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Biomedical subjects

D R Hoffman

Publications and source records attributed to D R Hoffman.

At least 109 records · Page 6Linked to original sources
PubMed1984

Effect of Friend virus infection on the biosynthetic enzymes of phosphatidylcholine biosynthesis in spleen microsomes.

The effects of Friend virus infection on phosphatidylethanolamine methyltransferase, phosphatidylmonomethylethanolamine methyltransferase, phosphatidyldimethylethanolamine methyltransferase and choline phosphotransferase in mouse spleen microsomes were investigated 14 days following viral inoculation. There was a significant 9.2 fold increase above control values in the specific activity (pmol phosphatidylcholine formed/min/mg microsomal proteins) of choline phosphotransferase. No stimulation occurred in the activities of phosphatidylethanolamine methyltransferase, phosphatidylmonomethylethanolamine methyltransferase or phosphatidyldimethylethanolamine methyltransferase, the three enzymes involved in the methylation phosphatidylethanolamine (PE) to phosphatidylcholine (PC). The concentration of S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy), the substrate and physiological inhibitor of transmethylation reactions, respectively, were measured in the spleens of control and viral infected mice. AdoHcy is a competitive inhibitor of the phosphatidylethanolamine methyltransferase. A significant increase in the AdoHcy concentration and the resultant decrease in the AdoMet/AdoHcy ratio are sufficient to prevent stimulation of the transmethylation of PE to PC.

Animals↗
PubMed1984

The effect of embryological development on phosphatidylethanolamine methyltransferase, phosphatidyldimethylethanolamine methyltransferase and choline phosphotransferase of rabbit liver microsomes.

The effect of embryological development on the two biosynthetic enzymes involved in phosphatidylcholine biosynthesis in liver microsomes of -12, -9, 0, +4, +14, +36 day old rabbits has been determined. The specific activity (pmol phosphatidylcholine formed/min/mg microsomal protein) of the phosphatidylethanolamine methyltransferase in the liver microsomes is very low before birth and a 33% increase at birth occurs when compared to the -12 day old fetal livers. The pmol of phosphatidylcholine formed/min/mg protein by the choline phosphotransferase pathway in fetal liver microsomes is 5, 10, 73, 199, 107 and 307 times greater than by the phosphatidylethanolamine methyltransferase pathway for -12, -9, 0, +4, +14, +36 day old rabbits, respectively. The specific activities of the choline phosphotransferase in the liver microsomes increased from the -12 day old fetal livers to 1.6, 19, 73, 39, 27 times for the -9, 0, +4, +14 and +36 day old animals, respectively. The choline phosphotransferase pathway in comparison to the phosphatidylethanolamine methyltransferase pathway is providing the major phosphatidylcholines in the membranes of the endoplasmic reticulum before birth and early fetal development of the rabbit.

Animals↗
PubMed1984

The effect of hyper and hypothyroidism, hypophysectomy and adrenalectomy on phosphatidylethanolamine methyltransferase, phosphatidyldimethyl-ethanolamine methyltransferase and choline phosphotransferase of rat liver microsomes.

The effect of hyper- and hypothyroid, hypophysectomy and adrenalectomy on phosphatidylcholine biosynthetic enzymes, phosphatidylethanolamine methyltransferase, phosphatidyldimethylethanolamine methyltransferase and choline phosphotransferase of liver microsomes was measured in rats. There was a significant increase in the specific activity of phosphatidylethanolamine methyltransferase in the hyperthyroid rats. There was a significant reduction in the specific activity of phosphatidylethanolamine methyltransferase and phosphatidyldimethylethanolamine methyltransferase in the hypothyroid states. The choline phosphotransferase increased significantly in the hyperthyroid state and decreased in the hypothyroid animals. Hypophysectomy resulted in a significant increase in specific activity of choline phosphotransferase. A reduction in the specific activity of the phosphatidylethanolamine methyltransferase occurred after 28 days of hypophysectomy. Adrenalectomy resulted in a significant stimulation of the specific activity of phosphatidylethanolamine methyltransferase and choline phosphotransferase in liver microsomes.

Adrenalectomy↗
PubMed1984

Allergens in Hymenoptera venom XI. Isolation of protein allergens from Vespula maculifrons (yellow jacket) venom.

