Acid pH augments excitatory action of ATP on a dissociated mammalian sensory neuron

ATP stimulates nociceptive neurons via an action on ligand-gated ion channels. Since tissue injury and inflammation result in both localized acidosis and release of ATP, we studied the effect of acid pH on ATP-gated ion channels in rat nodose ganglion neurons. Lowering pH dramatically increased membrane depolarization and action potential firing elicited by ATP. ATP-activated current was enhanced by acid pH and suppressed by alkaline pH. A pH of 7.2 produced the half-maximal effect. Acidification increased the apparent affinity of the receptor for ATP, as evidenced by a parallel shift of the ATP concentration-response curve to the left. The observations suggest that the localized acidosis associated with tissue injury may enhance pain perception via an action on ATP-gated ion channels on mammalian sensory neurons.     

Effects of configuration on the myocardial uptake of radioiodinated 3(R)-BMIPP and 3(S)-BMIPP in rats

Radioiodinated 3(R)-(+)- and 3(S)-(-)-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) were prepared and evaluated in rats to investigate the effects of absolute configuration of the 3(beta)-methyl group on myocardial uptake and release kinetics. METHODS: The 3(R)-(+)-BMIPP analog was synthesized by initial acylation of a thiophene template with the acid chloride of ethyl 3(R)-methylglutarate. 3(S)-(-)-BMIPP was obtained by separation from the mixture of diastereomeric amides prepared from reaction of the acid chloride of racemic BMIPP with the S-(-)-alpha-methylbenzylamine. The amide of synthetic 3(R)-BMIPP prepared from S-(-)-alpha-methylbenzylamine was identical to the chromatographically more polar isomer. Free acids were obtained by acid hydrolysis of the amides, fully characterized and then converted to the radioiodinated BMIPP isomers. RESULTS: Biodistribution studies in rats with the dual-labeled [(131)I]-3(S)-BMIPP/[(125)I]-3(R)-BMIPP mixture demonstrated greater myocardial uptake of 3(R)-BMIPP compared with the 3(S)-BMIPP isomer [60 min: 3(R)-BMIPP = 4.37 %ID/g; 3(S)-BMIPP = 3.44; p < 0.05; 180 min, 2.31 and 1.78 %ID/G, respectively, p < 0.01], although both isomers had similar myocardial washout curves (5-180 min). Percent ID/g values for other tissues which were examined (blood, lungs, thyroid) were similar. CONCLUSION: Higher myocardial uptake of the 3(R)-BMIPP isomer observed in these animal studies may suggest differences in carrier-mediated myocyte uptake of the two isomers. These studies suggest that [(123)I]-3(R)-BMIPP is a candidate for clinical evaluation and may show greater myocardial uptake than the 3(S)-BMIPP isomer and may thus require reduced injected dose.     

Naturally occurring truncated trkB receptors have dominant inhibitory effects on brain-derived neurotrophic factor signaling

trkB encodes a receptor tyrosine kinase activated by three neurotrophins--brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4/5. In vivo, three isoforms of the receptor are generated by differential splicing--gp145trkB or the full-length trkB receptor, and trkB.T1 and trkB.T2, two cytoplasmically truncated receptors that lack kinases, but contain unique C termini. Although the truncated receptors appear to be precisely regulated during nervous system development and regeneration, their role in neurotrophin signaling has not been directly tested. In this paper, we studied the signaling properties and interactions of gp145trkB, trkB.T1, and trkB.T2 by expressing the receptors in a Xenopus oocyte microinjection assay. We found that oocytes expressing gp145trkB, but not trkB.T1 or trkB.T2, were capable of eliciting 45Ca efflux responses (a phospholipase C-gamma-mediated mechanism) after stimulation by BDNF. When trkB.T1 and trkB.T2 were coexpressed with gp145trkB, they acted as dominant negative receptors, inhibiting the BDNF signal by forming nonfunctional heterodimers with the full-length receptors. An ATP-binding mutant of gp145trkB had similar dominant inhibitory effects. Our data suggest that naturally occurring truncated trkB receptors function as inhibitory modulators of neurotrophin responsiveness. Furthermore, the homodimerization of gp145trkB appears to be an essential step in activation of the BDNF signaling cascade.     

