Enzymes of type II fatty acid synthesis and apicoplast differentiation and division in Eimeria tenella.

Apicomplexan parasites, Eimeria tenella, Plasmodium spp. and Toxoplasma gondii, possess a homologous plastid-like organelle termed the apicoplast, derived from the endosymbiotic enslavement of a photosynthetic alga. However, currently no eimerian nuclear encoded apicoplast targeted proteins have been identified, unlike in Plasmodium spp. and T. gondii. In this study, we demonstrate that nuclear encoded enoyl reductase of E. tenella (EtENR) has a predicted N-terminal bipartite transit sequence, typical of apicoplast-targeted proteins. Using a combination of immunocytochemistry and EM we demonstrate that this fatty acid biosynthesis protein is located in the apicoplast of E. tenella. Using the EtENR as a tool to mark apicoplast development during the Eimeria lifecycle, we demonstrate that nuclear and apicoplast division appear to be independent events, both organelles dividing prior to daughter cell formation, with each daughter cell possessing one to four apicoplasts. We believe this is the first report of multiple apicoplasts present in the infectious stage of an apicomplexan parasite. Furthermore, the microgametes lacked an identifiable apicoplast consistent with maternal inheritance via the macrogamete. It was found that the size of the organelle and the abundance of EtENR varied with developmental stage of the E. tenella lifecycle. The high levels of EtENR protein observed during asexual development and macrogametogony is potentially associated with the increased synthesis of fatty acids required for the rapid formation of numerous merozoites and for the extracellular development and survival of the oocyst. Taken together the data demonstrate that the E. tenella apicoplast participates in type II fatty acid biosynthesis with increased expression of ENR during parasite growth. Apicoplast division results in the simultaneous formation of multiple fragments. The division mechanism is unknown, but is independent of nuclear division and occurs prior to daughter formation.

A complete shikimate pathway in Toxoplasma gondii: an ancient eukaryotic innovation.

The shikimate pathway is essential for survival of the apicomplexan parasites Plasmodium falciparum, Toxoplasma gondii and Cryptosporidium parvum. As it is absent in mammals it is a promising therapeutic target. Herein, we describe the genes encoding the shikimate pathway enzymes in T. gondii. The molecular arrangement and phylogeny of the proteins suggests homology with the eukaryotic fungal enzymes, including a pentafunctional AROM. Current rooting of the eukaryotic evolutionary tree infers that the fungi and apicomplexan lineages diverged deeply, suggesting that the arom is an ancient supergene present in early eukaryotes and subsequently lost or replaced in a number of lineages.

Ephedrine in the cat lung vasculature.

BACKGROUND: Ephedrine is one of the most commonly used non-catecholamine sympathomimetic agents. It is used in operating rooms and critical care settings worldwide. While it has many side effects, its ability to rapidly raise blood pressure makes it an ideal agent to maintain homeostasis as well as in emergency situations. While its effects are known to be mediated by an alpha-mediated mechanism, the exact alpha subtype is unknown. In addition, no studies using ephedrine have been performed in the pulmonary vascular bed of the cat. METHODS: The effects of phentolamine, a non-selective alpha-receptor blocker, and prazosin, an alpha1-selective antagonist, were investigated on pulmonary arterial responses to ephedrine, phenylepherine, norepinephrine, and U-46619. Lobar arterial perfusion pressure was continuously monitored, electronically averaged, and recorded with constant flow in the isolated left lower lobe vascular bed of the cat. RESULTS: Phentolamine and prazosin significantly reduced vasoconstrictor pulmonary perfusion pressure increases induced by ephedrine. CONCLUSION: Ephedrine has significant vasopressor activity in the pulmonary vascular bed of the cat meditated predominantly by alpha1 adrenergic receptor activation.

Tacit definitions of informal caregiving.

AIMS OF THE STUDY: This study describes three tacit definitions of informal caregiving and explores the extent to which differences in these tacit definitions explain variation in caregivers' negative mood over time. BACKGROUND/RATIONALE: There is a growing need to understand the sources of stress and gratification for informal caregivers. Tacit definitions of informal caregiving refer to caregivers' understanding of what caregiving entails. These definitions are tacit because they arise from caregivers' taken-for-granted understanding rather than formally articulated positions concerning caregiving. DESIGN/METHODS: A random sample of 60 men, all of whom were caregiving partners of men with acquired immunodeficiency syndrome (AIDS), was drawn from a larger cohort of 253 participants in the University of California San Francisco (UCSF) Coping Project (1990-1997). The caregivers were assessed bimonthly for 2 years with procedures that included a semi-structured interview focusing on a recent stressful event involving caregiving, and quantitative measures of well-being. RESULTS/FINDINGS: Interpretive phenomenological case studies of the narrative accounts of the 60 caregivers produced three tacit definitions of caregiving - engagement, conflict and distance. These three tacit definitions were distinguished by differences in learning about caregiving, involvement in health care decisions, caregiving activities and reported sources of stress. The three groups differed on measures of dyadic adjustment, depression, anger and anxiety. CONCLUSIONS: Better understanding of caregivers' tacit definitions can facilitate and enhance effective support and interventions for caregivers.

Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors.

Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are synthesized and released from adrenal cells. Therefore, the effects of TNF-alpha and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were investigated. IL-6 (10-1000 pg/mL) significantly increased basal and adrenocorticotropic hormone (ACTH)-stimulated cortisol release in a concentration-dependent manner. This stimulatory effect of IL-6 became apparent at intervals as short as 4 h and continued through 24 h. IL-6 also potentiated the cortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-alpha (0.1-10 ng) inhibited basal and ACTH-stimulated cortisol release in a concentration-dependent manner. The inhibitory effects of TNF-alpha on cortisol release were significant at time intervals as short as 4 h and continued through 24 h. TNF-alpha inhibited forskolin-stimulated cortisol release. Binding studies demonstrated that ZF cells have IL-6 receptors (100 receptors/cell, Kd of 7.5 x 10(-11)) and TNF receptors (200 receptors/cell, Kd of 2.4 x 10(-9) M). Immunohistochemical analysis provided evidence that the majority of ZF cells have IL-6 receptors, TNF type 1 receptors, and TNF type 2 receptors. Because IL-6 and TNF-alpha are released from the adrenal cortex and these cytokines modify the release of cortisol from the ZF, IL-6 and TNF-alpha may play a paracrine or autocrine role in the regulation of adrenal function.

Spiritual aspects of loss among partners of men with AIDS: postbereavement follow-up.

This article is a follow-up study of bereaved caregiving male partners of men with AIDS (T.A. Richards & S. Folkman, 1997). The earlier study examined spiritual beliefs, experiences, and practices reported in interviews with 125 caregivers conducted 2 and 4 weeks following bereavement. This follow-up study reports qualitative and quantitative data from 70 members of the earlier cohort, collected 3 to 4 years later, regarding the presence of spiritual phenomena. Spirituality increased or deepened in 77% of the entire cohort. An ongoing relationship with the deceased partner was reported by 70% of the cohort. The use of spirituality as coping appeared to decline as the bereaved moved further in time from the loss. Instead, spirituality was identified as a personal governing influence that provided value and direction to the individual. In general, relationships between the expression of spirituality and mood, coping, and physical health symptoms were not statistically significant owing to small samples, but there were medium effect sizes.

Spiritual aspects of loss at the time of a partner's death from AIDS.

Spiritual phenomena were spontaneously reported in interviews of 68 of 125 recently bereaved HIV-positive and HIV-negative partners of men who died from AIDS. Spiritual schemas involving beliefs, experiences, rituals, social support, and roles were used to help assimilate the fact of death and were appraised as sources of solace and meaning. The relationship between spirituality and coping, mood, and physical health was examined. Those reporting spiritual phenomena showed higher levels of depression and anxiety and lower levels of positive states of mind, used more adaptive coping strategies, and reported more physical health symptoms than those who did not report spiritual phenomena.

Appraisal and goal processes as predictors of psychological well-being in bereaved caregivers.

Narratives of 30 caregivers were scored for appraisals and coping responses following the death of their partners from AIDS. Appraisals were identified as valenced beliefs, emotions, and goal outcomes, whereas coping responses included goals and plans of action. The proportion of positive appraisals predicted long-term goals and plans and psychological well-being at both bereavement and 12 months later. Positive appraisals were correlated with positive moral and positive states of mind. The latter were negatively correlated with partner-centered, short-term plans. Positive appraisals were negatively correlated with depressive mood. Caregivers, who reported proportionately more positive appraisals during caregiving and after the loss of their partner, were more likely to have future- and self-oriented goals and plans and to demonstrate positive well-being at bereavement and better recovery 12 months later than were those who reported more negative appraisals.

A scale for predicting quality of recovery following the death of a partner.

Narrative accounts of bereaved partners of men with AIDS provided data regarding caregiving, bereavement, and the period immediately following bereavement. The findings of the Harvard Bereavement Study were used to develop the Bereavement Response Scale I (BR-I), containing 21 items within 6 categories. Total scores were correlated with scores from 4 mood measures taken at the time of bereavement and again 12 months following bereavement. A significant association was found with the Positive States of Mind Scale. Item analysis suggested that a shorter version containing 6 items, the Bereavement Response Scale II (BR-II), might be a more effective predictive instrument. Further development of the BR-I and BR-II is proposed as a means for using narrative data to predict bereavement outcomes.

A comparison of cesarean section morbidity in urban and rural hospitals. A three-year retrospective review of 1,177 charts.

To determine whether there was a significant difference in morbidity rates from cesarean section between urban and rural hospitals, we reviewed 742 maternal records from three urban hospitals and 435 records from 11 rural hospitals, along with the corresponding infant charts. When a comparison was made of advance in diet, day of discharge, elevations of temperature, number of positive cultures, use of two or more antibiotics, use of blood transfusions, and incidence of major complications, significant differences were found only in the number of positive cultures and use of antibiotics, which occurred more frequently in rural hospitals. Pediatric morbidity was evaluated by comparing Apgar scores, temperatures less than 36 degrees C, use of oxygen for longer than 15 minutes, number of infants intubated, use of intravenous fluids and antibiotics, incidence of respiratory distress syndrome and transient tachypnea, number of neonatal transfers, and major complications. Urban hospitals had significantly more Apgar scores of 4 to 6 at 5 minutes (p less than 0.01). Temperatures less than 36 degrees C were found more frequently in rural hospitals (p less than 0.001). No statistical difference was found in any other category. The results show little difference in maternal or pediatric morbidity rates between urban and rural hospitals and between obstetricians and family practitioners.

Arteriovenous malformation of the duodenum.

In their report of a 55-year-old woman with an arteriovenous malformation of the duodenum, the authors illustrate some of the interesting clinical features of this uncommon cause of chronic gastrointestinal bleeding. The lesion was treated by surgical resection. Arteriovenous malformations have been classified according to location, age of the patient and family history. In this patient the malformation was considered to be a type 2 or congenital lesion. The authors review the literature on arteriovenous malformations and emphasize the use of selective visceral angiography for diagnosing arteriovenous malformations of the gastrointestinal tract.

Continuing education for general practice--analysis of a programme.

General practitioners in the Northampton area were asked to assess the various meetings of a programme of continuing education they had attended between May 1969 and May 1970. Analysis of their replies suggests that meetings which depend on previous study and encourage participation are most likely to be successful.