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Biomedical subjects

J B Blumberg

Publications and source records attributed to J B Blumberg.

At least 19 recordsLinked to original sources
PubMed2006

Effects of consuming foods containing oat beta-glucan on blood pressure, carbohydrate metabolism and biomarkers of oxidative stress in men and women with elevated blood pressure.

OBJECTIVE: To assess the effects of consuming foods containing oat beta-glucan on blood pressure, carbohydrate homeostasis and biomarkers of oxidative stress. DESIGN: A randomized, double-blind, controlled clinical trial. SETTING: The trial was conducted at two clinics. SUBJECTS AND INTERVENTIONS: Ninety-seven men and women with resting systolic blood pressure 130-179 mm Hg and/or diastolic blood pressure 85-109 mm Hg were randomly assigned to consume foods containing oat beta-glucan or control foods for 12 weeks. Resting blood pressures, insulin and glucose values before and after standard breakfast meals, and four biomarkers of oxidative stress were measured before and at the end of the treatment period. RESULTS: Changes from baseline to week 12 in mean peak insulin and incremental area under the insulin curve differed significantly between groups (P=0.037 and 0.034, respectively), with the beta-glucan group showing declines and the control group remaining essentially unchanged. Blood pressure responses were not significantly different between groups overall. However, in subjects with body mass index above the median (31.5 kg/m(2)), both systolic (8.3 mm Hg, P=0.008) and diastolic (3.9 mm Hg, P=0.018) blood pressures were lowered in the beta-glucan group compared to controls. No significant differences in biomarkers of oxidative stress were observed between treatments. CONCLUSIONS: The results of the present trial suggest beneficial effects of foods containing beta-glucan from oats on carbohydrate metabolism, and on blood pressure in obese subjects.

Area Under Curve↗
PubMed2001

Endothelin-1 induces phosphorylation of GATA-4 transcription factor in the HL-1 atrial-muscle cell line.

The transcription factor GATA-4 plays a central role in the regulation of cardiac-muscle gene transcription. The present study demonstrates that endothelin-1 (ET-1) induces GATA-4 activation and phosphorylation. The treatment of HL-1 adult mouse atrial-muscle cells with ET-1 (30 nM) caused a rapid increase in the DNA binding activity of GATA-4 within 3 min. The activation was associated with an upward mobility shift of the GATA-4 band on native PAGE in an electrophoretic- mobility-shift assay. The upward shift of the GATA-4 band also occurred on SDS/PAGE as monitored by immunoblotting. The in vitro treatment of nuclear extracts with lambda-protein phosphatase abolished the upward shift, indicating that GATA-4 was phosphorylated. ET-1 activated the p44/42 mitogen-activated protein kinase (MAPK) and the MAPK kinase (MEK) within 3 min, and PD98059 (a specific inhibitor of MEK) abolished the ET-1-induced GATA-4 phosphorylation. PMA also caused the rapid activation of MAPK and the phosphorylation of GATA-4. In contrast, the activation of MAPK by phenylephrine or H(2)O(2) was weak and did not lead to GATA-4 phosphorylation. Thus ET-1 induces a GATA-4 phosphorylation by activating a MEK-MAPK pathway.

Animals↗
PubMed2001

Role of vitamin E and oxidative stress in exercise.

Reactive oxygen species (ROS) play an important role as mediators of skeletal muscle damage and inflammation after strenuous exercise. These ROS arise largely from increases in mitochondrial oxygen consumption and electron transport flux. Bouts of intense exercise are associated with increases in lipid peroxidation, generating malondialdehyde and F(2alpha)-isoprostanes, and the release of muscle enzymes like lactate dehydrogenase and creatine kinase. Dietary and enzymatic antioxidant defenses appear to play a protective role in muscle cells by reducing associated oxidative damage to lipids, nucleic acids, and protein. However, studies of the use of dietary antioxidants like vitamin E to reduce exercise-induced muscle injury have met with mixed success. The equivocal nature of these results appear to reflect a diversity of factors including the antioxidant(s) tested, the nature and timing of the exercise, the age and fitness of the subjects, and the methodology for assessing oxidative stress.

