The diagnostic accuracy of truncated cardiovascular MR protocols for detecting non-ischemic cardiomyopathies.

Cardiovascular magnetic resonance imaging is one of the most important diagnostic modalities in the evaluation of cardiomyopathies. However, significant limitations are the complex and time-consuming workflows and the need of contrast agents. The aim of this multi-center retrospective study was to assess workflows and diagnostic value of a short, contrast agent-free cardiac magnetic resonance protocol. 160 patients from Heidelberg, Germany and 119 patients from Montreal, Canada with suspected cardiomyopathy and 20 healthy volunteers have been enrolled. Scans were performed at a 1.5Tesla or 3Tesla scanner in Heidelberg and at a 3Tesla scanner in Montreal. We used single-slice T1 map only. A stepwise analysis of images has been performed. The possible differential diagnosis after each step has been defined. T1-values and color-encoded T1 maps significantly contributed to the differential diagnosis in 54% of the cases (161/299); the final diagnosis has been done without late gadolinium enhancement images in 83% of healthy individuals, in 99% of patients with dilated cardiomyopathy, in 93% of amyloidosis patients, in 94% of patients with hypertrophic cardiomyopathy and in 85% of patients with hypertensive heart disease, respectively. Comparing the scan time with (48 ± 7 min) vs. without contrast agent (23 ± 5 min), significant time saving could be reached by the short protocol. Subgroup analysis showed the most additional diagnostic value of T1 maps in amyloidosis and hypertrophic cardiomyopathy or in confirmation of normal findings. In patients with unclear left ventricular hypertrophy, a short, non-contrast protocol can be used for diagnostic decision-making, if the quality of the T1 map is diagnostic, even if only one slice is available.

Strengths and limitations of coronary angiography with turbo high-pitch third-generation dual-source CT.

AIM: To define practical limitations of diagnostic image quality for recently introduced turbo high-pitch scan mode (THP) in third-generation dual-source computed tomography (CT). MATERIALS AND METHODS: Two hundred and twenty-nine consecutive patients undergoing CT coronary angiography were included in this retrospective single-centre analysis. A contrast-enhanced volume dataset was acquired in THP. Image quality of coronary segments was classified as diagnostic or non-diagnostic by three blinded readers. Segments were stated as non-diagnostic if at least one of three readers could neither exclude nor confirm significant stenoses. Multivariable logistic regression was used to assess relationships between number of non-diagnostic segments and common influencing factors. RESULTS: Median effective radiation dose was 0.6 (interquartile range [IQR], 0.4-0.8) mSv overall and 0.3 (IQR, 0.3-0.4) mSv in the 70 kV subgroup of this middle aged, predominantly pre-obese cohort (age: 61 [IQR, 52-67] years; body mass index [BMI]: 26 [IQR, 23-29] kg/m2) with a low-moderate median Agatston score (AS) 0 (IQR, 0-70). Diagnostic image quality was found in 98.1% of 3,678 coronary segments. AS was independently associated with diagnostic image quality (B=0.34; p=0.02), whereas heart rate, BMI, and presence of arrhythmia were not. The portion of diagnostic coronary segments decreased slightly in obese patients with heart rates >65 beats/min and dropped significantly in patients with an AS >600 (p=0.003). CONCLUSION: THP enables CT coronary angiography with minimal radiation exposure and is most appropriate in non-obese patients with stable sinus rhythm ≤65 beats/min and a calcium score ≤600.

[Physiology of the upper esophageal sphincter]. / Physiologie des oberen Ösophagussphinkters.

The upper esophageal sphincter (UES) forms a barrier between the pharynx and the esophagus. When opened, the UES allows the food bolus to pass into the esophagus, as well as permitting emesis and eructation. The basal sphincter tone constitutes a barrier function which serves to prevent reflux and passive aerophagia in the case of deep breathing. Basal sphincter tone is dependent on several influencing factors; during swallowing, sphincter opening and closure follow a complex multiphase pattern. This article presents an overview of the current understanding of UES physiology.

[Anatomy of the upper esophageal sphincter]. / Anatomie des oberen Ösophagussphinkters.

