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The clonal proliferation of chicken granulocytic progenitors was inhibited 5-20-fold by the eicosanoid, 5-HETE, at 1.0 microM. Inhibition occurred at the lowest concentration measured (0.12 microM). This compound at 0.6 to 1.0 microM also inhibited the clonal proliferation of chick embryo fibroblasts by as much as 10-fold.

The skills of the Marketing Manager are rarely defined, too often subsumed in discussions of the 4 P's or the 3 C's. In this article the author has analysed, on the basis of contacts with practicing Marketing Managers, the nature of the range of skills possessed by those who are very good at their jobs.

The phthalate acid esters (PAEs), and, in particular, di(2-ethylhexyl) phthalate (DEHP) and its monoester, monoethylhexyl phthalate (MEHP), can adversely affect rodent testes but only at high doses. Rat gonadal zinc levels can be decreased by the injection of DEHP, but not MEHP. The rat prostate gland seems to be particularly sensitive to PAE-induced zinc depletion. PAE-induced changes in male reproductive organs were more evident in the rat than in the mouse. Some of the effects of MEHP can be demonstrated in vitro since it can alter the uptake of 65Zn in rodent gonads and accessory sex organs.

The conceptual problem associated with marketing productivity analysis is examined followed by an examination of currrent practice in marketing productivity in the following areas — on the product line, in advertising and promotional mix, in the salesforce, in distribution and in customer activity tracking. It provides UK companies with some guidance on how they can improve their performance measurement using marketing information systems and reorganising existing information for more effective marketing action. The research concentrates on 50 well‐known British companies in oil, chemicals, various engineering disciplines, food, pharmaceuticals, insurance, construction and chain‐store retailing. The findings are based on 28 viable responses, and a further 21 (different) responses from companies which were personally visited. Although the research techniques need to be refined they conclude that the management of resources invested in marketing activities can never be refined to the point where an incremental investment in any specific marketing application can be measured with great accuracy. Yet a great deal of measurement is possible and marketing managers can be well enough informed about the behaviour of marketing inputs so that allocation decisions in future periods will benefit.?

The nationalized British Gas Corporation is required by statute to consult with its customers through the medium of regionally organzed Gas Consumers' Councils. This paper describes the work of these Councils, reports on criteria for judging the effectiveness of them, and comments of an evaluation of them conducted by Justice.

1-O-Alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (AAGPC) triggered the release of [3H]arachidonate but not [14C]stearate from cellular phospholipids in cytochalasin B-treated rabbit polymorphonuclear leukocytes. Concentrations of AAGPC up to 20 nM caused a dose-dependent release and subsequent metabolism of the released [3H]arachidonic acid. Most of the release of the [3H]arachidonate had taken place within the first 2 min of stimulation. Phosphatidylinositol and phosphatidylcholine served as the sources of [3H]arachidonate with about 50% of the label coming from each pool. Challenge of cytochalasin B-treated polymorphonuclear leukocytes with AAPGC led to the production of [3H]hydroxyeicosatetraenoic acids and [3H]dihydroxyeicosatetraenoic acids. No significant production of [3H]prostaglandins or [3H]thromboxanes was detected. AAGPC also caused a dose-dependent degranulation of cytochalasin B-treated rabbit polymorphonuclear leukocytes as shown by the release of beta-glucuronidase and lysozyme. Both the AAGPC-stimulated production of arachidonate metabolites and the degranulation response were blocked by eicosatetraynoic acid and non-dihydroguaiaretic acid at similar inhibitor concentrations. These findings suggest the bioactions of AAGPC on polymorphonuclear leukocytes may be mediated by the release of arachidonic acid and the production of mono- and dihydroxyeicosatetraenoic acids.

The human polymorphonuclear neutrophil degranulation response to 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid was completely desensitized by preincubating the cells with small amounts of this same fatty acid. Desensitization developed within 1 min, persisted in thoroughly washed cells, and was not due to inactivation of the stimulus. These desensitized cells, however, degranulated partially in response to the ionophore A23187 and normally in response to C5a, N-formyl-methionyl-leucyl-phenylalanine, 1- 0 - alkyl-2- 0 - acetyl - sn - glycero-3-phosphocholine , and phorbol myristate acetate. Thus, the dihydroxy fatty acid is a unique stimulus which degranulates and desensitizes neutrophils by pathways at least partially distinct from those utilized by the other stimuli. The fatty acid, although rapidly formed in degranulating neutrophils, is unlikely to be an essential or universal mediator of the degranulation response.

