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Biomedical subjects

B M Waite

Publications and source records attributed to B M Waite.

At least 19 recordsLinked to original sources

Serum cholesterol concentrations and mood states in violent psychiatric patients: an experience sampling study.

The well-documented negative association between serum cholesterol and aggressive behavior has led Kaplan to propose a cholesterol-serotonin hypothesis of aggression. According to this hypothesis, low dietary cholesterol intake leads to depressed central serotonergic activity, which itself has been reported in numerous studies of violent individuals. In the present study, 25 violent psychiatric patients participated in a microbehavioral experience sampling procedure to examine differences in self-reports of affective and cognitive experiences as a function of serum cholesterol concentrations. For 7 days, they wore signaling devices that emitted an average of seven signals a day. Following each signal, patients filled out a mood questionnaire. Total serum cholesterol (TSC) concentration was positively associated with measures of affect, cognitive efficiency, activation, and sociability, suggesting a link between low TSC and dysphoria. These findings are consistent with the cholesterol-serotonin hypothesis and with the substantive literature linking both aggression and depression to depressed central serotonergic activity.

Adult↗

Anti-homosexual attitudes in college students: predictors and classroom interventions.

Undergraduate college students (N = 173) enrolled in business or psychology classes were studied to investigate (1) predictors of anti-gay and lesbian attitudes and (2) two educational approaches for counteracting negative attitudes toward homosexuality. Students' gender and other demographic characteristics, gender role orientation, gender role attitudes, and personal history variables were employed as independent variables in a multiple regression analysis to predict anti-homosexual attitudes. Results indicated that attitudes were significantly predicted by gender role attitudes, personal acquaintance with a gay man, lesbian, or bisexual person, and religious conviction. Gender, gender role orientation, age, prior participation in a workshop on homosexuality, sexual experience, and class type (psychology or business) were not significant predictors. One-way independent groups analysis of variance indicated no significant differences in level of anti-homosexual attitudes between heterosexual students who had interacted with gay and lesbian students in a one hour classroom panel discussion, viewed a video presentation on homosexuality, or had no classroom intervention.

Attitude↗

Influence of coenzyme A-independent transacylase and cyclooxygenase inhibitors on the proliferation of breast cancer cells.

Recent studies have demonstrated that arachidonic acid (AA) may serve as an important signal that blocks cell proliferation of certain neoplastic cells. The current study was conducted to determine whether disruption of AA homeostasis influences breast cancer cell proliferation and death. Initial experiments revealed that inhibition of AA remodeling through membrane phospholipids by inhibitors of the enzyme, coenzyme A-independent transacylase (CoA-IT), attenuates the proliferation of the estrogen receptor-negative, MDA-MB-231, and estrogen receptor-positive, MCF-7 breast cancer cell lines. This growth inhibition was accompanied by a marked accumulation of AA in both free fatty acid and triglyceride forms, a marker of intracellular AA stress within mammalian cells. Cell cycle synchronization experiments revealed that the CoA-IT inhibitor, SB-98625, blocked MDA-MB-231 cell replication in early to mid G1 phase. Time-lapse video microscopy, used to observe the changes in cell morphology associated with apoptosis, indicated that SB-98625 treatment induced early rounding and occasional blebbing but not late apoptotic events, blistering, and lysis. The cyclooxygenase inhibitors, NS-398 and indomethacin, were found to be less potent blockers of cell proliferation and poor inducers of cellular AA accumulation than CoA-IT inhibitors in these breast cancer cell lines. Finally, AA provided exogenously blocked the proliferation of MCF-7 cells, and this effect could be attenuated in MCF-7 cells overexpressing the glutathione peroxidase gene, GSHPx-1. Taken together, these experiments suggest that disruption of AA remodeling in a manner that increases intracellular AA may represent a novel therapeutic strategy to reduce cancer cell proliferation and that an oxidized AA metabolite is likely to mediate this effect.

Acyltransferases↗

The everyday experience of an institutionalized sex offender: an idiographic application of the experience sampling method.

The Experience Sampling Method (ESM) is a novel assessment strategy that allows random sampling of thoughts, affects, and behaviors. In ESM studies subjects wear beepers that signal at randomly generated, preprogrammed times at which subjects fill out a questionnaire containing items related to current activity, location, thought content, mood states, etc. The ESM was used to examine the relationship between mood states and thought content in a hospitalized sex offender. The patient exhibited a very high frequency of thoughts with sexual content, as well as thoughts indicative of anger against women, personal inadequacy, and distress. He appeared to be a poor judge of his state of optimal well-being. Whereas he considered support from others to be related to optimal well-being, it was actually sexual thoughts about a woman that were associated with his optimal well-being. The present case study illustrates the value of the ESM in the study of complex thought-affect-behavior relationships.

Activities of Daily Living↗

Abnormal lateralization in finger tapping and overt aggressive behavior.