The upper esophageal sphincter (UES) forms a barrier between the pharynx and the esophagus. When closed, the barrier function serves to prevent reflux and aerophagia; when open, swallowing, belching and vomiting are possible. The closing muscles include caudal parts of the inferior pharyngeal sphincter and cranial parts of the upper esophagus musculature. Sphincter opening is achieved by muscles that insert from the outside to connect to the larynx and pharynx in the sphincter region. The closing muscles are innervated by branches of the glossopharyngeal and vagal nerves, and central control is probably mediated by several reflexes. This article presents an overview of the current understanding of the complex UES anatomy.

A requirement for Nedd9 in luminal progenitor cells prior to mammary tumorigenesis in MMTV-HER2/ErbB2 mice.

Overexpression of the NEDD9/HEF1/Cas-L scaffolding protein is frequent, and drives invasion and metastasis in breast, head and neck, colorectal, melanoma, lung and other types of cancer. We have examined the consequences of genetic ablation of Nedd9 in the MMTV-HER2/ERBB2/neu mouse mammary tumor model. Unexpectedly, we found that only a limited effect on metastasis in MMTV-neu;Nedd9(-/-) mice compared with MMTV-neu;Nedd9(+/+) mice, but instead a dramatic reduction in tumor incidence (18 versus 80%), and a significantly increased latency until tumor appearance. Orthotopic reinjection and tail-vein injection of cells arising from tumors, coupled with in vivo analysis, indicated tumors arising in MMTV-neu;Nedd9(-/-) mice had undergone mutational selection that overcame the initial requirement for Nedd9. To better understand the defects in early tumor growth, we compared mammary progenitor cell pools from MMTV-neu;Nedd9(-/-) versus MMTV-neu;Nedd9(+/+) mice. The MMTV-neu;Nedd9(-/-) genotype selectively reduced both the number and colony-forming potential of mammary luminal epithelial progenitor cells, while not affecting basal epithelial progenitors. MMTV-neu;Nedd9(-/-) mammospheres had striking defects in morphology and cell polarity. All of these defects were seen predominantly in the context of the HER2/neu oncogene, and were not associated with randomization of the plane of mitotic division, but rather with depressed expression the cell attachment protein FAK, accompanied by increased sensitivity to small molecule inhibitors of FAK and SRC. Surprisingly, in spite of these significant differences, only minimal changes were observed in the gene expression profile of Nedd9(-/-) mice, indicating critical Nedd9-dependent differences in cell growth properties were mediated via post-transcriptional regulation of cell signaling. Coupled with emerging data indicating a role for NEDD9 in progenitor cell populations during the morphogenesis of other tissues, these results indicate a functional requirement for NEDD9 in the growth of mammary cancer progenitor cells.

Influence of age, social patterns and nasopharyngeal carriage on antibodies to three conserved pneumococcal surface proteins (PhtD, PcpA and PrtA) in healthy young children.

The acquisition of specific antibodies is paramount to protect children against pneumococcal diseases, and a better understanding of how age, ethnicity and/or Streptococcus pneumoniae (Spn) nasopharyngeal carriage influence the acquisition of antibodies to pneumococcal surface proteins (PSP) is important for the development of novel serodiagnostic and immunisation strategies. IgG antibody titres against three conserved PSP (PhtD, PcpA and PrtA) in the sera of 451 healthy children aged 1 to 24 months from Israel [Jewish (50.1 %) and Bedouin (49.9 %)] were measured by enzyme-linked immunosorbent assay (ELISA), while nasopharyngeal swabs from these children were assessed for the presence of Spn. Globally, anti-PhtD and anti-PrtA geometric mean concentrations (GMC; EU/ml) were high at <2.5 months of age [PhtD: 35.3, 95 % confidence interval (CI) 30.6-40.6; PrtA: 71.2, 95 % CI 60-84.5], was lower at 5-7 months of age (PhtD: 10, 95 % CI 8-12.4; PrtA: 17.9, 95 % CI 14.4-22.1) and only increased after 11 months of age. In contrast, an increase in anti-PcpA was observed at 5-7 months of age. Anti-PcpA and anti-PrtA, but not anti-PhtD, were significantly higher in Bedouin children (PcpA: 361.6 vs. 226.3, p = 0.02; PrtA: 67.2 vs. 29.5, p < 0.001) in whom Spn nasopharyngeal carriage was identified earlier (60 % vs. 38 % of carriers <6 months of age, p = 0.002). Spn carriage was associated with significantly higher anti-PSP concentrations in carriers than in non-carriers (p < 0.001 for each PSP). Thus, age, ethnicity and, essentially, nasopharyngeal carriage exert distinct cumulative influences on infant responses to PSP. These specific characteristics are worthwhile to include in the evaluation of pneumococcal seroresponses and the development of new PSP-based vaccines.