Aged↗
PubMed2001

Elevated plasma F2-isoprostanes in patients on long-term hemodialysis.

BACKGROUND: End-stage renal disease (ESRD) patients on long-term hemodialysis (HD) may be under increased oxidative stress, caused by either HD or renal failure. Plasma F2-isoprostanes have been established as an important indicator of in vivo oxidative stress. METHODS: Plasma esterified F2-isoprostanes were measured in 25 HD patients and 23 controls with normal renal function, employing gas chromatography-mass spectrometry with negative chemical ionization (GC-MS-NCI). C-reactive protein (CRP) was determined concurrently in patients and controls by enzyme-linked immunosorbent assay (ELISA). alpha-Tocopherol, retinol, albumin and creatinine were also determined. RESULTS: The average total esterified F2-isoprostanes in the ESRD patients was 1.62 +/- 0.73 vs. 0.27 +/- 0.10 ng/mL in controls (P < 0.001), with no overlap between patients and controls. Plasma F2-isoprostanes in diabetic ESRD patients were similar to F2-isoprostanes in patients with other causes for renal failure. In a subset of 10 of these ESRD patients evaluated eight months after the initial measurement, plasma-esterified F2-isoprostanes were not altered by an individual dialysis session. Average plasma CRP values were also higher in HD patients (P < 0.02), but some patients had CRP values that were similar to controls. In the HD patients, total plasma F2-isoprostanes and plasma CRP were correlated (r = 0.48, P = 0.015). Plasma alpha-tocopherol did not differ between patients and controls, but plasma retinol was higher in patients (3.15 +/- 1.71 micromol/L) than in controls (1.97 +/- 0.51 micromol/L, P < 0.05). CONCLUSIONS: These results are consistent with the hypothesis that oxidative stress in ESRD patients contributes to increased values of esterified plasma F2-isoprostanes, with concurrent increases in plasma CRP levels in some patients. Impaired clearance of esterified F2-isoprostanes may contribute to the elevated levels in renal failure. Plasma esterified F2-isoprostanes may be a useful indicator to evaluate effectiveness of interventions to decrease oxidative stress and associated inflammation.

Aged↗
PubMed2001

Effects of thiol antioxidants on hepatocyte growth factor signaling in cardiac myocytes.

We describe here novel antioxidant-sensitive events in which activation kinetics are delayed, leading to inhibition of cell signaling. Hepatocyte growth factor (HGF) transiently phosphorylated p44/42 mitogen-activated protein kinase (MAPK) with a peak at 3-5 min in HL-1 adult cardiac myocytes. Pretreatment of cells with thiol antioxidants, N-acetylcysteine or alpha-lipoic acid attenuated MAPK phosphorylation induced by a 3-min incubation with HGF. However, kinetic analysis revealed that the apparent inhibition of HGF signaling was due to a delay in the activation because HGF phosphorylated MAPK with a peak at 5-7 min in cells treated with thiol antioxidants. This 2-min delay in HGF activation of MAPK resulted in >5-min delay in phosphorylation of MAPK targets such as p90RSK and GATA-4. Hydrogen peroxide did not mimic HGF signaling, and HGF did not induce reactive oxygen species production. Thus, in cardiac myocytes, thiol antioxidants delay HGF-mediated MAPK activation and suppress subsequent signaling eventsvia reactive oxygen species-independent mechanism.

Animals↗
PubMed2000

Relative reactivity of lysine and other peptide-bound amino acids to oxidation by hypochlorite.