Pure Vespula maculifrons venom was demonstrated to contain five major allergenic proteins, which were all isolated from commercial venom sac extract. The five proteins: Vmacl, MW 97,000; hyaluronidase, MW 46,000; Vmac3, MW 39,000; phospholipase A and B, MW 34,000; and antigen 5, MW 22,000 were all demonstrated to be biochemically and immunologically distinct. All five proteins had significant allergenic activity, with phospholipase and hyaluronidase demonstrating the most IgE binding with 39 sera from allergic patients. Sera from honeybee-reactive patients, who had weak cross-reactions with yellow jacket venom, demonstrated strong IgE binding to purified V. maculifrons hyaluronidase and Vmacl. Dose-dependent inhibition of RAST was observed by use of honeybee hyaluronidase and high-molecular-weight fraction to inhibit the binding to the corresponding yellow jacket allergen.

Allergens↗
PubMed1984

Induction of mutations by chemical agents at the hypoxanthine-guanine phosphoribosyl transferase locus in human epithelial teratoma cells.

Induction of 6-thioguanine (TG) resistance by chemical mutagens was examined in a line of cells derived from a human epithelial teratocarcinoma cell clone. The cells, designated as P3 cells, have a stable diploid karyotype with 46(XX) chromosomes, including a translocation between chromosomes 15 and 20. Efficient recovery of TG-resistant mutants induced by the direct-acting mutagens: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG); 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10 -tetrahydrobenzo[a]pyrene (BPDE); and benzo[a]pyrene (B[a]P); activated in a cell-mediated assay, required an expression time of 7 days and a saturation density of 2 X 10(4) cells/60-mm petri dish. The TG-resistant mutant cells induced by MNNG and BPDE maintained their resistant phenotype 4-6 weeks after isolation. This mutant phenotype was associated with a more than 10-fold reduction in hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity relative to that of the parental P3 cell line, which was shown to catalyze the formation of 4.6 pmoles inosine-5'-monophosphate (IMP)/min/microgram protein. Induction of TG resistance was also observed in P3 cells cocultivated in a cell-mediated assay with human breast carcinoma cells, which are capable of polycyclic aromatic hydrocarbon (PAH) metabolism, after treatment with the carcinogenic PAHs: B[a]P, chrysene, 7,12-dimethylbenz[a]anthracene (DMBA), and 3-methylcholanthrene (MCA). The degree of mutant induction in this assay was related to the carcinogenic potency of these PAHs in experimental animals. The most potent mutagen was DMBA, followed in decreasing order by MCA, B[a]P, and chrysene. DMBA, at 0.4 microM, increased the frequency of mutants for TG resistance from 2 for the control to about 200 TG-resistant mutants/10(6) colony-forming cells (CFC). Benzo[e]pyrene (B[e]P) and pyrene, which are not carcinogenic, were not effective in the assay. None of the PAHs was mutagenic in the P3 cells cultivated in the absence of the PAH-metabolizing cells. These results indicate that the P3 cells can be useful for the study of mutagenesis at the HGPRT locus by direct-acting chemical mutagens, as well as by chemicals activated in a cell-mediated assay.

Biotransformation↗
PubMed1984

Cytotoxicity of platelet activating factor and related alkyl-phospholipid analogs in human leukemia cells, polymorphonuclear neutrophils, and skin fibroblasts.

A series of 11 alkyl-phospholipid analogs, structurally related to platelet activating factor (L-PAF), were analyzed for cytotoxic activity in human leukemic (HL-60) cells, human polymorphonuclear neutrophils, and Detroit 551 human skin fibroblasts. The order of selectiveness of the analogs in their cytotoxic response toward HL-60 cells in comparison to neutrophils is 1-alkyl-2-acetamide-GPC greater than 1-alkyl-2-methoxy-GPC greater than D-PAF greater than 1-acyl-2-lyso-GPC greater than 1-alkyl-2-lyso-GPC greater than L-PAF. A time-sequenced progression of events caused by the most potent cytotoxic alkyl-phospholipid analogs was characterized by (a) a rapid decrease in the cellular uptake and incorporation of 3H-thymidine into DNA that was detectable 4 hr after exposure to the analog, (b) a release of lactate dehydrogenase activity into the media at 8 hr after exposure, and (c) a decrease in cell number due to cell death that begins at 12 hr after exposure. Treatment of HL-60 cells with 1-alkyl-2-methoxy-GPC for 1 hr destroyed 40% of the cells after a subsequent 24-hr incubation period. The varied biologic activities of L-PAF, including how it affects serotonin release from platelets, blood pressure in rats, and cytotoxic responses in normal and leukemic cells, are discussed in relation to its D-enantiomer, 3-alkyl-2-acetyl-GPC, and the 2-acetamide analog. This report characterizes the kinetic events of the cellular responses in both normal and HL-60 cells in relation to the antineoplastic activities of unnatural ether-linked phospholipid analogs that are structurally related to L-PAF.