Failure to elicit seroresponses to pneumococcal surface proteins (pneumococcal histidine triad D, pneumococcal choline-binding protein A, and serine proteinase precursor A) in children with pneumococcal bacteraemia.

Pneumococcal surface proteins (PSPs) elicit antibody responses in infants and young children exposed to Streptococcus pneumoniae. These seroresponses could contribute to the aetiological diagnosis of pneumococcal disease, e.g. during the clinical development of novel PSP-based vaccines. In this study, we assessed the kinetics of antibody responses to three highly conserved and immunogenic PSPs (pneumococcal histidine triad D (PhtD), pneumococcal choline-binding protein A (PcpA), and serine proteinase precursor A (PrtA)) in 106 children (median age, 21.3 months; males, 58.5%) admitted for pneumococcal bacteraemia. Anti-PhtD, anti-PcpA and anti-PrtA antibodies were measured by ELISA, and compared in 61 pairs of acute (≤7 days) and convalescent (>14 days of admission) serum samples. Acute serum titres were similar to those observed in healthy children, and were unaffected by the acid dissociation of circulating immune complexes. Despite proven bacteraemia, seroresponses (≥2-fold increase in anti-PSP antibody concentrations) were only identified in 31 of 61 children (50.8%), directed against PrtA (n = 23, 37.7%), PcpA (n = 19, 31.1%), and PhtD (n = 16, 26.2%), or several PSPs (two PSPs, n = 13, 21.3%; three PSPs, n = 7, 11.5%). Certain seroresponses were very strong (maximal fold-increases: PhtD, 26; PcpA, 72; PrtA, 12). However, anti-PSP antibody concentrations failed to increase in the convalescent sera of 30 of 61 (49.2%) bacteraemic children, and even declined (≥2 fold) in 13 of 61 (21.3%), mostly infants aged <6 months (8/13, 61.5%), possibly through consumption of maternal antibodies. Thus, pneumococcal bacteraemia may fail to elicit antibody responses, and may even have an antibody-depleting effect in infants. This novel observation identifies an important limitation of serology-based studies for the identification of bacteraemic children.

[Pharmacogenomics of multiple sclerosis: association of immune response genes polymorphism with copaxone treatment efficacy].

Complex association analysis of copaxone (glatiramer acetate) immunotherapy efficacy with allelic polymorphism in the number of immune response genes, which encode interferone beta (IFNB1), transforming growth factor beta1 (TGFB1), interferone gamma (IFNG), tumor necrosis factor (TNF), interferon alpha/beta receptor 1 (IFNAR1), CC chemokine receptor 5 (CCR5), interleukin 7 receptor alpha subunit (IL7RA), cytotoxic T-lymphocyte antigen 4 (CTLA4) and HLA class II histocompatibility antigen beta chain (DRB1) was performed with APSampler algorithm for 285 multiple sclerosis patients of Russian ethnicity. The results show evidence for the contribution of polymorphic variants in CCRS, DRB1, IFNG, TGFB1, IFNAR1, IL7RA and, probably, TNF and CTLA4 genes to copaxone treatment response. Single alleles of CCR5 and DRB1 genes are reliably associated with treatment efficacy. Carriage of allelic variants of other above mentioned genes contribute with reliable effect to copaxone treatment response as part of bi- and three-allelic combinations only. Present investigation may support basis toward the future possibility of prognostic test realization, which can provide a personal choice of immunomodulatory treatment for a patient with multiple sclerosis.

