Transforming growth factor beta-1 (TGFB1) and peak bone mass: association between intragenic polymorphisms and quantitative ultrasound of the heel

Background  

Variance of peak bone mass has a substantial genetic component, as has been shown with twin studies examining quantitative measures such as bone mineral density (BMD) and quantitative ultrasound (QUS). Evidence implicating single nucleotide polymorphisms (SNPs) of the transforming growth factor beta-1 (TGFB1) gene is steadily accumulating. However, a comprehensive look at multiple SNPs at this locus for their association with indices of peak bone mass has not been reported.     

Prekallikrein-Kallikrein conversion rate as a predictor of contrast material catastrophies

An in vitro is described that attempts to detect patients with a potential for adverse systemic reactions to contrast material. This test involves measuring the rate of conversion of prekallikrein to kallikrein under certain standard conditions. In a preliminary retrospective study, the test could be used to identify such patients with a sensitivity of 88%, a specificity of 82%, and a predictive value of 79%.     

Noise trauma alters D-[3H]aspartate release and AMPA binding in chinchilla cochlear nucleus

Exposure of adults to loud noise can overstimulate the auditory system, damage the cochlea, and destroy cochlear nerve axons and their synaptic endings in the brain. Cochlear nerve loss probably results from the death of cochlear inner hair cells (IHC). Additional degeneration in the cochlear nucleus (CN) is hypothesized to stem from overstimulation of the system, which may produce excitotoxicity. This study tested these predictions by exposing one ear of anesthetized adult chinchillas to a loud noise, which damaged the ipsilateral cochlea and induced degeneration in the glutamatergic cochlear nerve. During the first postexposure week, before cochlear nerve axons degenerated, glutamatergic synaptic release in the ipsilateral CN was elevated and uptake was depressed, consistent with hyperactivity of glutamatergic transmission and perhaps with the operation of an excitotoxic mechanism. By 14 days, when cochlear nerve fibers degenerated, glutamatergic synaptic release and uptake in the CN became deficient. By 90 days, a resurgence of transmitter release and an elevation of AMPA receptor binding suggested transmission upregulation through plasticity that resembled changes after mechanical cochlear damage. These changes may contribute to tinnitus and other pathologic symptoms that precede and accompany hearing loss. In contrast, the other ear, protected with a silicone plug during the noise exposure, exhibited virtually no damage in the cochlea or the cochlear nerve. Altered glutamatergic release and AMPA receptor binding activity in the CN suggested upregulatory plasticity driven by signals emanating from the CN on the noise-exposed side.     

Randomised controlled trial of prophylactic etamsylate: follow up at 2 years of age

AIM: To assess the role of etamsylate in reducing the risk of haemorrhagic brain damage and its consequences. DESIGN: Follow up of babies recruited into a randomised controlled trial. METHODS: A total of 334 infants born before 33 weeks gestation in France and Greece were randomly allocated within the first four hours of birth either to receive etamsylate or to act as controls. The principal outcomes in the trial were death or impairment and/or disability at the age of 2 years. RESULTS: Fifty nine children were lost to follow up. A total of 115 (34%) either died or had some impairment or disability, and 88 (26%) either died or had severe impairment or disability at 2 years of age. These outcomes did not differ significantly between the two randomised groups: relative risks and 95% confidence intervals 1.14 (0.78 to 1.4) and 1.17 (0.82 to 1.68) respectively. The findings were similar for all the prespecified subgroup analyses stratified by key prognostic factors at trial entry: country of birth, gestational age < or >or= 29 weeks, inborn or outborn, age < or >or= 1 hour, and with or without cerebral scan abnormality. CONCLUSION: These findings do not support the use of etamsylate. Other strategies need to be evaluated for the prevention of mortality and morbidity in these vulnerable infants.     

Scales for the measurement of attitudes toward blood donation

Attitudes toward blood donation are frequently assumed to vary along a single dimension from unfavorable to favorable. In contrast, theories of attitude structure specify three distinct attitude components: affect, cognition, and behavior. This article describes the development of three new scales for the measurement of affective, cognitive, and behavioral components of attitudes toward blood donation. The scales were developed using the method of equal-appearing intervals and were administered to both donors of blood and nondonors. Correlations among the scales were relatively small and supported the three-component distinction. Affect was more strongly correlated with the number of prior donations than was cognition, which suggested an important role for emotional factors in blood donation. Scores on all three scales showed the attitudes of blood donors to be more favorable than those of nondonors.     

Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10.A recombinant mouse strains

Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.     

Large-volume leukapheresis in pediatric patients: processing more blood diminishes the apparent magnitude of intra-apheresis recruitment

Background: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. Study Design and Methods: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2–19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg × 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. Results: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean ± standard error [SE], 1.00 and 1.39 ± 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 ± 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). Conclusion: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients.     

Group II metabotropic glutamate receptors in anxiety circuitry: correspondence of physiological response and subcellular distribution

Activation of group II metabotropic glutamate receptors (mGluR2/3) in the amygdala plays a critical role in the regulation of fear and anxiety states. Previous studies using nonselective agonists have suggested this action can result from activation of either pre- or postsynaptic mGluR2/3. Here, we have used a combination of whole-cell patch clamp recording with highly selective agonists (LY354740 and LY379268) and immunoelectron microscopy to examine structure-function relationships for mGluR2/3 in the basolateral amygdala (BLA) and bed nucleus of the stria terminalis (BNST). Stimulation of mGluR2/3 evoked a direct, TTX-insensitive membrane hyperpolarization in all BLA projection neurons tested, but only about half of BNST neurons. The membrane hyperpolarization was mediated by activation of an outward potassium current or blockade of a tonically active inward I(h) current in different groups of BLA neurons. In both regions, mGluR2/3 caused a long-lasting reduction of glutamate release from presynaptic afferent terminals even at concentrations that failed to elicit a direct postsynaptic response. The localization of mGluR2/3 differed regionally, with postsynaptic labeling significantly more common in BLA than BNST, corresponding to the strength of postsynaptic responses recorded there. Our results demonstrate a complex role for mGluR2/3 receptors in modulating anxiety circuitry, including direct inhibition and reduction of excitatory drive. The combination of direct inhibition of projection neurons within the BLA and suppression of excitatory neurotransmission in the BNST may be responsible for the anxiolytic actions of group II mGluR agonists.