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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 397 records · Page 22Linked to original sources

Erythropoietin, granulocyte-colony stimulating factor, interleukin-1 beta and interleukin-6 during the normal menstrual cycle.

OBJECTIVE: Menstruation and ovulation are the main events during the menstrual cycle. Menstruation may influence the complete blood count because of its blood loss. Since ovulation is an inflammatory-like phenomenon, white blood cell count may change during ovulation. For these reasons, we have investigated the complete blood count and peripheral serum concentrations of associated cytokines during the normal menstrual cycle. MATERIALS AND METHODS: Normal healthy female volunteers (N = 9; age, 21-33 years) with menstrual cycles of 25-33 days recorded basal body temperature every day and venous blood samples were collected three times per week. Complete blood count was performed and erythropoietin, granulocyte-colony, stimulating factor, interleukin-1 beta, interleukin-1 beta, interleukin-6 and hormones (FSH, LH, estradiol and progesterone) were measured. RESULTS: The red blood cell, total white blood cell, granulocyte and platelet counts showed no statistically significant changes during the menstrual cycle when using analysis of variance with the Scheffe F-test. No changes in erythropoietin, interleukin-1 beta and interleukin-6 were seen throughout the menstrual cycle. In contrast, serum granulocyte-colony stimulating factor concentrations increased significantly to 28.0 +/- 3.1 pg/ml (mean +/- S.E.M.) during the ovulatory phase, compared to 10.7 +/- 0.6 pg/ml in other phases. CONCLUSION: These results indicate that menstrual blood loss does not affect the complete blood count and suggest that granulocyte-colony stimulating factor plays and important role in the mechanism of ovulation.

Adult↗

Dome formation induced by v-H-ras oncogene in a human choriocarcinoma cell line.

To investigate the role of ras genes in trophoblastic cell lineage, we transfected the viral H- or K-ras oncogene into a human choriocarcinoma cell line, CCI, and analysed the biological properties of CCI cells expressing an activated ras oncogene. All v-H-ras-expressing clones distinctively formed the hemispherical domes, which represents an in vitro morphological expression of vectorial transport function and are characteristic of the polarized epithelial cells, but none of v-K-ras-expressing clones and control clones did. Microscopic observation demonstrated that those domes were cavities filled with fluid which accumulated between the cell layer and the surface of culture dish. Scanning electron microscopy revealed that the domes were aggregates of round cells with long numerous microvilli and were morphologically similar to a blastocyst. Furthermore, Na(+)-K(+)-ATPase activity, which is associated with the vectorial fluid transport in transporting epithelial cells, was significantly higher in the v-H-ras-expressing clones than that in the v-K-ras-expressing clones and the parental cells. Those domes flattened within 24 h after treatment with a specific inhibitor of Na(+)-K(+)-ATPase, ouabain, and the number of domes decreased in dose-dependent manner, indicating that Na(+)-K(+)-ATPase activity was required for maintainance of domes. These results suggest that up-regulated activity of H-ras but not of K-ras facilitates the vectorial fluid transport through a chorionic cell layer and leads to the dome formation. The function of II-ras in trophoblasts, may therefore, be essential for embryogenesis, especially for supplying the nutrients.

Biological Transport↗

Contraction and relaxation responses of femoral artery and aorta to norepinephrine in young rats.

1. In femoral artery of 3-week-old rats, norepinephrine (NE) at 1 nM-0.1 microM concentration-dependently produced a contraction but, at higher concentrations (0.3-30 microM), NE relaxed the tissue. 2. In aorta of the 3-week-old rat, NE elicited a contraction at 1 nM to 0.3 microM and a relaxation at 1 microM and higher. 3. The magnitude of the NE-induced relaxation in the aorta was much less than that in the femoral artery. 4. Atenolol (a beta(1)-selective antagonist) modulated these NE responses in the femoral artery and butoxamine (a beta(2)-selective antagonist) in the aorta. 5. Subcutaneous application of propranolol and isoproterenol for 10 days in 4-week-old rats sensitized and desensitized the NE-induced relaxation, respectively. 6. It is suggested that, in the young rat, beta(1)- and beta(2)-adrenoceptors contribute the NE-induced relaxation in the femoral artery and aorta, respectively, and that beta-adrenoceptors may contribute to the limitation of NE-induced vasoconstriction in certain types of vascular beds.

