Core-shell inversion by pH modulation in dynamic covalent micelles.

Dynamic covalent surfactants have been obtained by the reversible condensation of a hydrophobic aldehyde (ended by an ionic tip) with various neutral polyethylene glycol based hydrophilic amines. In water, the duality between the two hydrophilic domains (charged and neutral) leads to their segregation when the surfactants are self-assembled within micelles. Depending on the number of polyethylene glycol units, a core-shell inversion leading to a switching orientation of the ionic tips from the inside to the outside of the micelles has been demonstrated by a combination of scattering techniques. In competition experiments, when several amines of different pKas and hydrophilic polyethylene glycol chains are competing for the same aldehyde, it becomes possible to trigger this core-shell inversion by pH modulation and associated dynamic constitutional reorganization.

Rodlike complexes of a polyelectrolyte (hyaluronan) and a protein (lysozyme) observed by SANS.

We study by small-angle neutron scattering (SANS) the structure of hyaluronan -lysozyme complexes. Hyaluronan (HA) is a polysaccharide of 9 nm intrinsic persistence length that bears one negative charge per disaccharide monomer (M(mol) = 401.3 g/mol); two molecular weights, M(w) = 6000 and 500,000 Da were used. The pH was adjusted at 4.7 and 7.4 so that lysozyme has a global charge of +10 and +8, respectively. The lysozyme concentration was varied from 3 to 40 g/L at constant HA concentration (10 g/L). At low protein concentration, samples are monophasic, and SANS experiments reveal only fluctuations of concentration, although, at high protein concentration, clusters are observed by SANS in the dense phase of the diphasic samples. In between, close to the onset of the phase separation, a distinct original scattering is observed. It is characteristic of a rod-like shape, which could characterize "single" complexes involving one or a few polymer chains. For the large molecular weight (500,000), the rodlike rigid domains extend to much larger length scale than the persistence length of the HA chain alone in solution and the range of the SANS investigation. They can be described as a necklace of proteins attached along a backbone of diameter of one or a few HA chains. For the short chains (M(w) ≈ 6000), the rod length of the complexes is close to the chain contour length (∼ 15 nm).

Room temperature dynamic polymers based on Diels-Alder chemistry.

Dynamers based on reversible Diels-Alder chemistry have been obtained and shown to undergo dynamic exchange at room temperature. Their study in solution by small-angle neutron scattering indicated the formation of long and highly flexible chains. Polydispersed molecules gave T(g) values below room temperature, permitting the generation of a dynamic elastomer upon introduction of a dynamic cross-linking agent. The use of a system with a low equilibrium constant gives access to materials with interesting self-healing properties.

Loose complexation of weakly charged microemulsion droplets and a polyelectrolyte.

The effect of polyelectrolyte addition on the properties of an oil-in-water (O/W) microemulsion of weakly charged spherical micelles is studied. The 81 A radius O/W droplets in this system can be charged by the partial substitution of the nonionic surfactant by a cationic surfactant. The effect of the addition of poly(acrylic acid) (PAA), which is a charged pH-dependent polyelectrolyte, on the interactions between charged or noncharged droplets has been investigated using SANS. We have characterized the phase behavior of this pH-smart system as a function of the microemulsion and the polyelectrolyte concentration and the number of charges per droplet at three pH values: pH = 2, 4.5, and 12. In particular, an associative phase separation due to the bridging of the droplets by the neutral PAA chains through H-bonds is observed with extremely low PAA addition at low pH. At the opposite, an addition of PAA at pH = 4.5 generates a strong repulsive contribution between neutral droplets. Electrostatic bonds between charged droplets and PAA, controlled by the number of charges per droplet, are responsible for a pH drift and then for an associative phase separation similar to that observed at low pH. Finally, at high pH, the creation of electrostatic bonds between fully charged PAA and charged droplets liberates sufficiently counterions in solution at high droplet charge density to screen the electrostatic interactions and to allow an associative phase separation.

Ethical and legal aspects of enteral nutrition.

European ethical and legal positions with regard to EN vary slightly from country to country but are based on a common tradition derived from Graeco Roman ideas, religious thought and events of the 20th century. The Hippocratic tradition is based on 'beneficience' (do good) and 'non-maleficience' (do no harm). Religious thinking is based upon the presumption of providing food and drink by whatever means unless burden outweighs benefit. The concept of 'autonomy' (the patients right to decide) arose following in the decades after the Second World War and is enshrined in Human Rights law. The competent patient has the right to participate in decision making and to refuse treatment although the doctor is not obliged to give treatment which he or she considers futile or against the patient's interests. The incompetent patient is protected by law. The fourth principle is that of 'justice' i.e. equal access to healthcare for all. The law regards withholding and withdrawing treatment as the same. It also defines the provision of food and drink by mouth as basic care and feeding by artificial means as a medical treatment. It requires doctors to act in the best interests of the patient.

Plasma vitamin E and beta-carotene concentrations during radiochemotherapy preceding bone marrow transplantation.