Antineoplastic Agents↗
PubMed1984

Allergens in hymenoptera venom XII: how much protein is in a sting?

The protein content of insect venoms was determined using a Coomassie blue dye binding assay as well as the Lowry phenol assay. The Lowry method tended to give excessively high values with many of the venoms because of the presence of low molecular weight phenolic compounds and other interfering substances. Using the dye binding method honey bee stings were found to contain 59 +/- 7 micrograms of protein, bumblebee and carpenter bee stings from 10 to 31 micrograms, yellow jacket stings from 1.7 to 3.1 micrograms, white faced hornet stings 2.4 to 5.0 micrograms and paper wasp stings from 4.2 to 17 micrograms protein. This is in good agreement with the value of 50 micrograms previously estimated for honey bee stings and is the first reported data for the other species.

Allergens↗
PubMed1984

Cytotoxicity of ether-linked phytanyl phospholipid analogs and related derivatives in human HL-60 leukemia cells and polymorphonuclear neutrophils.

A cytotoxic activity, highly selective for neoplastic cells, is expressed by 1-alkyl-2-methoxy-sn-glycero-3-phosphocholine and by other derivatives closely related to the chemical structure of platelet activating factor. The antineoplastic potencies of a new series of analogs tested in HL-60 human leukemia cells and human polymorphonuclear neutrophils are reported. The degree of cytotoxicity was documented according to the ability of each analog to 1) destroy leukemic or normal cells or 2) to release lactic acid dehydrogenase from these cells. An index of selectivity of the analogs for their cytotoxicity toward leukemia cells is presented. Substitution by the twenty carbon branched-chain phytanyl moiety in place of the straight chain alkyl ether-linked group at the sn-1 position of various phospholipid analogs resulted in a 3- to 10-fold reduction in their cytotoxic potency in HL-60 leukemia cells. The enantiomeric isomers (D-forms) of several of the analogs possessed slightly greater phospholipid analogs possessing the sn-2-acetyl (platelet activating factor) or sn-2- propionoyl substituents, both biologically active in their ability to aggregate platelets and to induce hypotension, were relatively innocuous in terms of the measured cytotoxic responses in both HL-60 cells and neutrophils.

Antineoplastic Agents↗
PubMed1983

Projecting the soft-tissue outcome of surgical and orthodontic manipulation of the maxillofacial skeleton.

A simple method is presented for developing one-to-one composite soft-tissue and radiographic patient images. Their use in diagnosis, treatment planning, and prediction of the outcome of surgical and orthodontic manipulations of the facial hard tissues to effect soft tissue change is discussed. Complementing cephalometric analysis and model surgery, this technique uses a 35 mm, slide, acetate tracing paper, a pencil, and a series of integumentary changes which follow rearrangements of the underlying skeleton, including the dentition, maxillae, zygomas, and nose. The pretreatment images is traced from a projected 35 mm, slide, which is sized to the cephalometric tracing to obtain a "life-sized" representation of the face. The image is then redrawn, adjusting the dysmorphic parts to the unchanged part of the face to effect balance of the profile and restore normal contours. This recreated image is used then as an objective to which the treatment planning is directed and through which it is commonly seen that the restoration of functional and esthetic balance is a mutually supportive goal. The projected image is of value to the clinician in formulating his treatment goal, but it is more valuable in the visible expression that it gives to his mental image of the ideal outcome. Moreover, it can be readily shared with the patient, who often better appreciates the changes in contours, which he sees daily, than the commonly employed profiles of cephalometric prediction, which are basically foreign to him. The technique is discussed, as are the ratios of hard-to-soft-tissue change, with case reports for demonstration.

