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Biomedical subjects

K Fujimori

Publications and source records attributed to K Fujimori.

At least 73 records · Page 4Linked to original sources

[The role of general pharmacological studies and pharmacokinetics in the evaluation of drugs (1): The role of general/safety pharmacology studies in the development of pharmaceuticals: international harmonization of guidelines].

The working group for reevaluation of the Guideline for General Pharmacology Studies has completed a draft guideline for Safety Pharmacology studies and plan to recommend replacing the existing guideline with the revised one. This proposed guideline is now subject to domestic and international consultation. The basic principle of the revision is to harmonize the guideline with the international concepts. The working group decided to change the title of "General pharmacology" to "Safety pharmacology", because the objective of this guideline is to assess the safety of a test substance in humans by examining the pharmacodynamic properties of the substance. The proposed guideline includes studies on vital functions as essential studies that should be performed prior to human exposure. Studies are also required to be conducted when predictable or unexpected observed effects are concerned. The working group recommends a case-by-case approach to select the necessary test items in consideration of the variable information available.

Animals↗

Geographical features of estuaries for neritid gastropods including Clithon retropictus to preserve thermostable direct hemolysin-producing Vibrio parahaemolyticus.

Thermostable direct hemolysin-producing strain of Vibrio parahaemolyticus was not detected from the alimentary tract of 7 neritid gastropods including Clithon retropictus at 9 estuaries of Southwest Islands in Japan in the present study. The strain has been detected from C. retropictus at 2 estuaries facing The Sea of Japan but not at 2 estuaries facing The Seto Inland Sea and The Pacific Ocean in Western Japan in our previous studies. In comparison with geographical features of the estuaries where the strain was detected and not, thick accumulation of muddy sediments at the riverbed and stagnation of brackish water at low tide seem to be essential for the strain to survive in neritid gastropods including C. retropictus.

Animals↗

A progress report of the Marshall Islands nationwide thyroid study: an international cooperative scientific study.

The objective of this report is to present a summary of progress of the Marshall Islands Nationwide Thyroid Study. As well known, the US atomic weapons testing program in the Pacific was conducted primarily between 1946 and 1958 in the Marshall Islands. The nuclear tests resulted in radioactive contamination of a number of atolls and resulted in exposure of Marshallese to undefined levels before our study. Little information has been paid to health consequences among residents of the nearly twenty inhibited atolls except for some information about nodular thyroid disease which was reported on by an US group. In a cooperative agreement with the Government of the Marshall Islands, between 1993 and 1997 we studied the prevalence of both thyroid nodules and thyroid cancer among 4766 Marshallese potentially exposed to radioiodines from bomb test fallout. That group represents more than 65% of the population at risk. We diagnosed 45 thyroid cancers and 1398 benign thyroid nodules. In addition, 23 study participants had been operated on prior to our study for thyroid cancer. Presently, we are developing a database of information to estimate radiation doses and planning a statistical analysis to determine if a dose-response relationship exists. These data will be important for the health promotion of exposed people all over the world including Hiroshima, Nagasaki, Semipalatinsk, Chernobyl and other locations. A timely completion is important for purpose of assisting Marshallese as well as to add the global understanding of radiation induced thyroid cancer.

Databases, Factual↗

[Investigation about usefulness of serum antibody of Helicobacter pylori and serum pepsinogen I/II ratio as a marker of the judgment after eradication therapy].

To clarify that serum antibody of Helicobacter pylori (H. pylori) and serum pepsinogen I/II ratio are useful or not as a marker of the judgment after eradication therapy, we followed up 84 cases who received eradication therapy comparing with culture and histology (Carnoy's fixation and immunostaining using anti-H. pylori antibody, MIA method). Successful eradication was recognized in 45 of 84 cases (successful group), and remaining 39 cases were unsuccessful (unsuccessful group). Titers of serum H. pylori antibody went down gradually in the successful group, on the other hand, they did not go down constantly and often re-went up in the unsuccessful group. The difference of the various rate of titers in the both groups became clear statistically since 6 months after eradication therapy (p < 0.05). Supposing that cut-off rate of titer was 60% of pre-eradicated titer, sensitivity, specificity, and accuracy were 86.2%, 77.7%, and 84.2%, respectively, at 6 months after eradication therapy. Serum pepsinogen I/II ratio increased regardless of successful or unsuccessful eradication, but the various rate of serum pepsinogen I/II ratio was different in both groups at 1 month and 3 months after eradication therapy (p < 0.05). Serum antibody of H. pylori and serum pepsinogen I/II ratio could be a marker of the judgment after eradication therapy, especially the various rate of serum antibody of H. pylori is useful for the monitor of H. pylori infection in the long term.

