Haematopoietic stem cells: entropic landscapes of differentiation.

The metaphor of a potential epigenetic differentiation landscape broadly suggests that during differentiation a stem cell approaches a stable equilibrium state from a higher free energy towards a stable equilibrium state which represents the final cell type. It has been conjectured that there is an analogy to the concept of entropy in statistical mechanics. In this context, in the undifferentiated state, the entropy would be large since fewer constraints exist on the gene expression programmes of the cell. As differentiation progresses, gene expression programmes become more and more constrained and thus the entropy would be expected to decrease. In order to assess these predictions, we compute the Shannon entropy for time-resolved single-cell gene expression data in two different experimental set-ups of haematopoietic differentiation. We find that the behaviour of this entropy measure is in contrast to these predictions. In particular, we find that the Shannon entropy is not a decreasing function of developmental pseudo-time but instead it increases towards the time point of commitment before decreasing again. This behaviour is consistent with an increase in gene expression disorder observed in populations sampled at the time point of commitment. Single cells in these populations exhibit different combinations of regulator activity that suggest the presence of multiple configurations of a potential differentiation network as a result of multiple entry points into the committed state.

[Intraobserver and interobserver reliability of introital ultrasound after tension-free vaginal tape (TVT) procedure]. / Reliabilität der Introitussonografie nach Einlage eines spannungsfreien Vaginalbands nach dem TVT-Verfahren.

PURPOSE: To date, the evaluation of TVT by ultrasound has not been standardized. The aim of this observational study was to evaluate the intraobserver and interobserver variability of introital ultrasound. MATERIALS AND METHODS: Follow-up was performed for 202 patients after TVT procedure. The tape was characterized by the position in relation to urethral length (%) and the distance to the hypoechoic center of the urethra (mm). Furthermore, we assessed the shape of the tape (straight, curved or folded). All evaluations were performed by two experienced examiners (A, B) at rest and during Valsalva maneuver. All sonograms were archived digitally without measurement results. After 6 to 12 months, the sonograms were re-evaluated by one investigator (A). Depending on the first investigator, the results were compared as intraobserver (A-A) or interobserver (B-A) agreement. The first results were blinded for the second measurement. Agreement concerning the distances was assessed using the intraclass correlation coefficient (ICC). The concordance of the descriptive evaluation of the shape of the tape was characterized by the kappa coefficient (KC). RESULTS: The tape was regularly identified as an echogenic structure dorsal to the urethra. The intraobserver reliability concerning the position of the tape in relation to urethral length showed good reproducibility (at rest ICC 0.90, Valsalva maneuver: ICC 0.96). For the distance between the tape and the urethra at rest (ICC 0.83), there was also good reproducibility, but not during Valsalva maneuver (ICC 0.74). The shape of the tape showed only moderate reproducibility with accordance of 81 % at rest (KC 0.68) and of 79 % during Valsalva maneuver (KC 0.6). The interobserver comparisons showed good concordance in measuring the POS at rest (ICC 0.93), and during Valsalva maneuver (ICC 0.89), and the DIS at rest (ICC 0.89), and during Valsalva maneuver (ICC 0.87). The congruence of the estimation of the shape was 71 % at rest (KC 0.44) and 72 % during Valsalva maneuver (KC 0.49). CONCLUSION: The characterization of the TVT in the sagittal view by introital ultrasound shows good reproducibility with respect to position and distance, but not shape.

Constant-atomic-final-state filtering of dissociative states in the O1s-->sigma* core excitation in O2.

The below-threshold region in core-excited O2 is very complex, consisting of a multitude of exchange-split states with mixed molecular orbital-Rydberg character. We have investigated the nature of these intermediate states by resonant Auger spectroscopy. In particular, we have obtained constant-atomic-final-state yield curves for several atomic peaks in the electron decay spectra which are stemming from ultrafast dissociation. The relative intensity of Auger decay leading to atomic final states is considered a signature of the relative weight of the sigma* character. This method allows one to "filter out" intermediate states with dissociative character. Extensive calculations have been performed by multi-reference configuration interaction at different interatomic distances in order to evaluate the potential curves of the core-excited states and propose a qualitative description of the dissociative molecular dynamics. The calculations show that the core-excited states have a relevant admixture of excitations to orbitals with Rydberg character and excitations to the sigma* orbital with different spin couplings. A diabatization of the adiabatic potential curves shows that the coupling between Rydberg and sigma* diabatic states is very different at the different crossing points and ultrafast dissociation occurs more easily on the lowest sigma* diabatic potential curve. As a consequence, the observation of atomic peaks only in the lower-energy region of the absorption curve is well justified.

Core excitation in O3 localized to one of two symmetry-equivalent chemical bonds: molecular alignment through vibronic coupling.

