IgG fractions from patients with antiphospholipid syndrome and systemic lupus erythematosus bind to platelets, but do not affect collagen-induced platelet activation.

Anti-beta-2 glycoprotein 1 (anti-ß2GP1) is an antiphospholipid antibody found in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Its presence commonly is associated with thrombosis; however, the mechanisms of interaction of anti-ß2GP1 antibodies and platelets remain unclear. We investigated the effects of APS and SLE patient-derived IgG fractions on collagen-mediated platelet aggregation and examined the binding of patient-derived IgG to platelets before and after activation by collagen. IgG fractions, 150, 200, 300 or 350 µg/ml, isolated from 11 patients with APS and SLE were incubated with two sets of platelet-rich plasma (PRP) in the incubation wells of an aggregometer. The first set was activated by collagen and the other set was incubated for an additional 10 min. All platelets were collected by centrifugation and fixed in cell blocks. We assessed binding of IgG to platelets using immunocytochemistry (ICC). Patient-derived IgG fractions did not affect collagen-induced platelet aggregation. ICC staining using anti-human IgG antibodies demonstrated that patient-derived IgG fractions had greater affinity for non-activated platelets than those activated by 0.75 µg/ml collagen. Patient-derived IgG fractions bound to the surface of platelets and potentially could be internalized by platelets. IgG fractions from APS and SLE patients may sensitize non-activated platelets, which could increase platelet reactivity and thrombotic risk in patients. We did not detect secondary effects of patient-derived IgG fractions.

Evaluation of the stability of (99m)Tc-ECD and stabilized (99m)Tc-HMPAO stored in syringes.

OBJECTIVE: To determine and compare the stability of (99m)Tc-ECD and stabilized (99m)Tc-HMPAO when stored in syringes over an 8-h period. METHODS: (99m)Tc-ECD and stabilized (99m)Tc-HMPAO were prepared according to the manufacturers' protocols, with the following exception: eluate less than 60 min old was used to prepare (99m)Tc-HMPAO rather than the recommended 30 min. Once prepared, 185 MBq (5 mCi) of both products were drawn into 5-mL syringes and allowed to sit at room temperature. At 2, 4, 6, and 8 h after preparation, the radiochemical purity (RCP) of the contents of the syringes was determined and compared to the RCP of the products in vials. Retention of activity of each product in syringes was also evaluated by measuring activity remaining in each syringe (and filter, in the case of (99m)Tc-HMPAO) after expressing its contents. RESULTS: The RCP of stabilized (99m)Tc-HMPAO stored in syringes decreased from a mean of 87.7% at 2 h to 74.0% at 8 h after preparation. In contrast, (99m)Tc-ECD retained an RCP of greater than 94% throughout the time tested. The impurity that appeared to increase over time with (99m)Tc-HMPAO was found to be sodium pertechnetate. Total retention of activity remaining in the syringe and filter ranged from 11.6% at 2 h to 9.5% at 8 h for (99m)Tc-HMPAO; the syringe itself retained less than 5% of the total activity at all time periods. (99m)Tc-ECD exhibited 6.2% to 11.3% retention of activity in the syringe. The sorption of sodium pertechnetate to the syringe for the same time period was less than 1%. CONCLUSIONS: (99m)Tc-ECD is a more stable product than stabilized (99m)Tc-HMPAO in a syringe. Both products demonstrate retention of radioactivity in the syringe. Some of this retention may denote sorption of the products to plastic.

Quality of life in HIV-infected women in the south-eastern United States.

The purpose of this study was to evaluate the relative importance of social (social support, material resources, disclosure, and family functioning) and psychological factors (stigma, emotional distress, intrusion, avoidance, and fatalism) as predictors of the quality of life of women infected with HIV. The cross-sectional data were drawn from interviews of a sample of 264 women recruited from 8 HIV/AIDS treatment sites in a south-eastern state. Variance in quality of life variables, included limited daily functioning, general anxiety, and HIV symptoms was analyzed using ANOVA, correlations, and hierarchical multiple regression analysis. Limited daily functioning was predicted by stigma, fatalism, employment status, and stage of disease (R2 = 0.179). General anxiety was predicted by emotional distress, intrusion, and marital status (R2 = 0.503). Reported HIV symptoms were predicted by material resources, disclosure, intrusion, age, employment status, and race (R2 = 0.294). The results of this study support that social and, particularly, psychological factors are important in their influence on quality of life in women with HIV infection and suggest the need for interventions which address such factors.