Antibacterial and inflammatory responses of neutrophils and macrophages produce hypochlorite as a major oxidant. Numerous side chains of amino acids found in extracellular proteins can be modified by hypochlorite, including His, Arg, Tyr, Lys, Trp, and Met. We studied the relative reactivity of each of these amino acid residues in short N-blocked peptides, where other residues in the peptide were highly resistant to hypochlorite attack. Hypochlorite treatment led to modified peptides in each case, which were detected by changes in retention on reversed-phase HPLC. A distinct single product, consuming two equivalents of hypochlorite per equivalent of peptide, was obtained from the Lys-containing peptides. UV spectroscopy, nuclear magnetic resonance (NMR), and electrospray/mass spectroscopy identified this product as the dichloramine at the epsilon-amino group of the Lys side chain. The dichloramine at Lys did not decompose to form a detectable amount of carbonyl reactive with dinitrophenylhydrazine. The dichloramine at Lys did however quantitatively revert back to Lys during HCl digestion of the tetrapeptide for amino acid analysis, with simultaneous modification of the adjacent Phe residue. The formation of the dichloramine at Lys was not blocked by peptides or acetylated amino acids that contained Tyr, His, or Arg. In contrast, the presence of equimolar Met-containing peptide, or N-Acetyl-Trp, both inhibited the formation of the dichloramine at Lys. Thus, Met and Trp side chains of proteins might be able to protect Lys from chloramine formation under some circumstances, but this interpretation must consider that Met and Trp are typically found in relatively inaccessible hydrophobic sites, whereas lysine is typically exposed on the protein surface. The hierarchy of amino acid reactivities examined here will aid in the prediction of residues in biological samples most likely to be modified by hypochlorite.

Acetylation↗
PubMed2000

Streamlined F2-isoprostane analysis in plasma and urine with high-performance liquid chromatography and gas chromatography/mass spectroscopy.

F2-Isoprostanes in plasma and urine are generally determined by labor-intensive methods requiring sample purification by solid-phase extraction and thin-layer chromatography (TLC). A streamlined and more sensitive method for the measurement of esterified plasma F2-isoprostanes was developed by replacing these steps with high-performance liquid chromatography (HPLC) using an amino column with a hexane/2-propanol gradient. Pentafluorobenzyl esters of F2-isoprostanes were prepared and purified by HPLC, silylated, and then analyzed by gas chromatography (GC) with negative chemical ionization mass spectroscopy (NCI-MS). This method permits analysis with lower plasma volumes (100 microL) and greater sensitivity (to 10 pg; allowing detection to 50 pg/mL) than provided by other methods. Urinary F2-isoprostanes can also be efficiently quantified by this method, with 8-iso-PGF2alpha being identified as a major isomer. With this procedure, esterified plasma F2-isoprostanes were found to be 8.3-fold higher in an end-stage renal failure patient on hemodialysis and urinary 8-iso-PGF2alpha was 7.1-fold higher in a cigarette smoker than respective control subjects. This method, particularly the substitution of the TLC step common to other methods with HPLC, results in a more sensitive and reproducible assay.

Chromatography, High Pressure Liquid↗
PubMed2000

Homocysteine exerts cell type-specific inhibition of AP-1 transcription factor.

Homocysteine (Hcy) exerts either promoting or suppressive effects on mitogenesis in a cell type-specific manner. Hcy elicits proliferation of vascular smooth muscle cells, but is rather inhibitory to growth of endothelial cells and NIH/3T3 cells. In NIH/3T3 cells, we found that physiologically relevant concentrations (20-100 microM) of Hcy inhibit the activity of activating protein-1 (AP-1) transcription factor, although it is capable of eliciting immediate-early signaling events. Hcy induced p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in control cells, but not in dominant negative p21ras transfected cells, indicating induction of the Ras-MAPK pathway. Hcy also induced the activity of serum response factor and expression of c-fos and c-jun genes. Despite the activation of these upstream events, Hcy potently inhibited AP-1 activity. Oxidized forms of Hcy (Hcy thiolactone, homocystine) were less effective in affecting AP-1. Hcy-mediated inhibition of AP-1 activity was not observed in A7r5 vascular smooth muscle cells. These results demonstrate that Hcy exerts cell type- and redox-specific inhibition of AP-1 dependent biological events.

3T3 Cells↗
PubMed2000

Assessment of healthcare professionals' knowledge about warfarin-vitamin K drug-nutrient interactions.

