Search PubMed⌕ Search

Biomedical subjects

A Furukawa

Publications and source records attributed to A Furukawa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Inhibition by retinoids of benzo(A)pyrene metabolism catalyzed by 3-methylcholanthrene-induced rat cytochrome P-450 1A1.

Benzo(a)pyrene, a well-known procarcinogen, is believed to be activated by microsomal cytochrome P-450 1A1 (CYP 1A1). We recently reported that rat CYP 1A1 induced by 3-methylcholanthrene (3-MC) catalyzed the conversion of retinal to retinoic acid. In this study, we investigated retinoid inhibition of the metabolism of benzo(a)pyrene and 7-ethoxyresorufin, another specific substrate of CYP 1A1, using liver microsomes prepared from control and 3-MC-pretreated rats as the enzyme source. In 3-MC-treated rats, retinal and retinol, but not retinoic acid, inhibited benzo(a)pyrene metabolism. The 50% inhibitory concentration (IC50) of retinal was about 11.5 micromol/L and the inhibition was competitive, with a Ki value of 5.8 micromol/L. Retinol is a more potent inhibitor than retinal. The IC50 was about 5 micromol/L and the inhibition was mixed, with a Ki value of 19.2 micromol/L and a Ki' value of 4.2 micromol/L. Almost the same results were obtained for the reaction of 7-ethoxyresorufin deethylation. In contrast, the metabolic activity of both benzo(a)pyrene and 7-ethoxyresorufin was much lower in untreated versus 3-MC-treated rats, and only weak inhibition by the retinoids was observed. The results suggest that retinoids inhibit the activation of benzo(a)pyrene and that the substrate specificity of cytochrome P-450 isozymes associated with retinoid metabolism should be taken into account when studying the anticarcinogenic action of retinoids.

Animals↗
PubMed1999

[CT findings of pulmonary infections].

Although many pulmonary infections are diagnosed using chest radiographs in combination with clinical findings and are treated empirically with antibiotics, there are situations in which chemotherapy is not effective and further examinations are necessary. In those cases, CT, especially high-resolution CT (HRCT), can provide additional information about detailed morphological changes of the lung that are sometimes indicative of the causative organisms of pneumonia, such as pulmonary tuberculosis. Although it is true that the same organism can present a wide spectrum of radiological findings, it is also important for differential diagnosis to understand the basic features of pathological changes of the lung and the CT findings caused by each of the various organisms. Such CT information would also be useful in differentiating infectious pneumonia from noninfectious pneumonia. This review article presents the principal CT findings of pulmonary infections and their pathological correlations with various pneumonias, including bacterial, tuberculous, fungal, and viral pneumonias.

Bronchi↗
PubMed1999

[Recent advances in CT diagnosis of chronic obstructive pulmonary diseases].

With high-resolution CT (HRCT), morphological changes of the lung caused by chronic obstructive pulmonary disease can be evaluated in detail at the level of secondary pulmonary lobule. The location of emphysematous lesions within the lobule can be judged on HRCT images and bronchiolar abnormalities are also demonstrated as thickening of peripheral bronchovascular bundles. In addition to early detection of morphological changes, quantitative evaluation of the severity of the disease is also important. For this purpose, visual assessment with CT scores, quantitative evaluation using "density mask" technique, or histogram analysis are employed. Quantitative parameters provided by these methods correlate well with pathological scores and results of pulmonary function tests. Furthermore, respiratory dynamic CT or paired inspiratory and expiratory CT is also useful to detect air trapping caused by bronchiolar stenosis.

Humans↗
PubMed1998

Essential dynamics of DNA containing a cis.syn cyclobutane thymine dimer lesion.

Conformational properties of a UV-damaged DNA decamer containing a cis.syn cyclobutane thymine dimer (PD) have been investigated by molecular dynamics (MD) simulations. Results from MD simulations of the damaged decamer DNA show a kink of approximately 21.7 degrees at the PD damaged site and a disruption of H bonding between the 5'-thymine of the PD and its complementary adenine. However, no extra-helical flipping of the 3'-adenine complementary to the PD was observed. Comparison to two undamaged DNA decamers, one with the same sequence and the other with an AT replacing the TT sequence, indicates that these properties are specific to the damaged DNA. Essential dynamics (ED) derived from the MD trajectories of the three DNAs show that the backbone phosphate between the two adenines complementary to the PD of the damaged DNA has considerably larger mobility than the rest of the molecule and occurs only in the damaged DNA. As observed in the crystal structure of T4 endonuclease V in a complex with the damaged DNA, the interaction of the enzyme with the damaged DNA can lead to bending along the flexible joint and to induction of adenine flipping into an extra-helical position. Such motions may play an important role in damage recognition by repair enzymes.

Adenine↗
PubMed1998

Serum levels of soluble interleukin-2 receptor in renal cell carcinoma.

