Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome as a Manifestation of Recurrent Ovarian Cancer.

We herein report a case of ovarian cancer recurrence detected every time with symptoms of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. A 46-year-old woman who had a history of ovarian cancer 9 months earlier developed joint pain along with pitting edema in both hands and was diagnosed with RS3PE syndrome. Two and four years after initial surgery for ovarian cancer, symptoms of RS3PE syndrome appeared, and a recurrent site was detected. With resection of the relapsed sites and increased maintenance dose of methylprednisolone, these symptoms improved within a month.

Antimicrobial Properties of a Copper/Silicone Composite Membrane Prepared Using a Two-Step Immersion Process in Iodine and Copper Sulfate Solutions.

Silicone (polydimethylsiloxane) materials are widely used in various applications. Due to microbe adherence and biofilm formation at the surface of silicone materials, silicone materials must possess antibacterial properties. To achieve this, we prepared copper (Cu)−silicone composite membranes using a simple two-step process of immersion in iodine and copper sulfate solutions. Subsequent scanning electron microscopy revealed Cu nanoparticles (CuNPs) of 10 to 200 nanometers in diameter on the silicone membrane surface, which were identified as copper iodide using energy-dispersive X-ray spectroscopy. The mechanical strength of the material did not change significantly as a result of the two-step immersion treatment and the Cu/silicone membrane showed excellent antibacterial efficacy against Escherichia coli and Staphylococcus aureus, maintaining R > 2 even after a physical impact such as stomacher treatment. Additionally, the Cu ions eluted from the Cu/silicone membrane remained at very low concentrations, suggesting firm immobilization of CuNPs on the silicone membrane. This proposed antimicrobial treatment method does not require special equipment, can be performed at room temperature, and has the potential for use on silicone materials other than membranes.

Effect of Dietary Carotenoid on Egg Yolk Color and Singlet Oxygen Quenching Activity of Laying Hens.

The effects of dietary carotenoids on egg yolk were investigated in this study. Forty Rhode Island Red (RR) and 40 Silky Fowl (SF) hens that were 60 weeks old were used. Hens of each breed were randomly divided into four dietary groups. One group was fed a basal diet (crude protein 17%, metabolizable energy 2800 kcal/kg) only, whereas the other groups received a specific additive, namely, paprika extract, marigold petal extract, or Paracoccus cell powder, in addition to the same basal diet. The color and carotenoid content of egg yolk and singlet oxygen quenching activity were measured after 4 weeks. The total carotenoid content, zeaxanthin content, and singlet oxygen quenching activity in the yolk differed significantly between breeds and between diets (two-way ANOVA). The lutein content in egg yolk was affected by breed and diet, as well as by the interaction between these two factors. Regarding the Roche Yolk Color Fan values, only the effect of diet was significant. In terms of objective egg yolk color, there was a significant difference in lightness and yellowness between breeds. The total carotenoid content was higher in SF than in RR in all the groups. Likewise, the levels of zeaxanthin and lutein in the yolk were higher in SF than in RR (P<0.05). The results of the present study suggest that dietary carotenoids are effective feed additives for laying hens, especially SF, to improve the color and singlet oxygen quenching activity of egg yolk.

Aryl Polyenes, a Highly Abundant Class of Bacterial Natural Products, Are Functionally Related to Antioxidative Carotenoids.

Bacterial pigments of the aryl polyene type are structurally similar to the well-known carotenoids with respect to their polyene systems. Their biosynthetic gene cluster is widespread in taxonomically distant bacteria, and four classes of such pigments have been found. Here we report the structure elucidation of the aryl polyene/dialkylresorcinol hybrid pigments of Variovorax paradoxus B4 by HPLC-UV-MS, MALDI-MS and NMR. Furthermore, we show for the first time that this pigment class protects the bacterium from reactive oxygen species, similarly to what is known for carotenoids. An analysis of the distribution of biosynthetic genes for aryl polyenes and carotenoids in bacterial genomes is presented; it shows a complementary distribution of these protective pigments in bacteria.

Multiple transformation with the crtYB gene of the limiting enzyme increased carotenoid synthesis and generated novel derivatives in Xanthophyllomyces dendrorhous.

