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Biomedical subjects

D R Hoffman

Publications and source records attributed to D R Hoffman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Docosahexaenoic acid in red blood cells of patients with X-linked retinitis pigmentosa.

PURPOSE: Abnormalities in the distribution of long-chain polyunsaturated fatty acids (LCPUFA) have been documented in plasma of patients with X-linked retinitis pigmentosa (XLRP). In this study, fatty acid profiles of red blood cells (RBC) were used as an index for LCPUFA metabolism in patients with XLRP because RBC lipids reflect membrane-associated fatty acids. Correlations between LCPUFA content and electroretinographic (ERG) function were assessed. METHODS: Mean ages for the XLRP group (n = 18) and control group (n = 28) were 22 +/- 18 years and 24 +/- 16 years, respectively. Electroretinographic assessment included the International Society for the Clinical Electrophysiology of Vision standard protocol. Methyl esters of RBC fatty acids were analyzed by capillary column gas chromatography. RESULTS: The content of the omega 3 fatty acid, docosahexaenoic acid (DHA), was 40% lower in the group with XLRP (23.1 +/- 5.9 micrograms/ml RBC [mean +/- 1 SD]) than in normal subjects (38.6 +/- 9.4 micrograms/ml RBC, t = 6.24, P < 0.0001). Total omega 3 LCPUFA content in patients with XLRP was reduced by 30% from normal levels compared to a 10% reduction in omega 6 LCPUFA levels. Elongation reactions for omega 3, omega 6, saturated fatty acids, and monounsaturated fatty acids were markedly lower for patients with XLRP than for normal subjects. Multiple regression analysis revealed that RBC-DHA was a significant determinant for amplitude and implicit time of cone ERG responses. CONCLUSIONS: The overwhelming majority of patients with XLRP have lower levels of DHA in RBCs compared to normally sighted control subjects. An analysis of fatty acid profiles suggests a metabolic defect in fatty acid chain elongation mechanisms. The significant association between DHA content and cone ERG response parameters is consistent with an effect of lipid abnormalities on membrane environment and physiology in retinal photoreceptors.

Adolescent↗
PubMed1994

Safety and efficacy of omega-3 fatty acids in the nutrition of very low birth weight infants: soy oil and marine oil supplementation of formula.

Because formula-fed preterm infants may be at risk of omega 3 essential fatty acid deficiency, we tested experimental formulas supplemented with soy oil to provide alpha-linolenic acid or marine oil to provide preformed omega 3 long-chain polyunsaturated fatty acids at a level comparable to that of human milk. This report addresses the effect of feeding formula supplemented with soy oil or with soy and marine oils on growth, clinical tolerance, coagulation test results, changes in erythrocyte membrane fluidity, and plasma concentrations of vitamins A and E in very low birth weight infants from 30 to 57 weeks of postconceptional age. "Healthy" preterm infants were maternally selected to receive human milk or selected at random to receive commercial ready-to-feed liquid formula, which provided limited omega 3 fatty acid, or experimental formulas supplemented with soy oil or soy and marine oils. Results of this study indicate that formula enriched with soy oil or soy and marine oils containing preformed omega 3 long-chain polyunsaturated fatty acids does not induce abnormalities in growth, clotting function, erythrocyte membrane fluidity, or vitamin A or E levels in healthy very low birth weight preterm infants. Additional studies to evaluate safety in a representative preterm population are required.

Analysis of Variance↗
PubMed1994

Essential fatty acid metabolism and requirements for LBW infants.

Humans are unable to synthesize linoleic acid (LA) (18:2 omega-6) and alpha-linolenic acid (LNA) (18:3 omega-3). Most formulas provide ample LA, yet infants are at risk for omega-3 deficiency unless they are fed human milk. Neonates born at 30 weeks received human milk or were randomized to three formulas: formula A, based on corn oil, similar to old commercial formula; formula B, based on soy oil supplied LNA; or formula C, a product similar to B with added marine oil to provide docosahexaenoic acid (22:6 omega-3). The fatty acids of plasma and red blood cells had marked diet-induced differences. The rod photo-receptor tests demonstrated higher threshold and decreased sensitivity in the omega-3-deficient infants. Visual acuity also showed improved function of the brain cortex in the human milk and group C infants at follow-up at 57 weeks. These results suggest that omega-3 fatty acids are needed for optimal development of visual function.

Docosahexaenoic Acids↗
PubMed1994

Allergens in hymenoptera venom. XXVI: The complete amino acid sequences of two vespid venom phospholipases.