The use of productivity measurement in relation to the marketing function is relatively new. The central role of marketing can be expressed as the management of consumer demand and the translation of this demand into sales and profits. Marketing productivity analysis is an important tool in evaluating the performance of the marketing department in carrying out this role. It measures the efficiency with which marketing inputs are used to generate target levels of marketing outputs.

— The aerobic dye-sensitized photooxygenation of monohydric phenols proceeds by way of singlet oxygen under the conditions studied. Various phenols give different proportions of reaction with and quenching of singlet oxygen. Para-substituted 2,6-di-t-butylphenols show a linear correlation between the log of the total rate of singlet oxygen removal and their halfwave oxidation potentials; the same correlation is given for certain phenol methyl ethers. A Hammett plot using s+ gives ρ - 1.72 ± 0.12, consistent with development of some charge in the quenching step. Reaction of photo-chemically generated singlet oxygen with 2,4,6-triphenylphenol gives 2,4,6-triphenylphenoxy radical as an intermediate in singlet oxygen quenching, although no overall reaction occurs. Kinetic analysis indicates that the radical is derived exclusively from the interaction of 2,4,6-triphenylphenol with singlet oxygen. A charge-transfer mechanism for quenching of singlet oxygen by phenols is proposed.

Esters of o-phthalic acid are widely distributed in the ecosystem. The phthalate acid esters (PAE's) are used as plasticizers in the manufacture of polyvinylchlorides. They are also used as solvents in certain industrial processes and as vehicles for pesticides. The PAE's are used in enormous quantities for a variety of industrial uses in the formulation of plastics. While there are a number of important PAE's, di-ethylhexyl phthalate has perhaps been used the most extensively in the formulation of plastics used in medical devices and blood bag assemblies. The metabolism, biodistribution and excretion varies to some extent among the various PAE's. There are species differences with respect to the metabolism of the PAE's. The route of administration, and the level and length of exposure, are known to affect the toxicological profile of the various PAE's. There is little evidence of bioaccumulation of the various PAE's, and only at very large doses have there been reports of overt toxicity. Evidence for the carcinogenicity of certain PAE's apparently is related to prolonged exposure to high levels.

For the diversified firm, business portfolio planning offers a way of determining its individual businesses' roles and developing a synergistic corporate strategy. In practice, however, the common tools of portfolio planning—the growth/share and market attractiveness/business position matrices—present problems in that often neither of the matrices is precisely suitable for a given individual business. This article makes use of modifications of the growth/share and market attractiveness/business position matrices in order to make them more operational. The authors believe that a step-by-step ‘shirt-sleeve’ approach to portfolio planning can make this type of analysis accessible and invaluable to a small diversified firm, as well as providing insights to larger corporations with formal planning departments.

(1979). The procedural planning theory of A. Faludi. Planning Outlook: Vol. 22, No. 2, pp. 72-76.

Dual radiolabel incorporation of [3H]arachidonic acid and [14C]palmitate or [14C]stearate by human neutrophils was employed to study both the release and metabolism of arachidonic acid. Results indicate the involvement of a phospholipase A2 mechanism causing [3H]arachidonate release from membrane phospholipid. Phosphatidylinositol and phosphatidylcholine were the sources of [3H]arachidonate; about twice as much radiolabeled phosphatidylinositol was degraded as phosphatidylcholine. Challenge of neutrophils with opsonized zymosan and calcium ionophores caused the release of [3H]arachidonate; however, ionophores but not opsonized zymosan led to the production of [3H]hydroxyicosatetraenoic acid and [3H]dihydroxyicosatetraenoic acid. These products were preferentially released by neutrophils into the extracellular milieu in contrast with free [3H]arachidonate which remained cell associated. One-third of the [3H]hydroxyicosatetraenoic acid but not [3H]dihydroxyicosatetraenoic acid was reincorporated into cellular lipid, primarily phospholipid. No significant production of [3H]prostaglandin or [3H]thromboxane was detected. In contrast to zymosan and ionophore, phorbol myristate acetate, another potent stimulant of neutrophil oxidative metabolism and degranulation, did not release [3H]arachidonate.

Summary Chemotactic factors, arachidonic acid and leukocyte-derived lipoxygenase products of arachidonate (5-hydroperoxy-, 5-hydroxy- and 5,12-dihydroxy-eicosatetraenoic acids) stimulated stereospecific uptake of 3 H-2-deoxyglucose by human neutrophils. However, of all stimuli tested, only the effects of 5-hydroxy-eicosatetraenoic acid were not inhibited by 5,8,11,14-eicosatetraynoic acid at concentrations which also inhibit release of arachidonate metabolites from leukocytes. The data suggest that 5-hydroxy-eicosatetraenoic acid mediates the coupling of membrane receptor stimulation to the functional response of hexose uptake in human neutrophils.

