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Biomedical subjects

D R Hoffman

Publications and source records attributed to D R Hoffman.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Essentiality of dietary omega 3 fatty acids for premature infants: plasma and red blood cell fatty acid composition.

Pre-term infants, that are not breast-fed, are deprived of vital intrauterine fat accretion during late pregnancy and must rely on formula to obtain fatty acids essential for normal development, particularly of the visual system. Preterm infants (30 wk postconception) receiving human milk were compared to infants given one of the following formulae: Formula A was a commercial preterm formula with predominantly 18:2 omega 6 (24.2%) and low (0.5%) 18:3 omega 3; Formula B was based on soy oil and contained similar 18:2 omega 6 levels (20%) and high 18:3 omega 3 (2.7%); Formula C was also a soy oil-based formula (20% 18:2, 1.4% 18:3) but was supplemented with marine oil to provide omega 3 long-chain polyunsaturated fatty acids (LCP) at a level (docosahexaenoic acid, DHA, 0.35%) equivalent to human milk. At entry (10 days of age), the fatty acid composition of plasma and red blood cell (RBC) membrane lipids of the formula groups were identical. By 36 wk postconception, the DHA content in lipids of group A was significantly reduced compared to that in the human milk and marine oil formula groups. Omega-3 LCP results were further amplified by 57 wk with compensatory increases in 22:5 omega 6 in both plasma and RBC lipids. Provision of 2.7% alpha-linolenic acid in formula group B was sufficient to maintain 22:6 omega 3 levels equivalent to those in human milk-fed infants at 36 wk but not at 57 wk. Effects on the production of thiobarbituric acid reactive substances and fragility of RBC attributable to the marine oil supplementation were negligible. The results support the essentiality of omega 3 fatty acids for preterm infants to obtain fatty acid profiles comparable to infants receiving human milk. Formula for preterm infants should be supplemented with omega 3 fatty acids including LCP.

Diet↗
PubMed1992

Safety and efficacy of fire ant venom in the diagnosis of fire ant allergy.

Thirty-three adult patients who had had systemic allergic reactions to fire ant stings and 33 insect-nonallergic control subjects were skin tested with single lots of Solenopsis invicta (Sol i) fire ant venom (IFAV) and two commercially available imported fire ant whole body extracts (IFA WBEs). All three extracts were analyzed for protein concentration. Sol i II and Sol i III concentrations were each assayed by means of two ELISAs with complementary monoclonal antibodies, one species specific and one cross-reactive. Radioallergosorbent test (RAST) to IFAV and both IFA WBEs was performed on sera from all study subjects. Both IFA WBEs contained high concentrations of fire ant body proteins. Sol i II and III concentrations each varied twofold between the two IFA WBE preparations. Patients were generally more reactive to IFAV than IFA WBE by skin testing and RAST. IFAV RAST appeared to be a more sensitive assay than IFA WBE RAST. No adverse reactions occurred to skin testing with IFAV, but intradermal testing with higher concentrations of IFA WBE caused delayed large local reactions in 16 of 30 (53%) control subjects. These reactions were attributed to the large amounts of extraneous body proteins in IFA WBE. These results (1) demonstrate that skin testing with IFAV is safe, (2) indicate that IFAV is more potent than IFA WBE, and (3) suggest that IFAV may be the superior reagent for diagnosis of fire ant allergy.

Adult↗
PubMed1992

Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids.