Immunity to pneumococcal surface proteins in children with community-acquired pneumonia: a distinct pattern of responses to pneumococcal choline-binding protein A.

The aetiological diagnosis of community-acquired pneumonia (CAP) is challenging in children, and serological markers would be useful surrogates for epidemiological studies of pneumococcal CAP. We compared the use of anti-pneumolysin (Ply) antibody alone or with four additional pneumococcal surface proteins (PSPs) (pneumococcal histidine triad D (PhtD), pneumococcal histidine triad E (PhtE), LytB, and pneumococcal choline-binding protein A (PcpA)) as serological probes in children hospitalized with CAP. Recent pneumococcal exposure (positive blood culture for Streptococcus pneumoniae, Ply(+) blood PCR finding, and PSP seroresponse) was predefined as supporting the diagnosis of presumed pneumococcal CAP (P-CAP). Twenty-three of 75 (31%) children with CAP (mean age 33.7 months) had a Ply(+) PCR finding and/or a ≥ 2-fold increase of antibodies. Adding seroresponses to four PSPs identified 12 additional patients (35/75, 45%), increasing the sensitivity of the diagnosis of P-CAP from 0.44 (Ply alone) to 0.94. Convalescent anti-Ply and anti-PhtD antibody titres were significantly higher in P-CAP than in non P-CAP patients (446 vs. 169 ELISA Units (EU)/mL, p 0.031, and 189 vs. 66 EU/mL, p 0.044), confirming recent exposure. Acute anti-PcpA titres were three-fold lower (71 vs. 286 EU/mL, p <0.001) in P-CAP children. Regression analyses confirmed a low level of acute PcpA antibodies as the only independent predictor (p 0.002) of P-CAP. Novel PSPs facilitate the demonstration of recent pneumococcal exposure in CAP children. Low anti-PcpA antibody titres at admission distinguished children with P-CAP from those with CAP with a non-pneumococcal origin.

Identification of aberrant pathway and network activity from high-throughput data.

The workshop focused on approaches to deduce changes in biological activity in cellular pathways and networks that drive phenotype from high-throughput data. Work in cancer has demonstrated conclusively that cancer etiology is driven not by single gene mutation or expression change, but by coordinated changes in multiple signaling pathways. These pathway changes involve different genes in different individuals, leading to the failure of gene-focused analysis to identify the full range of mutations or expression changes driving cancer development. There is also evidence that metabolic pathways rather than individual genes play the critical role in a number of metabolic diseases. Tools to look at pathways and networks are needed to improve our understanding of disease and to improve our ability to target therapeutics at appropriate points in these pathways.

[Complex analsis of association of inflammation genes with myocardial infarction].

Carriage frequencies of alleles and genotypes of functionally important polymorphous loci of some inflammation genes: proinflammatory cytokines genes IL-6, LTA and TNF, anti-inflammatory cytokine gene TGFB1 and CC chemokine receptor 5 gene CCR5 were analyzed in the patients with myocardial infarction (MI) of Russian ethnic descent (199 cases) and in the control group of the same ethnic descent (142 controls). Complex analysis using APSampler algorithm revealed MI association with carriage of all polymorphous variants studied, as individual risk factors (insertion/deletion polymorphism of CCR5 and SNP G252A LTA) or only in combination with other alleles/genotypes. Carriage of bi- or triallelic combinations was associated with MI more significantly than carriage of any their subsets: single alleles or allele pairs. Protective triallelic combination d*CCR5 + 252G*LTA(+) -174C*Ll-6 was found to be most significant (p = 0.0006, OR = 0.23, CI = 0.090-0.56). Separate analysis of genetic susceptibility to MI for men and women displayed sexual dimorphism for CCR5 gene.

Stereological estimation of the total number of ventilatory units in mice lungs.

