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Biomedical subjects

S Fujii

Publications and source records attributed to S Fujii.

At least 595 records · Page 33Linked to original sources
PubMed1990

Base recognition mechanism of bleomycin: solution structure of d(GGGGAGCTCCCC)2 based on 1H-NMR and restrained molecular dynamics.

The self-complementary d(GGGGAGCTCCCC) dodecanucleotide cleavage by bleomycin occurs at G(4)pA(5) site rather than G(6)pC(7) site which is known as the preferential sequence. The molecular structure of this dodecamer is observed as the distorted B-DNA by the CD spectra and proton NMR measurements. Three-dimensional structures in solution evaluated by molecular dynamics calculations with inter proton distance restraints have the distorted form of the minor groove structure at G(6)pC(7) site. These evidences offer the recognition mechanism model of the DNA base sequence by bleomycin.

Base Sequence↗
PubMed1990

An NMR study on the conformation of the chromomycin-d(GGGGCCCC)2 complex.

The conformation of the chromomycin-d(GGGGCCCC)2 complex in aqueous solution was studied by NMR spectroscopy. The NMR spectrum of the complex indicated that the chromomycin binds as a symmetry-related dimer to the minor groove of the central four residues of d(GGGGCCCC)2. The drastic conformational change in the central four residues of d(GGGGCCCC)2 from the B form family to the A-form was demonstrated by the characteristic NOEs and coupling patterns. The change seems to be indispensable for accommodation of the bulky chromomycin dimer in the minor groove. On the basis of the intermolecular NOEs between chromomycin and d(GGGGCCCC)2, the structure of the complex has been constructed and refined by energy minimization.

Chromomycins↗
PubMed1990

Optimized fluorometric determination of urinary delta-aminolevulinic acid by using pre-column derivatization, and identification of the derivative.

We previously reported the usefulness of a fluorometric method to determine urinary delta-aminolevulinic acid (ALA) concentrations by using post-column derivatization to monitor the effect of lead exposure. We have further improved the method by introducing pre-column derivatization by using reaction of ALA with acetylacetone and formaldehyde. Response of the hematopoietic system to lead exposure can now be easily detected at blood lead concentrations as low as 162 micrograms/L. The fluorescent ALA derivative, a new aromatic product, 2-methylideneamino-3,5-diacetyl-4,6-dimethylphenylpropionic acid, is separated on octadecyl silica column by high-performance liquid chromatography and the fluorescence intensity is detected with a fluorophotometer. Sample recoveries for 12 urine samples from workers exposed to lead and unexposed controls were 91.9-110.2%. The results obtained by the pre-column derivatization method agreed with those by the post-column derivatization method. The new method increases the sensitivity to a detection limit to 10 micrograms of delta-aminolevulinic acid per milliliter of urine and is simple enough to be used for routine monitoring of the biological effect of exposure to low concentrations of lead.

Aminolevulinic Acid↗
PubMed1990

[Immunohistochemical study of pleomorphic adenoma of the lacrimal gland].

We performed immunohistochemical examinations in 1 hypertrophy and 3 pleomorphic adenomas of the lacrimal glands with monoclonal antibodies to S-100 protein and GFAP (glial fibrillary acidic protein). It was thought that hypertrophy of the lacrimal gland would be cytological equivalent to normal lacrimal gland tissue because of the lack of cytological atypia except when accompanied by lymphoid infiltration. In hypertrophy of lacrimal gland, S-100 protein was identified in myoepithelial cells and parts of the ductal epithelia, but GFAP was not identified in any part. In pleomorphic adenomas of lacrimal glands, asteroid cells of myxoid and/or chondroid areas were strongly stained with both antibodies to S-100 protein and GFAP. In solid areas of pleomorphic adenomas, S-100 protein-positive fusiform or round cells and GFAP-positive round cells were observed. It was thought that S-100 protein-positive cells could have originated from myoepithelial cells and GFAP could be a tumor-associated antigen. The results coincided with recent immunohistochemical findings of pleomorphic adenoma of the salivary gland. It was suspected that pleomorphic adenoma of lacrimal gland could develop from mesenchymal metaplasia of myoepithelial cells as in the case of pleomorphic adenoma of salivary gland.

Adult↗
PubMed1990

[Levels of CA130 in maternal sera and amniotic fluid at various gestational ages].

We examined the CA130 concentration in the amniotic fluid, maternal sera, amnion, chorion, decidua and placenta. CA130 in the maternal sera showed an initial increase during early pregnancy, remained low from the 15th weeks of pregnancy until delivery, and then increased after term delivery (249u/ml, mean, n = 27) or mid-trimester abortions (844u/ml, n = 22). The CA130, concentration in the amniotic fluid was high in the mid-trimester and remarkably low at term. Among the tissues examined, amnion and decidua contained a relatively high concentration of CA130. Immunohistochemical examination also demonstrated abundant CA130 in the cytosol of amnion and decidua tissues. The pattern of changes in CA130 in amniotic fluid was similar to that in the amnion and decidua tissue. The results suggest that the amnion cells are the source of CA130 in the amniotic fluid and that the high concentration of CA130 in maternal serum after delivery originates in decidua tissue affected by the separation of the placenta.

