Characterization of organic ion transporters involved in renal excretion of xenobiotics.
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Amino Acid Sequence↗
Biomedical subjects
S Masuda
Publications and source records attributed to S Masuda.
[Descending necrotizing mediastinitis secondary to retropharyngeal abscess--a case report].
A 69-year-old man complained of a sore throat, neck swelling, and disturbance of swallowing with dyspnea. He underwent tracheostomy and cervical drainage. The plain chest roentgenogram and CT scans suggested mediastinitis, so he was transferred to our hospital. Cultures revealed a mixed aerobic and anaerobic infection. On hospital day 2, the neck was explored and pus was found in the connective tissue. Despite drainage and intravenous panipenem with betamipron and clindamycin, he remained febrile and a mediastinal abscess was seen on repeat CT. On hospital day 10, reexploration of the mediastinum was done through cervical and right thoracotomy incisions. A large amount of pus was drained from the posterior mediastinum and its necrotic tissue was debrided. Myocardial infarction occurred intraoperatively, but the patient was successfully resuscitated. Following this procedure, the patient's condition and radiologic findings gradually improved. Cultures of the drain fluid became negative, and he was discharged on hospital day 103. In conclusion, both transcervical drainage and aggressive mediastinal exploration via thoracotomy are essential to salvage a patient with descending necrotizing mediastinitis. CT scanning is useful for early diagnosis of mediastinitis and for follow up.
Aged↗
[Malignant lymphoma of the testis: report of two cases].
Two cases on non-Hodgkin's malignant lymphoma (NHL) of the testis are reported. A 63-year-old man with left painless scrotal swelling underwent orchiectomy. Although prophylactic irradiation was performed under the diagnosis of seminoma, subsequent immunohistochemistry revealed NHL, large diffuse cell type (B type). He had stage IEA disease. Chemotherapy with cyclophosphamide, adriamycin vincristine and prednisolone was performed. The second case was in a 63-year old man with right painless scrotal swelling. Orchiectomy revealed NHL, diffuse medium cell type (B type). Because of tumor in the retrosternum, he had stage IIIEA disease. Chemotherapy and irradiation to the contralateral testis was performed.
Antineoplastic Combined Chemotherapy Protocols↗
Interactions of nonsteroidal anti-inflammatory drugs with rat renal organic anion transporter, OAT-K1.
We recently cloned and characterized the rat kidney-specific organic anion transporter, OAT-K1, which was suggested to mediate renal tubular transport of methotrexate. In this study, we investigated the interactions of nonsteroidal anti-inflammatory drugs (NSAIDs) with OAT-K1 by evaluating the effects of these drugs on renal distribution of methotrexate in vivo, and on methotrexate accumulation in the stably transfected LLC-PK1 cells expressing OAT-K1 (LLC-OAT-K1). NSAIDs such as indomethacin and ketoprofen had significant inhibitory effects on renal accumulation of methotrexate in rats after coadministration. Indomethacin and ketoprofen inhibited methotrexate accumulation by LLC-OAT-K1 cells in a competitive manner with the apparent inhibition constant values of 1. 0 mM and 1.9 mM, respectively. Other NSAIDs including ibuprofen, flufenamate and phenylbutazone also showed potent inhibitory effects on methotrexate accumulation. However, indomethacin was not transported via OAT-K1. These results indicate that NSAIDs have potent inhibitory effects against the OAT-K1-mediated methotrexate transport, which suggests that the OAT-K1 may be one of interaction sites for methotrexate and NSAIDs in the kidney.
Animals↗
Cloning and functional characterization of a novel rat organic anion transporter mediating basolateral uptake of methotrexate in the kidney.
