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Biomedical subjects

K Fujimori

Publications and source records attributed to K Fujimori.

At least 55 records · Page 3Linked to original sources
PubMed2000

Identification of mu-class glutathione transferases M2-2 and M3-3 as cytosolic prostaglandin E synthases in the human brain.

Cytosolic prostaglandin (PG) E synthase was purified from human brain cortex. The N-terminal amino acid sequence, PMTLGYXNIRGL, was identical to that of the human mu-class glutathione transferase (GST) M2 subunit. Complementary DNAs for human GSTM2, GSTM3, and GSTM4 subunits were cloned, and recombinant proteins were expressed as homodimers in Escherichia coli. The recombinant GSTM2-2 and 3-3 catalyzed the conversion of PGH2 to PGE2 at the rates of 282 and 923 nmol/min/mg of protein, respectively, at the optimal pH of 8, whereas GSTM4-4 was inactive; although all three enzymes showed GST activity. The PGE synthase activity depended on thiols, such as glutathione, dithiothreitol, 2-mercaptoethanol, or L-cysteine. Michaelis-Menten constants and turnover numbers for PGH2 were 141 microM and 10.8 min(-1) for GSTM2-2 and 1.5 mM and 130 min(-1) for GSTM3-3, respectively. GSTM2-2 and 3-3 may play crucial roles in temperature regulation, nociception, and sleep-wake regulation by producing PGE2 in the brain.

Amino Acid Sequence↗
PubMed2000

Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase. Conservation of the ancestral genomic structure of sigma-class glutathione S-transferase.

Hematopoietic prostaglandin D synthase (H-PGDS) is the key enzyme for the production of the D and J series of prostanoids, and the first recognized vertebrate homolog of sigma-class glutathione S-transferase (GST). We isolated the genes and cDNAs for human and mouse H-PGDSs. The human and mouse cDNAs contained a coding region corresponding to 199 amino-acid residues with calculated molecular masses of 23 343 and 23 226, respectively. Both H-PGDS proteins recombinantly expressed in Escherichia coli showed bifunctional activities for PGDS and GST, and had almost the same catalytic properties as the rat enzyme. Northern analyses demonstrated that the H-PGDS genes were expressed in a highly species-specific manner. Whereas the human gene was widely distributed, in contrast, the mouse gene was detected only in samples from oviduct and skin. By fluorescence in situ hybridization, the chromosomal localization of the human and mouse H-PGDS genes were mapped to 4q21-22 and 3D-E, respectively. The human and mouse H-PGDS genes spanned approximately 41 and 28 kb, respectively, and consisted of six exons divided by five introns. The exon/intron boundaries of both genes were completely identical to those of the sigma-class GST subfamily, although the amino-acid sequences of the latter were only 17.0-21.5% identical to those of either H-PGDS. These findings suggest that the H-PGDS genes evolved from the same ancestral gene as the members of the sigma-class GST family.

Amino Acid Sequence↗
PubMed2000

Molecular cloning and characterization of ATP-phosphoribosyl transferase from Arabidopsis, a key enzyme in the histidine biosynthetic pathway.

We have characterized two isoforms of ATP-phosphoribosyl transferase (ATP-PRT) from Arabidopsis (AtATP-PRT1 [accession no. AB025251] and AtATP-PRT2), catalyzing the first step of the pathway of hisidine (His) biosynthesis. The primary structures deduced from AtATP-PRT1 and AtATP-PRT2 cDNAs share an overall amino acid identity of 74.6% and contain N-terminal chloroplast transit peptide sequences. DNA-blot analyses indicated that the ATP-PRTs in Arabidopsis are encoded by two separate genes with a closely similar gene structural organization. Both gene transcripts were detected throughout development, and protein-blot analysis revealed predominant accumulation of the AtATP-PRT proteins in Arabidopsis leaves. The His auxotrophy of a his1 mutant of Saccharomyces cerevisiae was suppressed by the transformation with AtATP-PRT1 and AtATP-PRT2 cDNAs, indicating that both isoforms are functionally active ATP-PRT enzymes. The K(m) values for ATP and phosphoribosyl pyrophosphate of the recombinant AtATP-PRT proteins were comparable to those of the native ATP-PRTs from higher plants and bacteria. It was demonstrated that the recombinant AtATP-PRTs were inhibited by L-His (50% inhibition of initial activity = 40-320 microM), suggesting that His biosynthesis was regulated in plants through feedback inhibition by L-His.

