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Biomedical subjects

I Fujii

Publications and source records attributed to I Fujii.

At least 19 recordsLinked to original sources
PubMed1992

Emodin O-methyltransferase from Aspergillus terreus.

Emodin O-methyltransferase, an enzyme catalyzing methylation of the 8-hydroxy group of emodin, was identified in the mould Aspergillus terreus IMI 16043, a (+)-geodin producing strain. The enzyme catalyzed the formation of questin from emodin and S-adenosyl-L-methionine. By chromatography on DEAE-cellulose, Phenyl Sepharose, Q-Sepharose, Hydroxyapatite, and CM-cellulose, emodin O-methyltransferase was purified to apparent homogeneity. The purified protein had a molecular weight of 322 kDa as estimated by gel filtration and 53.6 kDa as estimated by gel electrophoresis under denaturing conditions, suggesting that the active enzyme was a homohexamer. The enzyme showed pI 4.4 and optimum pH 7-8. Magnesium ion or manganese ion was not an absolute requirement, nor increased the enzyme activity. The enzyme had strict substrate specificity and very low Km values for both emodin (3.4 x 10(-7) M) and S-adenosyl-L-methionine (4.1 x 10(-6) M).

Aspergillus↗
PubMed1992

XELE--a polypeptide model-building program for a graphics workstation.

A model-building program, XELE, for use in protein crystallography has been written in C under UNIX on a graphics workstation. This program makes full use of the X Window system to display the electron density distribution and to manipulate the polypeptide model, and therefore is named XELE. It utilizes a fast three-dimensional rendering package, Dorè, and is portable to other types of graphics workstations. A part of the program for the man-machine interface uses the library of X Window and X Toolkit, and therefore is highly interactive. The structure analysis program package, PROTEIN, is also implemented in an interactive mode using X Window, and has been interfaced with XELE.

Computer Graphics↗
PubMed1992

Binding parameters of valproic acid to serum protein in healthy adults at steady state.

Two hundred milligrams of valproic acid (VPA) was administered orally to seven healthy adults at 9:00 and 21:00 h for 5 consecutive days, including the morning dose on day 6. On the sixth day, blood samples were drawn at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 3, and 6 h after the morning dose. Binding of VPA to serum protein was evaluated by ultrafiltration, and total and unbound VPA concentrations were determined by fluorescence polarization immunoassay. Binding parameters of VPA to serum protein were calculated for each subject by the Scatchard analysis. The binding parameters obtained from seven subjects showed that the mean association constant (K) was 2.72 x 10(4) L/mol while the total number of binding sites (nPt) was 789 mumol/L. There were marked interindividual variations and the coefficient of variation was 42% for K and 28% for nPt. These results show that endogenous free fatty acids (FFAs) significantly reduce the binding affinity of VPA to serum albumin (p less than 0.05). In addition, they suggest the possibility that the primary binding sites for VPA can be strongly reduced by FFAs. Therefore, we consider that interindividual differences in binding parameters may be clinically important.

Adult↗
PubMed1992

Prediction of unbound serum valproic acid concentration by using in vivo binding parameters.

In a previous study, we determined the in vivo binding parameters of valproic acid (VPA) to serum proteins in seven healthy young adults at steady state by using the Scatchard equation. To evaluate the ability of the Scatchard binding equation to predict steady-state unbound serum VPA concentrations (Cf), 39 adult patients receiving VPA monotherapy and ranging in age from 16 to 68 years were studied. The correlation between predicted and observed Cf was high (r = 0.865). Mean prediction error, mean absolute error (MAE), and root mean squared error (RMSE) were calculated, and served as a measure of prediction bias and precision. The MAE and RMSE were low (MAE = 12.9 mumol/L, RMSE = 17.7 mumol/L). It is feasible to use the Scatchard binding equation to predict Cf in patients receiving VPA monotherapy.

Adolescent↗
PubMed1992

The sequence of panic symptoms.