European surveillance of infectious diseases: the case of AIDS and tuberculosis

In 1992, the Maastricht treaty gave specific responsibilities to the European Community in the field of research, information and health education. Several European surveillance systems for infectious diseases have been organised. The surveillance of AIDS was set up in 1984 after the emergence of this new disease. Seven western European countries participated initially. The system currently covers 48 of the 51 countries of the WHO European region. Based on a common case definition, it enables analysis of trends and comparisons which considerably facilitate the understanding of the epidemic and its determinants, and the evaluation of preventive actions. European countries have now decided to set up a reporting system for HIV infection. The surveillance of tuberculosis started in 1996 in response to the reversal of trends in reported cases observed in western Europe and to the threat of multi-drug resistant tuberculosis epidemics. Common recommendations on definitions and data collection procedures facilitated its establishment. Most countries of the WHO European region participated in the first year, revealing a very heterogeneous epidemiological situation. The next objective is to set up a surveillance system for antituberculosis drug resistance. The European surveillance of AIDS and tuberculosis are examples of systems adapted to the specific characteristics of Europe: similarities in diagnostic procedures, similarities in access to treatments, and common requirements regarding both the exchange of information and the coordinated response to public health threats. They are not simply looking for a common denominator. They are creating a real momentum among participating countries towards a better quality and a higher level of pertinence of the information.     

Polymorphism of the h allele and the population frequency of sporadic nonfunctional alleles

This study has investigated the effect of elevating intracellular calcium levels, using an internal calcium ATPase inhibitor, 2,5-di(tert-butyl) hydroquinone (TBQ), on human sperm function. Isolated sperm samples from five fertile donors were incubated in a capacitating media for up to 6 hr. After 0, 3, and 6 hr incubation, sperm were exposed to a range of TBQ concentrations; 100 microM, 10 microM, and 1 microM, for a fixed incubation period of 5 min. Controls were run for each experiment where sperm were incubated for 5 min in the absence of TBQ. Sperm capacitation and the acrosome reaction were monitored prior to and after exposure to TBQ, using the Chlortetracycline assay. In addition, sperm motility was assessed at each time point and after sperm had been exposed to TBQ. The treatment of sperm with TBQ caused a significant increase in the number of capacitated sperm with an optimum response being achieved in the presence of 100 microM TBQ. However, sperm motility was found not to be effected by the addition of TBQ. The results from the present study suggest that elevating intracellular calcium levels in human sperm by short exposure to a high concentration of TBQ can rapidly accelerate the capacitation process. Furthermore, the observation that TBQ did not elicit a change in sperm motility suggests that TBQ may be highly specific in its mode of action by acting within the head region of human sperm.     

MRI-radiofrequency tissue tagging in patients with aortic insufficiency before and after operation

We examined the relation between language dominance and regional cerebral blood flow (rCBF) during the intracarotid amobarbital procedure (IAP). A previous report limited to three patients suggested that dominant rather than nondominant hemisphere IAP may have a differential effect on rCBF. Behavioral assessment during the IAP also suggests that dominant hemisphere injection results in a differential effect on memory and affective symptoms rather than nondominant injection. Thirteen patients were assessed using single-photon emission CT (SPECT) brain imaging during both left and right IAP. The SPECTs were coregistered with the individual's MRI. Changes in rCBF during each IAP were compared with the patient's baseline SPECT. Nine patients had left hemisphere dominance, two were right dominant, and two had bilateral speech representation. In the left dominant subjects, left-hemisphere injection had a consistently greater effect on rCBF than right-hemisphere injection in the anterior (p < 0.005) and posterior (p < 0.01) temporal neocortex. There was also a trend for greater hypoperfusion in the frontal lobe of the left hemisphere. rCBF in the ipsilateral hippocampus was not significantly different after each injection (p > 0.05). In the two patients with right hemisphere speech, the reverse pattern was seen, with greater hypoperfusion after right (dominant) hemisphere injection. There was no consistent asymmetry in the two patients with bilateral speech. Dominant hemisphere IAP results in significantly greater hypoperfusion than does nondominant injection. These data provide a physiologic basis for behavioral differences noted after dominant versus nondominant IAP.     

Structural and electrical properties of polycrystalline silicon films deposited by low pressure chemical vapor deposition with and without plasma enhancement

Silicon thin films prepared by chemical vapor deposition of silane at very low pressures (4 mTorr) in an experimental reactor that allows deposition with and without plasma enhancement have been characterized. The temperature range of the substrates on which the films were deposited was varied from 500 to 800° C for plasma-enhanced depositions and 600 to 800° C for nonplasma depositions. Conductivity measurements as a function of temperature as well as average grain size and crystallographic texture measurements were performed. The results indicate that the films deposited with the assistance of a plasma were amorphous at deposition temperatures of 650° C and below and polycrystalline at deposition temperatures of 700° C and above. In the temperature regime investigated, this amorphous-to-crystalline transition was not observed in films deposited without the assistance of a plasma. Furthermore, all the films deposited at temperatures of 650° C and below have been found to have significantly different properties from the similarly prepared films deposited at higher temperatures.