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1.
JA Clin Rep ; 6(1): 86, 2020 Oct 24.
Article in English | MEDLINE | ID: mdl-33099689

ABSTRACT

BACKGROUND: Currently, the occurrence of left atrial thrombus despite the provision of heparinization within a few days of hospitalization without atrial fibrillation (AF) and mitral stenosis (MS) is rarely reported. CASE PRESENTATION: A 71-year-old woman presented with chest discomfort and dyspnea. Examination revealed ST elevation with sinus rhythm, congestive heart failure, and moderate mitral regurgitation (MR) by transthoracic echocardiography (TTE). Diuretics, a coronary vasodilator, and unfractionated heparin (15,000 units/day) were administered. Four days after hospitalization, her C-reactive protein level had increased; therefore, TTE was repeated, revealing a thrombus in the left atrial appendage, which was probably affected by heparin resistance because of low antithrombin (49%). On day 5, the patient underwent emergency removal of the thrombus, mitral valve replacement, and coronary artery bypass. CONCLUSION: Patients can exhibit low left ventricular contractility, even sinus rhythm without MS. Thus, TTE and subsequent coagulation tests including antithrombin must be performed to prevent thrombus.

2.
PLoS One ; 14(6): e0218190, 2019.
Article in English | MEDLINE | ID: mdl-31181122

ABSTRACT

Diaphorin is a polyketide produced by Candidatus Profftella armatura (Betaproteobacteria), an organelle-like defensive symbiont harbored by a plant sap-sucking insect, Asian citrus psyllid Diaphorina citri (Hemiptera: Liviidae). Diaphorin belongs to the pederin family, a group of compounds that share much of their core structure with that of pederin, which is characterized by two dihydropyran rings bridged by an N-acyl aminal. Most members of this family have potent antitumor activity, making them promising anticancer drug candidates. The present study assessed the therapeutic potential of diaphorin for its antitumor activity against 39 human cancer cell lines including those from breast, brain, colon, lung, skin, ovary, kidney, stomach, and prostate. The results showed that diaphorin had inhibitory activity against all 39 cancer cell lines tested. The GI50, TGI, and LC50 values ranged from 0.28 µM- 2.4 µM, 1.6 µM -11 µM, and 7.5 µM-> 100 µM, respectively. These values are among the highest in the pederin family, indicating that the anticancer activity of diaphorin is milder than those of other pederin congeners. The inhibitory effects of diaphorin significantly differed among the distinct cancer types. The maximum difference was about 10-fold, which was similar to those of most other pederin congeners.


Subject(s)
Betaproteobacteria/metabolism , Hemiptera/chemistry , Polyketides/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Drug Screening Assays, Antitumor , Hemiptera/microbiology , Humans , Inhibitory Concentration 50 , Polyketides/pharmacology , Symbiosis
4.
J Anesth ; 33(1): 108-117, 2019 02.
Article in English | MEDLINE | ID: mdl-30535893

ABSTRACT

OBJECTIVE: The effects of hydroxyethyl starch (HES) on microcirculation, central venous oxygen saturation (ScvO2), and the central venous-to-arterial carbon dioxide gap (dCO2) are studied in a rabbit model of hemorrhagic shock for elucidating the advantages and drawbacks of resuscitation with HES compared with crystalloids. METHODS: An ear chamber and sublingual mucosa were used to examine blood vessels by intravital microscopy. Hemorrhagic shock was induced by removing nearly half of the blood volume. Twenty-two rabbits received 20 mL of HES by intravenous infusion immediately after bloodletting. Additional HES was then administered intravenously to a total volume of 100 mL. The other 22 rabbits (control) were intravenously given 40 mL of normal saline solution (NSS), followed by additional NSS to a total volume of 200 mL, administered under the same conditions as HES. RESULTS: After the infusion, the vessel density and perfusion rate of the sublingual microcirculation recovered in the HES group. The arteriolar diameter, blood flow velocity, and blood flow rate of the ear microcirculation were maintained in this group, and microcirculatory failure did not develop. In the NSS group, however, all 5 of the aforementioned measured variables were significantly smaller than those in the HES group after the completion of infusion. The recovery of ScvO2 and dCO2 to the respective baseline values was significantly better in the HES group than in the NSS group. CONCLUSION: Intravenous infusion of HES effectively maintains adequate tissue oxygenation and perfusion in hemorrhagic shock.