Full-field electroretinograms (ERGs) were obtained from very-low-birth-weight (VLBW) neonates to determine whether omega-3 (omega-3) fatty acids are essential for normal human retinal development. Eighty-one infants born at 30.4 (standard deviation, +/- 1.5) wk gestation were, within 10 d of birth, either enrolled to receive mother's milk (naturally containing both omega-6 and omega-3 essential fatty acids) or randomized to receive one of the infant formulas. Corn oil-based Formula A contained mainly linoleic acid (18:2 omega-6) and was low in all omega-3 fatty acids. Soy oil-based Formula B contained ample alpha-linolenic acid (18:3 omega-3) but no long-chain omega-3. Formula C, supplemented with both alpha-linolenic acid and marine oils, was comparable to human milk in long-chain omega-3. Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception. Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception. Significant differences were found among groups in rod ERG function. Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain omega-3 (human milk, Formula C, and intrauterine). Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition. Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level. Differences were not present in infants at 57 wk postconception. No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception. Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk. These findings suggest that retinal function varies with the dietary supply of omega-3 fatty acids in VLBW infants.

Breast Feeding↗
PubMed1992

Dietary essential fatty acid supply and visual acuity development.

The influence of dietary omega-3 fatty acid supply on visual acuity development was evaluated in very low birth weight (VLBW) infants using visual-evoked potential (VEP) and forced-choice preferential-looking (FPL) procedures at 36 and 57 wk postconception. The VLBW infants born at 27-33 wk postconception were randomized to one of three diet groups: corn oil, which provided solely linoleic acid; soy oil, which provided linoleic and alpha-linolenic acids; or soy/marine oil; which was similar to the soy oil formula but also provided preformed long chain omega-3 fatty acids. The VLBW infants in the soy/marine oil group had higher omega-3 levels in erythrocyte membranes and better VEP and FPL acuities at 36 and 57 wk than infants in the corn oil group. The soy oil group had intermediate omega-3 levels in erythrocyte membranes and significantly poorer VEP acuity at 57 wk compared with the soy/marine oil group. Only the soy/marine oil group had acuities comparable to the "gold standards" of VLBW infants fed human milk and preterm infants who were born and tested at 35-36 wk postconception. In addition, VEP and FPL acuity were poorer in a nonrandomized group of formula-fed full-term infants than in breast-fed full-term infants. The results suggest that dietary omega-3 fatty acid supply may play an important role in early human visual development.

Breast Feeding↗
PubMed1991

Prolongation of parturition in the pregnant rat following treatment with a platelet activating factor receptor antagonist.

The presence of platelet activating factor (PAF) in amniotic fluid of women only in labor is indicative of a role for PAF in parturition. In addition, stimulated amnion membrane produces both PAF and prostaglandin E2, each of which is capable of inducing myometrial contraction. To evaluate the involvement of PAF in the process of parturition, we administered the PAF receptor antagonist, L-659,989, to 17-day timed pregnant rats and followed the events of labor and delivery. Administration by mouth with L-659,989 of three concentrations (1.6, 16, and 48 mg/kg/day) did not alter the gestational period; however, the duration of parturition was increased from 2-fold to 5-fold by such treatment. No toxicity of the analog was apparent; treated dams showed no signs of morbidity, and fetal mortality was not significantly altered by treatment with the antagonist. Based on these experiments, it is suggested that the PAF receptor antagonist interferes with the normal progression of events of parturition and that PAF is an integral mediator in initiating the myometrial contraction necessary for expulsion of the fetus.

Animals↗
PubMed1991

Surgical orthodontics.

This was an interesting year for the surgical orthodontic literature. Excellent large long-term studies addressed the stability of rigid versus wire fixation, lag screws versus bicortical screws, and osteotomy site selection. The effect of orthognathic procedures on speech and hearing deficits, condylar position, and the patient's psyche were reported in detail. Possible solutions to financial difficulties and the concern about blood transfusions were presented. Treatment failures and prediction shortcomings were candidly discussed.

Humans↗
PubMed1991

Allergens in Hymenoptera venoms. XXIII. Venom content of imported fire ant whole body extracts.

