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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 271 records · Page 15Linked to original sources
PubMed1998

High-dose-rate intracavitary irradiation using linear source arrangement for stage II and III squamous cell carcinoma of the uterine cervix.

PURPOSE: The purpose of this article is to evaluate fractionated high-dose-rate (HDR) intracavitary irradiation using linear source arrangement (LSA) for patients with squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: The subjects consisted of 217 patients (71 patients with stage II and 146 with stage III disease) who received external beam therapy (EBT) followed by fractionated HDR intracavitary irradiation using LSA between January 1980 and June 1990. In EBT, 40 Gy in 20 fractions (40 Gy/20 Fr) or 39.6 Gy/22 Fr was delivered to the whole pelvis and an additional 10 Gy/5 Fr or 10.8 Gy/6 Fr was delivered to the parametrium. The intracavitary irradiation dose was 30 Gy/6 Fr or 35 Gy/7 Fr with a daily fraction size of 5 Gy and two fractions per week. During the intracavitary treatment, most patients were treated on an out-patient basis. RESULTS: Cause-specific 5-year survival rates were 77% for stage II and 50% for stage III. Pelvic failure rates were 13% for stage II and 36% for stage III. In multivariate analyses, improved cause-specific survival was significantly associated with stage II (P = 0.0003), higher pretreatment serum hemoglobin level (P = 0.0015), higher pretreatment serum total protein level (P = 0.0029), and shorter total treatment time (P = 0.0024). The rate of severe (grade 3 or 4) late complication was 2% for the rectum, 1% for the small intestine or sigmoid colon and 1% for the bladder. CONCLUSIONS: Fractionated HDR intracavitary irradiation using LSA is an effective treatment for patients with uterine cervical cancer without need for hospitalization.

Adult↗
PubMed1998

Antisense homology box-derived peptides represent a new class of endothelin receptor inhibitors.

Several peptides encoded by the sense and corresponding antisense DNA have been found to recognize and bind to each other. We developed software to search for sense-antisense regions within proteins taking into account the degeneracy of the genetic code, i.e., one amino acid can have several "antisense" counterparts. Using this approach, we searched endothelin receptor type A for intramolecular regions related in sense-antisense fashion. After locating these regions (termed "antisense homology boxes"), several corresponding peptides were synthesized. The four new ET(A) receptor fragment peptides ETR-P1 ("CALSVDRYRAVASW"), ETR-P3 ("QGIGPLITAIEI"), ETR-P4 ("IADNAERYSANLSSHV") and ETR-P6 ("LNRRNGSLRIALSEHLKNRREVA") reported here can inhibit ET-1 activity.

3T3 Cells↗
PubMed1998

Characterization of self-glutamic acid decarboxylase 65-reactive CD4+ T-cell clones established from Japanese patients with insulin-dependent diabetes mellitus.

To investigate autoimmunity to glutamic acid decarboxylase (GAD) 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM, type I diabetes), we established seven CD4+ T-cell clones, by stimulating peripheral blood mononuclear cells (PBMC) of six IDDM patients, using a mixture of overlapping human GAD65 peptides. No GAD65 autoreactive T-cell clones were evidenced in four healthy controls. Specificities of T-cell clones were as follows: (a) two clones specific to GAD65 p111-131 (residue 111 to 131) + DR53 (DRB4*0103); (b) one clone specific to GAD65 p413-433 + DR1 (DRB1*0101); (c) two clones specific to GAD65 p200-217 + either DR9 (DRB1*0901) or DR8 (DRB1*0802); and (d) two clones specific to GAD65 p368-388 + DP2 (DPA1*01 or 0201-DPB1*0201). Two DR53-restricted and one DR1-restricted T-cell clones, responded to a recombinant human GAD65 protein, and showed cytotoxicity against B lymphoblastoid cell lines pre-pulsed with the peptides. Six T-cell clones exhibited the Th1-like phenotype. Interestingly, two DR53-restricted T-cell clones killed a Fas-deficient B lymphoblastoid cell line, thereby indicating that cytotoxicity was not completely dependent on a Fas-Fas ligand interaction. Thus, the T-cell epitopes were mapped in a limited portion of GAD65 protein, with a tendency to be restricted by disease-associated HLA-DR, but not DQ molecules.

Adolescent↗
PubMed1998

myo-Inositol monophosphatase in the brain has zinc ion-dependent tyrosine phosphatase activity.