Xanthophyllomces dendrorhous (in asexual state named as Phaffia rhodozyma) is a fungus which produces astaxanthin, a high value carotenoid used in aquafarming. Genetic pathway engineering is one of several steps to increase the astaxanthin yield. The limiting enzyme of the carotenoid pathway is phytoene synthase. Integration plasmids were constructed for transformation with up to three copies of the crtYB gene. Upon stepwise transformation, the copy numbers of crtYB was continuously increased leading to an almost saturated level of phytoene synthase as indicated by total carotenoid content. Several carotenoid intermediates accumulated which were absent in the wild type. Some of them are substrates and intermediates of astaxanthin synthase. They could be further converted into astaxanthin by additional transformation with the astaxanthin synthase gene. However, three intermediates exhibited an unusual optical absorbance spectrum not found before. These novel keto carotenoid were identified by HPLC co-chromatography with reference compounds generated in Escherichia coli and one of them 3-HO-4-keto-7',8'-dihydro-ß-carotene additionally by NMR spectroscopy. The others were 4-keto-ß-zeacarotene and 4-keto-7',8'-dihydro-ß-carotene. A biosynthesis pathway with their origin from neurosporene and the reason for their synthesis especially in our transformants has been discussed.

Construction of transplastomic lettuce (Lactuca sativa) dominantly producing astaxanthin fatty acid esters and detailed chemical analysis of generated carotenoids.

The plastid genome of lettuce (Lactuca sativa L.) cv. Berkeley was site-specifically modified with the addition of three transgenes, which encoded ß,ß-carotenoid 3,3'-hydroxylase (CrtZ) and ß,ß-carotenoid 4,4'-ketolase (4,4'-oxygenase; CrtW) from a marine bacterium Brevundimonas sp. strain SD212, and isopentenyl diphosphate isomerase from a marine bacterium Paracoccus sp. strain N81106. Constructed transplastomic lettuce plants were able to grow on soil at a growth rate similar to that of non-transformed lettuce cv. Berkeley and generate flowers and seeds. The germination ratio of the lettuce transformants (T0) (98.8%) was higher than that of non-transformed lettuce (93.1 %). The transplastomic lettuce (T1) leaves produced the astaxanthin fatty acid (myristate or palmitate) diester (49.2% of total carotenoids), astaxanthin monoester (18.2%), and the free forms of astaxanthin (10.0%) and the other ketocarotenoids (17.5%), which indicated that artificial ketocarotenoids corresponded to 94.9% of total carotenoids (230 µg/g fresh weight). Native carotenoids were there lactucaxanthin (3.8%) and lutein (1.3 %) only. This is the first report to structurally identify the astaxanthin esters biosynthesized in transgenic or transplastomic plants producing astaxanthin. The singlet oxygen-quenching activity of the total carotenoids extracted from the transplastomic leaves was similar to that of astaxanthin (mostly esterified) from the green algae Haematococcus pluvialis.

Isolation and identification of 4, 4'-diapolycopene-4,4'-dioic acid produced by Bacillus firmus GB1 and its singlet oxygen quenching activity.

We succeeded in purifying the carotenoid produced by Bacillus firmus GB1 using chromatography on polystyrenic synthetic adsorbents, and identified it as 4,4'-diapolycopene-4,4'-dioic acid by HRESI-MS and NMR analyses of it and its dimethylester. In addition, we clarified the singlet oxygen (¹O2) quenching activities of 4,4'-diapolycopene-4,4'-dioic acid and its methyl esters (mono and dimethyl ester). Their IC50 values were 5.8 µM, 6.0 µM, and 6.2 µM, respectively. To our knowledge, this is the first report concerning the isolation and antioxidative activity of 4,4'-diapolycopene-4,4'-dioic acid, a product of the C30 carotenoid biosynthesis pathway.

3-ß-Glucosyl-3'-ß-quinovosyl zeaxanthin, a novel carotenoid glycoside synthesized by Escherichia coli cells expressing the Pantoea ananatis carotenoid biosynthesis gene cluster.

Escherichia coli cells that express the full six carotenoid biosynthesis genes (crtE, crtB, crtI, crtY, crtZ, and crtX) of the bacterium Pantoea ananatis have been shown to biosynthesize zeaxanthin 3,3'-ß-D-diglucoside. We found that this recombinant E. coli also produced a novel carotenoid glycoside that contained a rare carbohydrate moiety, quinovose (chinovose; 6-deoxy-D-glucose), which was identified as 3-ß-glucosyl-3'-ß-quinovosyl zeaxanthin by chromatographic and spectroscopic analyses. The chirality of the aglycone of these zeaxanthin glycosides had been shown to be 3R,3'R, in which the hydroxyl groups were formed with the CrtZ enzyme. It was here demonstrated that zeaxanthin synthesized from ß-carotene with CrtR or CYP175A1, the other hydroxylase with similar catalytic function to CrtZ, possessed the same stereochemistry. It was also suggested that the singlet oxygen-quenching activity of zeaxanthin 3,3'-ß-D-diglucoside, which has a chemical structure close to the new carotenoid glycoside, was superior to that of zeaxanthin.