Adrenergic beta-1 Receptor Antagonists↗

A case of ovarian carcinoma with production of granulocyte colony-stimulating factor.

A 60-year-old female with ovarian carcinoma showed marked leucocytosis. After exploratory laparotomy she had received carboplatin-based chemotherapy, but she died of respiratory failure. In this case the immunohistochemical examination of the tumour cells showed partial-positive staining for anti-G-CSF monoclonal antibody in addition to the elevation of the serum G-CSF concentration. This case is the first report of an ovarian carcinoma producing G-CSF.

Adenocarcinoma↗

Biochemical characterization of alpha-fetoprotein and other serum proteins produced by a uterine endometrial adenocarcinoma.

A high serum alpha-fetoprotein (AFP) level was found in a patient with endometrial adenocarcinoma of the uterus, which appeared to be hepatoid on histological examination. The AFP of this unusual patient was purified by immunoaffinity chromatography and characterized. The electrophoretic profiles on sodium dodecyl sulfate-polyacrylamide get electrophoresis both before and after glycopeptidase F treatment were indistinguishable from those of a hepatoma AFP. This indicates that the patient's AFP was also composed of a single polypeptide chain of Mr 67,000 and an N-linked sugar chain of Mr 3,000. Amino acid sequence analyses of this AFP, and of AFP from hepatoma and umbilical cord serum indicated that the N-terminal sequences were essentially the same. The sequence, Arg-Thr-Leu-His-Arg-Asn-Glu-Tyr-Gly-Ile, was slightly different from previous reports, but matched that deduced from the cDNA sequence. AFP isoforms due to microheterogeneity of the sugar chain were analyzed by lectin affinity electrophoresis using a series of lectins. The AFP isoform profiles were distinct from those of proteins derived from cord serum, hepatoma, yolk sac tumor and gastric cancer. The reverse-transcription of RNA from the tumor tissue followed by a polymerase chain reaction using primers with AFP-specific sequences gave a product of the size and nucleotide sequence expected for AFP. mRNAs possessing the requisite sequences for albumin and transferrin syntheses were also detected in the tumor. The expression of these hepatocyte-specific proteins supported the hepatoid nature of this tumor.

Adenocarcinoma↗

Parturition in six renal allograft recipients.

Between 1983 and 1994, we studied renal function and neonatal conditions for eight pregnancies and births to six women who had received renal transplants in order to assess the effect of an allograft on pregnancy and its outcome. The gestation period was 34 to 39 weeks (mean 36 weeks and 4 days), and four pregnancies ended before term. All eight babies were delivered by cesarean section. Intrauterine growth retardation (IUGR) was found in both babies of one woman who had been treated with conventional (without cyclosporin) immunosuppression. The serum creatinine level did not change during gestation in any of the women but was elevated after delivery in four. Four mothers suffered from proteinuria (25-364 mg/dl) during gestation, but the proteinuria disappeared after delivery in all but one case. The one exception, persistent proteinuria of 100-200 mg/dl, was assumed to result from the recurrence of the original renal disease (lgA nephropathy). The reduction of creatinine clearance and hydronephrosis of one graft noted during gestation were later reversed. None of the eight babies (four females and four males) was congenitally malformed, and their Apar scores were 6 to 9 (median 8). They are now 3 months to 11 years old, and seven of them are healthy and show good growth. One of the two IUGR babies has not grown well; her weight and height are more than 1 SD below the mean for her age, and she is mentally retarded and suffers from muscle weakness. Compared with dialysis patients, female renal allograft recipient have a better quality of life because they can safely deliver a child if they observe the criteria for pregnancy established for renal allogaft recipients.