Core excitation from terminal oxygen OT in O3 is shown to be an excitation from a localized core orbital to a localized valence orbital. The valence orbital is localized to one of the two equivalent chemical bonds. We experimentally demonstrate this with the Auger-Doppler effect which is observable when O3 is core excited to the highly dissociative OT1s(-1)7a1 1 state. Auger electrons emitted from the atomic oxygen fragment carry information about the molecular orientation relative to the electromagnetic-field vector at the moment of excitation. The data together with analytical functions for the electron-peak profiles give clear evidence that the preferred molecular orientation for excitation only depends on the orientation of one bond, not on the total molecular orientation. The localization of the valence orbital "7a1" is caused by mixing of the valence orbital "5b2" through vibronic coupling of antisymmetric stretching mode with b2 symmetry. To the best of our knowledge, it is the first discussion of the localization of a core excitation of O3. This result explains the success of the widely used assumption of localized core excitation in adsorbates and large molecules.

Anomalous natural linewidth in the 2p photoelectron spectrum of SiF4.

The silicon 2p photoelectron spectra for SiH4, SiF4, and SiCl4 have been analyzed to give the natural linewidths of the Si 2p hole states, which reflect the Auger decay rates of the states. For SiH4 the measured width of 38 meV is in approximate agreement with the prediction of the one-center model (32 meV), but that for SiF4 of 79 meV is more than 5 times the value of 14 meV predicted by this model. Approximate theoretical calculations indicate that valence electrons from the fluorine atoms of SiF4 play an important role in the Auger decay via interatomic processes.

Menière's syndrome: an atypical presentation of giant cell arteritis (temporal arteritis).

The authors discuss three patients with biopsy-proven giant cell arteritis (GCA) who experienced significant auditory and vestibular symptoms. Two of the patients who presented with audiovestibular symptomatology died as a direct result of GCA affecting the vertebral arteries. Postmortem findings are reported. This report illustrates the importance of maintaining a high index of suspicion of GCA in elderly patients who present with the acute onset of audio-vestibular symptoms. These symptoms can be a herald of brain stem infarction if giant cell arteritis is the underlying cause. High-dose prednisone and rheumatologic/neurologic consultation is required.

[Possibilities and results of surgical treatment of vertebro-basilar insufficiency associated with atherosclerosis of the extracranial cerebral arteries]. / Moznosti a výsledky chirurgické lécby vertebro-bazilární insuficience, podmínené aterosklerotick ým postizením extrakraniálních mozkových tepen.

The author describes his experience with the surgical treatment of processes leading to the syndrome of vertebrobasilar insufficiency. He differentiates between direct interventions focused primarily on the reconstruction of the pathologically altered vertebral artery. Interventions of the indirect type influence the vertebro-basilar insufficiency by modifying the deviated blood stream from the vertebrobasilar area. The author emphasizes reimplantation methods, as compared with desobliterations.

[Resection of the internal carotid artery and its replacement with a vein graft (possibilities of using this method in various conditions)]. / Resekce vnitrní krkavice a její náhrada zilním stepem (moznosti uplatnení metody v ruzných indikacích).

The author describes his experience with 51 reconstructions of the internal carotid artery made on account of different indications by the method of resection and substitution by venous graft. He draws attention to the fact that this method is the method of choice in some special morphological findings, in others it can be considered an alternative method beside much more frequently used endarterectomy. The author draws attention to some advantages of the method on account of which it holds a firm place in the series of reconstruction operations used by vascular surgeons.

Synthesis of 17 beta-(3'-thiophenyl)-5 beta-androstane-3 beta,14 beta-diol 3-D-glucopyranoside, an anti-inotropic cardiac glucoside.

In a continuing effort to synthesize cardiac glucoside analogs with modified 17 beta-functional groups for pharmacologic testing, we used 3 beta-benzyloxy-5 beta-androst-15-en-17-one as an efficient intermediate. This report describes a preparation of 17 beta-(3'-thiophenyl)-5 beta-androstane-3 beta,14 beta-diol 3-D-glucopyranoside.

[Reconstruction of an aneurysm of the abdominal aorta using a single-ring, fibrin-impregnated prosthesis with an intraluminal bifurcation]. / Rekonstrukce výduti brisní aorty pomocí jednoprstencové intraluminální bifurkacní protézy impregnované fibrinem.

The author reports on his initial experience with the use of an intraluminal prosthesis of his own design, used in radical operations of aneurysms of the abdominal aorta in the subrenal portion. He demonstrates on his material that this prosthesis implanted by intraluminal stitchless technique significantly reduces the time of clamping of the aorta and the total time needed for the operation. If the prosthesis is moreover fibrin-impregnated, blood losses associated with preliminary clotting as well as the period of aortal clamping are eliminated. The author recommends further to change the sequence of stitching of anastomoses. All mentioned factors: the time needed for operation, blood loss and the shortest time of necessary clamping of the aorta are closely linked with the results of operation. It appears that by means of this technique the operation of abdominal aortal aneurysms can be performed within a shorter time with a smaller blood loss. From the small group of patients operated hitherto by this method so far no general conclusions can be drawn on results of operations. Hitherto achieved results are very good.

[Angiodysplasia of the digestive tract as a cause of recurrent massive hemorrhage]. / Angiodysplazie trávicího traktu jako zdroj opakovaného masívního krvácení.

