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Biomedical subjects

Paul S Bernstein

Publications and source records attributed to Paul S Bernstein.

At least 19 recordsLinked to original sources
PubMed2006

Association of adipose and red blood cell lipids with severity of dominant Stargardt macular dystrophy (STGD3) secondary to an ELOVL4 mutation.

OBJECTIVE: To determine whether adipose and red blood cell membrane lipids, particularly long-chain polyunsaturated fatty acids such as docosahexaenoic acid and eicosapentaenoic acid, are significantly correlated with phenotype in a family with autosomal dominant Stargardt macular dystrophy (gene locus STGD3). A mutation in the ELOVL4 gene is responsible for the macular dystrophy in this family, and its disease-causing mechanism may be its possible involvement in fatty acid elongation in the retina. METHODS: The subjects in this study included 18 adult family members known to have a 2-base pair deletion in the ELOVL4 gene. Control subjects included 26 family members without the mutation. Each subject received a complete eye examination including fundus photographs, the results of which were used to grade the severity of macular dystrophy on a 3-tier scale. Red blood cell membrane and adipose tissue lipids were analyzed as an indication of short-term and long-term dietary fatty acid intake. RESULTS: When adipose lipids were analyzed, there was a significant inverse relationship between phenotypic severity and the level of eicosapentaenoic acid (r = -0.54; P = .04). When red blood cell lipids were analyzed, there were significant inverse relationships between phenotypic severity and levels of eicosapentaenoic acid (r = -0.55; P = .02) and docosahexaenoic acid (r = -0.48; P = .04). CONCLUSIONS: These results indicate that the phenotypic diversity in this family may be related to differences in dietary fat intake as reflected by adipose and red blood cell lipids. CLINICAL RELEVANCE: This study demonstrates that dietary factors can influence the severity of an inherited human macular dystrophy.

Adipose Tissue↗
PubMed2005

CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in the Complement Factor H (CFH) gene increases the risk for advanced AMD. However, its impact on soft drusen, GA, or neovascular AMD--or the relationship between them--is unclear. METHODS AND FINDINGS: We genotyped 581 Icelandic patients with advanced AMD (278 neovascular AMD, 203 GA, and 100 with mixed neovascular AMD/GA), and 435 with early AMD (of whom 220 had soft drusen). A second cohort of 431 US patients from Utah, 322 with advanced AMD (244 neovascular AMD and 78 GA) and 109 early-AMD cases with soft drusen, were analyzed. We confirmed that the CFH Y402H variant shows significant association to advanced AMD, with odds ratio of 2.39 in Icelandic patients (p = 5.9 x 10(-12)) and odds ratio of 2.14 in US patients from Utah (p = 2.0 x 10(-9)) with advanced AMD. Furthermore, we show that the Y402H variant confers similar risk of soft drusen and both forms of advanced AMD (GA or neovascular AMD). CONCLUSION: Soft drusen occur prior to progression to advanced AMD and represent a histological feature shared by neovascular AMD and GA. Our results suggest that CFH is a major risk factor of soft drusen, and additional genetic factors and/or environmental factors may be required for progression to advanced AMD.

Complement Factor H↗
PubMed2005

Microbial xanthophylls.

Xanthophylls are oxygenated carotenoids abundant in the human food supply. Lutein, zeaxanthin, and cryptoxanthin are major xanthophyll carotenoids in human plasma. The consumption of these xanthophylls is directly associated with reduction in the risk of cancers, cardiovascular disease, age-related macular degeneration, and cataract formation. Canthaxanthin and astaxanthin also have considerable importance in aquaculture for salmonid and crustacean pigmentation, and are of commercial interest for the pharmaceutical and food industries. Chemical synthesis is a major source for the heavy demand of xanthophylls in the consumer market; however, microbial producers also have potential as commercial sources. In this review, we discuss the biosynthesis, commercial utility, and major microbial sources of xanthophylls. We also present a critical review of current research and technologies involved in promoting microbes as potential commercial sources for mass production.

Bacteria↗
PubMed2005

Quantitative measurement of 3'-oxolutein from human retina by normal-phase high-performance liquid chromatography coupled to atmospheric pressure chemical ionization mass spectrometry.