A two-site immunoassay using monoclonal antibodies has been developed to measure the imported fire ant venom allergen Sol i III. The assay is specific for Solenopsis invicta venom, since one of the monoclonal antibodies does not react with Sol r III. A commercial imported fire ant whole body extract, known from RAST and skin test data to be potent, was found to contain 10.3 micrograms of Sol i III per milliliter. This was comparable to the content of an extract freshly prepared in our laboratory. The immunoassay detected Sol i III in an extract of fire ant abdomens, but not in head and thorax extract. The amount of imported fire ant venom in a potent whole body extract appears to be sufficient to provide possible protection for patients receiving it as immunotherapy, although this can only be verified by controlled clinical trials with intentional sting challenges.

Allergens↗
PubMed1990

Detection of platelet-activating factor in amniotic fluid of complicated pregnancies.

The ether phospholipid PAF (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was originally described as a potent bioactive lipid associated with inflammatory responses. More recently, we have suggested a functional role for PAF in fetal lung maturation and the initiation of parturition. Previously, PAF was detected in the amniotic fluid of women at term during labor. A significant proportion of this PAF was associated with a lamellar body-enriched fraction. In addition, the PAF concentration was elevated in fetal rabbit lung during the latter stages of gestation and in human fetal lung in organ culture. It was therefore concluded that the PAF present in amniotic fluid during labor was, in part, of fetal lung origin. In the reported study, amniotic fluid samples were obtained from a group of patients with uncomplicated pregnancies at term "not in labor" and "in labor" and a group with complicated pregnancies. We found an eightfold greater concentration of PAF in amniotic fluid obtained from the "term, in labor" samples compared with that of the "term, not in labor" samples (40 vs. 312 fmol/ml). A twentyfold elevation in PAF (838 fmol/ml) was evident in the amniotic fluid of patients incurring "preterm labor" with an average gestational age of 32 weeks compared with the "term, not in labor" group. PAF concentrations also were elevated to 756 fmol/ml amniotic fluid in a group of patients with an average gestational age of 31.5 weeks who had premature rupture of membranes. We have previously suggested that a second autacoid, PAF, in addition to eicosanoids, may function in the initiation of parturition at term in uncomplicated pregnancies. On the basis of our findings of a severalfold increase in the PAF concentration in amniotic fluid from complicated pregnancies, it is suggested that this potent activator of myometrial contraction, together with the eicosanoids, may be a contributing factor associated with premature labor.

Amniotic Fluid↗
PubMed1990

The role of fetal membranes in regulating production, transport, and metabolism of prostaglandin E2 during labor.

The level of prostaglandin E2, a potent stimulator of myometrial contractions, increases in amniotic fluid during labor. We tested whether amniotic prostaglandin E2 crosses the reflected fetal membranes to the myometrium during labor. Disks of amnion, chorion-decidua, and amnion chorion-decidua from 10 term pregnancies before labor and nine vaginal deliveries after normal spontaneous labor were incubated in two-sided perfusion chambers in the absence or presence of 1 mumol/L indomethacin, or in the presence of a bolus of prostaglandin E2 and radiolabeled prostaglandin E2 added to the fetal chamber. Net amniotic prostaglandin E2 increased significantly (p = 0.003) after labor. However, there was no significant difference in prostaglandin E2 concentrations on the maternal side of amnion chorion-decidua between labor conditions. High-pressure liquid chromatography identified the transport of intact tritiated prostaglandin E2 across amnion but not across chorion-decidua or amnion chorion-decidua in which prostaglandin E2 was completely metabolized. Because of 15-hydroxyprostaglandin dehydrogenase activity in chorion, we suggest that amniotic prostaglandin E2 transport to the myometrium is impaired. Thus the increase in prostaglandin E2 production that occurs in amnion tissue after labor commences does not result in an increase in prostaglandin E2 concentration on the myometrial side of the fetal membranes in the in vitro preparation.

Adult↗
PubMed1990

Allergens in Hymenoptera venom. XXII. Comparison of venoms from two species of imported fire ants, Solenopsis invicta and richteri.