OBJECTIVES: To evaluate increased serum soluble interleukin-2 receptor (sIL-2R) levels in patients with renal cell carcinoma (RCC). METHODS: Serum sIL-2R levels were measured in 52 patients with RCC and 10 control subjects by an enzyme-linked immunosorbent assay (ELISA) technique. The correlation between serum sIL-2R levels and clinical stage, disease prognostic value, and inflammatory marker levels was analyzed. RESULTS: Serum sIL-2R levels in patients with RCC were significantly higher than those in normal control subjects (857.2 +/- 660.0 versus 291.3 +/- 76.4 U/mL, P < 0.0001). High serum sIL-2R levels appeared to be related to advanced clinical stage (596.0 +/- 276.5 U/mL in Stage II, 776.1 +/- 398.8 U/mL in Stage III, and 1310.0 +/- 926.7 U/mL in Stage IV: Stage II vs. Stage III, P = 0.0078; Stage II vs. Stage IV, P < 0.0001). The overall cause-specific survival curves showed that patients with high sIL-2R levels (more than 1000 U/mL) had a significantly lower survival rate than those with low (less than 500 U/mL, P = 0.0003) or intermediate levels (500 to 1000 U/mL, P = 0.0007). C-reactive protein levels apparently increased in patients with high sIL-2R concentrations. CONCLUSIONS: Measurement of serum sIL-2R concentrations in patients with RCC provides useful information for predicting the extent of disease and length of survival.

Adult↗
PubMed1998

Role of the matrix metalloproteinase and tissue inhibitors of metalloproteinase families in noninvasive and invasive tumors transplanted in mice with severe combined immunodeficiency.

OBJECTIVES: To elucidate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human urothelial cancers, we studied gene expressions of MMPs, TIMPs, and membrane-type 1 matrix metalloproteinase (MT1-MMP) in noninvasive or invasive tumor lines transplanted in mice with severe combined immunodeficiency (SCID). METHODS: The UCT-1 tumor line, derived from bladder cancer, is a noninvasive transplantable tumor with no evidence of metastasis. The UCT-2 tumor line, derived from a renal pelvic tumor, extensively invades without metastasis. We examined gene expressions of MMPs-1, 2, 3, 7, 8, 9, 10, and 11, TIMPs-1, 2, and 3, and MT1-MMP in UCT-1 and 2 by semiquantitative polymerase chain reaction analysis. RESULTS: Significantly higher gene expression of MMP-2 was detected in the invasive UCT-2 tumor line than in the noninvasive UCT-1 tumor line. Although both tumor lines expressed TIMP-1 and MT1-MMP, stronger gene expression of MT1-MMP was observed in the UCT-2 tumor line than in the UCT-1 tumor line. The other MMPs or TIMPs were not detected in either of the lines. CONCLUSIONS: MMP-2 and MT1-MMP may have an important role in the invasion mechanism of urothelial cancers.

Aged↗
PubMed1998

Steroidogenic acute regulatory protein (StAR) transcripts constitutively expressed in the adult rat central nervous system: colocalization of StAR, cytochrome P-450SCC (CYP XIA1), and 3beta-hydroxysteroid dehydrogenase in the rat brain.

Steroidogenic acute regulatory protein (StAR) is a 30-kDa protein involved in the transport of cholesterol to the inner mitochondrial membrane and thus plays a key role in steroid biosynthesis. To clarify the implications of this protein in neurosteroid biosynthesis, we examined the possible expression of a StAR transcript in the adult rat CNS and detected it. cDNA cloning and sequencing analysis revealed that two forms of StAR mRNAs are expressed in the brain in the same manner as in the adrenal gland, indicating that they are fully functional and not minor gene transcripts. An RNase protection assay quantitatively revealed that the amount of the rat StAR transcript in brain was two to three orders of magnitude lower than that in the adrenal gland. An in situ hybridization study, involving antisense riboprobes, revealed that StAR transcripts were abundant in the cerebral cortex, hippocampus, dentate gyrus, olfactory bulb, cerebellar granular layer, and Purkinje cells. Furthermore, other steroidogenic enzymes, side-chain cleavage cytochrome P-450SCC (CYP XIA1) and 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (EC 1.1.1.145), were found to be coexpressed in the hippocampus, dentate gyrus, cerebellar granular layer, and Purkinje cells. These findings strongly indicate that neurosteroids are synthesized in a region-specific manner in the brain.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Non-fluorescent chromosome painting using the peroxidase/diaminobenzidine (DAB) reaction.