Child↗

Cytokines concentrations in the cervical mucus of pregnant women.

OBJECTIVE: Interleukin-1 alpha, interleukin-1 beta, interleukin-6 and interleukin-8 in specimens of cervical mucus were assayed to assess defense mechanisms against infection in the cervical canal during pregnancy. METHODS: Two hundred and thirty-nine pregnant women who attended the obstetrics outpatient clinic in our hospital were included as subjects. Cervical mucus was collected with a newly developed collection swab, and cytokines and granulocyte elastase in the samples of cervical mucus were quantified using enzyme immunoassay kits. The 1-factor ANOVA, the Kruskal-Wallis test, and scheffé's F were used for statistical analysis. RESULTS: Interleukin-1 alpha, interleukin-1 beta and interleukin-8 levels rose significantly as the concentrations of granulocyte elastase increased. High concentrations of interleukin-1 alpha (75.36 +/- 19.93 pg/ml), interleukin-1 beta (1005.29 +/- 238.75 pg/ml) and interleukin-8 (4822.4 +/- 633.2 pg/ml) were found in the specimens from the group of high granulocyte elastase levels. CONCLUSIONS: These cytokines might be involved in defense mechanisms against ascending infection from the vagina.

Adolescent↗

Role of pulmonary vascular disorder in determining exercise capacity in patients with severe chronic obstructive pulmonary disease.

In patients with chronic obstructive pulmonary disease (COPD), the primary cardiovascular complication is the development of pulmonary hypertension, especially during exercise. The purpose of this study was to determine whether pulmonary vascular disorder plays an important role in determining exercise capacity in patients with severe COPD. Twenty-one male patients with severe COPD (mean FEV1 = 0.91 +/- 0.26 1) performed a progressive incremental exercise test, until symptom-limited maximum, to determine maximal exercise capacity, and then a constant-load exercise test for 5 min at a workload (20-60 W) corresponding to 60% of maximal workload during right heart catheterization to characterize the haemodynamic behavior of pulmonary circulation during exercise. The severity of the pulmonary vascular disorder was assessed using the slope of the mean pulmonary arterial pressure (PAP) - cardiac index (CI) relationship during constant-load exercise (P-Q slope). A significant inverse correlation was found between the maximal oxygen consumption (VO2max) and P-Q slope (r = -0.669), but not between VO2max and indices of expiratory airflow obstruction. In addition, the P-Q slope was inversely correlated with mixed venous oxygen tension (PvO2) at the end of constant-load exercise (r = -0.679) and with the change in oxygen delivery relative to oxygen consumption (delta DO2/delta VO2) during constant-load exercise (r = -0.671). These findings suggest that in patients with COPD, the functional impairment of the pulmonary vasculature is associated with disturbance in oxygen transport to the peripheral muscle during exercise, resulting in reduction of exercise capacity. We conclude that pulmonary vascular disorder may be an important factor in determining the exercise capacity of patients with severe COPD.

Aged↗

Clinicopathologic characteristics of polymyositis patients with numerous tissue eosinophils.

INTRODUCTION: We evaluated associated clinicopathologic features of polymyositis (PM) patients with numerous tissue eosinophils. MATERIALS AND METHODS: 680 muscle biopsies were examined in our institution and eight were identified with greater than 0.3 eosinophils per square millimeter in the inflammatory infiltrate without concomitant peripheral eosinophilia. RESULTS: All eight patients had typical PM, but neither dermatomyositis nor inclusion body myositis was identified. Clinically, a large number of PM patients with eosinophils manifested an acute- or subacute-onset of symptoms, myoglobinuria, a marked elevation of serum creatine kinase, a good response to steroid therapy, and a relatively benign course compared with 26 PM patients without eosinophils. Muscle biopsies demonstrated necrotic fibers more frequently in PM patients with eosinophils than in PM patients without eosinophils. Hypertrophic fibers, fiber splitting, basophilic fibers, and lobulated fibers were less frequently observed in PM patients with eosinophils. CONCLUSION: These results suggest that the majority of PM patients with eosinophils may be steroid-responsive and suffer an acute or subacute onset of PM.

