Evaluation of biochemical changes during in vivo erythrocyte senescence in the dog

One hypothesis to explain the age-dependent clearance of red blood cells (RBCs) from circulation proposes that denatured/oxidized hemoglobin (hemichromes) arising late during an RBC's life span induces clustering of the integral membrane protein, band 3. In turn, band 3 clustering generates an epitope on the senescent cell surface leading to autologous IgG binding and consequent phagocytosis. Because dog RBCs have survival characteristics that closely resemble those of human RBCs (ie, low random RBC loss, approximately 115-day life span), we decided to test several aspects of the above hypothesis in the canine model, where in vivo aged cells of defined age could be evaluated for biochemical changes. For this purpose, dog RBCs were biotinylated in vivo and retrieved for biochemical analysis at various later dates using avidin-coated magnetic beads. Consistent with the above hypothesis, senescent dog RBCs were found to contain measurably elevated membrane-bound (denatured) globin and a sevenfold enhancement of surface-associated autologous IgG. Interestingly, dog RBCs that were allowed to senesce for 115 days in vivo also suffered from compromised intracellular reducing power, containing only 30% of the reduced glutathione found in unfractionated cells. Although the small quantity of cells of age >/=110 days did not allow direct quantitation of band 3 clustering, it was nevertheless possible to exploit single-cell microdeformation methods to evaluate the fraction of band 3 molecules that had lost their normal skeletal linkages and were free to cluster in response to hemichrome binding. Importantly, band 3 in RBCs >/=112 days old was found to be 25% less restrained by skeletal interactions than band 3 in control cells, indicating that the normal linkages between band 3 and the membrane skeleton had been substantially disrupted. Interestingly, the protein 4.1a/protein 4.1b ratio, commonly assumed to reflect RBC age, was found to be maximal in RBCs isolated only 58 days after labeling, implying that while this marker is useful for identifying very young populations of RBCs, it is not a very sensitive marker for canine senescent RBCs. Taken together, these data argue that several of the readily testable elements of the above hypothesis implicating band 3 in human RBC senescence can be validated in an appropriate canine model.     

Differential reactivity of the rat S100A4(p9Ka) gene to sodium bisulfite is associated with differential levels of the S100A4 (p9Ka) mRNA in rat mammary epithelial cells

Elevated intracellular levels of S100A4, an S100-related calcium-binding protein, induce metastatic capability in benign mammary tumor-derived epithelial cells and in transgenic mice bearing oncogene-induced benign mammary tumors. The S100A4(p9Ka) gene in rat mammary epithelial cells expressing low levels of S100A4 yields a reduced number of fragments upon digestion with the methylation-sensitive restriction enzyme, HpaII, compared with the gene from high S100A4-expressing cells. Genomic sequencing of two potential regulatory elements in the S100A4 gene, an intronic enhancer and TATA box region, revealed that in low S100A4-expressing cells, most cytosine bases exhibited high levels of resistance to conversion to thymine by sodium bisulfite. In derivative cell lines, which express high levels of S100A4, only a small number of cytosine bases were resistant to treatment with sodium bisulfite. In contrast, cytosine bases in the DNA surrounding an upstream regulatory region, which binds inhibitory GC factor in the low-expressing cell lines, are sensitive to conversion to thymine by sodium bisulfite in both low- and high-expressing cell lines. The results suggest that the rat S100A4 gene is maintained in a different state in the low-expressing cell lines and that this state might be a consequence of the pattern of methylation in this regulated gene that does not contain a CpG island.     

Influence of Acidity on the Electrostatic Stability of Alumina Suspensions in Ethanol

Alumina (Al₂O₃) powders have been dispersed in ethanol (EtOH) solutions of different acidity. In aqueous media, acidity is defined by pH. This definition can be extended to nonaqueous media using ion-transfer functions. The electrical charge on the particle surfaces has been found to be acidity dependent. The electrostatic stability of Al₂O₃EtOH suspensions has been evaluated via electrophoresis and turbidity. An electrostatic stabilization mechanism is proposed and analyzed via Derjaguin–Landau–Verwey–Overbeek (DLVO) theory.     

Lexical access and phonological decoding in adult dyslexic subtypes.

Lexical access and phonological decoding were tested in 100 normal adult readers and 21 adult dyslexic individuals. Within the dyslexic sample, 11 dysphonetic dyslexic and 10 dyseidetic dyslexic participants were classified on the basis of spelling patterns. In the 1st experiment, adult dyseidetic readers showed a marked deficit on the lexical-access decision task in comparison with adult dysphonetic readers. In the 2nd experiment, the phonological-decoding decision task did not separate the subtypes. A lexical-access deficit in adult dyseidetic dyslexia cannot be explained in terms of a developmental delay. A phonological-decoding deficit in adult dyseidetic dyslexia may be explained by increased involvement of the lexical procedure in phonological assembly under an analogy strategy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improved supercontinuum generation through UV processing of highly nonlinear fibers