PURPOSE: To develop and validate non-fluorescent chromosome painting for bright-field microscopy using the peroxidase/diaminobenzidine (DAB) reaction. MATERIALS AND METHODS: Peripheral blood lymphocytes were taken from patients with uterine cancer who had received heavy-ion radiation therapy. Chromosome slides were treated with RNase and pepsin, denatured mildly, hybridized with a biotinylated DNA probe specific for whole-chromosome 4 and stained using the peroxidase/DAB reaction with an avidin-biotin amplification. The slides were analysed under a bright-field microscope and an atomic force microscope. The detection rate of chromosome aberrations by DAB painting was compared with that obtained by dual analysis of Giemsa staining and FISH painting. RESULTS: When chromosomes 4 were painted, 11.5% of unstable aberrations were detected by DAB painting, while 10.8% of them were found by dual analysis of Giemsa staining and FISH painting. CONCLUSION: A DAB painting method that can effectively detect rearranged aberrations was established. It has advantages over FISH painting: the preparations can be analysed by bright-field microscope, can be preserved permanently and are suitable for analysis by an automated system.

3,3'-Diaminobenzidine↗
PubMed1998

Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptide in human plasma.

Recently, the N-terminal fragment of proatrial natriuretic peptide (N-terminal proANP) has been proposed as a marker of chronic congestive heart failure. In this study, we established a two-step immunoradiometric assay using monoclonal antibodies and synthetic N-terminal proANP (1-67) as a standard. It allows us to measure plasma N-terminal proANP in only 4 h without prior extraction. The detection limit of this assay was 15 pmol/L for a 100 microL sample of plasma. Within-run CVs ranged from 1.7% to 2.9% and between-run CVs ranged from 4.2% to 5.1%. The dilution curves of plasma samples showed good linearity and analytical recovery was 89-104%. The mean (+/-SD) N-terminal proANP in plasma of 33 healthy subjects was 188 (+/-71) pmol/L and 1030 (+/-411) pmol/L in 25 patients with heart failure. Our immunoradiometric assay is rapid and precise enough for routine determination of N-terminal proANP in human plasma.

Antibodies, Monoclonal↗
PubMed1997

Ophthalmic findings in a case of hemophagocytic syndrome.

PURPOSE: To report a case of hemophagocytic syndrome, which is characterized by hemophagocytosis of histiocytes; optic nerve involvement, and unusual retinal white patches. METHOD: Case report. A 10-year-old boy had repeated relapses of hemophagocytic syndrome. He complained of swelling of the right upper eyelid and bilateral visual disturbance. RESULTS: Ophthalmoscopic examination disclosed bilateral optic disk edema, retinal hemorrhages, and multiple perivenous white patches in the retina. Magnetic resonance imaging demonstrated enlargement of both optic nerves. After chemotherapy and bone marrow transplantation, his visual acuity improved in both eyes, and retinal patches changed to inactive-appearing scars. CONCLUSION: Hemophagocytic syndrome may manifest with ophthalmic findings such as optic nerve involvement, retinal hemorrhages, and multiple white perivenous retinal patches.

Child↗
PubMed1997

Rhabdomyoma of the orbit in a child.

PURPOSE: To study a case of rhabdomyoma of the orbit in a 16-month-old boy. METHOD: The child had progressive right proptosis for 1 month. He underwent a computed tomographic scan, which showed an irregular right retrobulbar mass and partial resection. RESULTS: Histologic examination disclosed well-differentiated striated muscle cells with a mixture of collagen fibers and immature striated muscle cells with centrally placed nuclei. The specimen lacked nuclear atypia, indicating benign rhabdomyoma of the orbit. During the 1 1/2-year follow-up, the patient did not receive additional treatment, and no regrowth occurred. CONCLUSION: Rhabdomyoma can occur in the orbit of a child. Because of differences in treatment, rhabdomyoma must be distinguished from rhabdomyosarcoma.

Humans↗
PubMed1997

Molecular cloning of sheep and goat ferredoxin reductase messenger ribonucleic acids, and identification of an alternatively spliced form of sheep ferredoxin reductase.

Complementary DNA clones of mRNAs for sheep and goat NADPH-ferredoxin reductases (ferredoxin NADP+ oxidoreductase, EC 1.18.1.2) were isolated by the reverse transcriptase polymerase chain reaction method, and the complete nucleotide sequences of the coding and 3'-flanking regions of these cDNA clones were determined. Comparative analysis using the deduced amino acid sequences of NADPH-ferredoxin reductases clarified the interspecific conservation of the ferredoxin-binding and flavin adenine dinucleotide (FAD)-binding regions, confirming the results reported previously. During this study, we happened to identify an alternatively spliced mRNA that completely lacks exon 3, just adjacent to the FAD-binding region of the sheep NADPH-ferredoxin reductase cDNA clone. In the screening of other alternatively spliced mRNAs of NADPH-ferredoxin reductases derived from several steroidogenic organs, such as adrenocortices, testes, and ovaries of sheep and goats, only one kind of alternatively spliced mRNA as described above was detected in sheep adrenocortices. Then, we constructed Escherichia coli expression systems for these two forms of mRNA and analyzed their enzymatic properties. We found that the ability of the alternatively spliced NADPH-ferredoxin reductase protein to transfer electrons to ferredoxin is completely abolished because FAD binding is inhibited.