1. myo-Inositol monophosphatase (E.C. 3.1.3.25) hydrolyzes inositol monophosphate to form free myo-inositol, the precursor for the inositol phospholipid second-messenger signaling systems. The biochemical properties of the enzyme were examined in detail. 2. The enzyme exhibited significant hydrolytic activity only on phosphotyrosine among physiological substrates tested in the presence of Zn2+ ions in an acidic environment. 3. The enzyme was recognized and immunoprecipitated with polyclonal antibodies developed against the Zn2+-dependent tyrosine phosphatase of bovine brain. 4. These results indicate that myo-inositol monophosphatase exhibits Zn2+-dependent tyrosine phosphatase activity in an acidic environment and has immunological identity with a Zn2+-dependent tyrosine phosphatase.

Acid Phosphatase↗
PubMed1998

Phospholipase C isozymes in the human brain and their changes in Alzheimer's disease.

Phosphoinositide-specific phospholipase C is a key enzyme in signal transduction. We have previously demonstrated that an isozyme of phospholipase C, phospholipase C-delta1, accumulates aberrantly in the brains of patients with Alzheimer's disease. In the present study, we examined the property of phospholipase C isozymes in human brains using the methods of chromatofocusing and gel filtration chromatography, and investigated their changes in Alzheimer's disease brains. The chromatofocusing profile of human brain phospholipase C activity on a Mono P HR column demonstrated that phospholipase C-gamma1, exhibiting an isoelectric point value of 5.2, and phospholipase C-delta1, exhibiting isoelectric point values of 5.2 and 4.6, are partly overlapped in their elution. In contrast, the elution profiles of control and Alzheimer's disease brain phospholipase C on Superdex 200 pg column gel filtration chromatography indicated that phospholipase C-gamma1 and phospholipase C-delta1 can be separated with the elution position having a molecular weight of about 240,000 and 140,000, respectively, in the human brain. Using this gel filtration chromatography it was revealed that the phospholipase C-gamma1 activity was significantly decreased and the phospholipase C-delta1 activity was significantly increased in Alzheimer's disease brains compared with controls. These results suggest that the phospholipase C isozymes are differentially involved in Alzheimer's disease.

Aged↗
PubMed1998

Contribution of long axis motion of left ventricular outflow to calculation of left ventricular stroke volume.

Stroke volume can be calculated by using noninvasive Doppler techniques. The products of pulsed Doppler stroke distance of left ventricular outflow and left ventricular outflow area can often be used to calculate stroke volume. However, left ventricular outflow also moves longitudinally toward the apex of the ventricle during systole, so that zero velocity flow cannot be detected by the usual pulsed Doppler studies. We evaluated the contribution of these zero velocity flow to the noninvasive estimation of left ventricular stroke volume in 20 patients with left ventricular disease and in 20 age matched healthy controls. Left ventricular stroke distance was calculated by summing the Doppler stroke distance and the outflow long axis motion. The percentage of zero velocity flow for total stroke volume was calculated in each group. Cardiac output was also measured by thermo-dilution technique. The percentage of zero velocity flow for total noninvasive stroke volume in patients with left ventricular disease was 2.5 +/- 1.1 ml (4.0 +/- 1.5%), significantly lower than in normal subjects, 3.6 +/- 1.0 ml (5.5 +/- 1.5%) (p < 0.05). These long axis motions are significantly reduced, especially in left ventricular disease. Amplitudes of the left ventricular outflow long axis motion were correlated with Doppler stroke distance in all (r = 0.54, p < 0.01). In patients with myocardial infarction, stroke volume by thermo-dilution methods and calculated stroke volume showed good correlation both only by Doppler stroke distance (y = 1.044x + 0.547, r = 0.968) and by Doppler and long axis motion (y = 0.989x + 0.521, r = 0.974). Compared with stroke volume measured by thermodilution method, stroke volume calculated only by Doppler stroke distance was underestimated. We thus demonstrated the influence of zero velocity flow on left ventricular outflow both in patients with left ventricular disease and in normal subjects.

Adult↗
PubMed1998

Estimation of the right ventricular volume and ejection fraction by transthoracic three-dimensional echocardiography. A validation study using magnetic resonance imaging.