3-Hydroxy-beta,epsilon-carotene-3'-one (3'-oxolutein) is the major oxidative metabolite of dietary carotenoids in the retina of the human eye. Elucidating the biochemical mechanism of its formation may provide helpful insight into the pathogenesis of age-related macular degeneration; however, it is found in relatively low quantities that require highly sensitive methods for quantitation from individual retinas. Normal-phase high-performance liquid chromatography coupled to atmospheric pressure chemical ionization mass spectrometry allowed us to do quantitative analysis of 3'-oxolutein from central and peripheral retinas obtained from individual human donors. The limit of quantification for 3'-oxolutein in human retina at a signal-to-noise ratio of 10 was 6 pg. The precision of the assay yielded a coefficient of variation ranging from 4.7 to 7.4% and accuracies of 106-108%. A statistically significant (R = 0.99, p < or = 0.001) linear working range was achieved between 5 and 7200 pg. The 3'-oxolutein contents from 8-mm punches of the central macula and peripheral retina were found to be 375+/-192 and 191+/-95 pg/tissue, respectively.

Adult↗
PubMed2005

Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation.

There is growing evidence that high levels of the macular xanthophyll carotenoids lutein and zeaxanthin may be protective against visual loss due to age-related macular degeneration, but the actual mechanisms of their protective effects are still poorly understood. We have recently purified, identified and characterized a pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye which specifically and saturably binds to the two forms of zeaxanthin endogenously found in the foveal region. In this report, we studied the synergistic antioxidant role of zeaxanthin and GSTP1 in egg yolk phosphatidylcholine (EYPC) liposomes using hydrophilic 2,2'-azobis(2-methyl-propionamidine) dihydrochloride (AAPH) and lipophilic 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) as lipid peroxyl radical generators. The two zeaxanthin diastereomers displayed synergistic antioxidant effects against both azo lipid peroxyl radical generators when bound to GSTP1. In the presence of GSTP1, nondietary (3R,3'S-meso)-zeaxanthin was observed to be a better antioxidant than dietary (3R,3'R)-zeaxanthin. This effect was found to be independent of the presence of glutathione. Carotenoid degradation profiles indicated that the zeaxanthin diastereomers in association with GSTP1 were more resistant to degradation which may account for the synergistic antioxidant effects.

Amidines↗
PubMed2005

Production of deuterated zeaxanthin by Flavobacterium multivorum and its detection by resonance Raman and mass spectrometric methods.

Flavobacterium multivorum, a zeaxanthin-producing organism, was grown aerobically in a medium prepared with deuterated water. Atmospheric pressure chemical ionization mass spectrometry (APCI-MS) and resonance Raman spectroscopy (RRS) analysis revealed approximately 75% replacement of hydrogen by deuterium atoms as indicated by the molecular mass cluster at around m/z 600. Deuterated zeaxanthin upon excitation with a 488 nm laser exhibited characteristic resonance Raman vibrational modes at 1,161 and 1,504 cm(-1) as compared to 1,007, 1,159 and 1,525 cm(-1 )for undeuterated zeaxanthin. HPLC/APCI-MS and HPLC/RRS were specific and sensitive with limits of detection of 2.5 pg and 50 ng, respectively.

Deuterium Oxide↗
PubMed2005

Postcataract endophthalmitis caused by Mycobacterium goodii.

This is the first reported case of delayed-onset postcataract endophthalmitis caused by Mycobacterium goodii, confirmed by multiple cultures. The patient had uneventful cataract removal by phacoemulsification with implantation of a posterior chamber intraocular lens (IOL). One month later, he developed redness, pain, a hypopyon, and a decrease in visual acuity to finger counting in the affected eye. A vitreous biopsy was performed for suspected endophthalmitis; culture results showed rapidly growing bacteria identified by DNA sequencing as Mycobacterium goodii. The eye ultimately required IOL explantation but had a good final outcome with 20/40 uncorrected vision. Mycobacterium goodii is a rapidly growing Mycobacterium with isolates more commonly occurring in cellulitis, osteomyelitis, and respiratory disease. Single-drug antibiotic therapy for nonocular disease is often sufficient if the correct antimicrobial agent is used. The newer fluoroquinolones are promising against rapidly growing Mycobacterium.

Aged↗
PubMed2004

Beta-carotene production by Flavobacterium multivorum in the presence of inorganic salts and urea.