Blood from 19 patients was examined for the essential antioxidants alpha-tocopherol and beta-carotene before, during, and after bone marrow transplantation (BMT). Marrow ablation and immunosuppression for BMT conditioning was achieved by treatment with high-dose chemotherapy, mostly combined with total body irradiation. All patients required total parenteral nutrition beginning 1 wk before BMT. After conditioning therapy the concentration of absolute and lipid-standardized alpha-tocopherol and beta-carotene in plasma decreased significantly, presumably as a result of an enhanced breakdown of these antioxidants. The loss of these lipid-soluble antioxidants has to be considered as a possible cause for early posttransplant organ toxicity.

Premature centromere division: a possible manifestation of chromosome instability.

Retrospective analysis of "routine" chromosome preparations from 2 patients with Fanconi anemia and 2 others with ataxia-teleangiectasia showed increased chromosome breakage and a tendency to premature centromere division (PCD) with special reference to early separation of the large acrocentric (13-15) chromosomes. The findings suggest that PCD may be a manifestation of chromosome instability related to potential malignancy.

The tricho-rhino-phalangeal syndrome(s): chromosome 8 long arm deletion: is there a shortest region of overlap between reported cases? TRP I and TRP II syndromes: are they separate entities?

Critical cytogenetic (re)evaluation of 2 of our own cases of tricho-rhino-phalangeal syndrome II (TRP II), or Langer-Giedion syndrome (LGS), and 10 cases from the literature, suggests that the shortest region of overlap of the 8q deletion is a part of band q24.1. This region is assumed to be causally related to this syndrome, and possibly also to TRP I syndrome which, therefore, may not be a causally separate entity.

Another model for the inheritance of Rett syndrome.

The fact that probably less than 1% of Rett syndrome cases are familial speaks in favor of a spontaneous mutation as the most common cause of Rett syndrome. However, the few familial cases (about 10) described in the literature, the elevated consanguinity rate in parents of Rett patients (2.4% vs. 0.5%), and the existence of "formes frustes" in relatives of Rett girls, suggest that inheritance must exist. A model based on a hypothetical form of inheritance, namely allelic and non-allelic metabolic interference, fits almost all available data, as well as the exclusive occurrence in females without increased abortion rate.

Delineation of a clinical syndrome caused by mosaic trisomy 15.

We report on a boy with mosaic trisomy 15. The clinical manifestations are compared with those of the few cases reported up to now. A clinical syndrome is delineated consisting of a characteristic shape of the nose and other minor craniofacial anomalies, as well as typical deformities of the hands and feet. Different degrees of mosaicism may explain the more or less severe manifestations in individual patients.

Depletion of plasma vitamin C but not of vitamin E in response to cardiac operations.

The whole-body inflammatory response produced by cardiopulmonary bypass is an important cause of perioperative morbidity after cardiac operations. This inflammatory response produces reactive oxygen species and other cytotoxic substances, such as the cytokines. The generation of reactive oxygen species might deplete principal antioxidant micronutrients, that is, vitamins C and E and the carotenoids. Therefore, we have investigated the time course of the plasma concentrations of vitamins C and E and the carotenoids in 18 patients undergoing coronary bypass operations after randomization for previous vitamin E supplementation (300 mg dl-alpha-acetyl-tocopherol 3 times daily for 4 weeks) or placebo. Supplementation with alpha-tocopherol doubled the lipid-standardized plasma vitamin E concentration to 63.7 +/- 14.5 mumol/L when compared with that of the control subjects (31.2 +/- 9.0 mumol/L) before the operation. The plasma concentrations of vitamin C (36.0 +/- 19.0 mumol/L and 44.0 +/- 21.7 mumol/L, respectively) and of the carotenoids were not statistically different between the two groups at baseline. The absolute plasma concentrations of both vitamin E and the carotenoids decreased during and after cardiopulmonary bypass, but after correction for hemodilution the plasma concentrations of vitamin E and the carotenoids showed no decrease. The vitamin E concentrations in the erythrocytes did not change either. In contrast, the plasma concentration of vitamin C decreased in all subjects within 24 hours after the operation by roughly 70%. Correction for hemodilution still revealed a significant decrease in plasma vitamin C that persisted in most patients up to 2 weeks. In conclusion, the vitamin E and the carotenoid plasma concentrations are of no major concern during and after cardiac operations. In contrast, the serious depletion of vitamin C may deteriorate the defense against reactive oxygen species-induced injury during cardiac operations.

Altered switch in lipid composition during T-cell blast transformation in the healthy elderly.

Decreased mitogen responsiveness of lymphocytes during aging correlates inversely with membrane microviscosity, which reflects an altered lipid composition. Therefore, we addressed the question, whether age-related alterations of lipid metabolism affect the switch in lipid composition during formation of blasts. Membrane lipids and fatty acids of peripheral blood lymphocytes from SENIEUR protocol compatible ("healthy") elderly donors (66-77 yr) and young controls (18-30 yr) were quantified after incubation with or without the mitogen phytohaemagglutinin. The blastic change in membrane lipid composition was different for young controls with respect to cholesterol, phosphatidylethanolamine, total phospholipids, as well as several fatty acids. Moreover, the age-related alterations in the switch of membrane lipids and fatty acids were significantly correlated with a decreased mitogen response. Thus, the alterations in membrane reorganization during blast formation of lymphocytes from the elderly point to a disturbed cellular lipid homeostasis with possible impact on the age-related reduction in immune function.