The author reports his experience with two cases of haemorrhage into the digestive tract caused by angiodysplasia in the intestinal wall. This disease cannot be detected by common macroscopic examination during operation. It is difficult to assess reliably the borderlines of this vascular malformation. This may lead to incomplete resection and a relapse. The authors describe methods which make it possible to diagnose the malformation reliably and to assess its extent.

Complement activation by 19S IgM rheumatoid factor: relationship to disease activity in rheumatoid arthritis.

19S IgM rheumatoid factor (RF) in rheumatoid arthritis (RA) are polyclonal autoantibodies directed against the Fc piece of IgG. Rheumatoid patients with RF tend to have aggressive synovitis, nodules, and extraarticular manifestations. Although RF titer does not correlate with disease activity, RF activates complement (C) by the classical pathway. Thus, we postulated that selective stimulation of cell clones producing efficient C activating RF molecules might be associated with disease flares, independent of changes in serum RF concentration. To address the question, 42 patients with RA were evaluated prospectively. Serum RF concentration was measured by radioimmunoassay (RIA) and C activating activity by hemolytic assay. We then calculated the mean hemolysis (MH) of sensitized sheep erythrocytes (SRC) produced/ml of RF serum (MH/ml) and MH/microgram of RF as an expression of RF C activating properties (CAP). The following observations were made: RF CAP varied among the patients studied; RF CAP varied over time in individual patients; RF CAP differences varied in both groups independently from RF concentration; RF CAP correlated with both systemic and articular disease activity; and total RF concentration correlated with articular findings and nodules but less well with systemic disease activity.

Serum IgG and IgM rheumatoid factors and complement activation in extraarticular rheumatoid disease.

Rheumatoid factors (RF) may participate in both synovial and extraarticular (EA) inflammation in rheumatoid disease (RD). The relative roles of serum IgG RF and IgM RF in extraarticular rheumatoid disease (EARD) are unclear, as is the importance of complement (C) activation by these proteins. To investigate the relation of C activating properties of IgM RF (RF CAP) and total IgG RF and IgM RF to EARD we compared 18 patients with only articular disease to 27 patients with various EA manifestations (nodules, cutaneous vasculitis, neuropathy, Felty's syndrome) using radioimmunoassays for IgG and IgM RF and an established hemolytic assay for C activation by IgM RF. We calculated RF CAP by determining the mean hemolysis of sensitized SRBC/ml of RF serum (MH/ml). Normal volunteers and patients with other inflammatory arthritides served as controls. Controls had negligible amounts of IgG RF, IgM RF, and RF CAP. Mean IgG and IgM RF levels and RF CAP values were significantly higher in patients with EARD than those in the arthritis-only (AO) group. Mean IgM RF concentrations and IgM RF CAP correlated with each other and EARD. IgG RF also correlated with IgM RF and EARD, but did not contribute to RF CAP or EARD when adjusted for IgM RF. Further, some patients had high RF CAP values despite modest IgM RF levels. These data suggest that quantitative differences in IgM RF CAP and total IgM RF may be more important than IgG RF as determinants of EARD.

The immune complex pathogenesis of glomerulonephritis and pulmonary vasculitis in Behçet's disease.

A kidney and lung biopsy were performed on a patient with active Behçet's disease with renal and pulmonary involvement. Histologic, immunohistochemical and electron microscopic studies of the kidney biopsy specimen revealed a focal segmental necrotizing glomerulonephritis characterized by the presence of numerous subendothelial and occasional intramembranous deposits containing immunoglobulin G (IgG), the third component of complement (C3), the fourth component of complement (C4) and fibrin(ogen). Histologic and immunohistochemical studies of the lung biopsy specimen showed an acute venulitis and septal capillaritis associated with the presence of identical deposits within the walls of affected vessels. Circulating immune complexes were detected in the patient's serum by Raji cell assay. The findings indicate that the glomerulonephritis and pulmonary vasculitis occasionally occurring in Behçet's disease are due to the deposition of circulating antigen-antibody complexes. In addition, they strongly suggest that the majority of the major and minor manifestations of the disease, such as uveitis, cutaneous vasculitis, synovitis and meningoencephalitis, are a result of vascular immune complex deposition.

Roentgenologic, immunologic, and therapeutic study of erosive (inflammatory) osteoarthritis.

The terms erosive or inflammatory osteoarthritis refer to an inflammatory condition of the interphalangeal joints of the hand. In this report, observations of 15 patients with erosive osteoarthritis are described. The principal clinical features are symmetrical synovitis of the interphalangeal joints of the hand, the knees, and the first carpometacarpal, interphalangeal, and metacarpophalangeal joints. The principal roentgenographic features are productive and destructive osseous changes. These changes, found particularly at the interphalangeal joints of the hand, consist of both central and peripheral articular erosions and cysts associated with adjacent osteophyte formation. Serologic abnormalities commonly found in rheumatoid arthritis are rarely encountered. In two thirds of the patients, the synovial fluid is noninflammatory; in the remainder, it is mildly to severely inflammatory. The injection of intra-articular corticosteroids predictably results in decreased synovitis but does not seem to affect the subsequent development of erosions.