The 2 major allergenic proteins in vespid venoms are antigen 5s and phospholipases (PLs). Vespid PLs have a molecular weight of about 34,000 and have been previously shown to have an A1B specificity, unlike the A2 specificity of bee PLs. The complete amino acid sequences of the venom PL from the yellow jacket, Vespula maculifrons, and the more acidic isoenzyme from the white faced hornet, Dolichovespula maculata, have been determined by sequencing overlapping peptides isolated from enzyme and chemical digests of the proteins. Ves m 1 is composed of 300 amino acids, with variants found at 3 positions. Dol m 1.02 is composed of 303 amino acids with variants at 2 positions. Comparison with the sequence of Dol m 1.01 determined by cDNA sequencing gave 66.7% identity with Dol m 1.01 with almost all variation in the first 131 positions. Ves m 1 showed 69% identity with Dol m 1.01 and 38.7% with Dol m 1.02. Comparison of the PL sequences with the Protein Identification Resource data base showed many similarities with the lipase family, but very little relationship to known PLs. The amount of structural similarity between Dol m 1 and Ves m 1 is similar to that found among antigen 5 molecules of different genera, and is sufficient to account for antigenic cross-reactivity. There appear to be a number of highly conserved regions of the PL molecules, especially in the C-terminal 168 residues. These regions may from common epitopes found in several species and genera of vespids. Antibodies against these common epitopes will not be able to distinguish among PLs from various vespids.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Development of an enzyme-linked immunosorbent assay for measurement of fire ant venom-specific IgE.

An enzyme-linked immunosorbent assay (ELISA) was developed for in vitro measurement of IgE specific for Solenopsis invicta venom. Enhanced binding microtiter plates were coated with S. invicta venom protein and incubated with sera from fire ant allergic patients and control subjects. Bound IgE was tagged with peroxidase-conjugated monoclonal anti-IgE and quantitated with the substrate/indicator system H2O2/tetramethylbenzidine. Absorbance (620 nm) represented venom-specific IgE values. The ELISA correlated well with the imported fire ant venom RAST (r = .87, P < .0001). Using skin test reactivity as the standard measure of venom-specific IgE, the venom ELISA appeared to be a sensitive in vitro assay comparable to venom RAST. ELISA is less expensive than RAST and does not require licensing or handling of radioisotopes.

Adult↗
PubMed1993

Platelet-activating factor in surfactant preparations.

Surfactant administration is used for treatment of neonatal respiratory distress syndrome. We studied whether currently used surfactant preparations contain platelet-activating factor (PAF), a potent lipid mediator produced by fetal lungs. Three surfactant preparations from animal sources contained between 36 and 218 pmol of PAF per mL, whereas PAF was undetectable in an artificial surfactant. Based on current recommendations, about 144-654 pmol PAF would be administered per dose of natural surfactant, sufficient to exert possible physiological effects on the lung. The action of PAF may be exacerbated by low activity of PAF-acetylhydrolase, which inactivates PAF, in tracheal fluid from infants with respiratory distress syndrome.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1993

Sequence analysis and antigenic cross-reactivity of a venom allergen, antigen 5, from hornets, wasps, and yellow jackets.

Ag 5 is a major allergen of vespid venom. The complete amino acid sequences of Ag 5 from two species each of hornets (Dolichovespula arenaria and maculata), wasps (Polistes annularis and exclamans), and yellow jackets (Vespula maculifrons and vulgaris) have been determined by amino acid sequencing and/or cDNA cloning. The sequence data reveal several conserved and variable regions for vespid Ag 5. The conserved regions show greater sequence similarity than do the less conserved regions to a family of proteins from human, mouse, and rat testis and to a class of pathogenesis-related proteins from tobacco and tomato leaves. Tests in the murine system for both T and B cell responses demonstrate a high degree of cross-reactivity of hornet Ag 5 with wasp or yellow jacket Ag 5 and a low degree of cross-reactivity of yellow jacket Ag 5 with wasp Ag 5. This pattern of cross-reactivity is in the same order as their sequence similarity.

Allergens↗
PubMed1993

Nucleotide sequence of cDNA encoding the fire ant venom protein Sol i II.

For the first time the cDNA encoding a fire ant venom protein has been sequenced. Oligonucleotides were designed according to the amino acid sequence. The cDNA sequence was obtained by hybridizing these primers to mRNA and enhancement by the PCR technique. Comparison to the amino acid sequence of the venom protein shows a leader sequence 19 amino acids long.

Amino Acid Sequence↗
PubMed1993

Red blood cell fatty acid levels in patients with autosomal dominant retinitis pigmentosa.