We present an unbiased estimator of the total number of alveolar structures distal to the transition from a bronchiole to an alveolar duct system ('ventilatory units', VUs). In species without respiratory bronchioles, including mice, the number of VUs is equivalent to the number of acini. The acinus is a functional unit of gas exchange, defined as a parenchymal unit distal to a terminal bronchiole in which all airways contain alveoli and thus participate in gas exchange. The estimator combines two different estimators of the number of VUs: (1) an estimator derived from the Euler number of all the openings of the bronchial tree and (2) an estimator derived from direct counts of topological changes occurring at bronchiole-alveolar duct junctions. Combining the two estimators eliminates the requirement to be able to identify even vanishingly small pieces of bronchial tissue in physical disectors. We implemented the fractionator estimator in five adult mice lungs using physical fractionators with varying but known sampling fractions (Horvitz-Thompson estimator). We obtained total values of about 4200 VUs (CV = 0.05) in 21-day-old and 4480 (CV = 0.06) in 69-day-old animals. Being fractionator estimates, these total numbers are independent of shrinkage. The densities of VUs per unit volume of tissue (values corrected for tissue shrinkage) were similar in left and right lungs.

[Complex analysis of genetic predisposition to ischemic stroke in Russians].

Carriage frequencies of alleles and genotypes of 10 functionally important single nucleotide polymorphisms that are located in genes FGA, FGB, APOE, LPL, ACE and CMA1 were analyzed in the ischemic stroke (IS) patients of Russian ethnic descent and in the control group of the same ethnic descent and of similar gender and age. Comparison between patients and control group revealed no significant differences in frequencies of individual alleles and genotypes for all the polymorphic loci studied. However, complex analysis of genetic predisposition using APSampler algorithm revealed carriage of allele (-491A) APOE as a predisposing factor for IS (p = 0.044, OR 3.8, 95% CI 1.0-15.1). Accordingly, carriage of genotype (-491T/T) APOE was associated with resistance to IS (p = 0.044, OR 0.26, 95% CI 0.07-1.0). The allele -249C FGB carriage addition to this genotype enhances its protective properties, p-value of the combination is 2-fold lower than that of the genotype (-491T/T) APOE (OR 0.17, 95% CI 0.04-0.8). Two more protective combinations were identified: biallelic (-427C) APOE + (1595G) LPL and triallelic (-491C) APOE + (1595G) LPL + (-1903G) CMAI (in both cases p = 0.0052, OR 0.18, 95% CI 0.05-0.66). Overall, involvement in formation of the risk of IS development in Russians was evidenced for alleles of four genes: APOE, FGB, LPL and CMA1, where APOE gene involvement was evidenced for alleles of two polymorphic loci, -491T and -427C. Linkage analysis suggested that involvement of these loci in insusceptibility to IS is mutually independent.

[Genetic predisposition to multiple sclerosis as a polygenic autoimmune disease].

Unrelated patients with definite multiple sclerosis (MS) and healthy controls of Russian descent were genotyped at 16 polymorphic loci of the DRB1, TNF, LTa, TGFb1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. The association of allelic variants with MS (p<0,01) was studied using the case-control method with the PSampler algorithm recently developed by our group. The previously described DRB1*15(2) allele, the TNFa9 allele and the biallelic combination (CCR5d32,DRB1*04) were reidentified as MS-associated in Russians. We also identified previously unknown MS-associated tri-allelic combinations: (-509 TGFb1*C, DRB1*18(3),CTLA4*G) and (-238TNF*B1, -308TNF*A2,CTLA4*G). The biological properties of the MS-associated genes support the notion that autoimmune inflammatory processes play an important role in MS, whereas an existence of mainly non-overlapping subgroups of patients bearing different predisposing genetic factors is consistent with the MS genetic heterogeneity.

Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion.