Amnion↗
PubMed1990

[Clinical features of uveitis in childhood during the past 20 years].

One hundred and fifty five cases (237 eyes) of children with uveitis were clinically observed in the past 20 years. There was no fluctuation in the number of patients during the period. Concerning the age as the first visit, the smallest group was under 4 years of age and the numbers of patients increased at ages 14 and 15. Chief complaints usually corresponded to the age of the cases. Cases with anterior uveitis accounted for 25% of all cases, intermediate uveitis 12%, posterior uveitis 45% and panuveitis consisted of 17% of all cases, respectively. In the course of treatment, improvement of visual acuity was not statistically significant; the visual prognosis of cases affected under age 7 years was relatively poor. At the time of final observation, the visual acuity of cases, who had first visited during the past 10 years, were better than those who presented during the previous decade. Uveitis had healed or improved in 68% of cases treated in our clinic. As complications, band-shaped keratopathy was seen in 8% of the patients, cataract in 22% and glaucoma in 5%, respectively. Thirty two per cent of the cases received systemic steroid therapy and the average duration was 3.8 months. Fifty two operations were performed in 30 cases (19%), 37 eyes (16%); 16 were cataract operations and 24 were operations for glaucoma.

Adolescent↗
PubMed1990

[Transesophageal echocardiography during coronary bypass surgery].

Transesophageal two-dimensional echocardiography (TEE) was evaluated in 14 patients who underwent coronary bypass surgery. The TEE transducer was positioned to view the left ventricular short axis at the level of the papillary muscle. Global left ventricular function was assessed by measuring left ventricular end-diastolic and end-systolic area and computing the fractional area change (FAC). Regional left ventricular function was analyzed after dividing the short axis view of the left ventricle into four anatomic segments. The mean FAC was 48% after intubation, 48% after skin incision, 47% after sternotomy, and 51% after pericardiotomy. The mean FAC increased significantly to 55% 0 to 30 minutes after cardiopulmonary bypass, and was 53% at the end of the operation. In 5 patients, FAC decreased and regional wall motion abnormalities appeared around sternotomy. These abnormalities was considered due to transient myocardial ischemia. In 7 patients, a paradoxical motion of the ventricular septum occurred at closing of the sternum. TEE was performed without complication and found to be a good method for assessing global and regional left ventricular function.

Coronary Artery Bypass↗
PubMed1990

[Metabolic characteristics and antitumor activity of BOF-A2, a new 5-fluorouracil derivative].

A new 5-fluorouracil (5-FU) derivative, BOF-A2 (3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl]-1- ethoxymethyl- 5-fluorouracil), is consisted of EM-FU (1-ethoxymethyl-5-fluorouracil) which is specifically and gradually converted to 5-FU by the drug-metabolizing enzyme of liver microsomes and CNDP (3-cyano-2,6-dihydroxypyridine), a potent inhibitor of 5-FU degradation in the liver. When BOF-A2 was given orally, blood levels of the main metabolites, EM-FU and CNDP, were maintained for a longer time in the tumor-bearing rats, and eventually the blood 5-FU levels were maintained over 12 hours. Moreover, 5-FU levels in the tumor tissue tended to be maintained higher and longer time over 24 hrs. than those in the blood of rats. Antitumor activity of such characterized BOF-A2 was investigated with transplantable tumors in rodents and DMBA-induced breast carcinomas in rats. The ED 50 (the dose for 50% inhibition of tumor growth) value was about 15 to 25 mg/kg against the tumors tested. These result may suggest that BOF-A2 has potent antitumor activity in accordance to the long persistence of 5-FU level in the tumor tissue.

Animals↗
PubMed1990

[Antitumor activity and metabolism of BOF-A2, a new 5-fluorouracil derivative, with human cancers xenografted in nude mice].

Antitumor activity of BOF-A2, a new 5-fluorouracil (5-FU) derivative, was evaluated with human gastric (H-111 and H-81), colorectal (H-143), pancreatic (H-48) and breast (H-31) cancers xenografted in nude mice. Twenty-five consecutive oral administration of BOF-A2 at 17.5 to 30 mg/kg over 4 weeks caused marked inhibition or regression (over 92% of inhibition rate) to the growth of H-81, H-143 and H-31 cancers. Moreover, BOF-A2 effected to both H-111 and H-48 which have low sensitivity to 5-FU and its known derivatives. Throughout the experiments, the mice seemed to tolerate the consecutive administration of BOF-A2 without severe toxicity. When BOF-A2 was given orally, 5-FU levels in the blood of mice was notably durative for a long time as compared to 5-FU and UFT. Furthermore, 5-FU levels in the tumor tissue tended to increase and persist much more than those in the blood. This maintenance and persistence of objective level of 5-FU in the blood would be concluded to produce a high antitumor effect of BOF-A2 against human cancers xenografted in nude mice.

Administration, Oral↗
PubMed1989

N-acetylglucosaminyltransferase III in human serum, and liver and hepatoma tissues: increased activity in liver cirrhosis and hepatoma patients.

