Reconstitution Properties of Thymus Stem Cells in Murine Fetal Liver

Injection of day-12 murine fetal liver cells into thymus lobes of Thy-1 congenic adult recipients results in a wave of thymocyte development. The kinetics of repopulation by donor cells reaches a peak after 20–25 days. The frequency of thymic stem cells (TSC) in day-12 fetal liver was estimated, by limit dilution, as 1 in 4x104 cells. Within 8 hr of injection into a thymus lobe, fetal liver TSC commit to T-cell development, losing stem-cell activity. When fetal liver cells are maintained in culture for 7 days, with no exogenous cytokines added, and then injected intra-thymically (I.T.), thymus recolonization is not observed. However, TSC can be maintained in culture for 7 days with IL-1β, IL-3, IL-6, or LIF added, alone or in combination, with steel factor (SLF). Poisson analysis of fetal liver cells cultured with SLF and IL-3 together revealed a precursor frequency of 1 in 1.8x 105 cells. In contrast, the frequency of TSC in adult bone marrow was estimated by limit dilution as 1 in 12,000 cells

An interaction of β-amyloid with aluminium in vitro

AbstractWe have used circular dichroism spectroscopy to confirm that, in a membrane-mimicking solvent, AβP(1–40) adopts a partially helical conformation and we have demonstrated the loss of this structure in the presence of physiologically relevant concentrations of aluminium. This is the first evidence of a direct biochemical interaction between aluminium and β-amyloid and may have important implications for the pathogenesis of Alzheimer's disease

Leg ulceration as a long-term complication of deep vein thrombosis

AbstractObjectiveTo evaluate the role of deep vein thrombosis as a cause of leg ulcers.Patients and methodsA population-based, case-control study was conducted in Central and North Auckland, New Zealand. Cases comprised 241 people aged 40 to 99 years and on the electoral roll, with current leg ulcers (all types). Cases were identified by means of notification from health professionals and by self-referral. Controls were 224 people in the same age group, without leg ulcers, who were selected from the electoral roll by using a stratified random sampling process.Main outcome measuresThe occurrence of leg ulceration as a consequence of exposure to deep vein thrombosis or being at high risk of deep vein thrombosis (that is, people with a family history of deep vein thrombosis, and/or a history of leg fracture and/or hip, leg, or foot surgery).ResultsAfter adjustment for age, sex, and other potential confounding factors, people who had a diagnosed thromboembolism were at almost three times higher risk of having a leg ulcer (odds ratio, 2.92; 95% confidence interval (CI), 1.47 to 6.08). In addition, people who had been at high risk of a venous thrombosis but were not diagnosed with this condition (eg, people with a history of major leg surgery) were also at increased risk of ulceration (odds ratio, 2.25; 95% CI, 1.49-3.42). Overall, 56% (95% CI, 33% - 71%) of leg ulcers were attributed to being at high risk of deep vein thrombosis.ConclusionsDeep vein thrombosis and factors that place people at high risk of deep vein thrombosis are an important cause of leg ulcers in older people. This finding strengthens the rationale for the routine and long-term use of thromboprophylaxis, particularly in high-risk patients

Reversible cooperative dihydrogen binding and transfer with a bis-phosphenium complex of chromium

The reversible reaction of H(2)with a bis-phosphenium complex of chromium provides a rare example of 3d transition metal/phosphenium cooperativity. Photolysis induces the activation of H(2)and yields a spectroscopically detectable phosphenium-stabilized (sigma-H-2)-complex, readily showing exchange with gaseous H(2)and D-2. Further reaction of this complex affords a phosphine-functionalized metal hydride, representing a unique example of reversible H(2)cleavage across a 3d MP bond. The same species is also accessibleviastepwise H+/H(-)transfer to the bis-phosphenium complex, and releases H(2)upon heating or irradiation. Dihydrogen transfer from the H-2-complex to styrene is exploited to demonstrate the first example of promoting hydrogenation with a phosphenium complex.Peer reviewe

Reactions of Imidazolio-Phosphides with Organotin Chlorides : Surprisingly Diverse

Reactions of primary imidazolio-phosphides ("imidazolylidene-phosphinidenes") with R2SnCl2 yield as main products spectroscopically detectable Lewis pairs which undergo base-induced dehydrochlorination in the presence of excess dichlorostannane to afford zwitterionic chloride adducts of distannylated imidazolio-phosphines. In contrast, reactions with R3SnCl proceed under dismutation to furnish mixtures containing imidazolium salts and stannylated (oligo)phosphines P(SnR3)(3) and P-7(SnR3)(3), respectively. DFT studies were used to rationalize the divergent behavior based on the presumption that the reactions proceed under thermodynamic control and the products observed represent the most stable species under the specific reaction conditions. Computational simulation of selected reaction steps provides a model mechanism for Lewis-acid promoted creation of PP-bonds, which is a prerequisite for oligophosphine formation. The computational studies further highlight parallels between reactions of imidazolio-phosphides with Lewis and Bronsted acids, and allow also to extrapolate the behavior of the P-nucleophiles towards other electrophiles than organotin chlorides.Peer reviewe