The optimal timing of exogenous surfactant application to reduce pulmonary injury and dysfunction was investigated in a rat lung ischaemia and reperfusion injury model. Lungs were subjected to flush perfusion, surfactant instillation, cold ischaemia (4 degrees C, 4 h) and reperfusion (60 min). Animals received surfactant before (group 1) or at the end (2) of ischaemia, or during reperfusion (3) or not at all (4). Control groups included "worst case" without Perfadex and surfactant (5), "no injury" without (6) or with surfactant (7), and ischaemia with pre-ischaemic surfactant (8). Intra-alveolar oedema and blood-air barrier injury were estimated by light and electron microscopic stereology. Perfusate oxygenation and pulmonary arterial pressure (P(pa)) were determined during reperfusion in groups 1 to 4. Intra-alveolar oedema was almost absent in groups 1, 6, 7 and 8, pronounced in 2, 3 and 4, and severe in 5. Blood-air barrier injury was moderate in groups 1 and 8, slightly pronounced in 2, 3 and 4, extensive in 5 and almost absent in 6 and 7. Perfusate oxygenation was significantly higher in group 1 compared with groups 2 to 4. P(pa) did not differ between the groups. In conclusion, exogenous surfactant attenuates intra-alveolar oedema formation and blood-air barrier damage and improves perfusate oxygenation in the rat lung, especially when applied before ischaemic storage.

Impairment of gastric acid secretion and increase of embryonic lethality in Foxq1-deficient mice.

The mouse Foxq1 gene, also known as Hfh1, encodes a winged helix/forkhead transcription factor. In adult mice, Foxq1 is highly expressed in kidney and stomach. Here, we report that Foxq1 is expressed during prenatal and postnatal stomach development and the transcripts are restricted to acid secreting parietal cells. Mice homozygous for a deletion of the Foxq1 locus on a 129/Sv x C57BL/6J hybrid genetic background display variable phenotypes consistent with requirement of the gene during embryogenesis. Approximately 50% of Foxq1-/- embryos die in utero. Surviving homozygous mutants are normal and fertile, and have a silky shiny coat. Although the parietal cell development is not affected in the absence of Foxq1, there is a lack of gastric acid secretion in response to various secretagogue stimuli. Ultrastructural analysis suggests that the gastric acid secretion defect in Foxq1-deficient mice might be due to impairment in the fusion of cytoplasmic tubulovesicles to the apical membrane of secretory canaliculi.

Preischemic iloprost application for improvement of graft preservation: which route is superior in experimental pig lung transplantation: inhaled or intravenous?

BACKGROUND: Optimal allograft protection is essential in lung transplantation to reduce postoperative organ dysfunction. Although intravenous prostanoids are routinely used to ameliorate reperfusion injury, the latest evidence suggests a similar efficacy of inhaled prostacyclin. Therefore, we compared donor lung-pretreatment using inhaled lioprost (Ventavis) with the commonly used intravenous technique. METHODS: Five pig lungs were each preserved with Perfadex and stored for 27 hours without (group 1) or with (group-2, 100 prior aerosolized of iloprost were (group 3) or iloprost (IV). Following left lung transplantation, hemodynamics, Po(2)/F(i)o(2), compliance, and wet-to-dry ratio were monitored for 6 hours and compared to sham controls using ANOVA analysis with repeated measures. RESULTS: The mortality was 100% in group 3. All other animals survived (P < .001). Dynamic compliance and PVR were superior in the endobronchially pretreated iloprost group as compared with untreated organs (P < .05), whereas oxygenation was comparable overall W/D-ratio revealed significantly lower lung water in group 2 (P = .027) compared with group 3. CONCLUSION: Preischemic alveolar deposition of iloprost is superior to IV pretreatment as reflected by significantly improved allograft function. This strategy offers technique to optimize pulmonary preservation.

Microvascular endowment in the developing chicken embryo lung.

In the current study, the contribution of the major angiogenic mechanisms, sprouting and intussusception, to vascular development in the avian lung has been demonstrated. Sprouting guides the emerging vessels to form the primordial vascular plexus, which successively surrounds and encloses the parabronchi. Intussusceptive angiogenesis has an upsurge from embryonic day 15 (E15) and contributes to the remarkably rapid expansion of the capillary plexus. Increased blood flow stimulates formation of pillars (the archetype of intussusception) in rows, their subsequent fusion and concomitant delineation of slender, solitary vascular entities from the disorganized meshwork, thus crafting the organ-specific angioarchitecture. Morphometric investigations revealed that sprouting is preponderant in the early period of development with a peak at E15 but is subsequently supplanted by intussusceptive angiogenesis by the time of hatching. Quantitative RT-PCR revealed that moderate levels of basic FGF (bFGF) and VEGF-A were maintained during the sprouting phase while PDGF-B remained minimal. All three factors were elevated during the intussusceptive phase. Immunohistoreactivity for VEGF was mainly in the epithelial cells, whereas bFGF was confined to the stromal compartment. Temporospatial interplay between sprouting and intussusceptive angiogenesis fabricates a unique vascular angioarchitecture that contributes to the establishment of a highly efficient gas exchange system characteristic of the avian lung.