1. The relationship between abnormal cerebral lateralization and overt aggressive behavior was examined in 41 violent psychiatric patients in a maximum-security hospital. 2. Cerebral lateralization was measured using the Finger Oscillation Test from the Halstead-Reitan Neuropsychological Battery, and aggressive behavior was measured during a six-month period of hospitalization using the Overt Aggression Scale. 3. Patients with the most abnormal pattern of lateralization exhibited the highest frequency as well as the highest severity of overt aggressive behavior. This pattern could not be explained by the influence of age, race, IQ, history of head trauma, brain damage, or psychiatric diagnosis. History of seizures, alcohol abuse, and drug abuse, however, were found to be intervening variables in the lateralization-aggression link. Once their influence was removed using analysis of covariance, there was no relationship between lateralization and aggression. 4. The results suggest that it is unlikely that there is a direct causal relationship between abnormal lateralization and aggressive behavior.

Adult↗

Lyso(bis)phosphatidic acid: a novel source of arachidonic acid for oxidative metabolism by rabbit alveolar macrophages.

To identify the source of arachidonic acid utilized for eicosanoid production, rabbit alveolar macrophages were challenged with 1.0 microM 12-O-tetradecanoylphorbol-13-acetate (TPA) or 3.8 microM Ca+2 ionophore A23187 for 3 h. Upon stimulation with TPA, a loss of [3H]arachidonic acid from phosphatidylcholine, phosphatidylethanolamine, lyso(bis)phosphatidic acid, and phosphatidylserine/phosphatidylinositol was observed. Although calcium ionophore stimulated the liberation of arachidonate solely from phosphatidyl-ethanolamine and phosphatidylcholine, it proved to be a poor stimulus for macrophage-synthesis of eicosanoids. Our evidence suggests that degradation of phosphatidylinositol and lyso(bis)phosphatidic acid induced by TPA yields a source of arachidonate which is the preferred substrate for oxidative metabolism by the cyclooxygenase and lipoxygenase pathways.

Animals↗

Co-localization of superoxide generation and NADP formation in plasma membrane fractions from human neutrophils.

In order to resolve discrepancies in the literature concerning the subcellular localization of NADPH oxidase, we disrupted human neutrophils by nitrogen cavitation and fractionated the subcellular organelles on a discontinuous sucrose density gradient. The lightest fraction was 20- to 40-fold enriched for plasma membranes as determined by the marker enzymes alkaline phosphatase and phosphodiesterase I as well as by the ratio of lipid phosphorus to protein. There was a significant decrease in the specific activities of the granule markers myeloperoxidase, lysozyme, and beta-glucuronidase. An intermediate fraction was enriched in membrane markers but not to the extent the lightest fraction was enriched. This fraction contained more granular contamination, as shown by the marker enzymes. In contrast, the densest bands of the gradient were enriched for granule markers with little contamination by plasma membrane. Superoxide generation and NADP formation were primarily associated with the two membrane-enriched fractions from polymorphonuclear leukocytes stimulated with phorbol myristate acetate. The NADP formation associated with a dense granule fraction observed previously in our laboratory was probably due to a cyanide-stimulated oxidation of NADPH by myeloperoxidase.

Alkaline Phosphatase↗

Arachidonate metabolism during chondrogenesis in vitro.

Chick embryo limb bud mesenchyme cells undergoing chondrogenesis in vitro were labeled with [3H] arachidonic acid and [14C] palmitic acid, and stimulated by mechanical means to convert a portion of their incorporated [3H] to radiolabeled compounds which co-chromatographed with authentic prostaglandins in the appropriate thin layer chromatography system. Chondrogenesis was (1) inhibited by concentrations of indomethacin or eicosa-5,8,11,14-tetraynoic acid which inhibited conversion of [3H] to prostaglandinlike compounds; and (2) stimulated by prostaglandin E2. We interpret these data to mean that (1) cells undergoing chondrogenesis in vitro are able to metabolize endogenous arachidonic acid to prostaglandins, and (2) synthesis of prostaglandinlike compounds is requisite to chondrogenesis in vitro.

Animals↗

Acyl composition and phospholipase activities in plasma membranes isolated from rat embryos.

A subcellular fraction enriched in plasma membranes and relatively poor in other subcellular membranes was isolated from homogenates of rat embryos obtained on the 15th day of gestation. Characterization of this fraction revealed a paucity of stearate, arachidonate and long chain polyunsaturated fatty acids relative to palmitic, oleic, linoleic and linolenic acids, in total phospholipids. Estimation of phospholipase A activity revealed that phospholipase A1 and A2 were present in plasma membranes from rat embryos. A relatively high lysophospholipase activity was also found in the PM-rf, and may be the metabolic basis for the paucity of long chain polyunsaturated fatty acids in the embryo-derived plasma membranes.