The effect of hydroxyperoxyoctadecadienoic acid, e.g. 13-hydroperoxy-cis,9,trans-11-octadecadienoic acid, on the autooxidation of linoleic acid induced by superoxide radical was examined in a system containing xanthine oxidase, acetaldehyde, and diethylenetriaminepentaacetic acid dissolved in an aqueous phosphate buffer containing 10% ethanol. The superoxide radical is required for autooxidation, as shown by essentially complete inhibition on the addition of superoxide dismutase. Pure linoleic acid was not readily oxidized, but the addition of lipid hydroperoxide markedly stimulated the autooxidation. Addition of 2.8 microM FeCl3 did not produce an increase in the rate of xanthine oxidase-induced autooxidation. Spontaneous autooxidation, a process slower than xanthine oxidase-induced autooxidation, was detectable on the time scale of these observations but was slower than the xanthine oxidase-induced autooxidation. Initiation of linoleic acid autooxidation is postulated to result from a reaction between superoxide and lipid hydroperoxide. The nature of this reaction is uncertain, but it does not appear to depend on iron catalysis.

Using dithionite difference spectra we have detected cytochrome b in highly purified human neutrophils at a concentration of 0.08 nmol/mg protein. The presence of quinone was identified in lipid extracts at a concentration of approx. 0.06 nmol/mg protein. It was identified as ubiquinone-10 by mass spectrographic analysis. Simultaneous measurements of cytochrome oxidase indicated that these compounds could not be attributed to mitochondrial contamination. These results are compatible with the hypothesis that initiation of the respiratory burst in human neutrophils involves a multicomponent electron-transport system.

Customer satisfaction is the key to repeat business. Dissatisfied customers not only switch brands but spread their dissatisfaction. Managing the customer requires a strategy for customer care that involves a number of interfaces: management‐customer, staff‐customer, management‐staff, customer‐system, and management‐system. Each interface is defined.

Ammonia desorption chemical ionization of ether-linked phospholipids of the type 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (platelet-activating factors) and a series of analogues revealed a systematic fragmentation pattern that is characteristic for these compounds. The predominant ions included the protonated molecular ion and a series of fragments derived from the molecular ion having the following nominal mass losses: MH-14, MH-42, MH-59, and MH-183. Deuterated ammonia was used to elucidate the nature of several fragments. In addition, desorption chemical ionization was used to quantitate 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphocholine at the nanogram/sample level.

We propose the creation of an on-line journal that integrates with a component framework. By means of the framework, simulations referenced in the paper can be run (or re-run) on journal supercomputers at will, allowing verification of the results or deeper analysis of the paper's problem space. The on-line journal would provide standardized job launch and control mechanisms, data formats, and address code portability issues. Through the use of the framework and its components authors can make use of built-in productivity and readability enhancing features (such as automatic parallelism), leverage code published in previous works, and gain stature as their published modules are used by others. We feel that Cactus is an ideal candidate for the on-line journal, therefore we propose the name “The Prickly Pear Archive” for the on-line journal, taking the name from a species of cactus that can be used to make paper.

The title of this chapter is deliberately ambiguous, for it raises two not necessarily related problems. If we recast the title of the chapter as the question ‘Can marketing be practised other than for profit?’, we can answer the question by two types of analysis.

Cellular functions of human polymorphonuclear leukocytes (PMNL) including phagocytosis, motility, and bactericidal activity require energy derived from glucose. Whereas insulin does not stimulate hexose transport in human PMNL, we have recently reported that chemotactic factors such as complement-derived C5a, the synthetic oligopeptide N-formyl-methionyl-leucyl-phenylalanine (fMLP), or the calcium ionophore A23187 stimulates transport of deoxyglucose (DOG) into human PMNL1,2. FMLP with an EC50 of 1.2 nM, C5a with an EC50 of 1 nM, and A23187 with an EC50 of 10 nM all cause at least a 5-fold stimulation of DOG uptake.

Stimulation of the Oxidase Phagocytes, such as neutrophils and macrophages, produce superoxide (02;-) and H202 by an enzymatic process in which electrons are transferred from NADPH to O2• This oxidase activity is low or nonexistent in resting cells. Stimulation of the oxidase is the process by which phagocytes transform this latent activity to an expressed activity. Another process, called "activation," involves transformation of phagocytes for greater phagocytic, secretory, and respiratory burst capacities before stimulation (81).