We have cloned a cDNA coding for a novel member of organic anion transporter, designated OAT-K1, expressed specifically in the kidney of rats. The rat OAT-K1 cDNA (2788 base pairs) had an open reading frame encoding for a 669-amino acid protein (calculated molecular mass of 74 kDa) which shows 72% identity with the cloned rat liver organic anion transporter, oatp. Northern hybridization and reverse transcription-coupled polymerase chain reaction revealed that the rat OAT-K1 messenger RNA transcript is expressed predominantly in the kidney. By use of stable LLC-PK1 cell monolayers transfected with the rat OAT-K1 cDNA, the transporter was suggested to mediate basolateral uptake of methotrexate, an anionic anticancer drug, but not taurocholate, p-aminohippurate, prostaglandin E2, and leukotriene C4. The methotrexate transport by rat OAT-K1 was unaffected by the presence of Na+ or Cl- gradient. The methotrexate accumulation by the OAT-K1-expressing cells showed saturability with the apparent Km value of 1.0 microM. Folate, sulfobromophthalein, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) inhibited the methotrexate accumulation markedly. These findings suggest that the rat OAT-K1 is localized in the basolateral membranes of renal tubules, where it mediates renal clearance of methotrexate from the blood.
Amino Acid Sequence↗
Anti-erythropoietin receptor monoclonal antibody: epitope mapping, quantification of the soluble receptor, and detection of the solubilized transmembrane receptor and the receptor-expressing cells.
A hybridoma cell line producing the monoclonal antibody against erythropoietin receptor (EpoR) was established using the soluble ectodomain of mouse erythropoietin receptor (sEpoR) as an antigen. The monoclonal antibody termed 1G3 bound to the denatured sEpoR. Epitope mapping with peptide library revealed that 1G3 recognized the amino terminal region including the hexapeptide (positions 6 to 11; LeuProAspProLysPhe). The amino acid sequence in this hexapeptide was identical in mice, rats, and humans, and therefore 1G3 bound to EpoR from all of these sources. Using 1G3, we evaluated sEpoR by a sandwich enzyme-linked immunoassay, and EpoR in the solubilized membrane preparation was detected by Western blotting. The cells expressing EpoR were identified with immunochemical staining. We confirmed the presence of EpoR in a neuronal cell line and PC12 cells, and EpoR was expressed in primary cultured hippocampal neurons.
Amino Acid Sequence↗
A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map.
The 718,122 base pair sequence of the Escherichia coli K-12 genome corresponding to the region from 12.7 to 28.0 minutes on the genetic map is described. This region contains at least 681 potential open reading frames, of which 277 (41%) have been previously identified, 147 (22%) are homologous to other known genes, 139 (20%) are identical or similar to the hypothetical genes registered in databases, and the remaining 118 (17%) do not show a significant similarity to any other gene. In this region, we assigned a cluster of cit genes encoding multienzyme citrate lyase, two clusters of fimbrial genes and a set of lysogenic phage genes encoding integrase, excisionase and repressor in the e14 genetic element. In addition, a new valine tRNA gene, designated valZ, and a family of long directly repeated sequences, LDR-A, -B and -C, were found.
DNA, Bacterial↗
A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map (supplement).
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Escherichia coli↗
In vitro metabolism of the vitamin D analog, 22-oxacalcitriol, using cultured osteosarcoma, hepatoma, and keratinocyte cell lines.
Using four cultured cell models representing liver, keratinocyte, and osteoblast, we have demonstrated that the vitamin D analog, 22-oxacalcitriol is degraded into a variety of hydroxylated and side chain truncated metabolites. Four of these metabolic products have been rigorously identified by high pressure liquid chromatography, diode array spectrophotometry, and gas chromatography-mass spectrometry analysis as 24-hydroxylated and 26-hydroxylated derivatives as well as the cleaved molecules, hexanor-1alpha,20-dihydroxyvitamin D3 and hexanor-20-oxo-1alpha-hydroxyvitamin D3. Comparison with chemically synthesized standards has revealed the stereochemistry of the biological products. Although differences exist in the amounts of products formed with the different cell types, it is apparent that 22-oxacalcitriol is subject to metabolism by both vitamin D-inducible and noninducible enzymes. Time course studies suggest that the truncated 20-alcohol is derived from a side chain hydroxylated molecule via a hemiacetal intermediate and the 20-oxo derivative is likely formed from the 20-alcohol. Biological activity measurements of the metabolites identified in our studies are consistent with the view that these are catabolites and that the biological activity of 22-oxacalcitriol is due to the parent compound. These results are also consistent with recent findings of others that the biliary excretory form of 22-oxacalcitriol is a glucuronide ester of the truncated 20-alcohol.