Adult↗

Gene transduction into murine primitive hematopoietic cells with 2-gene retroviral vectors using a Transwell coculture system.

The present study aims at expressing a reporter gene in hematopoietic cells in vivo by introducing it into primitive hematopoietic cells with a 2-gene retroviral vector. Various constructs of retroviral vectors containing the human IL-2 receptor alpha chain gene (TAC) as the reporter and the neomycin phosphotransferase gene (neo) as a selectable marker were engineered, and the effectiveness of these vectors for expression of the reporter gene was evaluated after transfection into the packaging cell line GP + E86. It was found that the highest levels of reporter gene expression were attained with constructs ordered 5' long terminal repeat (LTR)-TAC-internal promoter-neo-3' LTR. In experiments investigating the expression of a reporter gene in hematopoietic cells, we used the Escherichia coli beta-galactosidase gene (lacZ) instead of TAC, because a very sensitive detection method was available for lacZ. For transduction of hematopoietic progenitors, packaging cell lines producing recombinant viruses were cultured in a Transwell hung into a Dexter-type bone marrow (BM) culture. The BM cells were selected with G418, and transferred into irradiated recipient mice. LacZ enzyme activity was detectable in the peripheral blood lymphocytes (PBL) of recipients taken 8 wk after reconstitution.

Animals↗

Magnetic resonance imaging in children with neonatal asphyxia: correlation with developmental sequelae.

Magnetic resonance (MR) findings and developmental sequelae were examined in 60 patients with neonatal asphyxia. Nine patients with marked destruction of the cerebrum had the severest motor and mental disability. Six had lesions of the periventricular white matter and thalamus. Seven had border zone infarction with lesions of the white matter and thalamus. Nine had lesions of the middle-lateral part of the thalamus, putamen and peri-Rolandic area. Five with lesions of the thalamus, putamen and cerebral white matter had the severest motor and mental disability. Twenty with lesions of the thalamus and/or putamen had athetosis or clumsiness. Four with lesions of the opercular region, white matter and thalamus had feeding difficulty. Some correlation between MR findings and developmental sequelae was recognized.

Adolescent↗

Cloning and genetic organization of the bacteriocin 31 determinant encoded on the Enterococcus faecalis pheromone-responsive conjugative plasmid pYI17.

The conjugative plasmid pYI17 (57.5 kb) isolated from Enterococcus faecalis YI717 confers a pheromone response on the host and encodes the bacteriocin 31 gene. Bacteriocin 31 is active against E. hirae 9790, E. faecium, and Listeria monocytogenes. pYI17 was mapped physically by restriction enzyme analysis and the relational clone method. Deletion mutant and sequence analyses of the EcoRI fragment B cloned from pYl17 revealed that a 1.0-kb fragment contained the bacteriocin gene (bacA) and an immunity gene (bacB). This fragment induced bacteriocin activity in E. faecalis OG1X and E. hirae 9790. The bacA gene is located on the pYI17 physical map between 3.37 and 3.57 kb, and bacB is located between 3.59 kb and 3.87 kb, bacA encodes 67 amino acids, and bacB encodes 94 amino acids. The deduced amino acid sequence of the bacA protein contained a series of hydrophobic residues typical of a signal sequence at its amino terminus. The predicted mature bacA protein (43 amino acids) showed sequence homology with the membrane-active class II bacteriocins of lactic acid bacteria. Analysis of Tn5 insertion mutants and the resulting transcripts indicated that these genes are transcribed as an operon composed of bacA, bacB, and an open reading frame located downstream of bacB designated ORF3.

Amino Acid Sequence↗

Serum and tissue measurements of CA72-4 in patients with endometrial carcinoma.