The impact of HIV on emotional distress of infected women: cognitive appraisal and coping as mediators.

This study examined the role of psychological factors as mediators of the impact of HIV-related stressors on emotional distress of a clinic-based sample of 264 HIV+ women. Based upon Lazarus and colleagues' cognitively oriented theory of stress and coping, causal modeling was used to test for mediating effects of cognitive appraisal (intrusive thoughts and perceived stigma) and coping variables (avoidance and fatalism) on emotional distress within the context of HIV-related stressors (functional impairment and work performance impairment). The findings supported the mediating effects of cognitive appraisal but not of the coping variables. Consistent with theory, the effect of HIV-related stressors on emotional distress was indirect through cognitive appraisal; however, there were no significant direct effects of HIV-related stressors, fatalism or avoidance on emotional distress. The causal model accounted for significant portions of variance in emotional distress (R2 = .49) and the model fit, as a whole, was more than adequate. The findings indicate that how HIV+ women think about HIV-related stressors is an important factor that may account for individual variability in the ability to maintain a sense of subjective well-being in the face of a devastating fatal disease.

Prenatal administration of methadone in the rat: acoustic startle amplitude and the rest-activity cycle at 30 days of age.

Two doses of methadone were administered by osmotic minipump from Day 8 of gestation through parturition, a dosing technique previously shown to produce physical dependence in the dams. A pair-fed control group received sterile water via minipump and was allowed to eat and drink only the amount consumed by the high-dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. The effects of methadone on maternal and offspring toxicity replicated our previous findings. At 29-31 days of age each treated and control animal was tested either for changes in acoustic startle amplitude or the rest-activity cycle. Methadone treated offspring were no different from the controls on either measure. These findings support the hypothesis derived from our earlier research that prenatal exposure to methadone produces a prolonged but transitory opioid abstinence. This is evidenced by increased startle amplitude and a disturbed rest-activity cycle that peaks at approximately 3 weeks of age. We demonstrate that these effects are no longer evident at 4 weeks of age. Together, these findings define a state of hyperexcitability in the young rat that resolves by 1 month of age. This transitory state parallels clinical descriptions of human infants undergoing opiate abstinence.

Prenatal administration of methadone in the rat increases offspring acoustic startle amplitude at age 3 weeks.

Two doses of methadone were administered by osmotic minipump from Day 8 of gestation through parturition, a dosing technique previously shown to produce physical dependence in the dams. A pair-fed control group received saline via minipump and was allowed to eat and drink only the amount consumed by the high dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. The effects of methadone on maternal and offspring toxicity replicated our previous findings. At 21-23 days of age, acoustic startle amplitude was measured for each treated and control animal. Because prenatal methadone exposure resulted in reduced body weight at the time of testing, it was necessary to analyze startle amplitude using weight as a covariate. This analysis showed that the methadone treated offspring had a significantly enhanced mean startle amplitude compared with the controls. These findings support the hypothesis derived from our earlier research that prenatal exposure to methadone produces a prolonged state of CNS hyperexcitability similar to clinical descriptions of human infants undergoing opiate abstinence.

What's lost in inverted faces?

Disproportionate inversion decrements for recognizing faces and other homogeneous stimuli are often interpreted as evidence that experts use relational features to recognize stimuli that share a configuration. However, it has never directly been shown that inversion disrupts the coding of relational features more than isolated features. Here we report three studies that compare inversion decrements for detecting changes that span the isolated-relational features continuum. Relatively large inversion decrements occurred for relational features (Thatcher illusion changes, internal feature spacing), with smaller decrements for isolated features (presence/absence of facial hair or glasses). The one discrepancy was a relatively large inversion decrement for detecting changes to the eyes and mouth, which we had classified as an isolated feature change. However, this decrement disappeared when the features were presented out of the face context (Experiments 2 and 3), suggesting that it occurs because subjects spontaneously code relations between the features and the rest of the face. Although the results support the interpretation of disproportionate inversion effects as evidence of relational coding, the difficulty of classifying changes as isolated or relational highlights an undesirable ambiguity in the isolated-relational feature distinction. We therefore consider alternative construals of the configural coding notion.