Flavobacterium multivorum, a non-fermenting Gram-negative bacteria, normally produces zeaxanthin (3R, 3' R-beta, beta-carotene-3, 3' diol) as its main carotenoid. The effect of supplementation of various inorganic salts and urea on the growth, total carotenoid production, and proportion of beta-carotene (beta, beta-carotene), beta-cryptoxanthin (beta, beta-caroten-3-ol), and zeaxanthin produced by F. multivorum was investigated. Urea and several salts, such as calcium chloride, ammonium chloride, lithium chloride, and sodium carbonate, improved total carotenoid production by 1.5- to 2.0-fold. Urea and sodium carbonate had an unexpectedly strong positive effect on beta-carotene production at the expense of zeaxanthin formation. The effect was found to be independent of incubation time, and beta-carotene represented 70% (w/w) of the total carotenoid content. The cumulative effect of urea and sodium carbonate was further studied using response surface methodology. An optimum medium was found to contain 4,000 and 4,070 mg l(-1) urea and sodium carbonate, respectively. The maximum beta-carotene level was 7.85 microg ml(-1) culture broth, which represented 80% (w/w) of the total carotenoid produced. Optimization resulted in 77- and 88-fold improvements in the volumetric and specific beta-carotene levels, respectively, accompanied by a simultaneous decrease in the zeaxanthin level as compared to the control medium. The carotenoid production profile in the optimized medium indicated that beta-carotene was produced maximally during the late exponential phase at 0.41 microg ml(-1) h(-1). It is possible that this organism could be an excellent commercial source of either beta-carotene or zeaxanthin, depending on initial culture conditions.

Culture Media↗
PubMed2004

Resonance Raman measurement of macular carotenoids in the living human eye.

There is growing evidence that high levels of the macular xanthophyll carotenoids lutein and zeaxanthin may be protective against visual loss from age-related macular degeneration. To study this protective effect further, it is important to measure macular carotenoid levels noninvasively in a wide variety of subjects. We have developed and validated resonance Raman spectroscopy as a sensitive and specific objective method to measure macular carotenoid levels in the living human eye. In this minireview, the principles and implementation of ocular carotenoid resonance Raman spectroscopy are reviewed, and the results of observational cross-sectional studies and of prospective supplementation studies on subjects with and without macular pathology are summarized. We have recently extended this technology to an imaging mode which will further enhance our understanding of the roles of lutein and zeaxanthin in normal macular function and in the prevention of age-related visual loss.

Carotenoids↗
PubMed2004

Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye.

Uptake, metabolism, and stabilization of xanthophyll carotenoids in the retina are thought to be mediated by specific xanthophyll-binding proteins (XBPs). A membrane-associated XBP was purified from human macula using ion-exchange chromatography followed by gel-exclusion chromatography. Two-dimensional gel electrophoresis showed a prominent spot of 23 kDa and an isoelectric point of 5.7. Using mass spectral sequencing methods and the public NCBI database, it was identified as a Pi isoform of human glutathione S-transferase (GSTP1). Dietary (3R,3'R)-zeaxanthin displayed the highest affinity with an apparent Kd of 0.33 microm, followed by (3R,3'S-meso)-zeaxanthin with an apparent Kd of 0.52 microm. (3R,3'R,6'R)-Lutein did not display any high-affinity binding to GSTP1. Other human recombinant glutathione S-transferase (GST) proteins, GSTA1 and GSTM1, exhibited only low affinity binding of xanthophylls. (3R,3'S-meso)-Zeaxanthin, an optically inactive nondietary xanthophyll carotenoid present in the human macula, exhibited a strong induced CD spectrum in association with human macular XBP that was nearly identical to the CD spectrum induced by GSTP1. Like-wise, dietary (3R,3'R)-zeaxanthin displayed alterations in its CD spectrum in association with GSTP1 and XBP. Other mammalian xanthophyll carrier proteins such as tubulin, high-density lipoprotein, low-density lipoprotein, albumin, and beta-lactoglobulin did not bind zeaxanthins with high affinity, and they failed to induce or alter xanthophyll CD spectra to any significant extent. Immunocytochemistry with an antibody to GSTP1 on human macula sections showed highest labeling in the outer and inner plexiform layers. These results indicate that GSTP1 is a specific XBP in human macula that interacts with (3R,3'S-meso)-zeaxanthin and dietary (3R,3'R)-zeaxanthin in contrast to apparently weaker interactions with (3R,3'R,6'R)-lutein.

Adult↗
PubMed2004

Resonance Raman quantification of nutritionally important carotenoids in fruits, vegetables, and their juices in comparison to high-pressure liquid chromatography analysis.

A rapid nondestructive estimation of carotenoid levels in intact fruits and vegetables and their juices could have great value when selecting nutritionally valuable crops for further propagation and commercial use. Carotenoid levels of a variety of agricultural products and juices were measured using resonance Raman spectroscopy and compared to levels determined by extraction and high-pressure liquid chromatography. A strong correlation was observed between the two methods when evaluating juices and when comparing different strains of intact tomatoes at the same stage of ripening.

Beverages↗
PubMed2003

Resonance Raman measurement of macular carotenoids in retinal, choroidal, and macular dystrophies.