For phenomenological elucidation of panic attacks, 26 patients with panic attacks were requested to name the panic symptoms in order of their occurrence and specify the patterns of their abatement. Panic symptoms were found to be classifiable into three categories: early symptoms consisting of dizziness or faintness, palpitations, and sweating; intermediate symptoms dyspnea, nausea or abdominal distress, flush or chills, chest pain or discomfort, shaking, and choking; late symptoms paresthesias, fear of dying, and fear of going crazy. Panic symptoms disappeared in 61.6% irrespective of the sequence of their occurrence. Twenty-one patients were interviewed about the experience of nocturnal panic attacks, and 23.8% experienced them. These findings suggest that fear is caused by sudden physical abnormality triggered by some biological factors.

Adult↗
PubMed1992

Current views on panic disorder and its management in Japan: a national survey.

In a national random-sample survey, the views of 1,069 practicing clinicians, including internists, surgeons and psychiatrists, on panic disorder were surveyed by using a series of questionnaires. In spite of a high rate of clinical experience and agreements on the symptoms among clinicians, the nature of this disorder, such as a common descriptive diagnosis, and the preferred treatment have not been agreed upon by the Japanese medical community. Furthermore, respondents were questioned as to the preferred treatment for panic disorder, but no treatment was regarded as critical by a majority of clinicians. It is concluded that because of the high potential patient population with panic disorder, clinical research that will provide more adequate diagnosis and treatment for this disorder is necessary in Japan.

Adult↗
PubMed1992

Cloning of aklavinone biosynthesis genes from Streptomyces galilaeus.

Aklavinone is an aglycone of aclacinomycin A which is an important antitumor drug. Genes for the biosynthesis of aklavinone were cloned from Streptomyces galilaeus 3AR-33, an aklavinone-producing mutant, by use of the actI and actIII polyketide synthase gene probes. Restriction mapping and Southern analysis of the DNA cloned in a lambda phage vector established that the DNA represented three different regions of the S. galilaeus 3AR-33 genome that contained 3.4, 2.5, and 4.1 kb BamHI fragments which hybridized with actIII. Of those, only the 3.4 kb fragment also hybridized with actI. Complementation experiments with specifically blocked mutants confirmed that the cloned 3.4 kb BamHI fragment contains the genes required for the early stage of polyketide synthesis in aklavinone biosynthesis.

Antibiotics, Antineoplastic↗
PubMed1991

Evaluation of x-ray diffraction data from protein crystals by use of an imaging plate.

A system has been developed which uses an imaging-plate diffraction apparatus to obtain structure factors for protein crystals. The latter is connected to a graphics workstation through an Ethernet. Pixel data from an imaging plate are transferred via the Ethernet to a workstation and processed to give the structure factors. The quality and precision of the diffraction data were examined from the point of view of spatial uniformity, linearity with exposure, decay with time, and reproducibility. X-rays from an 55Fe source and Debye-Scherrer rings from Si powder were used for calibration purposes. Finally, diffraction data were obtained and evaluated for lysozyme and cytochrome c-553 using this system. The results were satisfactory in terms of sensitivity and precision.

Protein Conformation↗
PubMed1991

Identification of emodinanthrone oxygenase in fungus Aspergillus terreus.

Emodinanthrone oxygenase, which catalyzes the oxidation of emodinanthrone to emodin, has been identified in fungus, Aspergillus terreus. The fixation of an oxygen atom at the C-10 position of emodinanthrone from molecular oxygen catalyzed by the enzyme was proved by the 18O2 incubation experiment and analyses of the product emodin by mass spectrometry and nuclear magnetic resonance. The fact that the reaction did not require any foreign electron donor suggested the involvement of internal monooxygenase. Emodinanthrone oxygenase activities were found in other microbes which produce anthraquinone related metabolites.

Aspergillus↗
PubMed1990

Monocyte activation in early onset rheumatoid arthritis.