AIMS: To validate the use of three-dimensional transthoracic echocardiography compared with the magnetic resonance imaging for determination of right ventricular volume and ejection fraction. METHODS AND RESULTS: We recorded transthoracic echocardiographic images starting from the apical four-chamber view in which the RV is clearly visualized in 15 healthy volunteers. The scanning plane of the RV was obtained by the rotational scanning technique in 2 degree angular increments for three-dimensional reconstruction. The RV volumes in end-diastole and end-systole were calculated using a Tomtec three-dimensional reconstruction computer. We also assessed the RV by cine magnetic resonance imaging using the Siemens Magnetom Impact Expert (1.0 T). Cine gradient echo images were obtained in the short axis of the RV. The RV volume at each phase was calculated by Simpson's method. We also calculated the RV ejection fraction. The RV volumes in end-diastole and end-systole were 111 +/- 22 ml and 52 +/- 13 ml, respectively as determined by three-dimensional echo, and 115 +/- 18 ml and 55 +/- 14 ml determined by MRI. The right ventricular volumes at end-diastole and end-systole determined by three-dimensional echo were correlated with the volumes determined by MRI (r = 0.94 and 0.97, respectively, p < 0.001). The RV ejection fraction determined by three dimensional echo was also correlated with the ejection fraction determined by MRI (r = 0.90, p < 0.01). CONCLUSIONS: Three-dimensional transthoracic echocardiography provided reliable calculations of the right ventricular volume and ejection fraction.

Adult↗
PubMed1998

Assessment of the normal adult right ventricular diastolic function using M-mode echocardiographic measurement of tricuspid ring motion.

Right ventricular function can be evaluated echocardiographically by assessing the longitudinal motion of the tricuspid ring recorded in the apical four chamber view. In this study, we applied this technique to assess the right ventricular diastolic function in 10 healthy Japanese men (mean age: 28 +/- 6 years; age range: 20-43 years). Echocardiographic studies were performed with a phased-array imaging system using a 2.5 MHz probe. Tricuspid ring motion was measured by two-dimensional echo guided M-mode echocardiogram of the right lateral tricuspid ring. The excursion of the tricuspid ring during early diastole (DS; mm) and the peak rate of change of the excursion (dS/dt; mm/sec) were measured. We also assessed the right ventricular function by cine magnetic resonance imaging (MRI). Cine gradient echo images were obtained along the short axis of the right ventricle. The right ventricular volume at each phase of the cardiac cycle was calculated by Simpson's method and time-volume curves were constructed. The peak filling rate (dV/dt; ml/s) was determined from these time-volume curves. The dS was 12.8 +/- 2.5 mm, dS/dt was 132 +/- 27 mm/sec and dV/dt was 269 +/- 66 ml/s. There were significant positive correlations between dS and dV/dt (r = 0.80, P < 0.01), and between dS/dt and dV/dt (r = 0.45, P < 0.05). Based on our results, M-mode echocardiographic measurements of tricuspid ring motion may be used to assess the right ventricular diastolic function.

Adult↗
PubMed1998

Mutation of the p53 gene in human astrocytic tumours correlates with increased resistance to DNA-damaging agents but not to anti-microtubule anti-cancer agents.

Astrocytic tumours often become resistant to a variety of chemotherapeutic agents in advanced stages and frequently possess mutations in the p53 tumour-suppressor gene. Previous studies using established cell lines to investigate the relation between mutated p53 genes and altered resistance to anti-cancer agents brought inconsistent results. In this report, we examined the status of the p53 gene in 56 astrocytic tumour specimens by single-strand conformation polymorphism and their in vitro chemosensitivity to 30 different kinds of anti-cancer agents. The chemosensitivity was determined by drug-induced cell death using flow cytometry. We found that the mutated p53 gene correlated with increased resistance to DNA-damaging agents but the sensitivity to anti-microtubule agents was independent of the mutation, suggesting a clinical significance of the status of p53 gene in astrocytic tumours and a rational application of anti-microtubule agents to the patients with p53-mutated astrocytic tumours.

Antineoplastic Agents↗
PubMed1998

Gestational transient hyperthyroxinaemia (GTH): screening for thyroid function in 23,163 pregnant women using dried blood spots.