Fatty acid profiles were determined in red blood cell (RBC), plasma lipids and lipid fractions from 50 patients with autosomal dominant retinitis pigmentosa (ADRP) and 20 normal-sighted controls. In plasma of affected patients, significant increases in omega 6 long-chain derivatives compared to controls resulted in elevated fatty acid unsaturation whereas, in RBCs, significant decreases in the levels of omega 6 and omega 3 long-chain polyunsaturates and a reduced unsaturation index were demonstrated (P < 0.01). The disproportionate levels of long-chain fatty acids in plasma vs. RBCs were consistent with abnormal function of acyl group transfer from plasma lipids to target tissues such as RBCs or, possibly, retina. Metabolic lipid anomalies were evaluated in two sub-groups of patients with ADRP; ten with the highest and ten with the lowest RBC lipid levels of the omega 3 fatty acid, docosahexaenoic acid (DHA). Fatty acid product/precursor relationships in the sub-groups revealed reduced chain elongation and omega 3 fatty acid desaturation associated with reduced ratios of rod-to-cone electroretinographic amplitudes. Based on these results, we suggest that the heterogenic ADRP population includes a sub-group of patients characterized by abnormal fatty acid metabolism that may effect membrane structure and visual function.

Adolescent↗
PubMed1993

Allergens in Hymenoptera venom. XXV: The amino acid sequences of antigen 5 molecules and the structural basis of antigenic cross-reactivity.

The complete amino acid sequences have been determined by solid-phase protein sequencing for eight different vespid venom antigen 5 molecules. These include five species of yellow jackets, Vespula squamosa, V. flavopilosa, V. germanica, V. pensylvanica and V. vidua, representing all three species groups; two variants from the European hornet, Vespa crabro; and a species of paper wasp, Polistes fuscatus, from a second subgenus. The new sequences were compared with the seven previously published sequences from yellow jackets, hornets, and wasps, and to that of Solenopsis invicta 3 allergen from imported fire ant venom. These comparisons provided structural evidence to support the observed high degree of cross-reactivity among the antigens of the common group of yellow jackets and among those of the two common North American subgenera of paper wasps studied. The antigen 5 of V. squamosa and of V. vidua were significantly different from those of the vulgaris group. Common features that could generate immunologic cross-reactivity were seen among the antigen 5 molecules of hornets of both genera and among those of yellow jackets, hornets, and paper wasps. The imported fire ant allergen has only minimal conserved areas in common with the vespid allergens, which explains the lack of observed IgE cross-reactivity. These results provide the structural basis for the cross-reactivity patterns observed in clinical practice and suggest that the commercial extracts of yellow jacket and paper wasp could be prepared with fewer carefully selected species.

Allergens↗
PubMed1993

Allergens in Hymenoptera venom XXIV: the amino acid sequences of imported fire ant venom allergens Sol i II, Sol i III, and Sol i IV.

The most common cause of insect venom allergy in the Southeastern United States is the imported fire ant. The allergens are among the most potent known, with nanogram doses causing sensitization and provoking anaphylaxis. The complete amino acid sequences of imported fire ant venom allergens, Sol i II, III, and IV, were determined by solid-phase protein sequencing of overlapping peptide fragments. Sol i II has a single sequence of 119 amino acids and a molecular weight of 13,217. It has seven cysteine residues, and in its native form is a disulfide-linked dimer. The highly purified molecule does not have phospholipase activity and is not structurally related to phospholipases or other known proteins. Sol i IV has 117 amino acids, for a molecular weight of 13,340. It has six cysteines and is a monomer. Its sequence is 35% identical to Sol i II, but it is not significantly related to other proteins. The Sol i IV sequence showed two amino acid variations. Sol i III was found to consist of 212 amino acids of molecular weight 24,040 in good agreement with 26,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The sequence contained eight cysteine residues and was found to be 44% to 50% identical to five vespid venom antigen 5 molecules. IgE antibodies against Sol i III do not exhibit strong cross-reactivity with vespid antigen 5s. The sequence similarity is consistent with other data, suggesting that ants are related to wasps of the superfamily Vespoidea.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1993

Distribution of unsaturated fatty acids in phospholipids of arteries from nonpregnant, pregnant and fetal sheep.