OBJECTIVE: Dietary vitamin K can interact with oral anticoagulant drugs and interfere with their therapeutic safety and efficacy. Therefore, knowledge about drug-nutrient interactions involving vitamin K possessed by physicians, pharmacists, dietitians and nurses practicing anticoagulant therapy was assessed. METHODS: Healthcare practitioners were surveyed using a 30-question, 98-item questionnaire on the most common and/or important food interactions with warfarin, drug interactions with warfarin and general drug-nutrient interactions involving vitamin K. The study sample included 160 randomly selected healthcare providers (40 physicians, pharmacists, dietitians and nurses) from 10 hospitals with 200 to 1000 beds from six Massachusetts regions. Random selection was conducted from a pool of selected healthcare providers practicing anticoagulant therapy who counsel patients receiving warfarin. RESULTS: All surveys were completed within three months of the start of the study, and all participants provided usable data for statistical analysis. The mean scores (+/- SD) on the overall test were 72.5+/-9.0 for pharmacists, 62.51+/-10.6 for physicians, 56.9+/-8.8 for dietitians and 50.2+/-9.3 for nurses, with 100 being a perfect score. Pharmacists scored significantly higher in the area of drug interactions (75.9+/-11.3, p<0.05). Dietitians scored higher in the area of food interactions (73.0+/-10.3). No significant differences between physicians and pharmacists were evident on general drug-nutrient interactions. While over 87% of the healthcare professionals correctly identified some common foods containing large amounts of vitamin K, such as broccoli and spinach, fewer than 25% were able to identify others such as pea soup, coleslaw and dill pickles. CONCLUSIONS: Although the healthcare professionals surveyed in this study appear to have demonstrated some proficiency in their respective areas of expertise, they exhibited less knowledge in others. Therefore, additional training and integration of knowledge and expertise about drug-nutrient interactions among healthcare professionals are essential to provide appropriate patient counseling and optimal therapeutic outcomes.

Anticoagulants↗
PubMed2000

The effects of a multivitamin/mineral supplement on micronutrient status, antioxidant capacity and cytokine production in healthy older adults consuming a fortified diet.

BACKGROUND: Inadequate micronutrient intake among older adults is common despite the increased prevalence of fortified/enriched foods in the American diet. Although many older adults take multivitamin supplements in an effort to compensate, studies examining the benefits of this behavior are absent. OBJECTIVE: To determine whether a daily multivitamin/mineral supplement can improve micronutrient status, plasma antioxidant capacity and cytokine production in healthy, free-living older adults already consuming a fortified diet. METHODS: An eight-week double-blind, placebo-controlled clinical trial among 80 adults aged 50 to 87 years (mean = 66.5 +/- 8.6 years). RESULTS: Multivitamin treatment significantly increased (p<0.01, compared to placebo) plasma concentrations of vitamins D (77 to 100 nmol/L), E (27 to 32 micromol/L), pyridoxal phosphate (55.1 to 75.2 nmol/L), folate (23 to 33 nmol/L), B12 (286 to 326 pmol/L)), C (55 to 71 micromol/L), and improved the riboflavin activity coefficient (1.23 to 1.15), but not vitamins A and thiamin. The multivitamin reduced the prevalence of suboptimal plasma levels of vitamins E (p=0.003), B12 (p=0.004), and C (p=0.08). Neither glutathione peroxidase activity nor antioxidant capacity (ORAC) were affected. No changes were observed in interleukin-2, -6 or -10 and prostaglandin E2, proxy measures of immune responses. CONCLUSIONS: Supplementation with a multivitamin formulated at about 100% Daily Value can decrease the prevalence of suboptimal vitamin status in older adults and improve their micronutrient status to levels associated with reduced risk for several chronic diseases.

Aged↗
PubMed2000

The potential role of dietary xanthophylls in cataract and age-related macular degeneration.