Adult↗
PubMed1983

Two-dimensional polyacrylamide gel electrophoresis of hymenoptera venom and venom sac extracts.

Hymenoptera venom and venom sac extracts were studied by two-dimensional polyacrylamide gel electrophoresis using non-equilibrium pH gradient electrophoresis in the first dimension and sodium sulfate electrophoresis in the second dimension. Pure Apis mellifera (honeybee) venom collected by electrical stimulation was resolved into five major and more than 20 minor components. Polistes (paper wasp), Vespula (yellow jacket), Dolichovespula (aerial hornet) and Vespa (old world hornet) venom sac extracts contained more than 40 components each. These results illustrate the complexity of the mixtures in current use for immunotherapy for stinging insect hypersensitivity. The degrees of similarity observed between the various aspects of Polistes and Vespula studied correlate with the phylogenetic classification of these species.

Animals↗
PubMed1983

Demonstration of IgE and IgG antibodies against venoms in the blood of victims of fatal sting anaphylaxis.

Nine people died from insect sting anaphylaxis in North Carolina from 1979 to 1981. Postmortem blood specimens from eight of these subjects were analyzed for IgE and IgG antibodies against venoms. All eight were RAST positive to at least one of the venoms. IgE and IgG anti-venom levels were comparable to those of a group of untreated sting-allergic individuals. RAST to venoms was also performed on several control groups of sera and from 3% to 50% positive RAST results were found. The highest incidence was in rural North Carolina outdoor workers. The incidence of positive RAST results in the sting-death group was significantly different from that in the control groups. This is the first demonstration of IgE antibodies against venoms in the sera of victims of fatal anaphylaxis from stings and adds further evidence for the role of IgE in sting anaphylaxis.

Adult↗
PubMed1983

Immunochemical identification of the allergens in egg white.

The allergenic activities of egg white components were tested by radioimmunoelectrophoresis (RIEP) and RAST with highly purified proteins. Sera from 33 patients who reacted to egg ingestion were used for both methods. Ovalbumin and ovomucoid were shown to be strong allergens by both techniques. Patients varied in relative reactivity to these two allergens. Conalbumin was found to be an important allergen by RAST, but its activity was underestimated by RIEP. Lysozyme was only a weak allergen. Two sera reacted by RIEP with other neutral egg white components. Both ovalbumin and ovomucoid were found in hard- and soft-boiled egg white in immunologically recognizable form, and small amounts of conalbumin were also detectable in cooked egg. There was no significant association of pattern of reactivity with age, sex, or presence of eczema. The sera of patients who experienced gastrointestinal symptoms from ingestion of egg white were less reactive with ovomucoid than sera from patients with other symptoms.

Adolescent↗
PubMed1983

Allergens in hymenoptera venoms. X. Vespid venoms versus venom sac extracts: comparison by two-dimensional polyacrylamide gel electrophoresis.

Vespid venoms were compared to venom sac extracts by two-dimensional polyacrylamide gel electrophoresis using non-equilibrium pH gradient electrophoresis in the first dimension and sodium dodecyl sulfate electrophoresis in the second. The gels were stained with silver. Fresh venoms from four species, Vespula maculifrons, Polistes fuscatus fuscatus, P. metricus and P. exclamans, were compared with commercially available venom sac extracts from the same species. In each case the venom sac extract contained all of the proteins detected in the fresh venom plus numerous additional proteins which are probably sac components. Yellow jacket and bee (Apis mellifera) proteins were extracted from the gels and tested for IgE binding activity using pooled sera from RAST-positive individuals. Significant IgE binding activity was found for the five known bee allergens and for the major yellow jacket venom proteins. Fresh pure vespid venoms contain a relatively small number of major protein subunits. Venom sac extracts contain the same components plus many other proteins not found in the pure venoms.

Allergens↗
PubMed1983

Cytotoxicity of alkyl-lysophospholipid derivatives and low-alkyl-cleavage enzyme activities in rat brain tumor cells.

