Region of interest-based versus whole-lung segmentation-based approach for MR lung perfusion quantification in 2-year-old children after congenital diaphragmatic hernia repair.

OBJECTIVE: With a region of interest (ROI)-based approach 2-year-old children after congenital diaphragmatic hernia (CDH) show reduced MR lung perfusion values on the ipsilateral side compared to the contralateral. This study evaluates whether results can be reproduced by segmentation of whole-lung and whether there are differences between the ROI-based and whole-lung measurements. METHODS: Using dynamic contrast-enhanced (DCE) MRI, pulmonary blood flow (PBF), pulmonary blood volume (PBV) and mean transit time (MTT) were quantified in 30 children after CDH repair. Quantification results of an ROI-based (six cylindrical ROIs generated of five adjacent slices per lung-side) and a whole-lung segmentation approach were compared. RESULTS: In both approaches PBF and PBV were significantly reduced on the ipsilateral side (p always <0.0001). In ipsilateral lungs, PBF of the ROI-based and the whole-lung segmentation-based approach was equal (p=0.50). In contralateral lungs, the ROI-based approach significantly overestimated PBF in comparison to the whole-lung segmentation approach by approximately 9.5 % (p=0.0013). CONCLUSIONS: MR lung perfusion in 2-year-old children after CDH is significantly reduced ipsilaterally. In the contralateral lung, the ROI-based approach significantly overestimates perfusion, which can be explained by exclusion of the most ventral parts of the lung. Therefore whole-lung segmentation should be preferred. KEY POINTS: • Ipsilaterally, absolute lung perfusion after CDH is reduced in whole-lung analysis. • Ipsilaterally, the ROI- and whole-lung-based approaches generate identical results. • Contralaterally, the ROI-based approach significantly overestimates perfusion results. • Whole lung should be analysed in MR lung perfusion imaging. • MR lung perfusion measurement is a radiation-free parameter of lung function.

Assessing adaptability and reactive scope: Introducing a new measure and illustrating its use through a case study of environmental stress in forest-living baboons.

In order to maintain regulatory processes, animals are expected to be adapted to the range of environmental stressors usually encountered in their environmental niche. The available capacity of their stress responses is termed their reactive scope, which is utilised to a greater or lesser extent to deal with different stressors. Typically, non-invasive hormone assessment is used to measure the physiological stress responses of wild animals, but, for methodological reasons, such measurements are not directly comparable across studies, limiting interpretation. To overcome this constraint, we propose a new measure of the relative strength of stress responses, 'demonstrated reactive scope', and illustrate its use in a study of ecological correlates (climate, food availability) of faecal glucocorticoid (fGC) levels in two forest-living troops of baboons. Results suggest the wild-feeding troop experiences both thermoregulatory and nutritional stress, while the crop-raiding troop experiences only thermoregulatory stress. This difference, together with the crop-raiding troop's lower overall physiological stress levels and lower demonstrated fGC reactive scope, may reflect nutritional stress-buffering in this troop. The relatively high demonstrated fGC reactive scope levels of both troops compared with other baboons and primate species, may reflect their extreme habitat, on the edge of the geographic range for baboons. Demonstrated reactive scope provides a means of gauging the relative strengths of stress responses of individuals, populations, or species under different conditions, enhancing the interpretive capacity of non-invasive studies of stress hormone levels in wild populations, e.g. in terms of animals' adaptive flexibility, the magnitude of their response to anthropogenic change, or the severity of impact of environmental conditions.

Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNalpha.

Signal transducer and activator of transcription (Stat)3 is constitutively activated in cutaneous T-cell lymphoma (CTCL), where it protects tumour cells against apoptosis. The constitutive activation of Stat3 leads to a constitutive expression of suppressor of cytokine signalling (SOCS)-3. In healthy cells, SOCS-3 is transiently expressed following cytokine stimulation and functions as a negative feedback inhibitor of the Stat3-activating kinases. Here, we attempt to resolve the apparent paradox of a simultaneous SOCS-3 expression and Stat3 activation in the same cells. We show that (i) SOCS-3 expression in tumour cells is equal to or higher than in cytokine-stimulated nonmalignant T cells, (ii) SOCS-3 is not mutated in CTCL, (iii) overexpression of SOCS-3 blocks IFNalpha-mediated growth inhibition without affecting Stat3 activation, growth, and apoptosis, and (iv) inhibition of SOCS-3 by a dominant negative Stat3 (Stat3D) increases the IFNalpha-mediated growth inhibition. Taken together, these data show that SOCS-3 does not inhibit Stat3 activation, growth, and survival in CTCL. In contrast, SOCS3 protects tumour cells against growth inhibition by IFNalpha. Unlike SOCS-1, SOCS-3 is therefore not a tumour suppressor but rather a protector of tumour cells.