Animals↗
Radioprotective effects of antioxidative plant flavonoids in mice.
Radioprotective effects of tea infusions and plant flavonoids were investigated by using the micronucleus test for anticlastogenic activity and the thiobarbituric acid assay for antioxidative activity. A single gastric intubation of rooibos tea (Aspalathus linearis) infusion at 1 ml per mouse 2 h prior to gama-ray irradiation (1.5 Gy) reduced the frequency of micronucleated reticulocytes (MNRETs). After the fractionation of rooibos tea infusion, the flavonoid fraction was found to be most anticlastogenic and antioxidative. From this fraction, luteolin was isolated as an effective component. Then, anticlastogenic effects of 12 flavonoids containing luteolin and their antioxidative activities against lipid peroxidation by Fenton's reagent were examined. A good correlation (r=0.717) was observed between both activities. Luteolin showed the most effective potency. A gastric intubation of luteolin (10 micromoles/kg) 2 h prior to gamma-ray irradiation (6 Gy) suppressed lipid peroxidation in mouse bone marrow and spleen and a trend of protective effect of luteolin against the decrease of endogenous ascorbic acid in mouse bone marrow after gamma-ray irradiation (3 Gy) was observed. These results suggest that plant flavonoids, which show antioxidative potency in vitro, work as antioxidants in vivo and their radioprotective effects may be attributed to their scavenging potency towards free radicals such as hydroxyl radicals. Therefore, the flavonoids contained in tea, vegetables and fruits seem to be important as antioxidants in the human diet.
Animals↗
Erythropoietin in mouse avascular yolk sacs is increased by retinoic acid.
Erythropoiesis begins first in the visceral yolk sac (VYS) of the embryo; however, the involvement of erythropoietin (EPO) in yolk-sac erythropoiesis has not been studied adequately. This study reports the expression of EPO in normal and hypoxic VYSs and alterations in yolk sac components induced by retinoic acid (RA) in mice. Gravid mice (plug day = day 0 of gestation) were given one oral dose of 60 mg/kg of RA in olive oil on days 6, 6.5, 7, 7.5, or 8 of gestation and were sacrificed 2.5, 3, or 3.5 days later. Control mice received olive oil without RA. None of the dams developed anemia, but more than 80% of the embryos of the dams that received RA on day 6, 6.5, or 7 of gestation had avascular yolk sacs (AVYs) and anemia. In these AVYs, the adenosine triphosphate (ATP) level was as low as 18-59% of that in the control VYSs. Reverse transcription-polymerase chain reaction and Southern analysis of products demonstrated that mRNA for EPO receptor (EPR) was expressed in both VYSs and AVYs on days 9-11 of gestation, and EPO mRNA was present in VYSs and AVYs on days 9 and 10 of gestation and in vehicle-exposed VYSs on day 11 of gestation. Furthermore, enzyme immunoassay of EPO indicated that AVYs contained more EPO protein than control VYSs. Light microscopy revealed that, in AVYs, in addition to the defective hemopoietic cells, the endodermal layer was exclusively altered: The presence of focal proliferated regions and the separation from the mesenchyme led to a single layer from which some immature cells seemed to be migrating. Immunolocalization of EPO showed its presence in all components of VYSs with a characteristic distribution pattern: In the endodermal layer, cells with positive EPO staining decreased as gestation advanced, and erythroid precursor cells showed positive staining. In AVYs, the proliferated endodermal cells had EPO in abundance; in the separated regions, the distinction between positive and negative EPO staining became clearer than that in the control VYSs, and the immature cells in the lumens also had EPO. EPR was seen on the cell surface of the corresponding cells that reacted to EPO. These findings suggest that VYSs not only produce EPO temporarily but also respond to the oxygen content in situ. EPO and EPR appear to be synthesized in the endodermal cells of the VYSs that are likely to respond to the circumstances induced by RA.