An N-acetylglucosaminyltransferase III which catalyzes the addition of N-acetylglucosamine through a beta 1-4 linkage (bisecting N-acetylglucosamine) to the beta-linked mannose of the trimannosyl core structure of N-linked oligosaccharides of glycoproteins was measured in human serum, and liver and hepatoma tissues. The enzyme activity in serum was significantly elevated in patients with hepatomas and liver cirrhosis, and the activity markedly decreased on the transcatheter arterial embolization treatment. High activities were also found in the hepatoma and cirrhotic liver tissues, indicating that the serum activity reflected the activity in the tissues. The assaying of the enzyme activity in serum appears to be useful for the detection and monitoring of primary hepatomas.

Adult↗
PubMed1989

[A fundamental and clinical investigation of cancer antigen 130 (CA 130) in the field of obstetrics and gynecology].

Two murine monoclonal antibodies designated 130-22 and 145-9 have been recently established by immunizing mice with a pulmonary carcinoma cell line (PC-9). With use of these monoclonal antibodies a sensitive sandwich immunoradiometric assay (IRMA) for cancer antigen 130 (CA130) was developed in Daiichi Radioisotope Laboratories (Tokyo). Applying this IRMA kit CA130 concentrations were measured in various body fluids with special reference to obstetrics and gynecology. The results are as follows; 1) A CA130-IRMA showed excellent sensitivity, specificity, reproducibility and analytical recovery. The standard dose-response curve covered the range from 10 to 500 U/ml. 2) Serum CA130 levels measured by this assay system were closely correlated with serum CA125 levels, demonstrating quite a high correlation coefficient (r = 0.965). 3) In pregnancy maternal CA130 levels increased moderately (less than 300 U/ml) in the first trimester, and thereafter fell rapidly under normal upper limit (less than 35 U/ml). Immediately after deliveries maternal CA130 levels showed a rapid increase, reaching 269 U/ml (mean levels). In amniotic fluids CA130 concentrations were greatly elevated (3,236 U/ml mean levels), while the levels were almost within normal limit in the umbilical arterial and venous blood. Accordingly it is necessary to measure Schwangerschaftsprotein 1 or human chorionic gonadotropin simultaneously with CA130 to rule out possible pregnancy. 4) CA130 was clearly localized in the amniotic epithelium and umbilical sheath and other placental tissue components remained negative for this antigen. Taking the lower CA130 levels in the umbilical sera into consideration, these immunohistochemical results suggest CA130 is not oncofetal but oncoplacental. 5) Serum CA130 levels increased pretherapeutically beyond 35 U/ml in 87% of ovarian malignancies, and in 56% of endometrial carcinoma. The mean levels of serum CA130 reached 931 and 143 U/ml, respectively. These data indicate clinical usefulness of CA130 as a tumor marker for those diseases. By contrast serum CA130 levels were lower, and very few cases showed serum CA130 levels over 35 U/ml in cervical cancer. 6) In endometriosis 88% of the cases demonstrated increased serum CA130 levels, indicating its usefulness for monitoring therapeutic courses, just like CA125. In benign gynecologic diseases over 80% of cases showed increased serum CA130 levels while only slight increase in serum CA130 was found (mean levels less than 84.0 U/ml). This disadvantage could be lessened by a combination assay with CA72-4 and others whose serum levels were very low in the benign diseases.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1989

Potential attenuation of fibrinolysis by growth factors released from platelets and their pharmacologic implications.

Increased concentrations of the fast-acting tissue-type plasminogen activator (t-PA) inhibitor attenuate the fibrinolytic activity of pharmacologically administered activators of the fibrinolytic system such as t-PA. Accordingly, it was hypothesized that augmentation of synthesis and elaboration of inhibitor from the liver, leading to increased concentrations of inhibitor in plasma, or from endothelial cells in the vicinity of thrombi undergoing lysis, leading to increased concentrations locally, may contribute to failure of pharmacologically induced thrombolysis or to early reocclusion. Because platelets are rich in transforming growth factor beta and epidermal growth factor-like activity, it was thought that release of growth factors from platelets activated in vivo could mediate increases of the inhibitor in plasma by stimulating its formation in the liver and its local release from endothelial cells in the vicinity of thrombi. If so, fibrinolysis might be rendered more effective by concomitant prevention of platelet growth factor release. Transforming growth factor beta, a major constituent of platelets, increased concentrations of the t-PA inhibitor messenger ribonucleic acid (mRNA) in human hepatoma cells in a specific and dose-dependent manner. A peak effect was seen with 5 ng/ml and a 10-fold increase in 6 hours. Release of inhibitor protein into conditioned media increased as well. Induction of the inhibitor mRNA increase was elicited by exposure as brief as 30 minutes. Cycloheximide, an inhibitor of protein synthesis, was not inhibitory. The mechanisms responsible differed from those seen with epidermal growth factor, shown previously in the laboratory to increase inhibitor mRNA. In addition, the 2 factors were synergistic. Platelet lysates elicited effects simulating those of the purified growth factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