Acylation↗

Calcium ionophore A-23187 and 12-O-tetradecanoyl-phorbol-13-acetate stimulation of prostaglandin synthesis in herpes simplex virus type 2-transformed rat cells.

The purpose of this investigation was to determine whether cells transformed by herpes simplex virus type 2 (HSV-2) can be stimulated to synthesize prostaglandins (PG). Stimulation was determined by measuring the release of PG into overlay fluids from cell monolayers prelabeled with [3H]arachidonic acid. Results showed that Ca2+ ionophore A-23187 markedly stimulated arachidonic acid release starting 30 min after treatment of HSV-2-transformed and nontransformed rat embryo fibroblast cells. However, only HSV-2-transformed cells were stimulated in production of PG. HSV-2-transformed, nontumorigenic, rat embryo fibroblast, line G, clone 2.0 cells synthesize nearly equal amounts of prostaglandin E2 (PGE2) and prostaglandin F2 alpha, while tumor (rat fibrosarcoma) cells synthesize primarily PGE2. Stimulation of PGE2 synthesis by Ca2+ ionophore A-23187 or 12-O-tetradecanoyl-phorbol-13-acetate decreased as rat fibrosarcoma cells were serially passaged in tissue culture. At low passage of parental rat fibrosarcoma cells, four distinct morphological clonal cell lines were isolated, which varied markedly in their capacity to be stimulated in PG synthesis by 12-O-tetradecanoyl-phorbol-13-acetate. There was correlation between the capacity of clone 1 cells to be stimulated in PGE2 synthesis by serum alone and capacity of the tumors produced by the clone 1 cells to metastasize to the lungs of syngeneic tumor-bearing rats. In summary, cell transformation by HSV-2 appears to be essential for stimulation of PG synthesis in cells. The capacity to be stimulated in arachidonic acid metabolism and PG synthesis may be important in the process of carcinogenesis by a putative human cancer virus.

Animals↗

Platelet activating factor. Stimulation of the lipoxygenase pathway in polymorphonuclear leukocytes by 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine.

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.

Animals↗

Release and metabolism of arachidonic acid in human neutrophils.

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.

Arachidonic Acid↗

The acyl-CoA desaturases of microsomes from rat liver and the Morris 7777 hepatoma.

We have investigated the role of the microsomal oxidative desaturase in defining the aberrant phosphoglyceride fatty acid composition of hepatomas. The microsomal delta 9-stearoyl-CoA, delta 6-oleoyl(linolenoyl)-CoA, and delta 5-eicosatrienoyl-CA desaturase activities were studied in control and host liver and in the poorly differentiated Morris 7777 hepatoma. The delta 9-stearoyl-CoA desaturase of the hepatoma was significantly decreased (42%) relative to control liver, yet the hepatoma specific activity was twice that of host liver. Additionally, the specific activity of the delta 9-stearoyl-CoA desaturase of the tumor was found to decrease with increasing tumor weight. Also this desaturase was inactivated by freezing and thawing. The delta 6-oleoyl(linolenoyl)-CoA and delta 5-eicosatrienoyl-CoA desaturases of the hepatoma were 39% and 4% of control, respectively. The electron transport components involved in the desaturase system were reduced, although this did not appear to be rate-limiting. In addition, two competing metabolic reactions which could lower the observed desaturase activities, hydrolysis of the thioester and incorporation of substrate acyl-CoA molecules into glycerides, did not appear to be responsible for the lowered desaturase activities of the tumor. Thus, it appears that reduced levels of the desaturases themselves may be responsible for the observed activities. These results indicate that the capacity of the hepatoma to biosynthesize polyunsaturated fatty acids is greatly reduced and this is consistent with the decreased polyene content observed in many neoplasms.

Animals↗

Deacylation-reacylation of phospholipids by rat embryos and their associated placentas. I. Placental acyltransferase.

Homogenates and subcellular fractions of rat chorioallantoic placentas obtained on the 14th day of gestation were assayed for acyl-CoA: lysophospholipid acyltransferase activities using (14C)-linoleic acid, ATP, and CoA, or (14C)-oleoyl-CoA as acyl donor and 1-acylglycerophosphorylcholine or 1-acylglycerophosphorylethanolamine as acyl acceptor. We found that: (1) the Lands' deacylation-reacylation cycle is present in the rat placenta, (2) the enzymes were concentrated in the microsomal fraction, and (3) the optimal conditions for in vitro assay of those enzyme activities were similar to those reported for adult tissues. Comparison of the acyl composition of phospholipids in maternal blood with those in placental homogenates revealed similarities which are consistent with a role for this cycle in vivo in placental uptake of phospholipids. That this cycle may function also in placental transformation of phospholipids in vivo, is suggested by differences between the acyl composition of phospholipids in placental homogenates and microsomal fractions.

1-Acylglycerophosphocholine O-Acyltransferase↗