Adenosine Triphosphate↗
Systematic sequencing of the 283 kb 210 degrees-232 degrees region of the Bacillus subtilis genome containing the skin element and many sporulation genes.
As part of the Bacillus subtilis genome sequencing project, we have determined a 283 kb contiguous sequence from 210 degrees to 232 degrees of the B. subtilis genome. This region contains the 48 kb skin element which is excised during sporulation by a site-specific recombinase. In this region, 310 complete ORFs and one tRNA gene were identified: 66 ORFs have been sequenced and characterized previously by other workers, e.g. acc, ans, bfm, blt, bmr, comE, comG, dnaK, rpoD and sin operons; cwiA, gpr and lysA genes; many sporulation genes and operons, spo0A, spoIIA, spoIIM, spoiiP, spoIIIA, spoIIIC, spoIVB, spoIVCA, spoIVCB and spoVA, etc. The products of 84 ORFs were found to display significant similarity to proteins with known function in data banks, e.g., proteins involved in nucleotide metabolism, lipid biosynthesis, amino acid transport (ABC transporter), phosphate-specific transport, the glycine cleavage system, the two-component regulatory system, cell wall autolysis, ferric uptake and sporulation. However, the functions of more than half of the ORFs (52%, 160 ORFs) are still unknown. In the skin element containing 60 ORFs, 32 ORFs (53%) encode proteins which have significant homology to gene products of the B. subtilis temperate phage phi 105 and/or the defective phage PBSX.
Bacillus subtilis↗
Immunohistochemical study of hepatic angiomyolipoma.
An immunohistochemical study was performed on nine hepatic angiomyolipomas (AML) found in eight patients. Histologically, the tumors were fundamentally composed of the three heterogeneous tissue components of blood vessels, smooth muscle cells (SMC), and fat cells, although the proportions and distributions were quite variable from tumor to tumor and from area to area in the same tumor. Additionally, cellular pleomorphism and atypia with occasional bizarre giant cells were found in the SMC component. This histologic feature might lead to a mistaken diagnosis of malignant neoplasm, and pathologists should therefore be aware of the broad histologic spectrum of hepatic AML. However, the immunostaining patterns were basically the same in all nine tumors. All tumor components were negative for epithelial membrane antigen (EMA) and for cytokeratin. The spindle-shaped SMC component of the tumor was occasionally positive for vimentin, desmin and alpha-smooth muscle actin, whereas epithelioid SMC were negative for all three. Both the epithelioid and spindle-shaped SMC were occasionally positive for S-100 and neuron-specific enolase. All types of SMC in the tumor, whether spindle, epithelioid, intermediate or pleomorphic SMC, were strongly positive for HMB-45, a melanoma-specific monoclonal antibody. Fat cells were occasionally positive for S-100. Endothelial cells were positive for factor VIII-associated antigen. Among hepatic tumors HMB-45 reactivity is, so far as we know, found exclusively in the SMC of AML, and the HMB-45 reactivity of a hepatic tumor is thus clearly an important piece of information in the diagnosis of AML.
Adult↗
Myocardial ischemia due to vascular systemic amyloidosis: a quantitative analysis of autopsy findings on stenosis of the intramural coronary arteries.