The carotenoid xanthophylls, lutein and zeaxanthin, accumulate in the eye lens and macular region of the retina. Lutein and zeaxanthin concentrations in the macula are greater than those found in plasma and other tissues. A relationship between macular pigment optical density, a marker of lutein and zeaxanthin concentration in the macula, and lens optical density, an antecedent of cataractous changes, has been suggested. The xanthophylls may act to protect the eye from ultraviolet phototoxicity via quenching reactive oxygen species and/or other mechanisms. Some observational studies have shown that generous intakes of lutein and zeaxanthin, particularly from certain xanthophyll-rich foods like spinach, broccoli and eggs, are associated with a significant reduction in the risk for cataract (up to 20%) and for age-related macular degeneration (up to 40%). While the pathophysiology of cataract and age-related macular degeneration is complex and contains both environmental and genetic components, research studies suggest dietary factors including antioxidant vitamins and xanthophylls may contribute to a reduction in the risk of these degenerative eye diseases. Further research is necessary to confirm these observations.

Age Factors↗
PubMed2000

Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients.

BACKGROUND: Chemotherapy and radiation therapy result in increased free radical formation and depletion of tissue antioxidants. It is not known whether parenteral nutrition (PN) administered during bone marrow transplantation (BMT) supports systemic antioxidant status. OBJECTIVE: The aims of the study were to determine 1) whether high-dose chemotherapy decreases concentrations of major circulating antioxidants in patients undergoing BMT and 2) whether administration of standard PN maintains systemic antioxidant concentrations compared with PN containing micronutrients and minimal lipids alone. DESIGN: Twenty-four BMT patients were randomly assigned to receive either standard PN containing conventional amounts of dextrose, amino acids, micronutrients, and lipid (120 kJ/d) or a solution containing only micronutrients (identical to those in standard PN) and a small amount of lipid (12 kJ/d). Plasma antioxidant status was measured before conditioning therapy and serially at days 1, 3, 7, 10, and 14 after BMT. RESULTS: Plasma glutathione (GSH) and alpha- and gamma-tocopherol concentrations decreased and the GSH redox state became more oxidized after conditioning chemotherapy. Plasma cysteine concentrations were unchanged, whereas cystine concentrations increased. Plasma vitamin C and zinc concentrations and GSH peroxidase activity increased over time. Plasma alpha-tocopherol concentrations were lower in patients given standard PN. There were no differences in other plasma antioxidants between groups. CONCLUSIONS: A significant decline in GSH-glutathione disulfide, cysteine-cystine, and vitamin E status occurs after chemotherapy and BMT. Standard PN does not improve antioxidant status compared with administration of micronutrients alone. Further evaluation of PN formulations to support patients undergoing high-dose chemotherapy and BMT are needed.

Adult↗
PubMed2000

Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet.

Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease. Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies, no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine. We determined whether a multivitamin/mineral supplement formulated at about 100% Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid. In this randomized, double-blind, placebo-controlled trial, 80 free-living men and women aged 50-87 y with total plasma homocysteine concentrations of > or =8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet. After the 8-wk treatment, subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls (P: < 0.01). Plasma folate, pyridoxal phosphate (PLP) and vitamin B-12 concentrations were increased 41.6, 36.5 and 13.8%, respectively, in the supplemented group, whereas no changes were observed in the placebo group. The mean homocysteine concentration decreased 9.6% in the supplemented group (P: < 0.001) and was unaffected in the placebo group. There were no significant changes in dietary intake during the intervention. Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet.

Aged↗
PubMed2000

Differential regulation of MAP kinase signaling by pro- and antioxidant biothiols.