Anti-oxidative, anti-tumor-promoting, and anti-carcinogenic activities of adonirubin and adonixanthin.

Anti-oxidative, anti-tumor-promoting, and anti-carcinogenic activities of adonirubin and adonixanthin, which are biosynthetic intermediates from ß-carotene to astaxanthin, were investigated. Both adonirubin and adonixanthin showed almost the same activities for inhibition of lipid peroxidation and quenching of singlet oxygen as those of astaxanthin. Furthermore, adonirubin and adonixanthin exhibited an inhibitory effect on Epstein-Barr virus early antigen activation in Raji cells and carcinogensis of mouse skin tumors initiated by 7,12-dimethylbenz[a]anthracene and promoted by 12-O-tetradecanoylphorbol-13-acetate.

Characterization and singlet oxygen quenching activity of (3R)-3-hydroxy-4-ketotorulene and (3R)-3-hydroxy-4-keto-γ-carotene isolated from the yeast Xanthophyllomyces dendrorhrous.

Structures of (3R)-3-hydroxy-4-ketotorulene (1) and (3R)-3-hydroxy-4-keto-γ-carotene (2) isolated from the yeast Xanthophyllomyces dendrorhrous were fully characterized by FAB MS, ¹H NMR, ¹³C NMR and CD spectroscopic data. Both 1 and 2 showed potent singlet oxygen (¹O2) quenching activity as that of astaxanthin and lycopene, which were well known strong ¹O2 quencher.

Isolation of a novel carotenoid, OH-chlorobactene glucoside hexadecanoate, and related rare carotenoids from Rhodococcus sp. CIP and their antioxidative activities.

In the course of screening for antioxidative carotenoids from bacteria, we isolated and identified a novel carotenoid, OH-chlorobactene glucoside hexadecanoate (4), and rare carotenoids, OH-chlorobactene glucoside (1), OH-γ-carotene glucoside (2) and OH-4-keto-γ-carotene glucoside hexadecanoate (3) from Rhodococcus sp. CIP. The singlet oxygen ((1)O(2)) quenching model of these carotenoids showed potent antioxidative activities IC(50) 14.6 µM for OH-chlorobactene glucoside hexadecanoate (4), 6.5 µM for OH-chlorobactene glucoside (1), 9.9 µM for OH-γ-carotene glucoside (2) and 7.3 µM for OH-4-keto-γ-carotene glucoside hexadecanoate (3).

Production of caloxanthin 3'-ß-D-glucoside, zeaxanthin 3,3'-ß-D-diglucoside, and nostoxanthin in a recombinant Escherichia coli expressing system harboring seven carotenoid biosynthesis genes, including crtX and crtG.

The aim of this study was to produce rare ß-carotene-modified carotenoids possessing 2-O (-H or -glu) and/or 3-O (-H or -glu) functionalities in their ß-ionone ring(s) using a recombinant Escherichia coli approach. This involved expressing seven carotenoid biosynthesis genes (crtE, crtB, crtI, crtY, crtZ, crtX and crtG). From the cells of the recombinant E. coli, caloxanthin (ß,ß-carotene-2,3,2',3'-tetrol)-3'-ß-D-glucose, zeaxanthin (ß,ß-carotene-3,3'-diol) 3,3'-ß-D-diglucoside, and nostoxanthin (ß,ß-carotene-2,3,3'-triol) (rare carotenoids) were isolated and identified. Caloxanthin 3'-ß-D-glucose displayed potent (1)O(2) quenching activity (IC(50) 19 µM).

A 2-week prognostic prediction model for terminal cancer patients in a palliative care unit at a Japanese general hospital.