Subject(s)
Carbon Dioxide/metabolism , Hydroxyethyl Starch Derivatives/therapeutic use , Shock, Hemorrhagic/therapy , Animals , Arteries/drug effects , Blood Volume , Colloids/administration & dosage , Crystalloid Solutions/administration & dosage , Infusions, Intravenous , Microcirculation/drug effects , Oxygen/blood , Pulmonary Gas Exchange/drug effects , Rabbits , Resuscitation , Shock, Hemorrhagic/physiopathology
5.
Int J Syst Evol Microbiol ; 67(9): 3369-3374, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28875892

ABSTRACT

A strain of anoxygenic phototrophic bacteria isolated from paddy soil (designated strain TUT3615T) was studied taxonomically in comparison with Rhodopseudomonasstrain ATCC 17005 as its nearest phylogenetic relative. Strains TUT3615T and ATCC 17005 had budding rod-shaped cells and showed in vivo absorption maxima at 804 and 860 nm in the near infrared region, indicating the presence of bacteriochlorophyll a. The intracytoplasmic membrane system was of the lamellar type parallel to the cytoplasmic membrane. 16S rRNA gene sequence comparisons showed that strains TUT3615T and ATCC 17005 had a 99.7 % level of similarity to one another and were closest to Rhodopseudomonas palustris ATCC 17001T (98.6 % similarity) among the established species of the genus Rhodopseudomonas. Genomic DNA-DNA hybridization studies revealed that strains TUT3615T and ATCC 17005 had an average similarity level of 65 % to one another and of less than 40 % to the available type strains of Rhodopseudomonas species. Results of phenotypic studies showed that strains TUT3615T and ATCC 17005 could be differentiated from one another and from any previously described species of Rhodopseudomonas. The G+C contents of the genomic DNA of strain TUT3615T and ATCC 17005 were 66.3 and 66.5 mol%, respectively. Based on these data, we propose the name Rhodopseudomonas telluris sp. nov. for strain TUT3615T. The type strain is TUT3615T (=KCTC 23279T=NBRC 107609T). We suspend a proposal to reclassify strain ATCC 17005 as a novel species or subspecies until a genome-wide analysis provides more definite information on its taxonomic position.


Subject(s)
Oryza , Phylogeny , Rhodopseudomonas/classification , Soil Microbiology , Bacterial Typing Techniques , Bacteriochlorophyll A/chemistry , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Japan , Nucleic Acid Hybridization , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Rhodopseudomonas/genetics , Rhodopseudomonas/isolation & purification , Sequence Analysis, DNA , Ubiquinone/chemistry
6.
Int J Syst Evol Microbiol ; 67(5): 1540-1545, 2017 May.
Article in English | MEDLINE | ID: mdl-28005520

ABSTRACT

Previously we proposed the reclassification of a thermotolerant phototrophic bacterium, 'Rhodopseudomonas cryptolactis' Stadtwald-Demchick et al. 1990, as 'Rhodoplanes cryptolactis' nom. rev., comb. nov. with strain DSM 9987T (ATCC 49414T) as the type strain. However, while both the names 'Rhodopseudomonas cryptolactis' and 'Rhodoplanes cryptolactis' have not been validated, strain ATCC 49414T is no longer available from the culture collection. This situation indicates that the taxonomic status of the bacterium with both the names to be validated has been lost. In this study, we re-examined the taxonomic characteristics of strain DSM 9987T (TUT3520T as our own collection number) compared with those of six species of the genus Rhodoplanes with validly published names. The results of 16S rRNA gene sequence comparisons indicated that TUT3520T had a 99.0 % level of similarity to the type strains of Rhodoplanes oryzae and Rhodoplanes elegans as its closest relatives and 98.9-96.2 % similarities to other species of the genus Rhodoplanes. Genomic DNA-DNA similarities between TUT3520T and the type strains of the species of the genus Rhodoplanes were less than 50 %. Results of phenotypic testing indicated that TUT3520T could be differentiated from any species of the genus Rhodoplanes by a combination of in vivo absorption spectra, growth temperature, vitamin requirements, carbon nutrition and some other characteristics. Thus, we propose Rhodoplanes tepidamans sp. nov. to accommodate the bacterium previously referred to as 'Rhodoplanes (Rhodopseudomonas) cryptolactis'. The type strain is strain TUT3520T (=DSM 9987T=NBRC 104267T).


