Human leukocyte antigen DR15 is associated with reduced relapse rate and improved survival after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation.

Human leukocyte antigen (HLA) DR15 is associated with autoimmune cytopenia in patients with aplastic anemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria. Presence of this antigen also predicts response to immunosuppressive treatment. If DR15 expression on hematopoietic cells also favors induction of immune responses in an allogeneic setting, a lower relapse rate after hematopoietic stem cell transplantation (HSCT) might result through an enhanced graft-versus-leukemia effect. We retrospectively analyzed outcome of HLA-identical sibling HSCT in 192 consecutive patients with acute or chronic leukemia or non-Hodgkin lymphoma. Patients carrying the DR15 antigen had a higher estimated 5-year overall survival (76%) than did DR15-negative patients (55%; P = .04). Improved survival for DR15 patients was due to a significant decrease in death from relapse (5% for DR15(+) versus 24% for DR15(-); P = .02), whereas no difference was seen for rates of transplant-related mortality (19% and 21%, respectively; P = .76). Findings were confirmed by multivariate analyses. Our results show an association of DR15 with a decreased risk of disease relapse and improved survival after HSCT for leukemia or non-Hodgkin lymphoma. This adds to the growing list of links between DR15 and immune reactions in hematopoiesis.     

A multi-modal treatment program for childhood trauma recovery:Women Recovering from Abuse Program (WRAP).

This article describes the Women Recovering from Abuse Program (WRAP), an outpatient day-hospital program for women suffering from the sequelae of childhood abuse. WRAP was conceived in 1998 by clinicians who advocated for its development based on a growing need to provide women who had experienced childhood trauma an alternative to an inpatient program. WRAP draws from a Stage 1 treatment approach to address chronic interpersonal trauma and dissociation by incorporating psychopharmacology, individual and group psychotherapy. The program is structured into two phases: a preparatory Building Resources Group (BRG) and an intensive multimodal segment comprised of seven types of group therapy. Each group is described in terms of the treatment rationale and its structure and process. Two research studies to date support the effectiveness of WRAP.     

Nitric oxide: a local signalling molecule controlling the activity of pre‐autonomic neurones in the paraventricular nucleus of the hypothalamus

Abstract Aim: The gas molecule nitric oxide (NO) has been shown to modulate autonomic function by acting both peripherally and centrally. Accumulating evidence indicates that the paraventricular nucleus (PVN) of the hypothalamus is an important locus mediating central NO actions on autonomic function, under both physiological and pathological conditions. However, the cellular targets and mechanisms mediating NO actions within the PVN are still poorly understood. Results: By combining in vitro patch‐clamp recordings with neuronal tract tracing techniques, we show that neuronal excitability of autonomic‐related neurones in the PVN is tonically inhibited by an endogenous NO input. Furthermore, immunohistochemical studies show that ～25% of autonomic‐related PVN neurones express neuronal nitric oxide synthase, suggesting that at least a proportion of them contribute to the cellular sources of NO within the PVN. Conclusion: In summary, this work suggests that NO modulation of the firing activity of autonomic‐related PVN neurones constitutes an efficient mechanism mediated central NO regulation of autonomic function.     

The stress interview as a tool for examining physiological reactivity

Most studies of cardiovascular reactivity utilize tasks that are highly standardized and controlled. However, there is some concern whether the information obtained from these tasks is relevant to understanding the cardiovascular responses to behavioral stimuli encountered in real life. Historically, various forms of a stress interview have been used to examine physiological concomitants of emotional arousal. However, these tools fell into disuse because of ethical concerns, their intensive time requirements, and the perception that the interviews could not be standardized. We have developed a short (16-minute) interview that is not aversive or threatening. In studies on 24 normotensives and 19 hypertensives, the interview elicited greater blood pressure elevations than those elicited by mathematical calculations or cold pressor (p less than 0.0001). The interview increased systolic and diastolic pressures by 38/32 mm Hg in hypertensives and 31/24 mm Hg in normotensives. The variance in BP elicited by this interview is not appreciably greater than that found in highly structured tasks such as mathematical calculations. The test-retest stability of the interview is comparable to that of resting baseline blood pressure and is superior to that of mathematical calculations or cold pressor. Techniques such as the interview may be at least as useful as highly standardized tasks and possibly more valid as models for examining cardiovascular reactivity.     