OBJECTIVE: Transient elevation of serum free T4 (gestational transient hyperthyroxinaemia; GTH) occurs occasionally during normal pregnancy, especially in early gestation. However, the frequency of GTH and its clinical features remain unclear to date. The aim of this study was to determine the occurrence rate of GTH and the relation between serum levels of hCG, free T4 (fT4), and TSH in a large number of pregnant women. DESIGN: The four criteria of GTH were as follows: (1) no past history of thyroid disease, (2) negative tests for MCHA and TGHA, (3) no multiple pregnancies or trophoblastic disease and (4) transient hyperthyroxinaemia at less than 16 weeks of gestation. Thyroid function and hCG levels in 23,163 pregnant women were evaluated by mass sreening. If individual fT4 levels were more than the upper limit, blood re-sampling and the clinical and laboratory analysis of thyroid function were performed to exclude women with thyroid disease. The concentrations of hCG, fT4, and TSH in women with GTH and normal pregnant controls (n = 218) were compared. Regression analysis was performed for the comparison between hCG, fT4, and TSH levels in women with GTH. MEASUREMENTS: Blood samples were obtained using dried blood spots. Blood levels of fT4 was measured by radioimmunoassay, TSH and hCG were measured by fluoroimmunoassay. Anti-microsome antibody (MCHA) and anti-thyroglobulin antibody (TGHA) were measured by indirect agglutination reaction. RESULTS: GTH was observed in 66 of 23,163 women. The overall occurrence rate of GTH was 0.285%. In 22 of the 66 GTH women, serum TSH was undetectable. Using regression analyses, the concentration of fT4 was correlated with hCG levels in women with GTH (P < 0.05, r = 0.269), whereas the concentration of TSH was not correlated with hCG or fT4 level. The concentrations (M +/- SD) of fT4, TSH, and hCG in women with GTH were 42.5 +/- 12.3 pmol/l, 0.20 +/- 0.31 mU/l and 190.2 +/- 98.8 x 10(3) IU/l, whereas those of controls were 14.6 +/- 3.8 pmol/l, 1.43 +/- 1.25 mU/l and 60.1 +/- 45.1 x 10(3) IU/l. The concentrations of fT4 and hCG were significantly (P < 0.0001) higher than those of normal controls, and TSH was significantly (P < 0.0001) lower than those of normal controls. CONCLUSION: The occurrence rate of gestational transient hyperthyroxinaemia was 0.285%, and could possibly be attributed to increased levels of circulating hCG. Based on the data obtained from a large number of pregnant women, we propose gestational transient hyperthyroxinaemia as a definite clinical entity.

Blood Specimen Collection↗
PubMed1998

Region-specific expression of murine Hox genes implies the Hox code-mediated patterning of the digestive tract.

BACKGROUND: Hox genes encode transcription factors which are involved in the establishment of regional identities along the anteroposterior (AP) body axis. To elucidate the AP patterning of the digestive tract, we have systematically examined the expression patterns of Hox genes belonging to paralogue groups 6, 7, 8 and 9 by whole-mount in situ hybridization and by section in situ hybridization analyses. RESULTS: The expression patterns of these genes showed co-linearity along the wall of the digestive tract, thereby yielding the Hox code of the gut. The expression boundaries of the Hox genes at later stages (12.5 d.p.c.) corresponded to the morphological boundaries of individual gut subdomains. CONCLUSIONS: The visceral mesoderm-restricted expression suggested that the Hox code primarily functions in the mesenchymal specification which eventually leads to the regional differentiation of gut subdomains as the result of epithelial-mesenchymal interactions. Overlapping expression patterns were found among the paralogous Hox genes, indicating that the paralogues may have redundant functions in the specification of the gut.

Animals↗
PubMed1998

Beneficial effect of long-term combined treatment with voglibose and pioglitazone on pancreatic islet function of genetically diabetic GK rats.

Effects of voglibose (an alpha-glucosidase inhibitor) and pioglitazone (an insulin sensitizer) on glycemic control and on the function of pancreatic islets were evaluated using Goto-Kakizaki (GK) rats with non-insulin-dependent diabetes mellitus (NIDDM). Five week administration (8-13 weeks of age in GK rats) of voglibose alone (added to the chow at a concentration of 10 ppm), pioglitazone alone (10 mg/kg daily p.o.), or both of the agents together significantly improved fasting plasma glucose levels and those at 120 min in oral glucose tolerance tests. Insulin secretory capacity in response to glucose of the isolated islets, assessed by batch incubation, was significantly improved in the voglibose and in the voglibose plus pioglitazone groups. Eight-week administration (5-13 weeks of age) of voglibose and voglibose plus pioglitazone successfully lowered the fasting levels of plasma glucose and triglyceride. The glucose-responsiveness in insulin release from the islets was also significantly recovered by the therapy. The treatment increased the insulin content of the islets to almost twice that in untreated controls. Thus, treatment by these drugs can not only effectively ameliorate the metabolic derangement of NIDDM in GK rats, but it can also restore the deteriorated islet function, possibly through protection from glucose toxicity.

Animals↗
PubMed1998

Hematopoietic cytokine levels and in vitro colony formation assay in fetal anemia.