Subject(s)
Hyphomicrobiaceae/classification , Phylogeny , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Hyphomicrobiaceae/genetics , Hyphomicrobiaceae/isolation & purification , Nucleic Acid Hybridization , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA
7.
Am J Kidney Dis ; 65(3): 490-3, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25542412

ABSTRACT

A 28-year-old woman with systemic lupus erythematosus was referred to our hospital due to nephrotic-level proteinuria despite approximately 1 year of treatment with 50 to 60 mg/d of prednisolone and 100 to 150 mg/d of cyclosporine with methylprednisolone pulse therapy. Kidney biopsy showed diffuse global lupus nephritis (World Health Organization class 4-G A/C) with many intraglomerular foam cells containing cholesterol crystals. Surprisingly, proteinuria diminished after only 5 low-density lipoprotein (LDL) cholesterol apheresis sessions. This case demonstrated the potential of LDL apheresis to exhibit a remarkable effect on not only focal segmental glomerulosclerosis, but also other types of nephritis, particularly nephritis with intraglomerular foam cells.


Subject(s)
Blood Component Removal , Cholesterol/analysis , Foam Cells/chemistry , Lipoproteins, LDL/administration & dosage , Lupus Nephritis/therapy , Proteinuria/therapy , Adult , Crystallization , Female , Foam Cells/pathology , Humans , Kidney Glomerulus/chemistry , Kidney Glomerulus/pathology , Lupus Nephritis/complications , Lupus Nephritis/diagnosis , Proteinuria/complications , Proteinuria/diagnosis
8.
Int J Syst Evol Microbiol ; 65(Pt 1): 42-48, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25273513

ABSTRACT

Several strains of aerobic, acidophilic, chemo-organotrophic bacteria belonging to the genus Acidiphilium were isolated from an acid mine drainage (AMD) (pH 2.2) treatment plant. 16S rRNA gene sequence comparisons showed that most of the novel isolates formed a phylogenetically coherent group (designated Group Ia) distinguishable from any of the previously established species of the genus Acidiphilium at <98% similarity. This was supported by genomic DNA-DNA hybridization assays. The Group Ia isolates were characterized phenotypically by an oval cell morphology, non-motility, growth in the range pH 2.0-5.5 (optimum pH 3.5), lack of photosynthetic pigment and the presence of C19:0 cyclo ω8c as the main component of the cellular fatty acids and ubiquinone-10 as the major quinone. On the basis of these data, the name Acidiphilium iwatense sp. nov. is proposed to accommodate the Group Ia isolates, and the description of the genus Acidiphilium is emended. The type strain of Acidiphilium iwatense sp. nov. is MS8(T) ( =NBRC 107608(T)=KCTC 23505(T)).


Subject(s)
Acidiphilium/classification , Mining , Phylogeny , Wastewater/microbiology , Acidiphilium/genetics , Acidiphilium/isolation & purification , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Japan , Molecular Sequence Data , Nucleic Acid Hybridization , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Ubiquinone/chemistry , Waste Disposal Facilities
9.
Curr Biol ; 23(15): 1478-84, 2013 Aug 05.
Article in English | MEDLINE | ID: mdl-23850282

ABSTRACT

Diverse insect species harbor symbiotic bacteria, which play important roles such as provisioning nutrients and providing defense against natural enemies [1-6]. Whereas nutritional symbioses are often indispensable for both partners, defensive symbioses tend to be of a facultative nature [1-12]. The Asian citrus psyllid Diaphorina citri is a notorious agricultural pest that transmits Liberibacter spp. (Alphaproteobacteria), causing the devastating citrus greening disease or Huanglongbing [13, 14]. In a symbiotic organ called the bacteriome, D. citri harbors two distinct intracellular symbionts: a putative nutrition provider, Carsonella_DC (Gammaproteobacteria), and an unnamed betaproteobacterium with unknown function [15], for which we propose the name "Candidatus Profftella armatura." Here we report that Profftella is a defensive symbiont presumably of an obligate nature with an extremely streamlined genome. The genomes of Profftella and Carsonella_DC were drastically reduced to 464,857 bp and 174,014 bp, respectively, suggesting their ancient and mutually indispensible association with the host. Strikingly, 15% of the small Profftella genome encoded horizontally acquired genes for synthesizing a novel polyketide toxin. The toxin was extracted, pharmacologically and structurally characterized, and designated diaphorin. The presence of Profftella and its diaphorin-biosynthetic genes was perfectly conserved in the world's D. citri populations.