Adolescent↗

[Correlation of risk area and reverse redistribution of 99mTc-sestamibi SPECT in acute myocardial infarction following direct PTCA].

Redistribution of 99mTc-sestamibi is negligible in usual circumstances, but recent reports demonstrated reverse redistribution is detectable in acute myocardial patients. Correlation of risk area, observed in 99mTc-sestamibi "freezed" SPECT image at onset, and delayed images at 5-25 days after onset (post-PTCA image) is evaluated in 19 acute myocardial infarction patients treated with direct PTCA. Reverse redistribution was observed in 85% of reperfused area. Linear relationship of % uptake in each SPECT segment between onset and post-PTCA images (taken at 0.5, 4, and 6 hours after injection) is evaluated and the relationship improves over time course. The correlation coefficient between onset and 6 hours-delayed image is 0.88, and the visual concordance shows 77% of score matching. Delayed 99mTc-sestamibi SPECT image on reperfused AMI seems to represent risk area with some underestimation. It may be useful to estimate both risk and salvaged areas on early and delayed SPECT with a single 99mTc-sestamibi injection.

Adult↗

[Pranoprofen-induced lung injury manifesting as acute eosinophilic pneumonia].

A 48-year-old man was admitted to our hospital complaining of fever, dyspnea, and cough. He had been treated with pranoprofen and antibiotics by an outpatient clinic for the preceding 4 days. Chest X-ray films revealed Kerley B lines, perivascular cuffing, and hilar haze with pleural effusion in both lungs. Chest computed tomographic films showed non-segmental patchy infiltrates, and thickening of bronchovascular bundles and interlobular septa. Laboratory data showed eosinophilia in peripheral blood (28%) and severe hypoxemia (PaO2:60 torr). Bronchoalveolar lavage fluid disclosed an increased total cell count, eosinophils (39%), and CD 4/CD 8 ratio (2.1). Microscopic examination of transbronchial lung biopsy specimens showed infiltration of eosinophils and mononuclear cells into alveolar wall's and spaces. Acute eosinophilic pneumonia was suspected on the basis of Allen's diagnostic criteria (N Engl J Med: 1989). After discontinuation of pranoprofen, the patient's clinical symptoms, laboratory data, and chest X-ray findings improved rapidly without steroid therapy. A leukocyte migration test (LMT) for pranoprofen was positive and a challenge test for smoking was negative. An environmental provocation test in the patient's home gave negative results. A challenge test for pranoprofen was not performed due to the lack of informed consent. Based on these findings, our diagnosis was pranoprofen-induced lung injury manifesting as acute eosinophilic pneumonia.

Acute Disease↗

[The diagnostic role of the methacholine inhalation challenge in adult patients with chronic persistent cough].

Chronic persistent cough (CPC) is a common medical problem. We determined the value of the methacholine inhalation challenge (MIC) in the evaluation of CPC. We also sought other clinical factors that affect MIC. Patients were selected for the study if 1) CPC was the only presenting symptom, 2) a current roentgenogram did not contribute to the diagnosis, and 3) spirometry revealed a normal FEV1. We measured the minimum dose of methacholine (bronchial sensitivity, Dmin) by the "Asthograph" method. We determined the correlation between log Dmin and demographic and clinical variables, i.e. age, %FVC, %FEV1, FEV1%, %V50, %V25, eosinophil count in peripheral blood, and serum IgE level. The causes of CPC in 51 patients (20 men and 31 women, mean age 41 years) were cough-variant asthma in 29 patients, postinfectious persistent cough in 13 patients, atopic cough in 6 patients, and others in 3 patients. Log Dmin significantly but weakly correlated with %V25 (4 = 0.31, p = 0.02). The sensitivity and specificity of Dmin (< 10 units) in diagnosing cough-variant asthma was 93% and 87%, respectively. Demographic or clinical variables other than Dmin were not useful for the diagnosis of cough-variant asthma. We conclude that MIC is useful for the differential diagnosis of CPC while the usefulness is limited in some cases.

Adult↗

[Estimation of 99mTc-GSA receptor amount by non-linear 3-compartment model: ligand-receptor binding model without blood sampling].