Caesium sorption by hydrated cement as a function of degradation state: experiments and modelling.

To provide reliable K(d) data for Cs required for the performance assessment of cement-based radioactive waste repositories, two complementary approaches were followed. First, Cs sorption was determined on a range of hydrated cement paste (HCP) and mortar samples of CEM I and CEM V for different degradation states and solution compositions, as well as on some single mineral phases. Second, a surface complexation-diffuse layer model previously developed by Pointeau et al. [Pointeau, I., Marmier, N., Fromage, F., Fedoroff, M., Giffaut, E., 2001. Cs and Pb uptake by CSH phases of hydrated cement. Material Research Society Symposium Proceedings, 663, 105-113] for Cs sorption on synthetic CSH phases was simplified to facilitate its application to whole HCP and mortars or concrete, following re-assessment of the model parameters. All measurements were compared with model predictions. The sorption data obtained on the different solid phases as a function of conditions corroborate that CSH minerals are the main sorbing phase for Cs in HCP. The data also clearly show the important influence of pH and the dissolved concentration of Na, K and Ca on K(d). It is further suggested that a decrease of pH is concomitant with a decrease of the Ca/Si ratio and a corresponding increase in surface sites with high affinity for Cs and, thus, K(d). Elevated concentrations of cations able to compete with Cs for these sites lead to a decrease of K(d), on the other hand. The simplified model was applied to the sorption measurements performed within this study as well as to a variety of literature data, mainly K(d) values for a variety of fresh HCP and mortar or concrete samples based on different samples of Ordinary Portland Cement as well as blended cements. The results show that the model can be applied reasonably well to a very large variety of conditions in terms of solid and solution compositions that cover a range of K(d) values from 10(-4) to ca. 3.2m(3)/kg. The large scatter typically observed for Cs sorption, especially on fresh HCP samples prepared from different formulations, can be explained quantitatively by the variable concentrations of Na and K in the respective solutions, which compete with Cs for fixation sites. On the other hand, the comparatively uniform conditions in degraded HCP typically render the prediction of K(d) values less uncertain than in case of fresh HCP.

Surfactant proteins in pulmonary alveolar proteinosis in adults.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterised histologically by an intra-alveolar accumulation of fine granular eosinophilic and periodic acid-Schiff positive material. In a retrospective study, the composition of the intra-alveolarly accumulated material of adult patients with PAP was analysed by means of immunohistochemistry and Western blotting. In patients with PAP, the current authors found an intra-alveolar accumulation of surfactant protein (SP)-A, precursors of SP-B, SP-B, variable amounts of mono-, di-, and oligomeric SP-C forms, as well as SP-D. Only in one patient was a precursor of SP-C detected. By means of immuno-electron microscopy, the current authors identified not only transport vesicles labelled for precursors of SP-B and SP-C, but also transport vesicles containing either precursors of SP-B or SP-C in type-II pneumocytes in normal human lungs. It is concluded that pulmonary alveolar proteinosis in adults is characterised by an intra-alveolar accumulation of surfactant protein A, precursors of surfactant protein B, and surfactant proteins B, C and D. The current data provide evidence that not only an impairment of surfactant clearance by alveolar macrophages, but also an abnormal secretion of transport vesicles containing precursors of surfactant protein B (but not surfactant protein C) and an insufficient palmitoylation of surfactant protein C, which may lead to the formation of di- and oligomeric surfactant protein C forms, play a role in the pathogenesis of pulmonary alveolar proteinosis.