Subject(s)
Betaproteobacteria/genetics , Gammaproteobacteria/genetics , Genome, Bacterial , Hemiptera/microbiology , Symbiosis/genetics , Animals , Bacterial Toxins/chemistry , Bacterial Toxins/genetics , Bacterial Toxins/metabolism , Bacterial Toxins/toxicity , Biological Evolution , Cell Line/drug effects , Citrus , Gene Transfer, Horizontal , Molecular Sequence Data , Polyketides/metabolism , RNA, Ribosomal, 16S , Rats , Toxicity Tests
10.
Syst Appl Microbiol ; 36(5): 359-67, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23545471

ABSTRACT

This study investigated the relationship between the population dynamics of ammonia-oxidizing bacteria (AOB) and archaea (AOA), and changes in the concentrations of nitrogenous compounds during ammonia-rich livestock waste-composting processes. The data showed that ammonia in beef and dairy cow livestock waste-composting piles was slowly oxidized to nitrite and nitrate after approximately 21-35 days under thermophilic or moderately thermophilic and mesophilic conditions. Real-time quantitative PCR (qPCR) assays showed a relative abundance of betaproteobacterial AOB during ammonia oxidation but did not detect AOA in any composting stage. Furthermore, real-time qPCR and terminal-restriction fragment length polymorphism (T-RFLP) analyses for the AOB in two composting processes (beef and dairy cow livestock waste) out of the three studied found that thermophilic or moderately thermophilic uncultured betaproteobacterial AOB from the "compost AOB cluster" contributed to ammonia oxidation during hot composting stages. Non-metric multidimensional scaling analyses of the data from T-RFLP showed that only a few analogous species predominated during composting of beef, dairy cow and pig livestock wastes, and thus, the AOB community structures in the three composting piles operating under different conditions were similar. AOB-targeted clone library analyses revealed that uncultured members of the "compost AOB cluster", which could be clearly distinguished from the authentic species of the genus Nitrosomonas, were the major constituents of the AOB populations. These results suggested that a limited and unique species of AOB played a role in ammonia oxidation during the composting of ammonia-rich livestock waste.


Subject(s)
Ammonia/metabolism , Archaea/classification , Bacteria/classification , Biota , Livestock , Manure/microbiology , Animals , Archaea/enzymology , Archaea/genetics , Bacteria/enzymology , Bacteria/genetics , Oxidation-Reduction
11.
Curr Microbiol ; 65(2): 150-5, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22576373

ABSTRACT

Phototrophic bacteria necessarily contain carotenoids for photosynthesis, and accumulate unusual carotenoids in some cases. The carotenoids in all established species of Rhodoplanes (Rpl.), a representative of phototrophic genera, were identified using spectroscopic methods. The major carotenoid was spirilloxanthin in Rpl. roseus and Rpl. serenus, and rhodopin in "Rpl. cryptolactis". Rpl. elegans contained rhodopin, anhydrorhodovibrin, and spirilloxanthin. Rpl. pokkaliisoli contained not only rhodopin but also 1,1'-dihydroxylycopene and 3,4,3',4'-tetrahydrospirilloxanthin. These variations in carotenoid composition suggested that Rpl. roseus and Rpl. serenus had normal substrate specificity of the carotenogenesis enzymes of CrtC (acyclic carotene 1,2-hydratase), CrtD (acyclic carotenoid 3,4-desaturase), and CrtF (acyclic 1-hydroxycarotenoid methyltransferase). On the other hand, CrtC of Rpl. elegans, CrtD of "Rpl. cryptolactis", and CrtC, CrtD, and CrtF of Rpl. pokkaliisoli might have different characteristics from the usual activity of these normal enzymes in the normal spirilloxanthin pathway. These results suggest that the variation of carotenoids among the species of Rhodoplanes results from modified substrate specificity of the carotenogenesis enzymes involved.