Alternative Splicing↗
PubMed1997

No linkage of the cytochrome P-450IIE1 (CYP2E1) C1/C2 polymorphism to schizophrenia.

We investigated, using PCR-SSCP analysis, the relationship between schizophrenia and the polymorphism of d-benzphetamine N-demethylase (cytochrome P-450j or CYP2E1), which metabolizes psychotropic substances such as d-benzphetamine and alcohols. Among 41 patients with schizophrenia, no statistically significant change in the frequency of the mutant (C2) allele relative to in controls was found, and no novel structural mutation in the CYP2E1 gene, which would be expected to alter the CYP2E1 protein, was found. This could be explained by no linkage of the CYP2E1 gene (mutations in the exon 1-9, and C1/C2 polymorphism) to schizophrenia.

Adult↗
PubMed1997

Metabolism of the intravenously administered recombinant human basic fibroblast growth factor, trafermin, in liver and kidney: degradation implicated in its selective localization to the fenestrated type microvasculatures.

The fate of trafermin (recombinant human basic fibroblast growth factor) was examined after intravenous administration of its iodinated form to rats. Autoradiography at 5 and 30 min after the injection showed that 125I-trafermin is localized specifically in the fenestrated endothelium through binding to heparan sulfate proteoglycans (HSPG) in liver, kidney, adrenal, spleen, hypophysis and bone marrow. Metabolites in the organs were examined at 5 min and 24 h after the injection. More than 73% of radioactivity in liver and kidney was extractable at either time point, and a large majority of the extracted radioactivity was heparin-binding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed that the substantial radioactivity recovered from liver and kidney can commonly be attributed to a peptide with the same molecular weight as the intact trafermin (B-1, 17.7 kDa) and only three truncated metabolites (B-2, 15.0 kDa; B-3, 7.2 kDa; B-4, 4.2 kDa). Because no truncated metabolites were found in serum, these metabolites seem to be produced inherently in liver and kidney. Although they all retained heparin-binding capacity, only B-1 and B-2 exhibited a stimulatory effect on proliferation of endothelial cells, and these bioactive peptides disappeared completely from liver within a day, indicating a rapid inactivation process in the organs. Taken together with the morphological evidence on autoradiography, it seems most likely that the injected trafermin could be inactivated in sinusoidal endothelial cells, probably through a well-known internalization mechanism of the basic fibroblast growth factor-HSPG complex.

Animals↗
PubMed1996

Tissue-specific alternative splicing of mouse brain type ryanodine receptor/calcium release channel mRNA.

We detected alternative splicing of the mouse brain type ryanodine receptor (RyR3) mRNA. The splicing variant was located in the transmembrane segment. The non-splicing type (RyR3-II) included a stretch of 341 bp, and that of the 13th codon was stop codon TAA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis shows that RyR3-II mRNA was expressed in various peripheral tissues and brain at all developmental stages. However, interestingly, the splicing type (RyR3-I) mRNA was detected only in the cerebrum. These findings suggest that the splicing variants RyR3-I and RyR3-II may generate functional differences of RyR3 in a tissue-specific manner.

Aging↗
PubMed1996

A fluorometric assay for measuring deamidase (lysosomal protective protein) using high-performance liquid chromatography.

A rapid and sensitive assay method for the determination of deamidase activity is reported. This method is based on fluorometric detection of a dansylated dipeptide, 5-dimethylaminonaphthalene-1-sulfonyl-D-Tyr-Val (N-Dns-D-Tyr-Val), enzymatically formed from the substrate 5-dimethylaminonaphthalene-1-sulfonyl-D-Tyr-Val-NH2 (N-Dns-D-Tyr-Val-NH2), after separation by high-performance liquid chromatography (HPLC) using a C-18 reversed-phase column by isocratic elution. This method is sensitive enough to measure N-Dns-D-Tyr-Val at concentrations as low as 100 fmol, yields highly reproducible results and requires less than 8.5 min per sample for separation and quantitation. The optimum pH for deamidase activity was 4.0-4.5. Greater than 5 mM of reduced glutathione was needed for maximal enzyme activity. The Km and Vmax values were respectively 125 microM and 14.12 pmol/micrograms/h with the use of enzyme extract obtained from mouse spleen. Deamidase activity was strongly inhibited by Ag+, Cu2+, diisopropylfluorophosphate, and p-chloromercuriphenylsulfonic acid. Among the organs examined in a mouse, the highest specific activity of the enzyme was found in spleen. The sensitivity and selectivity of this method will aid in efforts to examine the physiological role of this enzyme.

Animals↗