Normal ovine pregnancy is associated with elevated levels of circulating vasodilator prostaglandins (PGs) and increases in PG production by uterine and systemic arteries. We hypothesized that the availability of fatty acid substrate may regulate PG production in vasculature from nonpregnant, pregnant and fetal sheep. In pregnant sheep, levels of arachidonic acid (20:4 omega 6), the immediate PG precursor, were significantly lower in phospholipids from uterine versus systemic (renal) arteries. Although linoleic acid (18:2 omega 6), the primary arachidonic acid precursor, was elevated (p < 0.001) in uterine arteries during pregnancy, levels in systemic arteries were decreased. Levels of omega 3 polyunsaturated fatty acids (PUFAs) also were increased (p < 0.001) in both uterine and systemic arteries during pregnancy. In fetal-placental arteries, the levels of arachidonic and linoleic acid were 50 and 90% less, respectively, than that in maternal arteries. We conclude that during ovine pregnancy vascular prostanoid production may be regulated, in part, by the availability of fatty acid precursors.

Animals↗
PubMed1993

Effects of supplementation with omega 3 long-chain polyunsaturated fatty acids on retinal and cortical development in premature infants.

Deficiency of omega 3 long-chain polyunsaturated fatty acids (LCPUFAs) in vertebrates produces subtle adverse effects on visual and neural function. Preterm infants 1) are deprived of vital intrauterine fat accretion during late pregnancy, 2) must rely solely on formula for fatty acid supplies if not breastfed, and 3) may have limited postnatal desaturase activity. In a study to evaluate the necessity of dietary omega 3 LCPUFAs, preterm infants were fed human milk, corn-oil-based formula (omega 3 fatty acid deficient), soy-oil-based formula (rich in precursor fatty acids), or marine-oil-supplemented formula (containing docosahexaenoic acid). At 36 and 57 wk postconception, the LCPUFA profiles in red blood cell lipids were nearly equivalent in the human-milk and marine-oil groups whereas the corn-oil group had markedly lower values for omega 3 fatty acids. Rod photoreceptor function was significantly less mature in the corn-oil group compared with the human-milk and marine-oil-enriched groups in early postnatal development (36 wk). The corn-oil group also had impaired visual acuity at both 36 and 57 wk. The potential benefit of omega 3 LCPUFA-enriched full-term formula is discussed. The study supports a role for omega 3 LCPUFAs as required nutrients for the optimal maturation of visual and cortical function in preterm infants.

Breast Feeding↗
PubMed1992

Inhibition of cellular transport systems by alkyl phospholipid analogs in HL-60 human leukemia cells.

Specific non-metabolizable alkyl-phospholipids selectively kill neoplastic cells, yet normal and more differentiated cells are relatively resistant. Although these highly selective anticancer lipids appear to target the cell membrane, their mechanism of cytotoxic action remains to be defined. We report here that treatment of 'sensitive' HL-60 leukemia cells with one of the most potent lipid agents, 1-alkyl-2-methoxy-glycero-3-phosphocholine, inhibits the cellular transport of multiple essential nutrients including choline, amino acids, fatty acids, and the non-metabolizable carbohydrate, 2-deoxy-D-glucose. Minimal inhibitory responses of the varied transport systems were noted in HL-60 cells treated with the less potent, 2-lyso analog, and in 'resistant' K562 leukemia cells, treated with the 2-methoxy lipid. Although both the 2-methoxy lipid and 12-tetradacanoylphorbol 13-acetate induce differentiation in HL-60 cells, significant differences in the interactions of these lipids on cellular choline transport were found. Based on these results, we conclude that multiple nutrient deprivation induced by the detergent-like action of the methoxy-containing alkyl phospholipid results in the selective destruction of neoplastic cells that are sensitive to this membrane-targeted antitumor agent.

Antineoplastic Agents↗
PubMed1992

Effect of docosahexaenoic acid on membrane fluidity and function in intact cultured Y-79 retinoblastoma cells.

Considerable metabolic energy is expended in ensuring that membranes possess a characteristic fatty acid composition. The nature of the specific requirement of the retina for high levels of docosahexaenoic acid (DHA) is as yet undefined. Previous work has speculated that DHA is required to maintain the fluid nature and permeability necessary for optimal retinal function. Cultured Y-79 retinoblastoma cells were grown in serum-containing media with and without supplemental DHA. Resultant changes in membrane fluidity were assessed using fluorescent probes. No differences were observed in rotational probe mobility as assessed by fluorescence polarization despite a fourfold increase in cellular DHA content. Lateral probe mobility as assessed by pyrene eximer formation was significantly enhanced in DHA-supplemented cells. Both the DHA content and total fatty acid unsaturation index in retinoblastoma cells were directly correlated with membrane fluidity as reported by eximer formation (Pearson's rho = 0.96 and 0.92, respectively). DHA supplementation also resulted in a significant increase in cellular choline uptake. We speculate that the effect of DHA content on retinal function may be mediated by changes in membrane fluidity and associated enzyme and transport activities.

Cell Line↗