Alkyl-lysophospholipids (ALP) and related derivatives inhibited the in vitro incorporation of [3H]thymidine into seven different permanent cell lines derived from rat brain tumors. The cytostatic effect of ALP was dependent on dosage and incubation time. Naturally occurring 2-lysophosphatidylcholine did not exhibit cytostatic effects; under these conditions, the incorporation rates of [3H]thymidine were generally more than 100% of the controls. The trypan blue dye exclusion test, which was used to assess severe cell damage, correlated with the extent that [3H]thymidine incorporation was inhibited by ALP. Preincubation of ALP (rac-1-octadecyl-lyso-glycero-3-phosphocholine) for more than 8 min with a tetrahydropteridine-dependent O-alkyl cleavage enzyme preparation from rat liver microsomes destroyed almost all of the cytotoxic properties of ALP when tested at a concentration that previously inhibited tumor growth by more than 50%. [3H]Thymidine incorporation rates were greater than 100% for astrocytoma cells incubated with ALP after exposure to the alkyl cleavage enzyme. Comparison of the microsomal activities of the tetrahydropteridine-dependent alkyl-cleavage enzyme present in astrocytoma 78-FR-G-299 cells and the pleomorphic glioma 78-FR-G-219/S4 cells to that found in normal skin fibroblasts and rat livers revealed a markedly reduced activity in the neoplastic cell lines. Moreover, those tumor cells that were more resistant to ALP cytotoxicity (pleomorphic glioma, 78-FR-G-219/S4) had a 3-fold higher tetrahydropteridine-dependent cleavage activity than a more cytotoxic sensitive line (astrocytoma cells, 78-FR-G-299). Our results indicate that the low-alkyl-cleavage enzyme activities in these neoplastic cells in comparison to normal cells might be a factor in explaining the relatively high cytotoxicity of ALP in tumor cells.

Animals↗
PubMed1982

The control of phospholipid methylation by phorbol diesters in differentiating human myeloid HL-60 leukemia cells.

Treatment of human HL-60 promyelocytic leukemia cells with phorbol-12-myristate-13-acetate (PMA), a tumor promoter and inducer of differentiation, stimulated the incorporation of label from L-[methyl-3H]methionine into the cellular phospholipids. Such a stimulation of phospholipid methylation was not observed in an HL-60 cell variant that is resistant to phorbol ester-induced differentiation. Enhanced methylation of phospholipids was detected 6 h after treatment and reached a maximum level of about twice the control level at 24-48 h. The degree of phospholipid methylation was dependent on the phorbol ester dose. The stimulation in phospholipid methylation by PMA was confirmed by measuring the activity of phosphatidylethanolamine methyltransferase in cellular lysates. After 24 or 48 h of exposure, the enzyme activity was elevated in the HL-60 cell lysates but not in the resistant cells. Phospholipid methylation was also stimulated after treatment of the HL-60 cells with the phorbol diester phorbol-12,13-dibutyrate or teleocidin, which is not a phorbol ester compound. These two chemicals and PMA are tumor promoters and inducers of cell differentiation in the HL-60 cells. Phorbol-12,13-diacetate and 4-O-methyl PMA, which are not tumor promoters or inducers of cell differentiation in the HL-60 cells, did not stimulate phospholipid methylation. The possible role of enhanced phospholipid methylation in cell differentiation of the HL-60 by these chemicals is discussed.

Alkaloids↗
PubMed1982

Allergens in hymenoptera venom. VIII. Immunologic comparison of venoms from six species of Vespula (yellow jackets).

Venoms from six species of ground dwelling yellow jackets of the genus Vespula were studied by direct and inhibition of RAST. Significant differences were found among the various species. Reactivity of patients showed significant correlation with insect distribution with the exception of some patients from the far west. The immunologic relationships observed among the venoms correlated well with the current phylogeny, which is based upon morphologic, behavioral and ecologic studies. The correlation with isoenzyme studies that have recently been reported was less complete. Individual patients exhibit highly significant differences in their reactivity to the various species, in many cases comparable to the differences seen in reactivity to yellow jackets and aerial hornets (Dolichovespula).

Allergens↗
PubMed1982

Allergens in hymenoptera venom. IX. Species specificity to Polistes (paper wasp) venoms.

Sera from 62 patients allergic to Polistes venom were used to study the allergenic relationships among four individual species of Polistes by both direct and inhibition RAST. Both direct and inhibition results showed that the four species' venoms were closely related. The species within the same subgenus were more closely related than those in different subgenera. The Polistes species were more closely related to each other than various yellow jacket (Vespula) species are to each other. The commercial Polistes venom mix appears to contain all of the relevant allergens.

Allergens↗