Subject(s)
Carotenoids/analysis , Enzymes/metabolism , Hyphomicrobiaceae/chemistry , Hyphomicrobiaceae/enzymology , Carotenoids/chemistry , Metabolic Networks and Pathways/genetics , Substrate Specificity
12.
FEMS Microbiol Lett ; 317(2): 138-42, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21255071

ABSTRACT

Two strains of aerobic acidophilic chemoorganotrophic bacteria designed strains AP8(T) and AP9 were isolated from acid mine drainage and acidic soil, respectively. These isolates were gram-negative, nonmotile cocci and coccobacilli measuring 0.5-0.8 µm in diameter. Cells were capsulated. Colonies on solid media were pink colored. The pH range for growth was 3.0-6.0 (optimum pH 4.5). Sugars, gluconate, and some amino acids were good carbon and energy sources for growth. The main components of cellular fatty acids were C(15:0) iso and C(16:1) ω7c. Menaquinone-8 was the major quinone. The G+C content of genomic DNA was 59.5%. Both strains had identical sequences of 16S rRNA genes that were most closely related to that of the type strain of Acidobacterium capsulatum (96% similarity). There were major differences between the isolates and A. capsulatum in cell morphology, carbon nutrition, and fatty acid profiles. Based on these phylogenetic and phenotypic data, we propose the name Acidipila rosea gen. nov., sp. nov. to accommodate the novel isolates. The type strain is AP8(T) (NBRC 107607(T), KCTC 23427(T)).


Subject(s)
Gram-Negative Bacteria/classification , Gram-Negative Bacteria/metabolism , Base Composition/genetics , Gram-Negative Bacteria/genetics , Phylogeny , RNA, Ribosomal, 16S/genetics , Vitamin K 2/metabolism
13.
J Gen Appl Microbiol ; 55(1): 43-50, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19282632

ABSTRACT

A photoorganotrophic alphaproteobacterium designated strain G2-11(T) was isolated from submerged paddy soil. This bacterium had relatively large, oval to rod-shaped cells (2.0-3.0x3.0-10 microm). Cells were motile by means of single polar flagella. The color of phototrophically growing cultures was reddish-brown. The cell extract had absorption maxima at 375, 465, 492, 529, 592, 804, and 844 nm, indicating the presence of bacteriochlorophyll a and carotenoides of the spirilloxanthin series. Vesicular intracytoplasmic membranes were present. The main component of cellular fatty acids was C(18:1)omega7c. Ubiquinone-10 and rhodoquinone-10 were the major quinones. A 16S rRNA gene sequence analysis revealed that the isolate is closest to the acidophilic aerobic photosynthetic bacterium Acidisphaera rubrifaciens strain HS-AP3(T) (93.3% similarity). The G+C content of genomic DNA is 67.8 mol%. The name Rhodovastum atsumiense gen. nov., sp. nov. is proposed for the novel isolate. The type strain is strain G2-11(T) (=NBRC 104268(T)=KCTC 5708(T)).


Subject(s)
Acetobacteraceae/classification , Geologic Sediments , Phototrophic Processes , Soil Microbiology , Acetobacteraceae/genetics , Acetobacteraceae/isolation & purification , Acetobacteraceae/physiology , Bacterial Typing Techniques , Bacteriochlorophyll A/metabolism , Base Composition , DNA, Bacterial/analysis , DNA, Bacterial/genetics , DNA, Ribosomal/analysis , Fatty Acids/analysis , Genes, rRNA , Japan , Molecular Sequence Data , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Species Specificity , Xanthophylls/metabolism
14.
Int J Syst Evol Microbiol ; 59(Pt 3): 531-5, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19244435

ABSTRACT

A bright pink to red-coloured, phototropic, purple non-sulfur bacterium, designated strain TUT3530(T), was isolated from pond water. Cells of the novel isolate were found to be Gram-negative, motile, budding rods. Cell extracts from phototrophically grown cultures had absorption maxima at 378, 482, 512, 550, 590, 800 and 850 nm, indicating the presence of bacteriochlorophyll a and carotenoids of the spirilloxanthin series. The intracytoplasmic membrane system was of the lamellar type. Anaerobic photo-organotrophy with simple organic acids such as pyruvate was the preferred mode of growth. Aerobic growth at full atmospheric oxygen tension and anaerobic denitrifying growth in darkness were also possible. Photolithotrophic growth occurred with thiosulfate, but not with sulfide or hydrogen, as the electron donor. No growth factors were required. The major whole-cell fatty acid was C(18 : 1)omega7c. The major quinones were ubiquinone-10 and rhodoquinone-10. A phylogenetic analysis based on 16S rRNA gene sequences and studies involving DNA-DNA hybridization demonstrated that strain TUT3530(T) occupies a distinct taxonomic position within the genus Rhodoplanes. On the basis of these data, strain TUT3530(T) represents a novel species of the genus Rhodoplanes, for which the name Rhodoplanes serenus sp. nov. is proposed. The type strain is TUT3530(T) (=DSM 18633(T)=NBRC 102049(T)).


