Invasion of hereditary ovalocytes by Plasmodium falciparum in vitro and its relation to intracellular ATP concentration

Hereditary ovalocytes (stomatocytic ovalocytes), when examined within 1-2 days from the time that the blood sample is drawn, are invaded by Plasmodium falciparum in culture to the extent of at least 55% of normal control cells. The ovalocytes have extremely rigid membranes, characterised by a shear elastic modulus some 3-4 times greater than that of normal cells. The extent of invasion falls off very much more rapidly than that into normal cells on storage, and we surmise that this is the reason for earlier reports of resistance of ovalocytes to malarial invasion in vitro. The initial loss of susceptibility to invasion with time is not accompanied by any change in membrane rigidity, but is primarily a consequence of a rapid decline in intracellular ATP concentration: this falls to below the threshold level required for invasion (approx. 0.1 mM) over a period in which the ATP in normal cells remains almost constant. Incubation in a metabolic regenerating medium leads to a rise in the intracellular ATP concentration and invasion by P. falciparum is recovered, though to a much lower extent than in normal cells. The resistance of ovalocytes to invasion becomes irreversible, due possibly to degradative processes in the membrane, on further storage. The developing parasites in ovalocytes have a reduced number of merozoites and show distinct morphological abnormalities.     

Bloom syndrome cells undergo p53-dependent apoptosis and delayed assembly of BRCA1 and NBS1 repair complexes at stalled replication forks

Bloom syndrome (BS) is a hereditary disorder characterized by pre- and postnatal growth retardation, genomic instability, and cancer. BLM, the gene defective in BS, encodes a DNA helicase thought to participate in genomic maintenance. We show that BS human fibroblasts undergo extensive apoptosis after DNA damage specifically when DNA replication forks are stalled. Damage during S, but not G1, caused BLM to rapidly form foci with gammaH2AX at replication forks that develop DNA breaks. These BLM foci recruited BRCA1 and NBS1. Damaged BS cells formed BRCA1/NBS1 foci with markedly delayed kinetics. Helicase-defective BLM showed dominant-negative activity with respect to apoptosis, but not BRCA1/NBS1 recruitment, suggesting catalytic and structural roles for BLM. Strikingly, inactivation of p53 prevented the death of damaged BS cells and delayed recruitment of BRCA1/NBS1. These findings suggest that BLM is an early responder to damaged replication forks. Moreover, p53 eliminates cells that rapidly assemble BRCA1/NBS1 without BLM, suggesting that BLM is essential for timely BRCA1/NBS1 function.     

High levels of serum allopregnanolone in women with premature ovarian failure

BACKGROUND: Blue-on-yellow (B/Y) perimetry can reveal visual field defects earlier and larger in extent than white-on-white (W/W) perimetry. The Heidelberg Retina Tomograph (HRT) produces a three-dimensional image of the optic disc. The aim of this study was to compare the strength of the association of the B/Y and W/W visual hemifield mean deviation (HMD) variables with the optic nerve head (ONH) morphological variables of the respective area. METHODS: We evaluated one randomly chosen eye of 40 normal subjects and 37 patients with ocular hypertension and different stages of glaucoma. The B/Y and W/W visual fields (program 30-2) were obtained with a Humphrey perimeter. Results of both visual fields were adjusted for the patient's age and lens transmission index measured with a lens fluorometer. HMD was calculated as the difference between the measured and expected hemifield mean sensitivity values, predicted by the regression model fitted in our nonglaucomatous subject data. The HRT with the software version 1.11 was used to acquire and evaluate the topographic measurements of the optic disc. RESULTS: The B/Y and W/W visual field HMDs showed statistically significant correlation with ONH parameters such as cup shape measure (CSM), rim volume, rim area, mean retinal nerve fiber layer (RNFL) thickness and RNFL cross-sectional area. With forward stepwise logistic regression analysis using B/Y hemifield data 38% of the glaucoma patient's normal W/W hemifields were classified abnormal. With the CSM alone in the model 52% of the cases were classified abnormal. CONCLUSIONS: B/Y visual field hemifield mean deviation values correlate well with ONH parameters examined with the HRT.     

Familial ring (19) chromosome mosaicism: case report and review

Ring (19) chromosomal mosaicism has been identified in a 14-month-old girl referred for cytogenetic evaluation due to microcephaly and developmental delay with autistic-like mannerisms. An analysis of her peripheral blood lymphocytes showed a 46,XX,r(19) cell line in 119/121 of cells examined. Of the two remaining cells, one had a normal female chromosome complement and the other showed loss of one of the chromosome 19 homologs. Further analysis by fluorescence in situ hybridization using an all human telomere probe showed the presence of a single hybridization signal on the r(19) chromosome. Subsequent cytogenetic characterization of cells derived from the patient's phenotypically normal mother also demonstrated the presence of a ring 19 chromosome in 4/100 cells. The remaining cells had a normal female chromosome complement. These findings represent the first reported case of familial ring 19 mosaicism. The cytogenetic and clinical findings in these two individuals are discussed in relation to six previously reported cases of de novo ring chromosome 19 mosaicism.     

Numerical convergence for the Bellman equation of stochastic optimal control with quadratic costs and constraints

A predictor-corrector, Crank-Nicolson computer algorithm is examined for the Bellman equation of stochastic optimal control with quadratic costs and constrained control. A linearized comparison equation is heuristically derived for the nonlinear and discontinuous Bellman equation. Convergence of the method is studied using von Neumann's Fourier stability method. A mesh-ratio-type condition for the convergence is derived for the comparison equation. This condition is uniform for both parabolic and hyperbolic versions of the nonlinear equation. The results are valid for Gaussian stochastic noise and Poisson noise.     

Electron transfer by domain movement in cytochrome bc1

The cytochrome bc1 is one of the three major respiratory enzyme complexes residing in the inner mitochondrial membrane. Cytochrome bc1 transfers electrons from ubiquinol to cytochrome c and uses the energy thus released to form an electrochemical gradient across the inner membrane. Our X-ray crystal structures of the complex from chicken, cow and rabbit in both the presence and absence of inhibitors of quinone oxidation, reveal two different locations for the extrinsic domain of one component of the enzyme, an iron-sulphur protein. One location is close enough to the supposed quinol oxidation site to allow reduction of the Fe-S protein by ubiquinol. The other site is close enough to cytochrome c1 to allow oxidation of the Fe-S protein by the cytochrome. As neither location will allow both reactions to proceed at a suitable rate, the reaction mechanism must involve movement of the extrinsic domain of the Fe-S component in order to shuttle electrons from ubiquinol to cytochrome c1. Such a mechanism has not previously been observed in redox protein complexes.     

Immunoreactivity of Brazilian HIV isolates with different V3 motifs

The influence of noncompetitive (MK-801), competitive (AP-7) and the antagonist of polyamines site of NMDA receptor (arcaine) on the central activity of angiotensin II (A II) was studied. The open field test, conditioning of active avoidance responses (CARs) and passive avoidance situation was used to investigate learning and memory in rats. All used antagonists decreased beneficial action of A II on these processes.