Prenatal administration of methadone using the osmotic minipump: effects on maternal and offspring toxicity, growth, and behavior in the rat.

Two doses of methadone were administered by osmotic minipump from day 8 of gestation through parturition. A pair-fed control group received saline via minipump and was allowed to eat and drink only the amount consumed by the high dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Naloxone challenge of the dams after parturition showed that drug treatment produced physical dependence. Methadone treatment reduced maternal weight gain but had no effect on either the frequency of resorptions or birthweight. Both doses of methadone increased perinatal mortality but only the high dose produced a decrement in postnatal growth. To examine the effects of methadone on the rest-activity cycle of the offspring, groups of three littermates from each of the treated and control groups were tested for an 8 h observation period on electronic activity monitors at 22 days of age. No behavioral effects were observed for either control group or the low dose methadone group. The high dose methadone offspring, however, spent less time resting, showed disrupted rhythmicity, and poor state regulation. These findings are discussed in relation to earlier studies using once per day methadone administration as well as clinical descriptions of infants undergoing opiate abstinence.

Prenatal delta-9-tetrahydrocannabinol in the rat: effects on auditory startle in adulthood.

Either 15 or 30 mg/kg of delta-9-tetrahydrocannabinol (delta-9-THC) was administered to pregnant rats by gastric intubation from Day 2 through Day 22 of gestation. Pair-fed and nontreated groups served as controls and all treated and control litters were surrogate fostered at birth to untreated dams. When treated and control male and female offspring were tested for differences in auditory startle at 57-60 days of age, no effects were observed among any of the groups. These findings are compared with other neurobehavioral studies of adult offspring prenatally exposed to cannabis.

Prenatal delta-9-tetrahydrocannabinol in the rat: effects on postweaning growth.

Either 15 or 30 mg/kg of delta-9-tetrahydrocannabinol (delta-9-THC) was administered from Day 2 through Day 22 of gestation. Pair-fed and nontreated groups served as controls and all treated and control litters were fostered at birth to untreated dams. When weighed at 57-60 days of age, pair-fed controls were significantly heavier than the nontreated, whereas the treated animals were intermediate between the controls. These findings are discussed with respect to nutritional studies that have reported postnatal growth enhancement following prenatal maternal undernutrition and the possibility that prenatal delta-9-THC inhibits this effect.

Expertise and configural coding in face recognition.

Diamond & Carey (1986) have argued that expertise in face recognition depends on the ability to code configural properties in addition to isolated features. We tested this hypothesis in two experiments by comparing the effect of inversion on recognition of 'own race' (high expertise) and 'other race' (low expertise) faces. Use of configural information should be associated with a larger inversion effect than use of isolated features, and therefore inversion should produce a larger recognition decrement for own race than for other race faces. In Expt 1 there was a larger inversion effect in reaction times for recognition of own race faces than other race faces, for both European and Chinese subjects (ceiling effects made interpretation of accuracy difficult). In Expt 2 a larger own race inversion effect was found for recognition accuracy, when test face pairs were randomly selected, but not when they were matched on isolated features. Our results are largely consistent with the hypothesis that expertise is associated with greater use of configural information in faces.

Delta-9-tetrahydrocannabinol during pregnancy in the rat: effects on development of RNA, DNA, and protein in offspring brain.

Either 15 or 50 mg/kg of delta-9-tetrahydrocannabinol (THC) was administered from Day 2 through Day 22 of gestation. Pair-fed and nontreated groups served as controls and all treated and control litters were fostered at birth to untreated dams. To determine the effects of THC on offspring brain development, DNA, RNA and protein values were determined at 7, 14, and 21 days of postnatal age. DNA and RNA levels appeared unaffected by THC but brain protein levels of the 50 mg/kg offspring were significantly lower than in the other groups at Day 7 and 14. This suggests that the high THC dose inhibited protein synthesis for at least the first 14 days of life. Subsequently, protein levels of the 50 mg/kg offspring increased rapidly so that there were no differences between any of the groups at 21 days of age. These findings for developing CNS parallel the delayed rate of somatic growth previously reported from our laboratory and suggest a transitory rather than a permanent effect of THC on both somatic and brain growth. We also found that THC produces a significant dose-related increase in the sex-ratio of live male-to-female offspring, a finding we have reported previously.

