Activity in fetal bovine serum that stimulates erythroid colony formation in fetal mouse livers is insulinlike growth factor I.

In the present study, the erythropoietic activity of fetal serum was characterized. Using fetal bovine serum (FBS) as a source of the erythropoietic activity and serum-free cultures of fetal mouse livers (FMLC assay) as a detection system, we found that FBS stimulated colony formation from late erythroid progenitor cells (CFU-E) in a dose-dependent fashion. The slope of the dose-response curve, however, was significantly different from that for erythropoietin (Ep), the best-characterized erythropoietic activity so far. The erythropoietic activity of FBS was found in the 120-160- and 40-70-kD range at neutral pH. In the presence of 1 M acetic acid, however, the erythropoietic activity had an apparent molecular mass between 3 and 13 kD. From ion exchange experiments with DEAE-cellulose, the isoionic point of the activity was estimated to about pH 5. Furthermore, the erythropoietic activity of FBS was found to be co-eluted on Sephadex G-150 with the binding proteins of insulinlike growth factors (IGF). The IGF I concentration determined by radioimmunoassay was 70 ng IGF I/ml. The Ep activity of FBS was less than 5 mU/ml when determined with the posthypoxic polycythemic mouse assay for Ep. These results suggest that the erythropoietic activity of FBS is related to IGF and not to Ep. The erythropoietic activity of FBS was abolished by an antiserum against IGF I. Furthermore, IGF I was a factor of approximately 40 more potent than IGF II in stimulating erythroid colony formation. All of these findings suggest that the erythropoietic activity of FBS is IGF I.     

Effects of vaporized perfluorohexane and partial liquid ventilation on regional distribution of alveolar damage in experimental lung injury

Objective To determine whether the patterns of distribution of histological effects of vaporized perfluorohexane (PFH) and partial liquid ventilation (PLV) differ significantly in acute lung injury. Design and setting Experimental study in an animal research laboratory. Subjects Eighteen pigs. Interventions After induction of acute lung injury by means of infusion of oleic acid animals were randomly assigned to PFH, PLV, or gas ventilation (GV) groups. Six hours thereafter animals were killed, and lung tissue samples were taken for analysis. Measurements and results Histopathological analysis revealed less damage with PFH than with GV or PLV in the nondependent and central regions. PFH and PLV showed less injury in the dependent regions than GV. GV and PFH were associated with less histological damage in the nondependent than the dependent regions, whereas PLV presented the opposite pattern. Morphometric analysis showed increased aeration in nondependent than dependent regions with PFH and GV. PLV led to more aeration in the periphery than in central areas. Conclusions PFH was associated with a more homogeneous attenuation of alveolar damage across the lungs, although this therapy had more pronounced effects in nondependent zones. PLV showed the opposite pattern, with more important reduction in alveolar damage in dependent lung regions. Interestingly, reduction in alveolar damage with PFH was as effective as with PLV in dependent zones. Our findings suggest that vaporized perfluorocarbon could be advantageous as adjunctive therapy in the treatment of acute lung injury. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. This work was supported by grant nos. AB 135/1-1 and HU 818/3-1 from the Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany An erratum to this article can be found at     

Callous–Unemotional Traits as Markers for Conduct Problem Severity in Early Childhood: A Meta-analysis

Extensive research has shown that callous–unemotional (CU) traits in middle-childhood and adolescence are markers for a particularly severe and chronic pattern of antisocial behavior (Frick et al. in Psychol Bull 140:1–57, 2014). Comparatively little, however, is known about the relationship between CU traits and antisocial behavior in early childhood. A meta-analysis of k = 10 studies comprising n = 5731 participants was conducted to examine the relationship between CU traits and conduct problem severity prior to 5 years of age. Overall, a significant positive relationship was found between CU traits and conduct problem severity, in the order of large effect size (r = .39, p < .001). Moderator analyses revealed that this relationship differed based on use of same versus different informant across measures, but was consistent across sex and sample type (at-risk/clinic referred or community). This supports the view that CU traits represent a potentially informative focus for clinical assessment in early childhood.     