OBJECTIVE: We aimed to develop a prognostic prediction model for 2-week survival among patients with terminal cancer in a palliative care unit (PCU). METHODS: A prospective cohort study was conducted on terminal cancer patients in the PCU for 11 months at a general hospital in Tokyo, Japan. We collected data regarding demographics, treatment history, performance status, symptoms, and laboratory results. Patients who survived more than 2 weeks were labeled 'long survivors' and those who died within 2 weeks were grouped as 'short survivors'. Stepwise logistic regression model was constructed for the model development and bootstrapping was used for the internal model validation. RESULTS: In 158 subjects whose data were available for the analysis, 109 (69%) subjects were categorized as long survivors and 49 (31%) subjects as short survivors. A prognostic prediction model with a total score of 8 points was constructed as follows: 2 points each for anorexia, dyspnea, and edema; 1 point each for blood urea nitrogen >25 mg/dl and platelets <260,000/mm(3). Area under the receiver operating characteristic (ROC) curve of this model was 83.2% (95% CI: 75.3-91.0%). Bootstrapped validation beta coefficients of the predictors were similar to the original cohort beta coefficients. CONCLUSION: Our prognostic prediction model for estimating 14-day survival for patients with terminal cancer on the PCU ward included five clinical predictors that are readily available in the clinical setting and showed a relatively high accuracy. External validation is needed to confirm the model's generalizability.

Characterization and antioxidative activities of rare C(50) carotenoids-sarcinaxanthin, sarcinaxanthin monoglucoside, and sarcinaxanthin diglucoside-obtained from Micrococcus yunnanensis.

While screening for antioxidative carotenoids from marine bacteria, we isolated and identified sarcinaxanthin and its glucosylated compounds (sarcinaxanthin monoglucoside and sarcinaxanthin diglucoside) from a moderately halophilic bacterium-Micrococcus yunnanensis strain AOY-1. In the singlet oxygen ((¹O2) quenching model, the IC(50) values of the antioxidative activities of these carotenoids were as follows: sarcinaxanthin , 57 µM; sarcinaxanthin monoglucoside, 54 µM; and sarcinaxanthin diglucoside, 74 µM. In addition, the complete proton nuclear magnetic resonance (¹H NMR) assignments of sarcinaxanthin monoglucoside pentaacetate and sarcinaxanthin diglucoside octaacetate, and fast atom bombardment mass spectrometry/mass spectrometry (FAB-MS/MS) analyses of sarcinaxanthin and sarcinaxanthin monoglucoside are reported for the first time.

5-Hydroxy-5,6-dihydro-apo-4,4'-lycopene and methyl 5-hydroxy-5,6-dihydro-apo-4,4'-lycopenoate, novel C(30)-carotenoids produced by a mutant of marine bacterium Halobacillus halophilus [corrected].

We performed the chemical mutagenesis of Halobacillus halophilus (the producer of a C(30) carotenoid, methyl glucosyl-3,4-dehydro-apo-8'-lycopenoate) to isolate novel carotenoids that are biosynthetic intermediates of methyl glucosyl-3,4-dehydro-apo-8'-lycopenoate. As a result, we isolated two novel C(30) carotenoids, hydroxy-3,4-dehydro-apo-8'-lycopene and methyl hydroxy-3,4-dehydro-apo-8'-lycopenoate, which were biosynthesized through a novel 8'-apo C(30) pathway. These carotenoids showed antioxidative activity in the (1)O(2) suppression model.

Synthesis of highly hydroxylated aromatics by evolved biphenyl dioxygenase and subsequent dihydrodiol dehydrogenase.

The evolved bphA1 (2049) gene, in which nine amino acids from the Pseudomonas pseudoalcaligenes KF707 BphA1 were changed to those from the Burkholderia xenovorans LB400 BphA1 (M247I, H255Q, V258I, G268A, D303E, -313G, S324T, V325I, and T376N), was expressed in Escherichia coli along with the bphA2A3A4 and bphB genes derived from strain KF707. This recombinant E. coli cells converted biphenyl and several heterocyclic aromatic compounds into the highly hydroxylated products such as biphenyl-2,3,2',3'-tetraol (from biphenyl), 2-(2,3-dihydroxyphenyl)benzoxazole-4,5-diol (from 2-phenylbenzoxazole), and 2-(2,5-dihydroxyphenyl)benzoxazole-4,5-diol [from 2-(2-hydroxyphenyl)benzoxazole]. The antioxidative activity of these generated compounds was markedly higher than that of the original substrate used.

Conversion from arenes having a benzene ring to those having a picolinic acid by simple growing cell reactions using Escherichia coli that expressed the six bacterial genes involved in biphenyl catabolism.

The comprehensive bioconversion of aromatic compounds with a benzene ring to a picolinic acid was achieved with a recombinant Escherichia coli strain that expressed the six genes involved in biphenyl catabolism, these being the bphA1(2072)A2A3A4 genes encoding the evolved biphenyl dioxygenase, the bphB gene encoding dihydrodiol dehydrogenase, and the bphC gene encoding catechol 2,3-dioxygenase.