In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3.

A characteristic feature of neoplastic transformation is a perpetual activation of oncogenic proteins. Here, we studied signal transducers and activators of transcription (STAT) in patients with mycosis fungoides (MF)/cutaneous T-cell lymphoma (CTCL). Malignant lymphocytes in dermal infiltrates of CTCL tumors showed frequent and intense nuclear staining with anti-PY-STAT3 antibody, indicating a constitutive activation of STAT3 in vivo in tumor stages. In contrast, only sporadic and faint staining was observed in indolent lesions of patch and plaque stages of MF. Moreover, neoplastic lymphocytes in the epidermal Pautrier abscesses associated with early stages of MF did not express activated STAT3. To address the role of STAT3 in survival/apoptosis, CTCL tumor cells from an advanced skin tumor were transfected with either wild-type STAT3 (STAT3wt) or dominant-negative STAT3 (STAT3D). Forced inducible expression of STAT3D triggered a significant increase in tumor cells undergoing apoptosis, whereas forced expression of STAT3wt or empty vector had no effect. In conclusion, a profound in vivo activation of STAT3 is observed in MF tumors but not in the early stages of MF. Moreover, STAT3 protects tumor cells from apoptosis in vitro. Taken together, these findings suggest that STAT3 is a malignancy factor in CTCL.

Homosexual mounting in free-ranging female Hanuman langurs (Presbytis entellus).

Female-female mounting was studied for 3233 hr in a bisexual one-male troop of free-ranging Hanuman langurs in northwestern India over a period of 6 years. The population breeds throughout the year and female-female mounts (n = 524) occurred during all months. All 15 adult females mounted and were mounted, although only 20% of the individuals exhibited more than half of all mounter activity and 33% more than half of all mountee activity. Various similarities with heterosexual mounting suggest that sexual arousal is a stimulus of the activity. Cycling, pregnant, and lactating females acted as mounters as well as mountees. However, ovulating individuals were greatly overrepresented concerning their likelihood of mounting and being mounted. Females of any given rank in the dominance hierarchy showed mounter as well as mountee activity, although mounters were higher ranking than mountees in 84% of cases. Young mounters were overrepresented and middle- to old-aged mounters underrepresented, whereas no such differences existed for mountees. Mounting relations among four young adult paternal half-sisters who occupied top positions in the dominance hierarchy were significantly overrepresented. Although the ultimate function of homosexual female mounting is not fully understood, it is suspected to be connected with intrasexual competition: If "pseudocopulations" induce mountees to reduce the number of solicitations addressed to the male, the probability of insemination decreases and mounters thus reduce the number of future competitors.

Immune complexes in skin of NZB/NZW mice.

Skin biopsies were performed on female (NZB X NZW)F1 mice (B/W) at ages ranging from 1 to 12 months. The control strain was the C57B1/6. Immunoglobulin G and beta 1C globulin deposition was sought using the indirect immunofluorescence method. Both globulins were detected consistently at the dermal-epidermal junction from the age of 6 months. The pattern of staining was granular, and progressed from focal deposition to confluent and diffuse involvement of the basement membrane at 9-10 months of age. No staining was observed in any of the C57B1/6 mice up to 14 months of age. These findings increase the resemblance of B/W disease to human systemic lupus erythematosus.

Reversibility of exercise-induced translocation of Na+-K+ pump subunits to the plasma membrane in rat skeletal muscle.

Exercise-induced translocation of Na+-K+ pump subunits to the sarcolemmal membrane was studied using sarcolemmal giant vesicles as a membrane purification procedure. The subunit content was quantified by Western blotting or by ouabain labeling. Low-intensity treadmill running increased (P<0.01) the alpha1, alpha2, beta1, and beta2 subunit contents by 19-32% in membranes from oxidative muscle fibers and the alpha1, alpha2, and beta2 contents increased by 13-25% in membranes from glycolytic muscle fibers. Ouabain labeling of membranes from mixed fibers was increased by 29% after exercise. A similar increase in subunit content could be induced by 5 min of fatiguing, high-intensity electrical stimulation of isolated soleus muscles. An increased subunit content was just detectable in vesicles produced 30 min after exercise, and the content was completely back to control levels 3 h after exercise. It is concluded that both low-intensity long-lasting running and short-lasting high-intensity contractions are able to induce a translocation of pump subunits to the sarcolemmal membrane. The post-exercise disappearance of the extra subunits (half-time approximately 20 min) from the membrane demonstrates the reversible nature of the translocation process.