Fetal anemia causes hydrops fetalis and fetal ascites/hydrothorax, and in severe cases the prognosis is poor. Little other than alloimmunity and viral infections are known as mechanisms causing fetal anemia. The aim of this study was to elucidate any pathogenesis in fetal anemia due to otherwise idiopathic etiology. The levels of three hematopoietic cytokines, IL-3, erythropoietin (EPO), and granulocyte colony-stimulating factor (G-CSF) were measured in blood samples obtained by cordocentesis from six fetuses with anemia (Hb <10.0 g/dl) and 34 fetuses without anemia. Cordocentesis was performed prior to the onset of labor or uterine contractions in all pregnant women. The concentration of IL-3 in fetuses with anemia [M+/-(SD), 8.3 (10.1) pg/ml] was significantly lower than that in fetuses without anemia [59.9 (71.0) pg/ml]. EPO and G-CSF levels were not different between the two groups. In addition, through in vitro colony formation assay, using blood stem cells from two fetuses with severe anemia and three fetuses without anemia, it was found that colony forming unit-erythroid, burst forming unit-erythroid and granulocyte macrophage-colony forming unit were significantly suppressed in blood stem cells from the two fetuses with severe anemia. Thus, the malfunction of differentiation and proliferation of blood stem cells and the decrease of hematopoietic cytokine levels in the fetal circulation may be responsible for the occurrence of fetal anemia.

Colony-Forming Units Assay↗
PubMed1998

In vitro production of progesterone and estradiol by rat granulosa cells regulated by cabergoline and prolactin.

Cabergoline (CG), a dopamine agonist, and prolactin (PRL) added in vitro to isolated granulosa cells from immature rats cultured in serum-free medium inhibited FSH-stimulated production of progesterone. The lowest effective concentrations of CG and PRL were 10(-8)M and 1 ng/mL, respectively. In combination, the inhibitory activities were additive. CG at 10(-8) M also suppressed estradiol production by isolated rat granulosa cells; whereas PRL did not. In conclusion, CG inhibits FSH-stimulated progesterone and estradiol production by rat granulosa cells.

Animals↗
PubMed1998

Massive immunoglobulin treatment in women with four or more recurrent spontaneous primary abortions of unexplained aetiology.

The aim of this trial was to investigate the efficacy of massive i.v. immunoglobulin (MIVIg) treatment for women with a history of recurrent spontaneous abortion (RSA) due to unexplained aetiology. The study included nine women (11 pregnancies) with a history of four or more consecutive RSA with unexplained aetiology and no live births. The mean number of fetal losses was 4.5 (range 4-6 abortions). Over the course of 5 days, immunoglobulin (20 g/day) was infused i.v. at gestational weeks 4-7. No additional infusions were carried out. Two pregnancies out of the 11 conceptions resulted in missed abortions at gestational weeks 6 and 7 respectively. Mosaicism (46XX/ 48XX, +16, +20), and tetraploidy (92XXXX) were found by chromosome analyses of the two aborti. Eight out of the other nine pregnancies resulted in full term deliveries of healthy neonates. One pregnancy developed intrauterine growth retardation and fetal distress, resulting in a premature delivery (30 gestational weeks) by Caesarean section. Thus, excluding the two abortions with chromosome aberrations, the MIVIg treatment was effective in all nine pregnancies of RSA women with unexplained aetiology. This MIVIg treatment (100 g administered in early gestation) may be a beneficial alternative to previous IVIg infusion methods, and should be further evaluated in a multicentric, placebo-controlled study, employing a larger number of homogeneous patients who fall into a high risk category of first trimester abortions.

Abortion, Habitual↗
PubMed1998

Immunolocalization of fibronectin and its receptors integrin alpha 3 and alpha 5 subunits in the rat limb development.

In the rat hind limb bud aged between prenatal days 14 and 16, immunoreactions of fibronectin in the apical ectodermal ridge were localized on the plasma membranes of epidermal cells and cytoplasmic projections of the underlying mesenchymal cells, which are in contact with the basal lamina. Those of integrin alpha 3 and alpha 5 subunits also appeared on such areas. Definite immunoreactions of fibronectin and both integrin subunits were seen in cell to cell contact areas of mesenchymal cells which are associated with the marginal vein, or with each other forming solid cell cords, and appeared on the basal plasma membrane of endothelial cells of the growing capillaries arising from the marginal vein. These findings suggest that fibronectin may work as a ligand for alpha 3 beta 1 and/or alpha 5 beta 1 integrins expressed by the mesenchymal and vasoformative cells in developing limb bud.

Animals↗