Time-resolved particle image velocimetry and laser doppler anemometry study of the turbulent flow field of bileaflet mechanical mitral prostheses

Dynamic particle image velocimetry (PIV) was applied to the study of the flow field associated with prosthetic heart valves. The results were compared with those of laser Doppler anemometry (LDA). Anatomically and antianatomically oriented Jyros (JR) and St. Jude Medical (SJM) valves were compared in the mitral position to study the effects of valve design on the downstream flow field. The experimental program used a dynamic PIV system utilizing high-speed, high-resolution video to map the true time-resolved velocity field inside the simulated ventricle. This system was complemented by a study using the more traditional LDA system for comparison. Based on the experimental data, the following general conclusions can be made. High-resolution dynamic PIV can capture true chronological changes in the velocity and turbulence fields. It also produces very detailed velocity and turbulence information comparable to the LDA results. In the vertical measuring plane that passes both the center of the aortic and mitral valves (A-A section), the two valves (the SJM and the JR) show distinct circulatory flow patterns when the valve is installed in the antianatomical orientation. Small differences in valve design can generate noticeable differences, particularly during the accelerating flow phase. The SJM valve maintains a relatively high velocity through the central orifice; the curved leaflets of the JR valve generate higher velocities with a divergent flow during the accelerating and peak flow phases. In the velocity field directly below the mitral valve and normal to the previous measuring plane (B-B section), where characteristic differences in valve design will be visible, symmetrical twin circulations were observed because of the divergent nature of the flow generated by the two inclined half-disks installed in the antianatomical orientation. The SJM valve, with a central downward flow near the valve, is contrasted with the JR valve, which has a peripheral downward circulation with higher, turbulent stresses.     

Murine embryonal carcinoma cells express class I MHC-like antigens

Previous work has concluded that murine embryonal carcinoma (EC) cells, the oncogenic stem cells of teratocarcinomas, do not express class-I, H-2K or D/L gene encoded products. Experiments using cell-mediated lysis, serological and molecular biological approaches show that EC cells do express some major histocompatibility complex (MHC) class I or class I-like molecules.     

Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages

Aspergillus fumigatus is the most prevalent airborne fungal pathogen responsible for fatal invasive aspergillosis in immunocompromised patients. Upon arrival in the lung alveolus, conidia of A. fumigatus are phagocytosed by alveolar macrophages, the major phagocytic cells of the lung. Engulfment and intracellular trafficking of A. fumigatus conidia in alveolar macrophages of two different origins, the murine cell line MH-S and human pulmonary alveolar macrophages, were analyzed by electron microscopy and immunofluorescence. Phagocytosis of A. fumigatus conidia required actin polymerization and phosphatidylinositol 3-kinase activity. Fusion of A. fumigatus phagosomes with early and late endosomes was shown by immunolabeling with specific markers for the transferrin receptor, early endosome antigen, and Rab7. Maturation of A. fumigatus phagolysosomes was monitored by using a fixable acidotropic probe, LysoTracker Red DND-99, and an anti-cathepsin D antibody. Bafilomycin A-induced inhibition of lysosomal acidification abolished the conidial killing by the macrophages. These data suggest that the maturation of A. fumigatus phagosomes results from fusion with the compartments of the endocytic pathway and that the killing of conidia depends on phagolysosome acidification. A model for the phagocytosis of A. fumigatus conidia by alveolar macrophages is proposed on the basis of these results.     

Plasticity of epidermal stem cells

The keratinocyte cell compartment in the continuously renewing epidermis of the skin is maintained by undifferentiated, self-renewing stem cells. We show that a small subpopulation of epidermal stem cells (EpiSCs) have the capacity to integrate into multiple tissues. These EpiSCs can change their phenotype in direct response of changes in cytokines in vitro, changes in cocultured cells, after injection into damaged environments in vivo. These changes appear to be unrelated to the age of the EpiSC. Even though we can isolate these cells and show that the age of thses cells appears to be irrelevant to this multipotent function, we still do not know how such cells are defined within a tissue or what the life span of a multipotent stem cell is.