99mTc-GSA (galactosyl serum albumin) receptor amount (Ro) was estimated by a non-linear 3-compartment model of the ligand-receptor binding without blood sampling. Forward/reverse rate constants and receptor amount were assumed to be variable. Relationship between this parameter and other conventional parameters including ICG R15 (15-minutes retention rate of indocyanine green) was evaluated for 43 surgical candidates with liver tumors. Linear relationships between Ro and HH15 and LHL15 were R2 = 0.73 and 0.72, respectively. Linear relationship between Ro and Rmax, the maximum removal rate, is also good (R2 = 0.84), and the regression line (y = 0.038x + 0.066) was slightly over 0 at y-interception. Linear relationship between Ro and ICG R15, was poor (R2 = 0.39) and relationship was rather a concave shape. Linear relationship of reduction rate between Ro and non-tumor tissue volume of the liver, which assessed at the same day of two weeks after the operation, was y = 1.09x - 0.01 (R2 = 0.82). GSA receptor amount, Ro, seems to change proportional to non-tumor liver tissue volume changing before and after hepatectomy. Complementary to ICG R15, it may be an useful and intuitive parameter for hepatectomy.

Asialoglycoprotein Receptor↗

Re-assessment of stage I uterine cervical carcinoma according to revised JSGO (1997) staging.

BACKGROUND: The Japanese Society of Gynecologist and Obstetrician (JSGO) revised criteria for early uterine cervical cancer. OBJECTIVE: In this study, we investigated the value of the revised JSGO criteria. METHOD: Retrospective review was performed for 70 patients with tumors limited to the uterine cervix who were classified stage I under old JSGO criteria. RESULT: Forty patients were re-classified into stage IA1 and 4 patients into stage IA2. Incidence of lymph-vascular infiltration (LVI) in stage IA1 and IA2 were 5% and 25%. There was one patient with stage IA1 disease who had nodal metastasis and no patients with stage IA2 disease. There were 14 patients with stage IB1 disease and 12 patients with stage IB2 disease. Mortality of patients with stage IB2 disease was 25% and significantly higher than that of patients with stage IA and IB1 disease (P<0.001 and <0.05) CONCLUSION: Although the revised JSGO criteria for early cervical cancer are acceptable for assessment of patients, the therapy of patients is still controversial. We recommend that patients with stage IA1 and negative LVI should have less radical hysterectomy and patients with stage IA1 with LVI or stage IA2, IB should have radical hysterectomy.

Adult↗

Inactivation of bacterial respiratory chain enzymes by singlet oxygen.

To distinguish the bactericidal action of singlet oxygen (1O2) from hypohalous acids, wild-type and lycopene transformant E. coli strains were exposed to each of the oxidants and then bacterial viability was investigated. 1O2 was generated by chemical and enzymatic systems at pH 4.5. ExpoSure of wild-type E. coli to 1O2 caused a significant loss of E. coli viability due to inactivation of membrane respiratory chain enzymes by 1O2. This action of 1O2 could be attenuated by lycopene in the bacterial cell membrane. In the lycopene transformant strain of E. coli, inactivation of NADH oxidase and succinate oxidase by hypohalous acids were significantly suppressed, but E. coli viability was unaffected. Based on these findings, we suggest that phagocytic leukocytes produce 1O2 as a major bactericidal oxidant in the phagosome.

Bromides↗

Useful 1O2 (1delta g) generator, 3-(4'-methyl-1'-naphthyl)-propionic acid, 1',4'-endoperoxide (NEPO), for dioxygenation of squalence (a skin surface lipid) in an organic solvent and bacterial killing in aqueous medium.

3-(4'-Methyl-1'-naphthyl)-propionic acid, 1',4'-endoperoxide (NEPO) provides singlet state of oxygen (1O2, 1delta g) at 37 degrees C in sodium phosphate buffer (pH 7.2), acetate buffer (pH 4.5), methanol or chloroform, through the retro-Diels-Alder reaction. The total amount of 1O2 generated by NEPO was calculated using the following equation: [1O2]= [NEPO]0[1-exp(-kt)], where [1O2], [NEPO]0 and k are the total amount of 1O2 produced during the time t, initial concentration of NEPO and the first-order reaction rate constant, respectively. When squalene was exposed to 1O2 which was generated thermolytically from NEPO, it was oxidized to three hydroperoxides, mono-, di- and tri-hydroperoxides, in amounts proportional to the dose of NEPO. The oxidizability of squalene was much more extensive compared with unsaturated phospholipids. Additionally, when wild-type E. coli and lycopene-producing mutant E. coli were exposed to NEPO-derived 1O2, there was significant loss of viability of wild-type E. coli but no significant loss of viability in lycopene-producing strain, suggesting that lycopene by scavenging 1O2 protected E. coli against 1O2 toxicity.