A neutral analogue of a phosphamethine cyanine

Reaction of an imidazolio-phosphide with an N-heterocyclic bromo-borane and NaH afforded a neutral analogue of a phosphamethine cyanine cation. DFT studies were used to analyse the dative bonding across P-C/B bonds and the conformational preferences and imply that the observed conformation is imposed by sterics.Peer reviewe

Annellated 1,3,4,2-Triazaphospholenes-Simple Modular Synthesis and a First Exploration of Ligand Properties

The successful use of 1,3,4,2-triazaphospholenes (TAPs) as organo-catalysts stresses the need for efficient synthetic routes to these molecules. In this study, we establish the [1 + 4]-cycloaddition of PBr3 to azo-pyridines as a new approach to preparing pyrido-annellated TAPs in a single step from easily available precursors. The modular assembly of the azo-component via condensation of primary amines and nitroso compounds along with the feasibility of post-functionalization at the P–Br bond under conservation of the heterocyclic structure allows, in principle, to address a wide range of target molecules, which is illustrated by prototypical examples. The successful synthesis of a transition metal complex confirms for the first time the ability of a TAP to act as a P-donor ligand. Crystallographic studies suggest that hyperconjugation effects and intermolecular interactions induce a qualitatively similar ionic polarization of the P–Br bonds in TAPs as in better known isoelectronic diazaphospholenes

Annellated 1,3,4,2-Triazaphospholenes-Simple Modular Synthesis and a First Exploration of Ligand Properties

The successful use of 1,3,4,2-triazaphospholenes (TAPs) as organo-catalysts stresses the need for efficient synthetic routes to these molecules. In this study, we establish the [1 + 4]-cycloaddition of PBr3 to azo-pyridines as a new approach to preparing pyrido-annellated TAPs in a single step from easily available precursors. The modular assembly of the azo-component via condensation of primary amines and nitroso compounds along with the feasibility of post-functionalization at the P-Br bond under conservation of the heterocyclic structure allows, in principle, to address a wide range of target molecules, which is illustrated by prototypical examples. The successful synthesis of a transition metal complex confirms for the first time the ability of a TAP to act as a P-donor ligand. Crystallographic studies suggest that hyperconjugation effects and intermolecular interactions induce a qualitatively similar ionic polarization of the P-Br bonds in TAPs as in better known isoelectronic diazaphospholenes.Peer reviewe

Annellated 1,3,4,2-Triazaphospholenes-Simple Modular Synthesis and a First Exploration of Ligand Properties

The successful use of 1,3,4,2-triazaphospholenes (TAPs) as organo-catalysts stresses the need for efficient synthetic routes to these molecules. In this study, we establish the [1 + 4]-cycloaddition of PBr3 to azo-pyridines as a new approach to preparing pyrido-annellated TAPs in a single step from easily available precursors. The modular assembly of the azo-component via condensation of primary amines and nitroso compounds along with the feasibility of post-functionalization at the P–Br bond under conservation of the heterocyclic structure allows, in principle, to address a wide range of target molecules, which is illustrated by prototypical examples. The successful synthesis of a transition metal complex confirms for the first time the ability of a TAP to act as a P-donor ligand. Crystallographic studies suggest that hyperconjugation effects and intermolecular interactions induce a qualitatively similar ionic polarization of the P–Br bonds in TAPs as in better known isoelectronic diazaphospholenes

Proton transfer vs. oligophosphine formation by P-C/P-H sigma-bond metathesis : decoding the competing Bronsted and Lewis type reactivities of imidazolio-phosphines

Studies of the protonation and alkylation of imidazolio-phosphides and deprotonation of imidazolio-phosphines reveal a complex behaviour that can be traced back to an interplay of Bronsted-type proton transfers and Lewis-type P-P bond formation reactions. As a consequence, the expected (de)protonation and (de)alkylation processes compete with reactions producing cyclic or linear oligophosphines. A careful adjustment of the conditions allows us to selectively address each reaction channel and devise specific synthesis methods for primary, secondary and tertiary imidazolio-phosphines, imidazolio-alkylphosphides, and cyclic oligophosphines, respectively. Mechanistic studies reveal that oligophosphines assemble in sequential P-P bond formation steps involving the condensation of cationic imidazolio-phosphines via sigma-bond metathesis and concomitant elimination of an imidazolium ion. Imidazolio-phosphides catalyse these transformations. Computational model studies suggest that the metathesis proceeds in two stages via an initial nucleophilic substitution under expulsion of a carbene, and a subsequent proton transfer step that generates an imidazolium cation and provides the driving force for the whole transformation. As energy barriers are predicted to be low or even absent, different elementary steps are presumed to form a network of mutually coupled equilibrium processes. Cyclic oligophosphines or their dismutation products are identified as the thermodynamically favoured final products in the reaction network.Peer reviewe