Platelet-activating factor, 1 (PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine), and octadecyl-PAF were synthesized chemically as the racemates. The sn-1-O-alkyl isomers were isolated after treatment of the racemates with phospholipase A2 and subsequent reacetylation of the 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholines released. Analogues of PAF containing unsaturated alkyl moieties at the sn-1 position (2, 4, 5) were synthesized by utilizing the methoxyethoxymethyl protecting group as a novel method for preparing unsaturated alkyl lipids. This procedure provides a facile means for preparing unsaturated either phospholipids of defined structure that may be tritiated to high radiospecific activity for metabolic studies. Unsaturation in the alkyl chain had minimal effect on the bioactivities examined in this study.

5(S)-Hydroxyicosatetraenoate stimulates human polymorphonuclear neutrophils (PMNs) to raise their cytosolic calcium. It also potentiates the cells' degranulation responses to platelet-activating factor and diacylglycerols. We synthesized 5(R)-hydroxyicosatetraenoate and found it to be 20–100-fold weaker than the natural isomer in these assays. Thus, the arachidonic acid metabolite activates PMNs by a stereospecific possibly receptor-mediated mechanism.

The following racemic hydroxyicosatetraenoic acids were prepared and assayed for their ability to stimulate hexose transport in human polymorphonuclear leukocytes: 15-, 12-, 11-, 9-, 8-, and 5-hydroxyicosatetraenoic acids. The compounds were isolated from reduced, autoxidized arachidonic acid. The results demonstrate that only the 12- and 5-hydroxyicosatetraenoic acids are biologically active inducing half-maximal responses at 820 and 176 nM, respectively. Thus, the bioactions of hydroxicosatetraenoates ae crucially dependent upon the position of the hydroxy residue. Response to both hydroxyicosatetraenoates was effectively blocked by two inhibitors of arachidonic acid metabolism: nordihydroguaiaretic acid and indomethacin. A third arachidonic acid antimetabolite, 5, 8, 11, 14-eicosatetraynoic acid, completely inhibited the response to 12-HETE but caused only partial inhibition of the response to 5-HETE.

5(S), 12(S)-Dihydroxy-cis-14,trans-6,8,10-eicosatetraenoate (compound I), 5(S),12(R)-dihydroxy-cis-14,trans-6,8,10-eicosatetraenoate (compound II), and 5(S),12(R)-dihydroxy-cis-6,14,trans-8,10-eicosatetraenoate (compound III) were prepared from rabbit peritoneal neutrophils challenged with arachidonic acid plus ionophore A23187. Each arachidonate metabolite caused rabbit neutrophils to aggregate and, in cells treated with cytochalasin B, release granule-bound enzymes. Compound III was 10- to 100-fold more potent than compounds II and I. When intravenously infused into rabbits at doses of 100--1,000 ng/kg, compound III induced abrupt, profound, transient neutropenia associated with a rapidly reversing accumulation of neutrophils in the pulmonary circulation. This in vivo action correlated closely with the ability of the fatty acid to activate neutrophils in vitro: neutropenia, aggregation, and degranulation occurred at similar doses of stimulus and the rapid, reversing kinetics of the neutropenic response paralleled the equally rapid, reversing formation of aggregates. The fatty acid did not alter the circulating levels of lymphocytes or platelets and did not aggregate platelets in vitro. At comparable doses (i.e., 100--1,000 ng/kg), compounds I and II did not cause neutropenia. Thus, compound III possesses a high degree of structural and target-cell specificity in stimulating neutrophils in vitro and in vivo. Clinical and experimental syndromes associating neutropenia with increased levels of circulating arachidonate metabolites may involve compound III as a mediator of neutrophil sequestration in lung.

A variety of phospholipid vesicles (liposomes) induce morphological differentiation in murine neuroblastoma cells in vitro. This effect is observed when such vesicles are incubated with cells either continuously or for short periods of time in the presence or absence of serum, is not mediated by a specific mode of liposome-cell interaction, and is accompanied by a significant retardation of cell proliferation. Besides phospholipids, fatty acids are also capable of inducing neurite outgrowth in a dose-dependent fashion and thus appear to mediate this effect.

We demonstrated earlier 6 that prelabeled human neurotrophils released [3H]arachidonic acid ([3H]20:4) from cellular phospholipid when challenged with opsonized zymosan. Prelabeled [l'~C]palmitate ([z'~C] 16:0j was not released nor was it recovered as any degradation product such as lysophospholipids or partial glycerides. In order to determine whether this release was related to the formation of bioactive prostanoids '~ or hydroxylated 20:4 derivatives, a2 we undertook a study to determine the source of the 20:4, the mechanism of its release, and its metabolic fate. Further, we compared the effect of the phagocytic challenge with that of Ca 2 + ionophores A23187 and ionomycin, lonophores were used since Ca z+ influx has been shown to stimulate the metabolism of exogenously added 20:4.

A study of the reactivity of HO2/O2- with unsaturated hydroperoxides/peroxides was carried out in a stopped-flow spectrophotometer equipped with an O2--generating plasma lamp. The results show that, in 80% aqueous ethanol solution containing either 0.05 M H2SO4 (for HO2 studies) or 0.005 M KOH (for O2- studies), these oxy-radicals do not react with oleic acid hydroperoxide, linoleic acid hydroperoxide, 1-hydroperoxy-2-cyclooctene, and tert-butyl allyl peroxide. These findings are discussed in the light of conflicting evidence concerning the reaction of HO2/O2- with organic hydroperoxides/peroxides.

Challenge of human neutrophils prelabeled with [3H]arachidonate and [14C] palmitate or [14C]-stearate with opsonized zymosan or the Ca2+ ionophores A23187 or Ionomycin caused the release of [3H], but not [14C], fatty acid. With the ionophores, but not zymosan, considerable conversion of the [3H] arachidonate to hydroxyeicosatetraenoates occurred. Although various isomers were recovered, the 5-hydroxyeicosatetraenoate appeared to be the major product. In these experiments, no [14C] products were detected such as lysophospholipid, diglyceride or monoglyceride. Although no definitive statement can be made about the mechanism of release of arachidonate, our data are most easily interpreted as the result of the action of a phospholipase A2.

The phagocytosing human polymorphonuclear leukocyte (PMN) generates large quantities of oxidants: superoxide (HO2 and ·O 2 - , H2O2, and a chlorine-containing oxidant reputed to be hypochlorite. These oxidants are believed to aid in the killing of microorganisms since patients whose PMNs cannot undergo this “respiratory burst” suffer severe, recurrent infections. There appears to be good,1 but not unequivocable evidence for the participation of superoxide in bacterial killing by the human PMN. Extensive2 research has shown that ·O 2 - is neither a strong oxidant nor a strong reductant and, therefore, it is probably not a potent bactericide. The conjugate acid, HO$, should be sufficiently reactive3 to attack many components of the bacterial cell. Since the human PMN phagosome generally is assumed to be acidic, the acid-base equilibrium will be shifted toward HO2. However, the disproportionation reaction rate increases rapidly as the pH approaches the pKa of HO2, 4.8.3 It is not clear that attack on the susceptible bacterial cell components would be competitive with disproportionation.

Human polymorphonuclear leukocytes produce large quantities of superoxide when they attack and kill bacteria. However, superoxide is a weak oxidizing and reducing agent, and other more reactive oxygen species derived from reactions of superoxide are suggested to participate in the killing processes. To test the hypothesis that a reactive free radical or singlet oxygen is involved in bactericidal activity, human polymorphonuclear leukocytes were exposed to phagocytozable particles containing lipids that contain the easily autoxidized 1,4-diene moiety. After incubation the preparations were extracted and the extracts reduced with NaBH4 to convert hydroperoxides to stable alcohols. Using gas chromatography/mass spectrometry to analyze the extracts, we were unable to detect products unless iron salts were added to the medium. The products obtained by extraction are those that would be expected if both free radical chain autoxidation and 1O2 oxidation were taking place. In summary, we find that polymorphonuclear leukocytes do not cause peroxidation, implying that formation of strongly oxidizing free radicals is not an intrinsic property of the leukocyte. Added iron catalyzes peroxidation by activated leukocytes yielding an unusual distribution of hydroxylated products.

The human polymorphonuclear neutrophil (PMN) aggregation responses to 5(S),12(R)-dihydroxy- cis -6,14- trans -8,10-eicosatetraenoate (diHETE), C5a, N-formyl-methionyl-leucyl-phenylalanine (FMLP), and 1- 0 -alkyl-2- 0 -acetyl- sn -glycero-3-phosphocholine (AAGPC) were desensitized by preincubating the cells with small amounts of diHETE. Desensitization developed rapidly, persisted in washed cells, and was not due to stimulus inactivation. The desensitized cells exhibited normal aggregation responses to ionophore A23187 and phorbol myristate acetate (PMA). Thus, responsiveness to diHETE appears necessary for the aggregation response to C5a, FMLP, and AAGPC. Endogenous diHETE, which forms rapidly in cells challenged with these latter stimuli, may mediate their aggregating actions.