Venoms were collected by electrical stimulation from the two major species of imported fire ants found in the United States, Solenopsis invicta (Sol i) and S. richteri (Sol r). Antigens similar to three of the four known Sol i venom proteins (I, II, III, and IV) were isolated from Sol r. The N-terminal amino acid sequences for the antigens III were identical; but those for the antigens II demonstrated only nine of 20 residues to be identical. Two monoclonal antibodies raised against Sol i II did not react to Sol r. No protein IV could be detected in Sol r by molecular weight, charge, or immunologically with either polyclonal mouse antibodies or five monoclonal antibodies. Both venoms were compared with a panel of 60 sera from Sol i-allergic individuals; mean bindings were similar with an r = 0.94 for linear regression. RAST inhibition was performed with 17 individual sera representing a variety of Sol i allergen specificities. Four sera were tested from patients resident in the Sol r endemic area and five sera from patients who experienced reactions to S. xyloni stings. All sera reacted comparably to both imported fire ant venoms. The two venoms appear to be allergenically similar, although antigen IV is absent from Sol r and the antigens II have significant sequence variation. Sol i venom appears to be sufficient for diagnostic purposes.

Allergens↗
PubMed1990

Effect of dietary omega-3 fatty acids on retinal function of very-low-birth-weight neonates.

Retinal function was assessed by electroretinogram in 32 neonates randomly assigned to formulas of different omega-3 fatty acid content and in 10 infants fed human milk. All neonates had a birth weight of 1000-1500 g and were fed study diets from d 10 to 45 or discharge. Group A received formula containing predominantly 18:2 omega-6. Group B received a balanced mix of 18:2 omega-6 and 18:3 omega-3. Group C was given a formula containing both essential fatty acids and supplemented with marine oil to provide 22:6 omega-3 content similar to that of human milk. The fatty acid composition of plasma and red blood cell (RBC) lipids were similar for all groups on entry but marked diet-induced differences were found after feeding the study diets. Group C was comparable to the human milk-fed group, but group A had lower 22:6 omega-3 and omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in plasma and RBC membranes. Cone function was not affected by dietary essential fatty acids. Rod electroretinogram thresholds were significantly higher for group A relative to the human milk-fed group and group C and significantly correlated with RBC omega-3 LCPUFA (r = -0.63, p less than 0.0001); 44% of the variance could be explained by RBC and plasma omega-3 LCPUFA content.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1990

Comparison of in vivo and in vitro tests in the diagnosis of imported fire ant sting allergy.

The specificities and sensitivities of skin test reactivity to imported fire ant (IFA) whole body extract (WBE) and IFA venom were compared with IFA WBE RAST and IFA venom RAST in the diagnosis of IFA allergy. Study groups consisted of 18 IFA allergic patients and 21 control subjects with no history of allergy to insect stings. All IFA allergic patients had positive skin tests to both IFA WBE and IFA venom. Six of 21 (29%) control subjects also had positive skin tests to both IFA WBE and IFA venom. A commercial IFA WBE RAST was positive in 10 of 18 (56%) IFA-allergic patients and 2 of 21 (10%) control subjects. Imported fire ant aqueous venom RAST was positive in 11 of 11 (100%) IFA-allergic patients and three of ten (30%) control subjects. Vespa IFA venom RAST was positive in 16 of 18 (89%) IFA-allergic patients and 5 of 21 (24%) controls. The sensitivities and specificities of IFA WBE skin testing, IFA venom skin testing, and IFA venom RAST did not differ significantly. Imported fire ant WBE RAST was less sensitive than the other diagnostic methods.

Adolescent↗
PubMed1989

Three cases of fatal anaphylaxis to antibiotics in patients with prior histories of allergy to the drug.

Three cases of fatal anaphylaxis to penicillin and cephalexin are described. All three patients had prior histories of severe allergic reactions to the antibiotics they were given. The radioallergosorbent test was positive on post-mortem blood to the appropriate antibiotic in all three cases. RAST can be performed on post-mortem specimens of serum, sodium fluoride-treated blood, or whole blood.

Adult↗