AIMS: To evaluate the clinical usefulness of CA72-4 as a serum tumour marker for endometrial carcinoma and to investigate its immunohistochemical localisation in endometrial carcinoma cells. METHODS: Serum concentrations of CA72-4 were determined in 72 patients with endometrial carcinoma. Immunohistochemical localisation of CA72-4 was investigated using the streptavidin-biotin method, using monoclonal antibodies B72.3 and CC49. RESULTS: Serum CA72-4 was increased above the cut off value in 31.9% of the patients with endometrial carcinoma. Serum CA72-4 positivity was correlated with depth of myometrial invasion, adnexal metastasis, lymphovascular space involvement, and pelvic and para-aortic lymph node metastasis. Multivariate analysis showed a significant correlation between serum CA72-4 positivity and adnexal metastasis. The serum concentrations of CA125 and CA19-9, which could be tumour markers for endometrial carcinoma, were measured at the same time. In seven of 72 patients increased concentrations of serum CA72-4 were found while those for CA125 and CA19-9 were within the normal ranges; in four of the seven patients the disease had spread beyond the uterus. Immunohistochemical positivity for CA72-4 antigen was 76.9% and occurred in the tumour cell membrane and cytoplasm. There was no significant difference in immunohistochemical positivity between patients with increased CA72-4 and those with normal CA72-4 values. CONCLUSIONS: The measurement of serum concentrations of CA 72-4 could be useful for predicting and monitoring the progress of disease-for example, extracorporeal spread.

Adult↗

Alpha-fetoprotein production by a hepatoid adenocarcinoma of the uterus.

A case of a 62 year old Japanese woman with an endometrial adenocarcinoma producing alpha-fetoprotein (AFP) is described. Microscopically, the tumour was composed of a major medullary portion and a minor tubular adenocarcinoma which had invaded the myometrium, the myometrial lymphatics and blood vessels. Neoplastic cells in the medullary portion were polygonal with glycogen-rich cytoplasm. Vascular permeation by neoplastic cells was prominent. Extensive hepatoma-like features were observed. The tumour cells lacked features suggestive of a diagnosis of embryonal carcinoma or endodermal sinus tumour. The production of AFP by the tumour cells was demonstrated immunohistochemically using the PAP technique. Only two cases of AFP producing endometrial adenocarcinomas have been reported previously.

Adenocarcinoma↗

Inhibitory effect of acetylshikonin on the activation of NADPH oxidase in polymorphonuclear leukocytes in both whole cell and cell-free systems.

The effects of acetylshikonin (AS) on the activation of NADPH oxidase (EC 1.6.99.6) in guinea pig polymorphonuclear leukocytes (PMNs) in both whole cell and cell-free activation systems were investigated. When PMNs were treated with AS before exposure to phorbol myristate acetate (PMA), superoxide (O2-) generation in these cells was significantly reduced, but after exposure of PMNs to PMA, inhibition of O2- generation by AS did not occur. Thiol compounds completely abolished the inhibitory effect of AS on the O2- generating activity of PMNs. In the cell-free system, AS inhibited the activation of NADPH oxidase induced by myristate in a combination of cytosol and membrane fractions obtained from intact PMNs, but did not inhibit the activity of NADPH oxidase already induced. These results suggest that AS inhibits the generation of NADPH oxidase complex in the activation of respiratory burst of PMNs, but does not directly inhibit the activity of NADPH oxidase already generated.

Animals↗

Zinc-ion-dependent acid phosphatase exhibits magnesium-ion-dependent myo-inositol-1-phosphatase activity.