We demonstrate that UV exposure of highly nonlinear, germano-silicate fibers can significantly broaden the infrared supercontinuum generated by femtosecond pulses in these fibers. Both simulations and measurements of the fiber chromatic dispersion show that UV-induced refractive index changes increase the waveguide dispersion by up to 5 ps/(nm-km) at 1570 nm and shift the dispersion zero by over 100 nm. We examine fibers with a range of UV exposure levels and show that the short wavelength edge of the supercontinuum can be continuously changed by more than 100 nm. We also show that the long wavelength edge is extended beyond that of the unexposed fiber. The resulting continuum spans from 0.85 to 2.6 /spl mu/m. Cutback measurements show that the supercontinuum in the exposed fiber is generated in as little as 1 cm of fiber. A nonlinear Schro/spl uml/dinger equation (NLSE) model of the supercontinuum generation in the nonlinear fiber shows that the short wavelength behavior of the continuum is primarily controlled by changes in the fiber dispersion caused by the UV-induced change in refractive index of the fiber core.     

Development of attitude strength over the life cycle: surge and decline

This article explores the relation of age to manifestations and antecedents of attitude strength. Three studies demonstrate that susceptibility to attitude change is greater during early and late adulthood than during middle adulthood. Three additional studies demonstrate that attitude importance, certainty, and perceived quantity of attitude-relevant knowledge are greater in middle adulthood than during early or late adulthood. These antecedents may therefore explain life cycle shifts in susceptibility to change. Susceptibility to change, importance, certainty, and perceived knowledge differ from one another in terms of their correlations with education, gender, and race, challenging the notion that attitude strength is a unitary construct. Evidence that people incorrectly believe that susceptibility to change declines steadily over the life course reinforces the distinction between operative and meta-attitudinal measures of attitude strength.     

Selective serotonin reuptake inhibitors in pregnancy and lactation

Selective serotonin reuptake inhibitors (SSRIs) have become the agents of first choice in the treatment of depression because of their safe side effect profile. This paper reviews the current literature on the use of SSRIs in pregnancy and lactation concerning their safety. There are human studies that only used fluoxetine in pregnancy, which established its safety. SSRIs are excreted in breast milk, and their long-term effects on the newborn are unknown at this time. The decision to use SSRIs in pregnancy should be made on a case by case basis with active involvement of the patient in the informed consent process during which the risks and benefits are discussed and documented.     

AIDS Clinical Trials Group Study 094: a phase I/II trial of ABV chemotherapy with zidovudine and recombinant human GM-CSF in AIDS-related Kaposi''s sarcoma

The aim of this study was to evaluate psychosocial quality of life after heart transplantation. We examined 29 patients (25 M and 4 F), average age was 43.5 y (18-62 y). The age at time of heart transplantation was 43 years (17-55 y). The time after heart transplantation was 3.3 year (0.3-9 y). Spielberger's Questionnaire of Anxiety, Knobloch's inventory of neuroticism, Freiburg's Personality Inventory and Quality of Life Inventory were used, 33% of patients demonstrated increasing frequency and 29% of patients increasing intensity of neurotic symptoms. 23% of patients presented increasing levels of anxiety (as a state). The personality dimensions (depression, excitability and low emotional stability) displayed high frequency. The results showed that patients were more satisfied with family support, with sexual activities, and less satisfied with financial situation, social activities, social isolations, sleep, memory, excitability, fatigue. 41.5% of patients returned back to work. The results indicate that these psychosocial factors play an important role in quality of life after heart transplantation. That is why if is necessary to dedicate an increasing attention to them. (Tab. 1, Fig. 6, Ref. 14.)     

Effect of a nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, including inflammatory epithelial cells. NO has been detected in the exhaled air of normal human subjects, and its concentration is raised in asthmatic patients. To study whether exhaled NO arises from the respiratory tract, we administered a NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA), by inhalation (490 mg) in a double-blind randomized manner in nine normal and six asthmatic subjects. Because exhaled NO may arise from an inducible isoform of NO synthase that may be inhibited by glucocorticosteroids, we also studied the effects of oral prednisolone (30 mg orally for 3 d) in seven normal and six asthmatic subjects in a separate double-blind crossover study with matched placebo. After nebulized L-NMMA, there was a significant fall in peak exhaled NO compared with saline control values, with a mean fall of 43.6 +/- 5.6% in normal subjects (p < 0.01) and of 39.7 +/- 6.5% (p < 0.01) in asthmatic subjects, which persisted for 4 h. There were no effects of L-NMMA inhalation on heart rate, blood pressure, or FEV1 in either normal or asthmatic patients. Administration of oral prednisolone (30 mg) resulted in a fall in exhaled NO concentrations in asthmatic subjects by 21.6 +/- 5.0% at 48 h (p < 0.01) but no significant change in normal subjects. These data suggest that NOS inhibitors may be safely given in normal and asthmatic patients and that the increased exhaled NO seen in asthmatic patients is likely to be caused by induction of inducible NOS.