Anti-Bacterial Agents↗

An Arabidopsis cDNA encoding a bifunctional glutamine amidotransferase/cyclase suppresses the histidine auxotrophy of a Saccharomyces cerevisiae his7 mutant.

A cDNA encoding a glutamine amidotransferase and cyclase catalyzing the fifth and sixth steps of the histidine (His) biosynthetic pathway has been isolated from Arabidopsis thaliana. The N- and C-terminal domains of the primary structure deduced from a full-length Arabidopsis hisHF (At-HF) cDNA showed significant homology to the glutamine amidotransferase and cyclase of microorganisms, respectively. Effective suppression of the His auxotrophy of a Saccharomyces cerevisiae his7 mutant with the At-HF cDNA confirmed that the At-HF protein has bifunctional glutamine amidotransferase (HisH) and cyclase (HisF) activities.

Amino Acid Sequence↗

Trace elements found to be variable in two coral reef species, Heliofungia actiniformis and Galaxea fascicularis, collected from the Ryukyu Islands.

Biominerals and metals of intertidal corals of two species (Heliofungia actiniformis, Quoy and Gaimard; Galaxea fascicularis, Linnaeus), collected from the Iriomote Island of Ryukyu, were examined with an inductively coupled plasma atomic emission spectrometer (ICP-AES). Twelve elements were detectable in the coralline skeletons dissected radially along the growth axis. The relative content (RC) of Hg periodically fluctuated and was minimum at the hollow sites of the coralline slab of Heliofungia sp., corresponding to the cyclic growth. There were two types of elements: constant elements and variable elements along the growth axis. RCs of Ca, Mg, Al, Si, and P were nearly constant. RCs of Fe, Mn, Cu, and Ba were variable, but not as regularly changed as Hg. There were positive mass correlations of Hg to Mn, Cu and Zn, but not to Ba and Fe. In contrast, these relationships were not prominent and were likely degraded by aging in the skeleton of Galaxea sp., suggesting a different mode from that of the Heliofungia sp.

Animals↗

Molecular cloning and characterization of the gene encoding N'-[(5'-phosphoribosyl)-formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (BBM II) isomerase from Arabidopsis thaliana.

We have isolated an Arabidopsis BBM II isomerase cDNA from an Arabidopsis cDNA library, by means of functional complementation of the E. coli hisA mutant strain HfrG6. The isolated cDNA encodes a polypeptide of 304 amino acids with a calculated molecular weight of 33,363. Sequence comparison with the HIS6 proteins of yeasts revealed that Arabidopsis BBM II isomerase contains an N-terminal extension of approximately 40 amino acids that shows the general properties of chloroplast transit peptides. This finding is consistent with the localization of other histidine biosynthetic enzymes, such as imidazoleglycerolphosphate dehydratase and histidinol dehydrogenase, in the chloroplasts in higher plants. The primary structure of the mature protein was 50% and 42% identical, respectively, to the HIS6 proteins of Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively, while no prominent sequence similarity to the bacterial BBM II isomerase was found. That the isolated Arabidopsis cDNA actually encodes a functionally active BBM II isomerase activity was confirmed in an in vitro enzyme assay using a crude extract prepared from strain HfrG6 transformed with the Arabidopsis BBM II isomerase cDNA.

Aldose-Ketose Isomerases↗

Age-specific incidences of chromosome abnormalities at the second trimester amniocentesis for Japanese mothers aged 35 and older: collaborative study of 5484 cases.

The aim of this study was to calculate the expected incidences of chromosome abnormalities found at amniocentesis in Japanese women aged 35 and older. From four clinics in Japan, we gathered genetic amniocentesis data on 5484 pregnant women at risk only due to their advanced age, 35 years and older. We analyzed the data using the logistic regression model. Of the 5484 fetuses, 117 (2.1%) were diagnosed with a chromosome abnormality. The abnormal karyotypes included 42 cases of trisomy 21; 13 of trisomy 18; 7 of trisomy 13; 10 of 47,XXY; 4 of 47,XXX; 1 of 47,XYY; 27 with various structural aberrations; and 13 with various types of mosaicism. The incidences of trisomy 21, lethal autosomal aneuploidies (trisomy 18 and trisomy 13), and sex-chromosome abnormalities (XXY, XXX, XYY) increased with maternal age. Parameters of the regression equations with their standard errors were calculated and the expected incidences of chromosome abnormalities at each maternal age were derived. The expected incidences of chromosome abnormalities obtained in this study are the first data published for Japan and will be useful for the counseling of pregnant women. The incidence of trisomy 21 is not different from the rates published previously for Western countries. The incidences of chromosome abnormalities are not affected by race or by geographic factors.

Age Factors↗