Monocytes from peripheral blood and synovial fluid of patients with definite and classic rheumatoid arthritis spontaneously produced significantly greater amounts of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and interleukin-1 beta (IL-1 beta) than samples of peripheral blood from normal controls. Peripheral blood monocytes from patients with rheumatoid arthritis produced significantly greater amounts of PGE2 than control samples when stimulated with lipopolysaccharide. There were no significant differences in the spontaneous release of superoxide or N-acetyl-beta-D-glucosaminidase by peripheral blood monocytes between patients and healthy controls. Both stimulated and unstimulated peripheral blood monocytes from patients with definite or classic rheumatoid arthritis produced significantly greater amounts of PGE2 than samples from normal controls. This was true, regardless of the stage of disease and the presence or absence of roentgenological joint abnormalities. Amounts of N-acetyl-beta-D-glucosaminidase released by peripheral blood monocytes from patients correlated positively with the erythrocyte sedimentation rate (ESR) and negatively with duration of disease. Amounts of IL-1 beta and N-acetyl-beta-D-glucosaminidase released from the peripheral blood monocytes of patients who had had their disease for less than one year were significantly higher than those of normal controls. There were no significant correlations between the types of treatment and the amounts of PGE2, LTB4, IL-1 beta or N-acetyl-beta-D-glucosaminidase released by peripheral blood monocytes in patients with rheumatoid arthritis. The findings suggest that monocytes are activated in patients with rheumatoid arthritis both at the onset of disease and during its chronic phase, and that they produce large amounts of mediators which may have a role in the induction and extension of the inflammatory process which leads to tissue damage.

Acetylglucosaminidase↗
PubMed1990

Arterial chemoembolization for multiple liver metastases of uterine cancer. Two case reports.

Transcatheter arterial chemoembolization (TACE) is one of the established therapeutic modalities for treatment of metastatic liver cancer originating in the gastrointestinal tract. However, TACE is seldomly applied to metastatic liver cancer from gynecological regions. We present two cases of multiple liver metastases of uterine cervical cancer, treated with TACE using cisplatin 60 mg/m2, etoposide 200 mg/m2 and lipiodol. In both cases, hepatomegaly was markedly reduced, tumor-markers dropped to within or close to the normal range, and subjective symptoms disappeared. No serious complications occurred, and symptomatic side effects and laboratory abnormalities were all transient and curable by conservative therapies. Under adequate medical care, TACE can safely be applied, although there are some reports about fatal complications. The present cases encourage us to actively treat liver metastases of gynecologic neoplasms by TACE, as we do those of gastrointestinal neoplasms.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Is the clinical course of non-rheumatic aortic regurgitation the same as that of rheumatic aortic regurgitation?].

To determine whether non-rheumatic (NR) aortic regurgitation (AR) has the same clinical and postoperative courses as rheumatic (R) AR, we performed a retrospective study using pre- and postoperative M-mode echocardiograms in 23 patients who underwent aortic valve replacement (AVR) under myocardial protection with hypothermic cardioplegia. The etiology of AR was diagnosed by two-dimensional echocardiography. The NR-AR group consisted of nine patients including four with aortic valve prolapse (AP) and five with bicuspid valve (BV), and the R-AR group included 14 patients. Patients with preoperative end-diastolic dimensions (EDD) of less than 6.0 cm were excluded from this study. The indication for AVR was NYHA functional class III or severer. The severity of preoperative NYHA functional class was similar among these three groups. During the 18-month follow-up period (range 2-32 months), there were no post-operative deaths nor congestive heart failure. Ages at surgery ranged from 17 to 54 years; 10 (71%) of 14 patients with R-AR were 40 years old or older, while seven (78%) of nine with NR-AR were under 39 years old (p less than 0.05). The pre-operative left ventricular end-diastolic pressure (LVEDP) in patients with BV-AR was highest among these three groups (R-AR: 14.5 +/- 3.9 mmHg, AP-AR: 9.5 +/- 4.1 mmHg, BV-AR: 22.0 +/- 2.7 mmHg, p less than 0.05). There was no significant difference in pre-operative M-mode echocardiographic results, except for the end-systolic dimension (ESD) between R-AR (5.20 +/- 0.55 cm) and BV-AR (4.78 +/- 0.18 cm) (p less than 0.05). The EDD one month after AVR was still abnormal (greater than or equal to 5.4 cm) in seven of the 14 patients with R-AR, and three of the four patients with AP-AR but none of the patients with BV-ARs (p less than 0.05 vs AP-AR). All patients with pre-operative ESD of less than 5.2 cm had normal EDD one month after AVR. In conclusion, the clinical course of NR-AR is different from that of R-AR. Furthermore, AP-AR regresses more differently after AVR than does BV-AR. Therefore, it is important to consider the etiology of chronic AR in determining the timing of surgery.