We have purified bovine brain Zn(2+)-dependent acid phosphatase (Zn(2+)-APase), which requires Zn2+ ions to hydrolyze the substrate p-nitrophenyl phosphate (pNPP) in an acidic environment. The substrate specificity and metal requirement of Zn(2+)-APase at a physiological pH was also studied. The enzyme exhibited hydrolytic activity on myo-inositol-1- and -2-monophosphates, 2'-adenosine monophosphate, 2'-guanosine monophosphate, and the alpha- and beta-glycerophosphates, glucose-1-phosphate, and fructose-6-phosphate in 50 mM Tris-HCl buffer (pH 7.4) in the presence of Mg2+ ions, but not on pNPP and phosphotyrosine. Zn2+, Mn2+ and Co2+ ions were less effective for activation. Among the above substrates, myo-inositol-1-phosphate was the most susceptible to hydrolysis by the enzyme in the presence of 3 mM Mg2+ ions. The enzyme exhibited an optimum pH at around 8 for myo-inositol-1-phosphate in the presence of 3 mM Mg2+ ions. The Mg(2+)-dependent myo-inositol-1-phosphatase activity of the enzyme was significantly inhibited by Li+ ions. The Zn(2+)-dependent p-nitrophenyl phosphatase activity and Mg(2+)-dependent myo-inositol-1-phosphatase activity of the purified enzyme fraction exhibited similar behavior on Sephadex G-100 and Mono Q colomns. These findings suggest that Zn(2+)-APase also exhibits Mg(2+)-dependent myo-inositol-1-phosphatase activity under physiological conditions.

Acid Phosphatase↗

Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery.

The aim of this study was to investigate the correlation between the cytokine levels in the amniotic fluid (AF) and the histological stage of chorioamnionitis (CAM) in premature labor. AF of 6 cases (7 samples of AF were obtained as one was a twin pregnancy) in whom CAM was diagnosed histologically, and 12 cases without CAM were included in this study. Amniotic fluid was obtained within 24 hours prior to delivery. Cytokine levels (IL-2, -4, -6, TNF-alpha, IFN-gamma) in AF were measured by an ELISA method. Levels of IL-2 and -6 in the CAM-positive group (mean +/-S.E., 52.9 +/- 83.9 pg/ml, and 20,537.9 +/- 8853.7 pg/ml, respectively) were higher than those in the CAM-negative group (i.e. undetectable, and 65.6 +/- 27.5, respectively) with a statistical significance of p < 0.05, p < 0.001, respectively. There was a positive linear relationship between IL-6 levels of AF and the placental histological inflammatory stages of Blanc in the CAM-positive group. From these results it would appear that the IL-6 level in AF is the most sensitive test in the detection of extraamniotic infection or intraamniotic infection in preterm labor with intact membranes and also indicates the severity infection.

Amniocentesis↗

Relation between perinatal factors and outcome of very low birth weight infants.

In order to better understand the effect of obstetric management on the prognosis of very low birth weight (VLBW) fetuses, we retrospectively studied perinatal factors and the outcome of two hundred twenty-eight VLBW infants without major anomaly excluding cases of multiple pregnancy. The frequency of malpresentation were significantly high in the early neonatal death group (p < 0.05) and in the cerebral palsy/mental retardation (CP/MR) group (p < 0.01). A stepwise regression analysis for the CP/MR detected dependent variables as malpresentation, use of tocolytic agents (beta(2)-stimulant plus MgSO4) and pH < 7.20 in cord artery. Delivery method was not a dependent variable for the early neonatal death or the CP/MR. We analyzed a relation between fetal presentation-delivery method, and the prognosis. Among four groups (cephalic-vaginal, cephalic-cesarean, breech-vaginal, breech-cesarean), the cephalic-vaginal group had the lowest incidence of the poor prognosis (death and major handicap) where the breech-vaginal had the highest incidence. Breech groups (vaginal plus cesarean) had significantly high incidence of the poor prognosis when compared with that of cephalic groups (vaginal plus cesarean) (p < 0.05). Significant difference of the prognosis between the cephalic-vaginal group and the cephalic-cesarean group was not observed. These findings suggest that the delivery method is not a risk factor, but the malpresentation itself may be a risk factor for the poor prognosis of VLBW infants.

Cerebral Palsy↗