Insulin-like growth factor I and II in 14 animal species and man as determined by three radioligand assays and two bioassays

Insulin-like growth factor I and II (IGF I and II) were determined by five different assays in human serum, in the sera of ten mammalian species and in chicken, turtle, and frog serum. Sera of all tested mammals contain two different IGFs corresponding to human immunoreactive IGF I and receptor reactive IGF II. Receptor reactive IGF II of most animal species does not show significant cross-reactivity in the RIA for human IGF II. IGF activity was also detected in sera of non-mammals, such as chicken and turtles, but not in frog serum. The IGF values obtained with the different assay system corresponded rather well: there is a good correlation between the values obtained in the protein binding and the fat cell assay, and between the results of the latter assays and the sum of immunoreactive IGF I and receptor reactive IGF II. The results suggest that those regions in the IGF I and II molecules which are responsible for reactivity with the type I IGF and the insulin receptor have not essentially changed during evolution. Similarly, the C-region, which mainly determines the immunological properties of IGFs, appears to have remained relatively constant in the IGF I, but not in the IGF II molecule.     

Role of FAS in HIV infection

Direct cytopathic effects cannot explain the massive CD4+ T cell depletion in acquired immunodeficiency syndrome (AIDS) patients and several indirect mechanisms may be involved. A role has been proposed for apoptosis of uninfected lymphocytes, since lymphocytes from human immunodeficiency virus-1+ (HIV-1) individuals display increased levels of spontaneous apoptosis. This process may be ascribed in part to cell exhaustion by the chronic uncontrolled infection, but can also be directly induced by viral components, such as gp120, tat or nef. A key role is played by the death receptor Fas, but a role can also be played by other death receptors, such as the TNF and TRAIL receptors. By contrast, death of HIV-infected cells seems to be Fas-independent and driven by other viral components such as vpr and HIV proteases. A further role may be played by depletion of CD4+ T cell itself and hence the withdrawal of survival factors such as cytokines. Different ability of HIV strains to induce death of infected and uninfected cells might play a role in the clinical and biological differences displayed by HIV strains. A further variability may be ascribed to the intrinsic resistance of cells to apoptosis, which may depend on the individual genetic background or the use of drugs inhibiting apoptosis. The observation that when progression of HIV infection is slow due to "apoptosis-resistant" genetic backgrounds of the patients, or defective HIV-1 strains, or successful highly active antiretroviral therapy (HAART), generally also T cell apoptosis is low, suggests that HIV-infected subjects may benefit from therapies aimed to inhibit Fas function and/or spontaneous apoptosis.     

Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates

IGF-I and -II share specific serum carrier proteins which elute on neutral Sephadex G-200 gel permeation chromatography at apparent molecular masses of 50 and 200 kD. The half-lives of free and carrier protein-bound 125I-IGF-I and -II were determined after bolus injections of the tracers into two normal adults. Labelled IGF-I and -II migrated first with the 50-kD and later with the 200-kD complex. In these complexes their apparent half-lives were 20-30 min and 12-15 h, respectively. The apparent half-life a free 125I-IGF-I and -II was 10-12 min. In a second set of experiments, recombinant human insulin-like growth factor I was infused during 6 days in two healthy adults at a dose of 20 micrograms.kg-1.h-1 (corresponding to around 30 mg/day). Serum obtained before and during the infusion was subjected to neutral Sephadex G-200 gel permeation chromatography and fractions were pooled according to the apparent molecular masses at which the carrier protein complexes elute. IGF-I and -II in these pools were determined by RIA. Before the IGF-I infusion, 92 and 272 micrograms/l of IGF-I and -II were found in the 200-kD complex, 45 and 91 micrograms/l in the 50-kD complex, and 15 and 5 micrograms/l were present in the free form. Corresponding figures during the IGF-I infusion were 389 and 18 micrograms/l for the 200-Kd complex, 201 and 54 micrograms/l for the 50-kD complex, and 80 and less than 1 microgram/l for free IGF-I and -II. Using the half-lives of the tracer studies and the levels of the different molecular weight forms of IGF in serum, the production rates for IGF-I and -II were calculated to be 10 mg and 13 mg per day.     