Adolescent↗
PubMed1989

Accuracy of diagnosis on death certificates for underlying causes of death in a long-term autopsy-based population study in Hisayama, Japan; with special reference to cardiovascular diseases.

Major categorical diagnosis by International Classification of Diseases and type-specific diagnosis for cardiovascular diseases in death certificates were compared to the diagnosis made at autopsy in 864 consecutive autopsy cases aged 20 or over, among the Japanese residents in Hisayama town. Cerebral stroke was correctly diagnosed in 84%, malignant neoplasms in 78% and cardiac disease in 66%. Cerebral stroke and cardiac disease tended to be overdiagnosed, while malignant neoplasms were underdiagnosed. The validation of certified diagnosis was less reliable in the aged population, and in type-specific diagnosis of cardiovascular diseases. Cerebral hemorrhage with false negative or false positive diagnoses was usually classified into type unspecified stroke or different categories of cerebral stroke, while those misdiagnosed as cases of cerebral infarction frequently had no significant lesions in the autopsied brain. Finally, the relationship between the validation of diagnosis on the death certificates and the secular trend in cardiovascular disease in the Japanese vital statistics was discussed.

Adult↗
PubMed1989

Aminoglycosides enhance the adherence of Staphylococcus aureus to HeLa cells.

Sub-lethal concentrations of aminoglycosides enhanced the adherence of Staphylococcus aureus FDA 209P to HeLa cells, whereas beta-lactams, pyridone carboxylic acid derivatives and chloramphenicol did not. Treatment with aminoglycosides also enhanced the bacterial adherence of these cells to immobilized fibronectin and laminin, and changed the bacterial cell surface to a more hydrophilic state than exists in non-treated cells. The adherence of S. aureus was not inhibited by lipoteichoic acid, extracted from the same strain, regardless of whether the bacterial cells were treated with an aminoglycoside or not. No correlation was observed between the adherence and zeta-potential of S. aureus.

Aminoglycosides↗
PubMed1988

A novel anthraquinone ring cleavage enzyme from Aspergillus terreus.

An enzyme activity which catalyzes the ring cleavage of the anthraquinone questin to form benzophenone desmethylsulochrin was found in the cell-free extract of Aspergillus terreus, a (+)-geodin producer. The product was identified as desmethylsulochrin by high-resolution mass spectroscopy and chemical carrier dilution analysis. The enzyme showed an absolute requirement of NADPH and molecular oxygen. Therefore, the enzyme, named questin oxygenase, was considered to be classified as a monooxygenase. The optimum pH was around 7.5. The enzyme was very unstable and lost its activity completely after storage overnight at 4 degrees C in 0.05 M phosphate buffer, pH 7.5. The instability of the questin oxygenase was partially overcome by the addition of polyols and the non-ionic detergent Tween 80 to the buffer. By DEAE-cellulose column chromatography, two protein fractions, named DE-I and DE-II, were obtained. Neither fraction reacted with questin by itself. However, the combination of DE-I and DE-II reconstituted the questin oxygenase system to convert questin to desmethylsulochrin. This result suggested that the system is not a simple combination of oxygenase and hydrolase, but requires some additional factor(s) such as electron transfer protein.

Anthraquinones↗