ATP Phosphoribosyltransferase↗
PubMed2000

[Multiple nodular and patchy shadows in chest radiograph in a patient with autoimmune hemolytic anemia associated with chronic thyroiditis].

A 65-year-old woman was admitted because of dyspnea and persistent cough. Her chest radiograph and CT films revealed multiple nodular and patchy shadows in bilateral lungs, indicating bronchiolitis obliterans organizing pneumonia (BOOP)-like shadows. Autoimmune hemolytic anemia was diagnosed because peripheral blood cell analysis revealed anemia (hemoglobin, 5.5 g/dl) with increased reticulocytes (253/1000), and positive direct and indirect Coomb's tests. In addition, decreased diffusion capacity and mild hypoxemia (PaO2, 71 Torr) were recognized. Bronchoalveolar lavage fluid (BALF) showed the increased number of total cells and lymphocytes, and a decreased CD4(helper)/CD8(suppressor) ratio (= 0.65). Histopathological features of transbronchial lung biopsy showed an infiltration of lymphocytes in the alveolar walls and spaces, and thickening of the alveolar walls. A discrepancy was apparent among roentgenogram, histopathological findings and BALF results. Open lung biopsy had not been performed because of severe hemolytic anemia and lack of informed consent. In addition, the patient suffered from chronic thyroiditis with positive thyroid autoantibody. After oral administration of prednisolone, both pulmonary shadows and anemia improved. We concluded that autoimmune hemolytic anemia may be associated with steroid-sensitive interstitial lung lesions in some cases. Further immunologic studies are necessary to elucidate the relationship between autoimmune hemolytic anemia and interstitial lung shadows.

Aged↗
PubMed2000

[Levofloxacin-induced eosinophilic pneumonia complicated by bronchial asthma].

A 76-year-old woman who had complained of cough and productive sputum since mid-January, 1999, was admitted to our hospital with fever and dyspnea on February 4, 1999. She had been treated with levofloxacin at an outpatient clinic. On admission, she had orthopnea, and auscultation revealed coarse crackles and wheeze in the bilateral lung fields. Chest x-ray and CT films showed non-segmental infiltration in bilateral lung fields. Laboratory data revealed eosinophilia in peripheral blood (= 24%) and sputum (= 10%), airflow limitation, hypoxemia (PaO2: 46 Torr), and increased airway responsiveness to methacholine (Dmin: 0.127 units). A bronchoalveolar lavage (BAL) fluid showed increased total cells and a 55% increase in eosinophils, and CD4/CD8 ratio was decreased to 0.8. In addition, IL-5 was increased in BAL fluid. Transbronchial lung biopsy specimens revealed infiltrations of eosinophils in the alveolar and interstitial compartments. Histological features of the bronchial biopsy specimens included increased eosinophils in the submucosa and goblet cell metaplasia. The woman was diagnosed with eosinophilic pneumonia complicated by bronchial asthma. She was given theophylline, pranlukast hydrate, and an inhaled beta 2 receptor agonist (procaterol hydrochloride), and pre-admission drugs including Levofloxacin were discontinued. Her symptoms were improved, peak expiratory flow rate and PaO2 increased, airway responsiveness to methacholine decreased (Dmin: 0.615 units), and radiographic abnormalities disappeared without steroid therapy. A leukocyte migration test for levofloxacin was weakly positive. An environmental provocation test in the patient's home gave negative results. A challenge test for levofloxacin was not performed due to a lack of informed consent. Based on these findings, we diagnosed this case as levofloxacin-induced lung injury manifesting as eosinophilic pneumonia complicated by bronchial asthma. Levofloxacin should be added to the list of agents that can produce eosinophilic pneumonia.

Aged↗
PubMed1999

Matrix metalloproteinases and lysosomal cysteine proteases in osteoclasts contribute to bone resorption through distinct modes of action.