A case is reported of a 65 year old man who suffered myocardial ischemia resulting from extensive stenosis of the intramural coronary arteries secondary to systemic vascular involvement by primary amyloidosis. In the myocardium, there were multiple fibrotic foci scattered mainly in the subendocardial region of the ventricle. Intramural coronary arteries were stenotic or occlusive due to amyloid-induced luminal narrowing, but there was no significant stenosis of the epicardial coronary arteries. Quantitative analysis of amyloid deposits in the intramural coronary arteries demonstrated that occlusive arteries were predominant in the surrounding area of myocardial fibrosis, and the extent of coronary stenosis by amyloid deposition was significantly more severe than in hearts of the five control patients who had coronary amyloidosis without myocardial fibrosis. These results indicate that myocardial fibrosis originates from coronary ischemia due to vascular amyloid deposition. This is the first time that the relationship between myocardial lesions and coronary amyloid deposition has been elucidated using histopathologic quantitative analysis.
Aged↗
Synthetic studies of vitamin D analogs. XXII. Synthesis and antiproliferation activity of putative metabolites of 1 alpha, 25-dihydroxy-22-oxavitamin D3.
As putative metabolites of 1 alpha,25-dihydroxy-22-oxavitamin D3 (OCT), 24-hydroxylated OCT in 24(R) and 24(S) forms, 24-ketoOCT, 26-hydroxylated OCT in 25(S) and 25(R) forms, pentanorOCT and pentanor-ketoOCT were synthesized from the steroidal 20(S)-alcohol. Their antiproliferation activities towards human promyelocytic leukemia cells (HL-60 cells) are also reported. Oxidized derivatives at the C-24 position, 24-ketoOCT, 24(R)-hydroxylated OCT and 24(S)-hydroxylated OCT, showed activities comparable to or slightly weaker than that of OCT, while 26-hydroxylated OCT was less active than OCT. Truncated OCT, pentanor OCT and pentanor-ketoOCT, were inactive at 10(-7)-10(-10) M.
Animals↗
Concurrent pulmonary arterial dissection and saccular aneurysm associated with primary pulmonary hypertension.
We report concurrent pulmonary arterial dissection and saccular aneurysm resulting from primary pulmonary hypertension in a 26-year-old man. The pulmonary trunk was dissected 9 cm along its entire circumference, 3 cm above the pulmonary valvular cusps. In addition, a saccular aneurysm 3.5 cm in diameter had formed at the right pulmonary hilus. Histopathology revealed marked medical degeneration and fragmentation of the elastic laminae in the former lesion and a true aneurysm with attenuation and fragmentation of elastic laminae in the latter. The peripheral vasculature in the lungs showed evidence of increased pulmonary arterial pressure, including plexiform and angiomatoid lesions. We present this unique case and discuss the pathomorphogenesis of these lesions in conjunction with primary pulmonary hypertension.
Adult↗
[The pollen count of Cryptomeria japonica and nasal symptom of Cryptomeria japonica pollinosis patients in recent three years in Mie Prefecture].
Airborne scattering of Cryptomeria japonica pollen depends on climate. Total pollen count and scattering pattern varies from one year to another. We counted Cryptomeria japonica pollen in February and March from 1993 to 1995 at several points in Mie Prefecture. One-third to two-thirds of all the patients who visited our clinic for the first time in the pollen period were occupied by allergic patients. The pollen count in 1995 amounted to 17943/cm2 at Tsu and 99512/cm2 in the whole prefecture, which is the largest in the past 12 years. The number of days in which patients severely suffered was correlated to the pollen count for the past three years. It was shown that nasal symptoms developed after certain amount of pollen had scattered, but the severity of symptoms thereafter largely depended on the total pollen count. At Tsu in 1995, we scarcely had pollen scattering in February but had tremendous amount of pollen count in March. Percentage of development of nasal symptoms among thirty patients was well correlated to the logarithm of accumulated pollen count. When accumulated pollen count reached to 100/cm2, half the patients developed symptoms. Most of the patients developed symptoms when it reached to 1000/cm2. Since there is a great interindivisual difference in when and how much patients have nasal symptoms, the choice of therapy should be based not only on the pollen count but also on the symptom and condition of each patient.
Adult↗
[A case report of primary Burkitt lymphoma of the rectum].
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Antineoplastic Combined Chemotherapy Protocols↗