD3, CD4, CD8, CD16, and CD56, using a FACScan, and for natural killer (NK) cell cytotoxicity, using a 51Cr assay. Endometrial samples obtained at a previous phase of the IVF cycle were analyzed for the expression of CD16 and CD56, using a FACScan. RESULTS: The percentages of CD56+ cells and CD16+CD56+ cells in the peripheral blood on the day of ET were significantly higher in the failed group than in the implanted group. In the endometrial tissue, the increase of the percentage of CD16+CD56dim cells and the decrease of the percentage of CD16-CD56bright cells in the aborted group were significant when compared with the those of the delivered group. CONCLUSIONS: The increase of cytotoxic NK cells in the peripheral blood and the endometrium may affect the therapeutic results of IVF-ET. It was suggested that modifications of NK cytotoxicity or of NK subpopulations might contribute to the improvements of IVF outcomes.

Adult↗
PubMed1999

Unusual appearances of uterine leiomyomas: MR imaging findings and their histopathologic backgrounds.

Typical appearances of uterine leiomyoma at magnetic resonance (MR) imaging are well established, and diagnosis is usually easy. However, cases that, are extremely difficult to differentiate from other conditions are occasionally encountered. To understand the wide spectrum of MR imaging findings, such unusual appearances can be classified into three categories: degeneration and other histopathologic findings, specific types of unusual leiomyomas, and unusual growth patterns. The common types of degeneration are hyaline (>60% of cases), cystic (approximately 4%), myxoid, and red. Edema is not a phenomenon of degeneration but is a common histopathologic finding (approximately 50% of cases). Hemorrhage, necrosis, and calcification (approximately 4% of cases) may also be observed. Specific types of unusual leiomyomas include lipoleiomyoma and myxoid leiomyoma, which may have MR imaging features characteristic enough to allow differentiation from other gynecologic and nongynecologic diseases. Intravenous leiomyomatosis, metastasizing leiomyoma, diffuse leiomyomatosis, and peritoneal disseminated leiomyomatosis represent unusual growth patterns; other unusual growth patterns are retroperitoneal growth, parasitic growth, and the pattern that may occur in cervical leiomyoma. Because leiomyomas are the most common gynecologic tumors and are exclusively benign, it is important to be familiar with the variety of MR imaging appearances of uterine leiomyomas to distinguish them from other significant diseases.

Female↗
PubMed1999

TNF-alpha and insulin, alone and synergistically, induce plasminogen activator inhibitor-1 expression in adipocytes.

Obesity is associated with hyperinsulinemia and elevated concentrations of tumor necrosis factor-alpha (TNF-alpha) in adipose tissue. TNF-alpha has been implicated as an inducer of the synthesis of plasminogen activator inhibitor-1 (PAI-1), the primary physiological inhibitor of fibrinolysis, mediated by plasminogen activators in cultured adipocytes. To identify mechanism(s) through which TNF-alpha induces PAI-1, 3T3-L1 preadipocytes were differentiated into adipocytes and exposed to TNF-alpha for 24 h. TNF-alpha selectively increased the synthesis of PAI-1 without increasing activity of plasminogen activators. Both superoxide (generated by xanthine oxidase plus hypoxanthine) and hydrogen peroxide were potent inducers of PAI-1, and hydroxyl radical scavengers completely abolished the TNF-alpha induction of PAI-1. Exposure of adipocytes to TNF-alpha or insulin alone over 5 days increased PAI-1 production. These agonists exert synergistic effects. Results obtained suggest that TNF-alpha stimulates PAI-1 production by adipocytes, an effect potentiated by insulin, and that adipocyte generation of reactive oxygen centered radicals mediates the induction of PAI-1 production by TNF-alpha. Because induction of PAI-1 by TNF-alpha is potentiated synergistically by insulin, both agonists appear likely to contribute to the impairment of fibrinolytic system capacity typical in obese, hyperinsulinemic patients.

3T3 Cells↗
PubMed1999

The predictive value of benzodiazepine tolerance in persistently aggressive schizophrenia.

The aim of this study was to determine whether benzodiazepine tolerance might provide a predictive marker for persistent aggression in schizophrenia. Seventy-seven male schizophrenic patients newly admitted to our psychiatric intensive care unit due to violent behavior during a 4-month period were examined. As a result, a high dose of benzodiazepine required for sedation or a short duration until regaining consciousness after the initial sedation, was related to severer aggression on waking up after sedation. Despite the small number of subjects examined, a conservative claim can be made that the level of the effect of benzodiazepine required for sedation seems to predict persistent severe aggression in schizophrenia.

Adolescent↗
PubMed1999

Fibromuscular dysplasia involving coronary arteries--a case report.

The authors report a young patient with fibromuscular dysplasia involving multivessels including coronary arteries. If young patients have chest pain on effort, fibromuscular dysplasia of coronary arteries must be considered. As fibromuscular dysplasia is a chronic progressive disease and some cases progress rapidly in a few months, careful follow-up and comprehensive medical management may be necessary in such patients.

Adult↗
PubMed1999

Creatinine clearance as a substitute for the glomerular filtration rate in the assessment of glomerular hemodynamics.

A method for the clinical assessment of glomerular hemodynamics has been published previously. We here examined whether, when using this method, renal creatinine clearance (Ccr) can be substituted for the glomerular filtration rate (GFR). The study subjects comprised 57 inpatients from Osaka City General Hospital: 30 with type 2 diabetes mellitus and 27 with chronic glomerulonephritis. During the 2-wk study, patients received a high-salt diet for 1 wk and a low-salt diet for 1 wk. Urinary sodium excretion and systemic blood pressure were measured daily. The renal plasma flow, Ccr, and plasma total protein concentration were also evaluated simultaneously on the last day of the high-salt diet. The GFR was also calculated from the fractional renal accumulation of 99mTc-diethylenetriaminepentaacetic acid (DTPA). Glomerular hemodynamics, represented by the glomerular capillary hydraulic pressure and the resistance of afferent and efferent arterioles, were calculated using the renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Values for renal hemodynamics with the Ccr-derived GFR were compared with those from the 99mTc-DTPA-derived GFR. Ccr values of 53 to 169 ml/min correlated with the 99mTc-DTPA-derived clearance of 39 to 179 ml/min (n=57, r=.71, p<.001). Values for the glomerular pressure and the resistances of afferent and efferent arterioles calculated using the Ccr-derived GFR correlated significantly with those calculated using the 99mTc-DTPA-derived GFR (r=.99, p<.001 and r=.99, p<.001, respectively). These results indicate that the Ccr is an accurate representation of the GFR for use in glomerular hemodynamic analysis of the pressure-natriuresis relationship.

Chronic Disease↗
PubMed1999

Membrane-bound cell surface peptidases in reproductive organs.

Membrane-bound cell surface peptidases including aminopeptidase-N (EC 3.4.11.2), dipeptidyl peptidases IV (EC.3.4.14.5), carboxypeptidase-M (EC 3.4.17.12), neutral endopeptidase (EC 3.4.24.11) and endothelin converting enzyme-1 (EC 3.4.23) were shown to be differently expressed on human ovarian granulosa, theca interna and luteal cells and on endometrial epithelial and stromal cells. These peptidases have their catalytic sites extracellularly and can metabolize biologically active peptides at the cell surface, serving as local regulators of peptide concentrations. In the ovary and endometrium, numerous peptides are considered to be locally produced and play an important role in the follicular growth, ovulation, corpus luteum function, endometrial differentiation and embryo implantation in an autocrine and/or paracrine fashion. The inhibition of aminopeptidase activity by bestatin affected murine follicular growth, steroidogenesis by porcine ovarian cells and progesterone-induced decidualization of human endometrial stromal cells in vivo or in vitro. These findings suggest that membrane-bound peptidases are important regulators of the function and differentiation of the ovarian cells and endometrial cells including embryo. In the near future, the physiological roles of these peptidases will be clarified and clinical use of peptidase inhibitors may be applied to the various reproductive disorders.

Animals↗
PubMed1999

Collagen-phagocytosing ability of periodontal osteoblasts at the bone surface.

The collagen-phagocytosing activity of osteoblasts at the alveolar bone-ligament interface of rat mandibular first molars was investigated both histologically and histochemically. Alveolar bones of male Wistar rats (6 months old) were used in this study. Collagen-containing phagosomes appeared in cuboidal osteoblasts aligned on the bone surface. The 5.7% of the osteoblasts exhibiting alkaline phosphatase activity revealed collagen-containing phagosomes, and the collagen fibrils within the phagosomes were at various stages of degradation. In addition, acid phosphatase activity and the immunocytochemical distribution of cathepsin B were found in these collagen-containing phagosomes at similar locations. The presence of both enzymes in the phagosomes suggests that an intracellular degradation of collagen occurs. Therefore, in addition to the osteoblastic functions of synthesizing and secreting bone matrices, osteoblasts are also capable of phagocytosis and the intracellular disintegration of collagen. Our findings suggest that osteoblasts at the alveolar bone-periodontal ligament interface have a collagen-phagocytosing ability and play an important role in the physiological remodeling and metabolic breakdown of collagen fibrils of periodontal ligament without osteoclastic bone remodeling.

Animals↗
PubMed1999

Dermoid cysts of the ovary with malignant transformation: MR appearance.

OBJECTIVE: This study presents the MR appearances of five women with a total of six proven dermoid cysts of the ovary with malignant transformation. To our knowledge, the MR findings of this entity have not been reported. CONCLUSION: The lesions appeared to be fat-containing tumors with a solid component (4/6) that extended transmurally (4/6) and extensively invaded neighboring pelvic organs (3/6). The supervening malignancy was squamous cell carcinoma in four tumors, melanoma in one, and transitional cell carcinoma in one. The mode of spread differed from that of common ovarian tumors in that it included transmural extension and local invasion, reflecting squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed1999

MR imaging of endometrial stromal sarcoma: correlation with pathologic findings.

OBJECTIVE: This study describes MR imaging of eight patients with endometrial stromal sarcoma and correlates the imaging findings with histopathologic findings. To our knowledge, the radiologic findings of this entity have not been reported in the literature. CONCLUSION: Endometrial stromal sarcoma typically presents with extensive myometrial involvement, which is either sharply demarcated or diffusely infiltrative. Bands of low signal intensity are observed within the areas of myometrial involvement on T2-weighted images. These bands correspond to the preserved bundles of myometrium on pathologic examination. Tumor extension along the vessels or ligaments is another characteristic of MR imaging of endometrial stromal sarcoma.

Adult↗