The effects of inhibitors of matrix metalloproteinases (MMPs) and lysosomal cysteine proteases on osteoclastic pit formation in dentine slices were investigated. A nonspecific cysteine protease inhibitor, E-64, inhibited pit formation on naked slices in a concentration-dependent manner, and at 10 microM E-64 reduced the pit volume by 70%. However, up to 10 microM of the MMP inhibitor, BB-94, did not show any inhibition of pit formation. On the other hand, on slices coated with reconstituted basement membrane, both BB-94 and E-64 at 10 microM showed a marked decrease in pit volume by 73% and 68%, respectively. By a combination of treatment with both BB-94 and E-64, pit formation could be completely suppressed. These results suggest that MMPs are necessary for the migration of precursor and/or immature osteoclasts to bone surface through basement membranes, while cysteine proteases are essential for the osteoclastic degradation of bone collagen.

Animals↗
PubMed1999

Antepartum diagnosis of fetal intracranial hemorrhage due to maternal Bernard-Soulier syndrome.

BACKGROUND: Bernard-Soulier syndrome, a lack of glycoprotein IB/IX, is a rare autosomal recessive bleeding disorder characterized by platelet dysfunction. Women with Bernard-Soulier syndrome are at risk of being immunized against glycoprotein IB/IX, leading to severe isoimmune neonatal thrombocytopenia. CASE: A 26-year-old Japanese woman, gravida 1, para 0, with Bernard-Soulier syndrome presented at 35 weeks' gestation with changes in fetal heart rate patterns and ultrasonographic findings that strongly suggested fetal intracranial hemorrhage. Management was by cesarean hysterectomy and bilateral salpingo-oophorectomy at 36 weeks, but the neonate died 6 hours after birth. CONCLUSION: Maternal immunization to glycoprotein IB/IX during pregnancy can cause severe fetal thrombocytopenia and massive intracranial bleeding.

Adult↗
PubMed1999

Eye-head coordination abnormalities and regional cerebral blood flow in Alzheimer's disease.

1. Three patients with Alzheimer's disease (AD) and three healthy controls (HC) were examined for eye-head coordination. Regional cerebral blood flow (rCBF) was measured in AD patients. 2. Eye-head coordination was analyzed using a Vision analyzer, and magnetic sensors. The authors measured the rCBF with 123I-IMP, and 99mTc-ECD SPECT. 3. AD reduced gaze accuracy and head movements, and prolonged the latency of saccade as compared to HC. AD patients had a tendency to focus on the target by using eye movements only. 4. AD reduced the rCBF in the inferior parietal part and the visual area, relative to the motor area. Damage of these areas may have caused the eye-head coordination disorders in the AD patients.

Adult↗
PubMed1999

Bis-N-nitroso-caged nitric oxides: photochemistry and biological performance test by rat aorta vasorelaxation.

Three new caged nitric oxides (NOs)-BNN3, BNN5Na, and BNN5M were tested for biological use. BNNs have a strong ultraviolet (UV) absorption band (lambda(max): 300 nm, epsilon: 13.5 mM(-1) cm (-1)) extended to 420 nm and produce NO upon irradiation with 300-360 nm light in quantum yields about 2. A photoexcited BNN molecule yields two NOs with time constants of less than 10 ns for phase 1 and less than 20 micros for phase 2 at 37 degrees C, suggesting usefulness of BNNs for measuring in vivo and in vitro fast NO reactions. Upon irradiating with UV light, caged nitric oxides-loaded rat aortic strips maintained in a state of active tonic contraction effectively relaxed ( < 3 microM BNN5M loading solution concentration). BNN3 is incorporated in the lipid membrane. BNN5Na, insoluble in organic solvents but water soluble, localizes in the water phase. BNN5M, is muscle-cell-permeable and hydrolysed to BNN5Na to remain in cytosol. BNNs were thermally stable and demonstrated no observable toxicity.

Animals↗
PubMed1999

Thyroid nodules, thyroid function and dietary iodine in the Marshall islands.

BACKGROUND: Thyroid nodules have been found to be common in the population of the Marshall Islands. This has been attributed to potential exposure of radioiodines from the nuclear weapons tests on Bikini and Eniwetok between 1946 and 1958. METHODS: In order to get a full picture of thyroid pathology in the Marshallese population potentially exposed to radioactive fallout we performed a large thyroid screening programme using palpation, high resolution ultrasound and fine needle biopsies of palpable nodules. In addition, various parameters of thyroid function (free T3, free T4, thyroid stimulating hormone [TSH]) and anti-thyroid antibodies were examined in large proportions of the total population at risk. Since dietary iodine deficiency is an established risk factor for thyroid nodules, iodine concentration in urine samples of 362 adults and 119 children was measured as well as the iodine content of selected staple food products. RESULTS: The expected high prevalence of thyroid nodules was confirmed. There was no indication of an increased rate of impaired thyroid function in the Marshallese population. A moderate degree of iodine deficiency was found which may be responsible for some of the increased prevalence of thyroid nodules in the Marshallese population. CONCLUSIONS: Studies on the relationship between exposure to radioiodines and thyroid nodules need to take dietary iodine deficiency into account in the interpretation of findings.

Adult↗
PubMed1999

Prenatal diagnosis of intrapericardial teratoma: a case report.

A hydropic fetus that exhibited intrapericardial teratoma with marked pericardial effusion was prenatally diagnosed. Intrauterine pericardiocentesis was performed to diagnose and to treat hydrops. Pericardiocentesis for tamponade secondary to a fetal intrapericardial teratoma might prevent fetal death and premature delivery.

Adult↗
PubMed1999

Risk of recurrence of fetal chromosomal aberrations: analysis of trisomy 21, trisomy 18, trisomy 13, and 45,X in 1,076 Japanese mothers.

OBJECTIVE: To evaluate the risk of recurrence of fetal chromosomal aberrations in women who had offspring with numeric chromosomal abnormalities. SUBJECTS AND METHODS: This collaborative study consisted of 1,076 Japanese women with a history of offspring with trisomy-21, -18, -13, or 45,X. Second-trimester amniocenteses were performed, resulting in 1,248 fetal karyotypes that were analyzed with reference to prior offspring karyotypes and maternal age. RESULTS: Of the 842 women with trisomy-21 offspring, 10 conceived another such fetus. In 2 women with 3 or more such offspring, parental mosaicism of trisomy-21 was suspected. The incidence of recurrence of trisomy-21 increased with age, and significantly exceeded the incidence of trisomy-21 fetuses in the general population. None of the 170 women with trisomy-18 offspring, and none of the 46 women with trisomy-13 offspring, had another such fetus. Of the 18 women with 45,X offspring, 1 with mos 45,X/46,XX had another such fetus. CONCLUSIONS: The risk of recurrence of trisomy-21 is affected by maternal age and parental germline mosaicism. The risk of recurrence of trisomy-18 or -13 appears to be much lower than that of trisomy-21. Women who give birth to more than 1 offspring with 45,X should be examined for mos 45,X/46,XX.

Adult↗
PubMed1999

[Pulmonary complications in adult measles].

The clinical features of pulmonary complications were evaluated in 15 patients with adult measles diagnosed by clinical and serologic investigations. Of those 15 patients, 12 were admitted because of high fever, sever anorexia and dyspnea. Almost all patients were found to have thrombocytopenia, elevations of LDH and aminotransferase. Pulmonary infiltrates were present in only 2 of the 12 patients (16.7%) on whom chest roentgenograms were performed, but hypoxemia (PaO2 < 70 Torr) were present in 8 of the 12 patients (66.7%). Pulmonary function tests in 8 patients showed mild decrease in VC, moderate decrease in FEV1 and severe decrease in V25. These findings suggest that hypoxemia in patients with normal chest radiographs may be largely caused by bronchiolitis. The observations of sequential peak flow rate measurement showed that severe pulmonary dysfunction continued for 4-5 days after the onset of the rash. To avoid the development of respiratory failure, patients with measles should be carefully monitored for bacterial superinfections of the respiratory tract especially within several days after the appearance of the rash.

Adolescent↗