Effects of perfluorohexane vapor in the treatment of experimental lung injury

RationaleWe investigated the effects of vaporized perfluorohexane (PFH) on pulmonary vascular tone, pulmonary vascular resistance and peak inspiratory pressure as well as lipid mediator formation in the treatment of calcium ionophore induced lung injury in a model of the isolated perfused and ventilated rabbit lungs.MethodsLung injury was induced in isolated perfused and ventilated rabbit lungs by calcium ionophore A23187. Lungs were treated with either 4.5 vol.% (4.5 vol.% PFH; n = 6) or 18 vol.% (18 vol.% PFH; n = 6) PFH. Six lungs remained untreated (Control). In addition 5 lungs (PFH-sham) remained uninjured receiving 18 vol.% PFH only. Mean pulmonary artery pressure (mPAP), peak inspiratory pressure (P_max), and lung weight (weight) were monitored for 120 min. Experiments were terminated before when the increase in lung weight exceeded 40 g. Perfusate samples were taken at regular intervals for analysis of TXB₂, 6-keto-PGF₁ and LTB₄.ResultsControls reached the study end point significantly earlier than both PFH groups. Significant differences were found for a weight gain of 10 g and 20 g between the control and the 4.5 vol.% PFH and the 18 vol.% PFH. Differences in mPAP were more pronounced in the 4.5 vol.% PFH. However increases in P_max were more marked in 4.5 vol.% PFH. TXA₂-, PGI₂-, and LTB₄-levels were significantly lower in PFH groups. Uninjured lungs remained unaffected by the presence of 18 vol.% PFH.ConclusionInflammatory lung injury was attenuated by the treatment with 4.5 vol.% PFH and 18 vol.% PFH vapor in the isolated perfused rabbit lung. Therapeutic effects were more pronounced with a concentration of 4.5 vol.% PFH.     

Unmet information needs about the delivery of rheumatology health care services: a survey among patients with rheumatoid arthritis

Objective

To measure patient-perceived knowledge and information need regarding regional health care services and their determinants among 400 patients with rheumatoid arthritis (RA) and to identify the preferred method of information provision.

Methods

Postal survey on knowledge and information need (content and accessibility) of 18 regional health care services and preferences for the mode of delivery of information. Logistic regression analyses determined which factors were associated with insufficient knowledge and information need.

Results

Two-hundred and thirty-seven (94%) patients reported insufficient knowledge about the contents and 235 (94%) about the accessibility of at least one health care services, whereas 172 patients (69%) reported an information need about the content and 154 (61%) on the accessibility. Age was significantly associated with knowledge whereas both age and physical functioning were significantly associated with information need. Seventy-nine percent of the patients mentioned written information, 21% the Internet and 12% personal contact with a professional as a preferred method of information delivery.

Conclusion

Many RA patients reported a lack of knowledge or information need concerning the contents and accessibility of regional health care services.

Practice implications

Active strategies to provide practical information about health care services are needed for RA patients.     

Force-induced polarized mitosis of endothelial and smooth muscle cells in arterial remodeling

Arteries display highly directional growth and remodeling that are specific to increases in the mechanical loads imposed on them by blood pressure, blood flow, and lengthwise tensile forces that are transmitted from the tissues to which they are attached. This study examined the effect of mechanical forces on the direction in which mitosis delivers daughter cells, as a mechanism for directional growth. Lateral forces were imposed on surface integrins of cultured endothelial cells by seeding the cells with arginine-glycine-aspartate peptide-coated magnetic microspheres and applying a magnetic field. Video images revealed that the mitotic axis of dividing cells became highly biased in the direction of applied force. Distribution of cortactin, which participates in polarized mitoses driven by other stimuli, was highly sensitive to mechanical loading and interfering with cortactin function arrested cell growth. Smooth muscle cell mitoses also proved to be sensitive to mechanical force: when lengthwise force imposed on rabbit carotid arteries was altered by excision of a vessel segment and reanastomosis of the cut ends, direction of mitosis was dramatically altered. These findings indicate that influences of mechanical force can modulate the manner in which mitosis of vascular cells contributes to reorganization of arterial wall tissue.