PubMed Health⌕ Search

Biomedical subjects

D R Hoffman

Publications and source records attributed to D R Hoffman.

At least 127 records · Page 7Linked to original sources
PubMed1981

Microsomal phosphatidylethanolamine methyltransferase: inhibition by S-adenosylhomocysteine.

Inhibition by S-adenosylhomocysteine (AdoHcy) of the three reactions of phosphatidylethanolamine methyltransferase which catalyzes the production of phosphatidylcholine from phosphatidylethanolamine in guinea pig and rat liver microsomes has been evaluated. Five of the six methylation reactions in these two species exhibit greater affinity for inhibitor, AdoHcy, than for substrate, S-adenosylmethionine (AdoMet). The Ki values for the rate-limiting reactions were 3.8 microM and 68 microM in rat and guinea pig livers, respectively. An AdoMet : AdoHcy ratio of 12 : 1 in developing liver was found to decline to a constant value in the adult of 5 : 1. The concentration of AdoHcy in rat and guinea pig liver increases markedly following death of the animal. A concomitant decrease in the AdoMet level was observed in guinea pig liver. A comparison of phosphatidylethanolamine methyltransferase activity with the hepatic concentrations of AdoMet and AdoHcy in mouse, rat, rabbit and guinea pig is presented. Regulation of the methylation pathway is discussed.

Animals↗
PubMed1981

Microsomal phosphatidylethanolamine methyltransferase: some physical and kinetic properties.

Some physical and kinetic properties of the microsomal enzyme(s) that convert phosphatidylethanolamine to phosphatidylcholine in rat and guinea pig livers have been investigated. The pH optima of the reactions were 9.8, 9.3 and 9.5 for the first, second and third methylation reactions, respectively. Incomplete heat denaturation of the protein catalyzing the first reaction contrasts with inactivation at 60 C of the enzymes catalyzing the second and third methylations. The maximal velocity of the first reaction of the guinea pig liver enzyme is 48 pmol/min/mg protein, substantially less than exhibited rate-limiting reaction of the three step methylation sequence in rat liver, 114 pmol/min/mg. The affinity of the microsomal enzyme for S-adenosylmethionine is greater in rat liver (Km = 18.2 microM) than in guinea pig liver (Km = 302 microM).

Animals↗
PubMed1981

Anaphylaxis after sesame seed ingestion.

Four patients with histories of systemic anaphylaxis or angioedema and urticaria after ingestion of sesame seed or sesame oil-containing products were studied for anti-sesame seed extract IgE by the radioallergosorbent test (RAST). Three of four were found to be positive. RAST inhibition after density-gradient ultracentrifugation of sesame seed extract indicates that the most active allergens appear to have molecular weights between 8,000 to 62,000 daltons.

Adult↗
PubMed1981

Effects of a methyl-deficient diet on rat liver phosphatidylcholine biosynthesis.

To produce a severe choline-methionine deficiency, a synthetic L-amino acid diet, free of choline, methionine, vitamin B12, and folic acid and supplemented with guanidoacetic acid, a methyl group acceptor, was fed to female rats for 2 weeks. The in vitro activity of liver microsomal phosphatidylethanolamine methyltransferase was stimulated twofold when compared with basal diet controls. The activity of choline phosphotransferase was depressed by 86%; thus, the contribution of the methyltransferase in the overall synthesis of phosphatidylcholine apparently increased. However, measurement of the in vivo methylation of phosphatidylethanolamine by incorporation of [1,2-14C]ethanolamine into phosphatidylcholine indicates that the methylation pathway is markedly depressed in methyl deficiency. Hepatic concentrations of the methyltransferase substrate, S-adenosylmethionine, and the inhibitory metabolite, S-adenosylhomocysteine, were significantly altered such that an unfavorable environment for methylation was present in the deficient animal. The ratio of substrate to inhibitor was depressed from 5.2:1 in the controls to 1.7:1 in the livers of methyl-depleted rats. Control of transmethylation in accordance with the availability of substrates, phosphatidylethanolamine, or S-adenosylmethionine, and the level of S-adenosylhomocysteine is discussed.