Subject(s)
Alphaproteobacteria/classification , Fresh Water/microbiology , Phototrophic Processes , Alphaproteobacteria/genetics , Alphaproteobacteria/isolation & purification , Alphaproteobacteria/physiology , Bacterial Typing Techniques , DNA, Bacterial/analysis , DNA, Ribosomal/analysis , Genes, rRNA , Japan , Molecular Sequence Data , Nitrates/metabolism , Nucleic Acid Hybridization , Phenotype , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Species Specificity
15.
J Gen Appl Microbiol ; 55(6): 469-78, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20118611

ABSTRACT

The intrageneric structure of the genus Rhodopseudomonas was evaluated by studying sequence information on 16S rRNA genes, 16S-23S rRNA gene internal transcribed spacer (ITS) regions, and puf genes using 33 test strains. The topology of phylogenetic trees based on these sequences was similar to those of every other independent method for tree construction. These phylogenetic data indicated that the test strains were grouped into at least 7 clusters possibly at the species level. This was supported by genomic DNA-DNA similarities among 12 representative test strains selected from these clusters. Our molecular data confirmed that the currently available strains of Rhodopseudomonas (Rps.) palustris are genetically quite heterogeneous within the genus. For example, Rps. palustris strains DSM 123(T) and ATCC 17001(T) are different from each other at the species level despite their status as the type strain of the species. Rps. palustris strain ATCC 17005 and the full genome-sequenced strains BisA53, BisB18, BisB5, and HaA2 should be re-classified into different species from Rps. palustris or as novel species of the genus Rhodopseudomonas.


Subject(s)
Bacterial Typing Techniques , Genetic Variation , Rhodopseudomonas/classification , Rhodopseudomonas/genetics , Bacterial Proteins/genetics , DNA, Bacterial/analysis , DNA, Ribosomal Spacer/analysis , DNA, Ribosomal Spacer/genetics , Light-Harvesting Protein Complexes/genetics , Molecular Sequence Data , Nucleic Acid Hybridization , Photosynthetic Reaction Center Complex Proteins/genetics , Phylogeny , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 23S/genetics , Sequence Analysis, DNA , Species Specificity
17.
Jpn J Cancer Res ; 93(2): 209-15, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11856485

ABSTRACT

One of the most important causes of anticancer treatment failure is the development of multidrug resistance (MDR). The main characteristics of tumor cells displaying the MDR phenomena are cross-resistance to structurally unrelated cytotoxic drugs having different mechanisms of action and the overexpression of the MDR1 gene, which encodes a transmembrane glycoprotein named P-glycoprotein (P-gp). This study evaluated whether bromocriptine, a D2 dopaminergic receptor agonist, influenced anticancer drug cytotoxicity and P-gp activity in a P-gp-expressing cell line compared to a non-expressing subline. The K(i) values for P-gp of cyclosporine and verapamil were 1.09 and 540 microM, respectively, and that of bromocriptine was 6.52 microM in a calcein-AM efflux assay using porcine kidney epithelial LLC-PK1 and L-MDR1 cells, overexpressing human P-gp. Bromocriptine at 10 microM reduced the IC50 of doxorubicin (DXR) in K562-DXR from 9000 to 270 ng/ml and that of vincristine (VCR) in K562-VCR from 700 to 0.30 ng/ml, whereas the IC50 values of DXR and VCR in the K562 subline were only marginally affected by these drugs. Bromocriptine restored the anticancer effect of DXR, VCR, vinblastine, vinorelbine and etoposide on MDR-tumor cells overexpressing P-gp. These observations suggest that bromocriptine has the potential to reverse tumor MDR involving the efflux protein P-gp in the clinical situation.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/drug effects , Bromocriptine/pharmacology , Dopamine Agonists/pharmacology , Drug Resistance, Neoplasm , ATP Binding Cassette Transporter, Subfamily B, Member 1/physiology , Animals , Cell Line , Doxorubicin/metabolism , Drug Resistance, Multiple , Fluoresceins/metabolism , Humans , Rhodamine 123/metabolism , Swine
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