Sapid savvy in sucklings: the effect of quinine hydrochloride on intraoral negative pressure and intake by 11-13-day-old rat pups.

Three experiments describe the consummatory behavior of 11-13-day-old rat pups during and following experience with a model aversive taste, quinine hydrochloride. Pups were observed while away from the dam and while suckling. Results show that pups actively reject quinine adulterated solutions in both situations. They do so by spitting the solution from the mouth when away from the nipple and by leaving the nipple and/or decreasing their sucking effort when with the dam.

Delta-9-tetrahydrocannabinol during pregnancy in the rat: I. Differential effects on maternal nutrition, embryotoxicity, and growth in the offspring.

Either 15 or 50 mg/kg of delta-9-tetrahydrocannabinol (THC) in sesame oil was administered by gastric intubation to gravid rats during the last two weeks of gestation. A pair-fed control group was administered the vehicle alone and allowed to eat and drink only the amount consumed by the 50 mg/kg group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Among the dams receiving 50 mg/kg of THC, food and water intake was initially reduced to 75-80% of nontreated controls but then recovered over 3-4 days to approximately a 15-20% reduction until term. Compared with the nontreated dams, both THC dose-level groups and pair-fed control dams gained significantly less body weight from conception to term. Offspring mortality did not differ between the nontreated and pair-fed controls but was significantly higher among both dose-level THC exposed groups. In addition, there was a dose-related increase in the sex-ratio of live male to female offspring as well as significant effects on rate of growth for both sexes. The results are discussed with respect to published animal and clinical studies of cannabinoid exposure during pregnancy.

Delta-9-tetrahydrocannabinol during pregnancy in the rat: II. Effects on ontogeny of locomotor activity and nipple attachment in the offspring.

Either 15 or 50 mg/kg delta-9-tetrahydrocannabinol (THC) in sesame oil was administered by gastric intubation to gravid rats during the last two weeks of gestation. A pair-fed control group was administered the vehicle alone and allowed to eat and drink only the amount consumed by the 50 mg/kg group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Intact litters from the two THC treated and the two control groups were tested at 3-day intervals from birth to 32 days of age for differences in locomotor activity. In addition, pups were tested for nipple attachment on days 2, 5, 8, 11, and 14 of age. There were no differences in locomotor activity among any of the groups although activity level varied during development. Pups from dams exposed to 50 mg/kg of THC, as well as the pair-fed controls, displayed significantly longer latencies to attach to a nipple. These results suggest that the impaired nipple attachment observed among the high-dose offspring was not a primary effect of THC, but rather was secondary to the significant reduction of food and water intake among the dams. The behavioral findings are discussed with respect to other animal and clinical reports of prenatal cannabinoid exposure.

Olfactory-guided orientation in neonatal rats is enhanced by a conditioned change in behavioral state.

In Experiment 1, 3-6-day-old rats were simultaneously exposed to an unfamiliar odor which they will normally avoid (orange extract) and the odor of maternal saliva, or to either orange alone or saliva alone. One hour later, in a two-odor choice test, those pups which were simultaneously exposed to orange and saliva exhibited an enhanced orientation to the orange odor. In Experiment 2, orange odor was presented while pups were exposed to the odor of saliva, or while they received one of two types of tactile stimulation (stroking or tailpinching). Pups in control groups were first presented with saliva or tactile stimulation and then the orange odor. Pups that had received any of the three simultaneous exposure treatments subsequently exhibited an enhanced orientation toward the orange odor, but not the pups in the control groups. The results suggest that the tendency of neonates to avoid a novel odor can be reversed by pairing that odor with events that elicit significant increases in behavioral activity. The possibility that this phenomenon reflects a classical conditioning process is discussed.

Huddling and independent feeding of neonatal rats can be facilitated by a conditioned change in behavioral state.

Infant rat pups were exposed to a novel odor (orange or cedar) while they received tactile stimulation (stroking of the body) or were presented with odor or stroking alone. The effects of these treatments were assessed on pups' performance in a huddling test (Experiment 1 and 2) and an independent feeding test (Experiment 3). During these tests, only pups that had received the simultaneous presentation of the odor and stroking exhibited an increase in huddling and feeding. The increase in these behaviors was dependent on the presence of the conditioned odor during testing.