Animals↗
PubMed1981

Correlation of IgG and IgE antibody levels to honey bee venom allergens with protection to sting challenge.

A group of 25 honey bee venom allergic patients were treated with commercial honey bee venom at a monthly maintenance dose of 100 micrograms for approximately one year. At the end of one year 24 patients were intentionally challenged and one was accidentally challenged. Three patients experienced significant systemic reactions to challenge and three experienced minor reactions. Sera obtained before commencing therapy, at maintenance and before challenge were tested by radioallergosorbent test (RAST), double antibody technique and protein A RAST for IgE and IgG antibody levels to all five known honey bee venom allergens. All of the treatment failures experienced at least a two-fold rise in IgG antibody against phospholipase. The ratios of IgG to IgE antibodies in the pre-challenge specimens were analyzed by a graphical method. Four patients had inadequate responses to at least three of the five allergens and three of these patients were those who experienced severe reactions to challenge. Sixteen patients had adequate responses to all five allergens, four patients to four allergens and one patient to three allergens; three of these patients experienced minor or local reactions to challenge and the remainder no reaction. No single allergen identified only the three severe reactors but three allergens identified all three reactors. The diagnostic efficiency of the criteria used for assessing protection was 0.96. The only non-correlating case was classifying a single nonreactor as at risk. No patients were misclassified as protected.

Allergens↗
PubMed1981

Isolation of spore specific allergens from Alternaria.

Extracts of Alternaria alternata spores and mycelia were prepared. Crossed immunoelectrophoresis showed the presence of at least 40 antigens in these extracts. Analysis of seven commercial extracts by CIEP and isoelectric focusing showed many fewer components and a high degree of variability. Eight of the antigens in the spore extract demonstrable by CIEP were not present in mycelia extracts. This spore-specific fraction was isolated by solid phase immunoadsorption and shown to be potent antigenically and allergenically. The extracts of mycelia, spore and spore-specific fraction demonstrated strong reactivity with 92 Alternaria sensitive patients by both RAST and skin test. About half of the patients were significantly more reactive to spore and/or spore-specific than the mycelia. Many of the spore antigens are either common to or cross-reactive between spore and mycelia but there are a minimum of eight spore-specific antigens, at least one of which is a strong allergen.

Allergens↗
PubMed1981

Allergens in hymenoptera venom. VI. Cross reactivity of human IgE antibodies to the three vespid venoms and between vespid and paper wasp venoms.

A substantial degree of immunologic cross-reactivity is demonstrated among yellow jacket (YJV), yellow hornet (YHV) and white-faced hornet (WFHV) venoms and between the vespid venoms and paper wasp venom (PWV) by RAST inhibition studies of individual sera from allergic patients. Cross-reactivity is shown to be complete, partial or absent in various cases. In many cases RAST inhibition studies are able to demonstrate the primary sensitivity. Specificity by RAST inhibition did not always agree with specificity by quantitative RAST. A variety of patterns of cross-reaction are shown to exist between the pairs of venoms studied. There is no general pattern of cross-reactivity among the vespids or between vespid and paper wasp. Some cross-reactivity appears to result from multiple stings by different insects.

Allergens↗
PubMed1981

The major heat stable allergen of shrimp.

Serum from a patient who had experienced several episodes of anaphylaxis after eating shrimp was used to monitor the isolation of a major allergen from shrimp, which was then tested with sera from 10 other shrimp-reactive patients. The allergen was isolated from a fresh extract of boiled shrimp by gel filtration and from raw shrimp by gel filtration and agarose electrophoresis. The purity of the allergen was established by crossed immunoelectrophoresis against rabbit and guinea pig antisera; it gave only a single peak in each case. The native allergen was excluded on Sephadex G-200 but showed a single band at 38000d in SDS-PAGE with or without reduction. The isoelectric point was about 4.5. The allergen contained about 4% carbohydrate and only 7 Tyr and 9 Phe out of 341 amino acid residues. Using the RAST with 11 allergic sera, the allergen gave a correlation coefficient of 0.98 with whole cooked shrimp extract and of 0.66 with raw shrimp extract. The allergen was a potent inhibitor of RAST to both cooked and raw shrimp. A second, weaker allergen of 21000d chain size was isolated from raw shrimp in highly purified form.

Allergens↗
PubMed1981

Allergens in hymenoptera venom. VII. Species specific reactivity to yellow jacket venoms.

Venom from three species of yellow jacket, Vespula maculifrons, V. squamosa and Vespa crabro, was tested in direct and inhibition of RAST with a panel of 39 sera from three regions of the U.S. V. squamosa venom was found to be missing at least one allergen present in V. maculifrons. Patterns of reactivity were highly correlated with geography; reactivity with V. squamosa correlated with distribution of the species. Sera fron California recognized Vespa crabro; however, the insect is not found west of Indiana. This suggests that there are also some differences in the venom from the western species, V. pennsylvanica. No correlations were found with reactivity to hornet, wasp or bee venoms.

Allergens↗
PubMed1980

S-Adenosylmethionine and S-adenosylhomocystein metabolism in isolated rat liver. Effects of L-methionine, L-homocystein, and adenosine.

The effects of varying concentrations of L-methionine, L-homocysteine, and adenosine on the tissue levels of S-adenosylmethionine (AdoMet) and S-adenosyl-homocystein (AdoHcy) were investigated in perfused liver. In the normal liver, the intracellular concentration of AdoMet was dependent upon the availability of methionine. In the presence of high concentrations of methionine the maximum level of AdoMet attainable was 300 nmol/g of liver. The exogenous concentration of methionine did not alter the hepatic concentration of AdoHcy (8 to 20 nmol/g) while adenosine or homocysteine blocked hydrolysis of AdoHcy resulting in elevated levels of AdoHcy (400 to 600 nmol/g) and AdoMet (300 to 600 nmol/g). The addition of both adenosine (4mM) and homocysteine (3.4 mM) to the perfusate further increased the levels of AdoHcy (4 mumol/g) and AdoMet (1.2 mumol/g). As the concentration of AdoHcy increased, significant amounts of this compound were released into the perfusate, while AdoMet was not detected. Under all conditions where AdoHcy accumulated in the cell, a concomitant increase in the AdoMet level occurred. Apparently AdoHcy acts as a positive effector of the S-adenosylmethionine synthase. The hepatocytes did not take up significant amounts of [methyl-14C]AdoMet from the perfusate nor were any [14C]methyl groups from this compound incorporated into histones, DNA, or phospholipids. In contrast, [14C]methyl groups were readily incorporated into these macromolecules from exogenous [methyl-14C]methionine. The addition of adenosine (4 mM) and homocystein (3.4 mM) shifted the AdoMet:AdoHcy ratio from 8.2 to 0.3. Under these conditions, transmethylation was inhibited markedly.

Adenosine↗
PubMed1980

Identification of allergens in dog dander extract. I. Clinical and immunological aspects of allergenicity activity.

Allergenic activity of mixed dog dander extract was compared with dog serum albumin by skin testing, RAST testing and RAST inhibition. Whereas albumin is a potent allergen, additional lower molecular weight allergens determined by sucrose density gradient centrifugation and immunoelectrophoresis were found. Identification of the most potent allergens and standardization of extract used for testing and treatment is a necessary prerequisite in understanding dog dander hypersensitivity.

Albumins↗
PubMed1980

Dog and cat allergens: urinary proteins or dander proteins?

Allergens prepared from male dog and cat urines can be used for RAST diagnosis of dog and cat allergy. Only one out of 15 patients positive to epithelia or danders was negative to the urine. The urine antigens appear to be more specific than either epithelia or danders.

Allergens↗