Some biologically derived thiol-containing compounds have potential for health benefits whereas others elicit biochemical events leading to pathogenesis. Effects of two biothiols, alpha-lipoic acid (alpha LA), a therapeutic antioxidant, and homocysteine (Hcy), a risk factor for age-associated cardiovascular disease, on cell signaling events involving p44 and p42 MAP kinases (p44/42 MAPK) were evaluated in cell culture. Treatment of serum-deprived NIH/3T3 cells with Hcy (20 microM) resulted in the activation of p44/42 MAPK as determined by Western blot analysis using the phospho-specific p44/42 MAPK antibody. p44/42 MAPK phosphorylation was rapid and transient with maximal activation occurring at 10-30 min. Transient activation of p44/42 MAPK was also observed in response to treatment of serum-deprived cells with alpha LA. In cells grown in serum, serum-dependent p44/42 MAPK phosphorylation was transiently enhanced by Hcy or Hcy thiolactone, but inhibited by alpha LA. Thus, alpha LA and Hcy differentially influence signal transduction events depending on the state of cells. These observations may be important in understanding how some biothiols are associated with pathogenic events while others have potential as therapeutic agents.

3T3 Cells↗
PubMed1999

Purification of fatty acid methyl esters by high-performance liquid chromatography.

The determination by gas chromatography (GC) of fatty acid methyl esters (FAMEs) prepared from complex biological samples is subject to interference from cholesterol. During sample injection on the GC system of FAMEs prepared from tissues that contain cholesterol, we observed a major contaminant that co-eluted with docosahexaenoic acid (DHA, 22:6n-3). To address this problem, FAMEs were purified on an amino-phase high-performance liquid chromatography (HPLC) column using a hexane-isopropanol gradient. The HPLC retention times for both the FAME fraction and cholesterol were stable and reproducible when the amino column was used for sample purification. The purified extracts were analyzed by GC without artifacts or impurity peaks after 50 analytical runs. The method described here will be useful for measurement of 22:6n-3 and other fatty acids important for studies of nutrition or pathology.

Butylated Hydroxytoluene↗
PubMed1999

Effect of dietary fish oil, vitamin E, and probucol on renal injury in the rat.

Dietary fish oil, vitamin E, and probucol have been considered in a variety of human and experimental models of kidney disease. Using subtotal nephrectomized cholesterol-fed rats as a model for progressive kidney disease, we examined the effect of 5% dietary fish oil, or a combination of 5% dietary fish oil with 500 IU vitamin E/kg diet or 1% probucol on renal injury. Three-month-old Sprague Dawley rats were fed a control diet (C group) or a cholesterol supplemented (2%) diet (Ch group) containing either fish oil (FO group) or fish oil plus vitamin E (FO+E group) or fish oil plus probucol (FO+P group). After 4 weeks of dietary treatment, the right kidney was electrocoagulated and the left kidney nephrectomized. After 8 weeks, 24-hour urine was collected before sacrifice. No effect of the dietary treatments was noted on serum creatinine, blood urea nitrogen, or proteinuria, except that proteinuria was highest in FO+P group. Rats receiving the cholesterol diets had higher serum low density lipoprotein (LDL) + very low density lipoprotein (VLDL) cholesterol (P < 0.05). In contrast, rats in the FO+P group had the lowest serum total cholesterol and LDL+VLDL cholesterol among all groups. The FO group had 26% lower kidney alpha-tocopherol concentrations than the C group. However, inclusion of vitamin E in the diet (FO+E group) increased the kidney alpha-tocopherol status to a level comparable to that in the C group, whereas inclusion of probucol in fish oil diet (FO+P group) did not improve the kidney alpha-tocopherol status. Rats fed the cholesterol diet had a 2.5-fold higher glomerular segmental sclerosis (GSS) score and 1.5-fold higher glomerular macrophage (GM) subpopulation than the C group. These effects of the cholesterol diet were ameliorated by a fish oil diet (FO group: GSS by 30%, GM by 24%). The inclusion of vitamin E in the fish oil diet (FO+E group) did not further improve the GSS score or GM subpopulation. However, inclusion of probucol in fish oil diet (FO+P group) lowered the GSS score by 73% and reduced GM subpopulation by 83% compared with the Ch group. These remarkable changes can be attributed to the powerful hypocholesterolemic activity of probucol. Our findings indicate that progression of glomerular sclerosis in the rat remnant kidney model of progressive kidney disease can be significantly modulated with fish oil treatment.

Journal Article↗