BACKGROUND: It has been hypothesized that the macular carotenoid pigments lutein and zeaxanthin may protect against macular and retinal degenerations and dystrophies. OBJECTIVE: To test this hypothesis by objectively measuring lutein and zeaxanthin levels in a noninvasive manner in patients who have retinitis pigmentosa (RP), choroideremia (CHM), and Stargardt macular dystrophy and comparing them with an age-matched healthy control population. METHODS: Using resonance Raman spectroscopy, a novel objective noninvasive laser-optical technique, we measured macular carotenoid levels in 30 patients (54 eyes) who have RP, CHM, and Stargardt macular dystrophy and compared them with 76 age-matched subjects (129 eyes) who did not have macular pathologic conditions in a case-control study. RESULTS: As a group, patients with RP and CHM had the same macular carotenoid levels as age-matched healthy control subjects (P =.76, 2-way analysis of variance). Patients with Stargardt macular dystrophy tended to have levels of macular carotenoid pigments that, on average, were about 50% lower than healthy controls (P =.02,unpaired 2-tailed t test). CONCLUSIONS: The patients with RP and CHM had normal levels of macular carotenoids, suggesting that nutritional supplementation with macular carotenoids such as lutein, zeaxanthin, or both will be unlikely to affect the clinical course of RP and CHM. Although the number of patients with Stargardt macular dystrophy examined was limited, their macular carotenoid levels were usually lower than those of subjects of a similar age with no macular pathologic condition.

Adult↗
PubMed2003

Resonant Raman quantification of zeaxanthin production from Flavobacterium multivorum.

Resonant Raman scattering was used as a novel, rapid, non-destructive optical technique to measure zeaxanthin levels in Flavobacterium multivorum ATCC 55238. Culture broth, after bacterial growth for 40 h, exhibited characteristic resonance Raman vibrational modes at 1159 cm(-1) (C-C stretch) and 1525 cm(-1) (C=C stretch) upon excitation at 488 nm. A striking correlation was observed between the carotenoid level as estimated by HPLC and by resonance Raman spectroscopy.

Chromatography, High Pressure Liquid↗
PubMed2003

Dietary modification and moderate antioxidant supplementation differentially affect serum carotenoids, antioxidant levels and markers of oxidative stress in older humans.

Oxidative stress is thought to be a factor in the progression of chronic diseases, and even the aging process itself. We examined the effect of two moderate vitamin, mineral and phytochemical supplements and a dietary intervention on markers of oxidative stress and antioxidant status in older humans. Subjects (n = 60, 65-85 y old) were enrolled in a 5-wk, double-blind, placebo-controlled study. The subjects were randomly assigned to a group with one of four interventions: antioxidant supplement capsule, antioxidant supplement tablet, high carotenoid diet or placebo. Postintervention serum levels of some of the supplemented carotenoids and alpha-tocopherol were higher in all treated groups compared with the placebo group and with preintervention levels within groups. Markers of oxidative stress or antioxidant capacity were not significantly different from preintervention levels, although the diet and supplement capsule groups had lower levels of some of those markers than the placebo group postintervention. The results suggest that both moderate antioxidant supplementation and a diet high in carotenoids elevate serum carotenoids and antioxidant levels in an older adult population, although with different specific effects.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Photophysical properties of xanthophylls in carotenoproteins from human retinas.

The macula of the human retina contains high amounts of the xanthophyll carotenoids lutein and zeaxanthin [a mixture of (3R,3'R)-zeaxanthin and (3R,3'S-meso)-zeaxanthin]. Recently, it was shown that the uptake and the stabilization of zeaxanthin and lutein into the retina are likely to be mediated by specific xanthophyll-binding proteins (XBP). Here, we have used femtosecond pump-probe spectroscopy to study the dynamics of the S1 state of these xanthophylls in xanthophyll-enriched and native XBP. The results from the native XBP and the enriched XBP were then compared with those for carotenoids in organic solvents and in detergent micelles. Steady-state and transient absorption spectra show that the incorporation of xanthophylls into the protein causes a redshift of the spectra, which is stronger for lutein than for zeaxanthin. The transient absorption spectra further indicate that a part of the xanthophylls remains unbound in the xanthophyll-enriched XBP. The transient absorption spectra of the native XBP prove the presence of both xanthophylls in native XBP. Although the S1 lifetime of lutein does not exhibit any changes when measured in solution, micelles or XBP, we have observed the influence of the environment on the S1 lifetime of meso-zeaxanthin, which has a longer (12 ps) lifetime in XBP than in solution (9 ps). The most pronounced effect was found for vibrational relaxation in the S1 state, which is significantly slower for xanthophylls in XBP compared with micelles and solution. This effect is more pronounced for meso-zeaxanthin, suggesting a specific site of binding of this carotenoid to XBP.

Carotenoids↗