Indium-labeled presensitized T cells for diagnosis of graft rejection.

The aim of this experiment was to test a safe, noninvasive method for necessary, accurate diagnosis of early allograft rejection. Heart-lung allograft was performed heterotopically using Brown Norway (BN) rats as the donor and Lewis (LEW) rats as the recipient. T cell suspensions were prepared from lymphnodes of specifically sensitized LEW rats that had acutely rejected full-thickness BN skin graft. Cell count was adjusted 50 x 10(6) cells/ml. The suspension was incubated in vitro with 111I oxide (1 m Ci-ml). An aliquot of labeled cell suspension containing 40 x 10(6) cells and a total radioactivity of 200 mCi was administered intravenously to each animal 3 and 6 days after heart-lung transplant. The traffic of T cells was followed in vivo and in isolated organs under large field view gamma camera. The gamma camera revealed radioactivity on the graft starting Postoperative Day 5 when the heart was actively beating; no radioactivity was revealed at the site of the isografted organs. The histology showed mild to moderate cellular infiltration parallel to the grade of radioimaging intensity. The injection of indium-labeled presensitized T cells was able to detect the rejection process in an early phase when there are no clinical symptoms of rejection and/or the rejection cascade can be reversed. These results suggest that a similar method can be used in human organ transplantation for early diagnosis of rejection.     

Postmenopausal HRT is not independent risk factor for dural sinus thrombosis

While a dural sinus thrombosis (DST), is a well-known consequence of the use of oral contraceptives, the role of hormone replacement therapy (HRT) in DST was not previously evaluated. We report two postmenopausal women, presenting with DST under HRT. Antiphospholipid antibodies in one case and borderline protein S deficiency in another were diagnosed. Only five cases of DST under HRT were previously reported and in two of them additional prothrombotic risk factors were found. According to these and previous cases, HRT is not an independent risk factor for DST.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute G_i/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca²⁺/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

Toward a comprehensive model of death anxiety

An integrative, comprehensive model of death anxiety is presented. The model postulates three immediate antecedents of death anxiety: past-related regret, future-related regret, and meaningfulness of death. Past-related regret refers to a person's unfulfilled aspirations that should have been achieved but were not. Future-related regret refers to the anticipation that, as a result of premature death, one cannot achieve important goals in the future. Meaningfulness of death refers to one's concept of death and ability to make sense of it. These three antecedents are related to death salience in a complex way, mediated by coping mechanisms and their effects on one's beliefs about self and the world. The coping mechanisms include (but are not necessarily limited to) life review, life planning, identification with culture, and self-transcending processes. The model's developmental and practical applications are explored.     

Ultrasound-diagnosed puerperal osteopenia in young primiparas

OBJECTIVE: To study whether osteopenia occurs following pregnancy and to evaluate its severity in young primiparas. STUDY DESIGN: A prospective case control study. Sixty-one young primigravidae early after birth and 59 nulligravidae matched for age and BMI participated in the study. Bone status was examined using ultrasonic bone transmission velocity over the tibia; Z-score and T-score for bone density were calculated. Serum bone alkaline phosphatase, osteocalcin and urinary N-telopeptide crosslinks were evaluated as bone remodeling biochemical markers. RESULTS: Ultrasonic parameters of bone status following delivery were significantly lower in the puerperal group as compared to the nulligravida group. Serum mean bone alkaline phosphatase levels and urinary N-telopeptide crosslinks secretion were higher by 50% in the puerperal group, while serum osteocalcin levels were significantly lower (by 25%) than in the nulligravida controls. A positive correlation between ultrasonic measurements and biochemical markers was demonstrated in the postpartum group, whereas the control group showed a negative correlation. CONCLUSION: Women at their early puerperium demonstrate a significant cortical bone mass reduction as measured by ultrasonograph and markers of bone turnover. It appears that pregnancy is a state of unbalanced accelerated bone turnover that may be associated with reduced osteoblastic activity.     

Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease

ObjectivePreclinical and genetic epidemiologic studies suggest that modulating cytochrome P450 (CYP)-mediated arachidonic acid metabolism may have therapeutic utility in the management of coronary artery disease (CAD). However, predictors of inter-individual variation in CYP-derived eicosanoid metabolites in CAD patients have not been evaluated to date. Therefore, the primary objective was to identify clinical factors that influence CYP epoxygenase, soluble epoxide hydrolase (sEH), and CYP ω-hydroxylase metabolism in patients with established CAD.MethodsPlasma levels of epoxyeicosatrienoic acids (EETs), dihydroxyeicosatrienoic acids (DHETs), and 20-hydroxyeicosatetraenoic acid (20-HETE) were quantified by HPLC–MS/MS in a population of patients with stable, angiographically confirmed CAD (N = 82) and healthy volunteers from the local community (N = 36). Predictors of CYP epoxygenase, sEH, and CYP ω-hydroxylase metabolic function were evaluated by regression.ResultsObesity was significantly associated with low plasma EET levels and 14,15-EET:14,15-DHET ratios. Age, diabetes, and cigarette smoking also were significantly associated with CYP epoxygenase and sEH metabolic activity, while only renin-angiotensin system inhibitor use was associated with CYP ω-hydroxylase metabolic activity. Compared to healthy volunteers, both obese and non-obese CAD patients had significantly higher plasma EETs (P < 0.01) and epoxide:diol ratios (P < 0.01), whereas no difference in 20-HETE levels was observed (P = NS).ConclusionsCollectively, these findings suggest that CYP-mediated eicosanoid metabolism is dysregulated in certain subsets of CAD patients, and demonstrate that biomarkers of CYP epoxygenase and sEH, but not CYP ω-hydroxylase, metabolism are altered in stable CAD patients relative to healthy individuals. Future studies are necessary to determine the therapeutic utility of modulating these pathways in patients with CAD.     

Amygdala kindling modifies interhemispheric dopaminergic asymmetry

Brain dopamine is known to retard the development of kindled seizures, but it is uncertain whether kindling affects dopamine function. In the present study, rats were screened for cerebral dominance by recording their preferred direction of rotation when injected with d-amphetamine. Bipolar stimulating electrodes were then implanted in the amygdaloid complex of either the dominant or nondominant hemisphere (i.e., respectively, contra- and ipsilateral to the preferred direction of rotation; the dominant hemisphere identified in this way has been shown to contain higher concentrations of dopamine than the nondominant hemisphere). Kindling stimulation (or sham-kindling, in control rats) was applied through the electrodes two or three times daily for 21 days, and the rats were reassessed for amphetamine- and apomorphine-induced rotation, during and after the course of treatment. Kindling of the originally dominant hemisphere caused a diminution of rotational asymmetry as measured in tests 2 to 3 h after stimulation sessions, and in some rats led to a reversal in the preferred direction of amphetamine-induced rotation. Kindling of the nondominant hemisphere tended to accentuate the original amphetamine-induced asymmetry. The direction of rotation induced by a direct postsynaptic DA-receptor agonist (apomorphine) was not significantly affected by kindling of either hemisphere. It appears that kindling stimulation brings about a relatively inferior level of DA function on the stimulated vs. the nonstimulated side of the brain, and that this process depends mainly on changes occurring at a presynaptic level.