Rett syndrome and genetic drift.

An X chromosome gene is assumed to be responsible for the cause of Rett syndrome (RS). However, new genealogical observations suggest involvement of autosomal recessive gene(s) as well, at least in familial cases. To account for these and other recent observations, the theoretical model presented in 1990 by the authors of this paper is applied to the calculation of gene frequencies. Observed frequencies of sporadic and familial cases of RS are used, taking into account genetic drift in inbreeded areas. Moreover, an attempt is made to use the proportion of RS variants in familial and sporadic cases for the explanation of so called 'formes frustes', and as evidence for the existence of female as well as male carriers. The estimated frequency of the recessive autosome mutation, or possibly a frequent polymorphism, is 22.5%.

Presumptive monosomy 21 with neuronal migration disorder re-diagnosed as de novo unbalanced translocation t(18p;21q) by fluorescence in situ hybridisation.

We present clinical and cytogenetic data of a one year old boy with partial monosomy for both 21q and 18p, resulting from a de novo unbalanced translocation. The initial diagnosis of a seemingly full monosomy 21 was revised after fluorescence in situ hybridisation (FISH) with whole chromosome painting probes and a locus-specific chromosome 21 probe. The karyotype was reinterpreted as 45,XY,der(18)t(18;21)(p11.2;q22.1),-21. This karyotype, to our knowledge, has not been previously described. The boy presented with a spectrum of clinical features previously described for (partial) monosomy 18p only, for monosomy 21q only, or for both of these aneusomies. The radiological finding of a neuronal migration disorder with localised polymicrogyria (cortical dysplasia) has not been described for either monosomy before.

Low density lipoprotein for oxidation and metabolic studies. Isolation from small volumes of plasma using a tabletop ultracentrifuge.

A rapid method is described for the isolation of small volumes of plasma low density lipoprotein (LDL) free of plasma protein contaminants using the TL-100 Tabletop Ultracentrifuge (Beckman). The isolation of LDL was achieved by a 25 min discontinuous gradient density centrifugation between the density range of 1.006 and 1.21 g/ml, recovery of LDL by tube slicing followed by a 90 min flotation step (d = 1.12 g/ml). The purity of LDL and apolipoprotein B100 (apo B100) were monitored by agarose electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), radial immunodiffusion and micropreparative fast protein liquid chromatography (FPLC). The ability of LDL oxidation was assessed by following absorbance at 234 nm after addition of copper ions. The functional integrity of the isolated LDL was checked by clearance kinetics after injection of [125I]-labelled LDL in estrogen-treated rats. The additional purification step led to LDL fractions free of protein contamination and left apo B100, alpha-tocopherol and beta-carotene intact. The LDL prepared in this way was free of albumin, as evident from analytic tests and from its enhanced oxidative modification by copper ions. Used for analytical purposes, this method allows LDL preparations from plasma volumes up to 570 microliters. This method is also convenient for metabolic studies in small animals, especially those relating to the determination of kinetic parameters of LDL in which LDL-apo B100 has to be specifically radiolabelled.

Increase of gingival hydroxyproline and proline by improvement of ascorbic acid status in man.

The 4-hydroxyproline and proline content of periodontal tissue was measured in 24 adult volunteers with initially low and partially even deficient plasma vitamin C values, before and after peroral supplementation with 70 mg ascorbic acid daily for six weeks. The latter caused a statistically significant rise and normalization respectively of plasma ascorbic acid and simultaneously a statistically significant increase of the hydroxyproline and proline in periodontal tissue (p less than 0.01) but not before the plasma vitamin C level was above 0.9 mg/dl. The optimal plasma vitamin C level which was associated with the highest hydroxyproline and proline content in periodontal tissue ranged between 1.00-1.30 mg/dl corresponding to the total daily dietary ascorbic acid intake of about 100 mg.

Sequence of centromere separation in cultured human amniotic cells.

The sequence of centromere division was analysed in 100 selected late metaphase mitoses of cultured human amniotic cells. The pattern obtained was very similar to that of the previously studied lymphocytes; Chromosomes 18, 12, 17, 5 and X proved to be early dividing, and the acrocentrics were the last to separate in both amniotic cells and blood lymphocytes.

[Roberts-SC phocomelia syndrome]. / Roberts-SC-Phokomelie- oder Pseudothalidomid-Syndrom.

The Roberts-SC phocomelia syndrome is a rare autosomal recessive inherited disorder clinically manifested by tetraphocomelia, pre- and postnatal growth retardation, and craniofacial abnormalities (skull, eyes, lip, and palate), accompanied at times by centromer puffing and splitting, renal abnormalities, heart defect, clitoral or penile enlargement, and bilateral corneal opacities. Mental retardation is common in surviving patients.

Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model.

Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1(+/-) mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (