The public health and brief interventions for excessive alcohol consumption: The british experience

Widely disseminated brief interventions against excessive drinking, as part of the new public health movement, have a potentially crucial role in reducing alcohol-related harm on a national scale. However, a number of conceptual problems and practical barriers to progress in this area can already be identified. This article focuses on the British experience of research and implementation of community-based brief interventions, which is longer than that of other countries, as a means of discussing these problems. Rather than being pessimistic about the possible impact of brief interventions, the article is based on the assumption that it is only by clearly recognizing and solving such problems that the potential of brief interventions in the alcohol field will be fully realized.     

The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: A 31P, 23Na and 87Rb NMR spectroscopic study

An increase in intracellular Na⁺ during ischaemia has been associated with myocardial injury. In this study, we determined whether inhibition of Na⁺/K⁺ ATPase activity contributes to this increase and whether Na⁺/K⁺ ATPase activity can be maintained by provision of glucose to perfused rat hearts during low flow, 0.5 ml/min, ischemia. We used ³¹P NMR spectroscopy to determine changes in myocardial energetics and intracellular and extracellular volumes. ²³Na NMR spectroscopy, with DyTTHA^3- present as a shift reagent, was used to measure changes in intracellular Na⁺ and ⁸⁷Rb NMR spectroscopy was used to estimate Na⁺/K⁺ ATPase activity from Rb⁺ influx rates, Rb⁺ being an NMR-sensitive congener of K⁺. In hearts provided with 11 mM glucose throughout ischemia, glycolysis continued and ATP was twofold higher than in hearts without glucose. In the glucose-hearts, Rb⁺ influx rate was threefold higher, intracellular Na⁺ was fivefold lower at the end of ischemia and functional recovery during reperfusion was twofold higher. We propose that continuation of glycolysis throughout low flow ischemia allowed maintenance of sufficient Na⁺/K⁺ ATPase activity to prevent the increase in intracellular Na⁺ that would otherwise have led to myocardial injury.     

Tritiated Uridine Uptake in the Retinal Ganglion Cell Layer of the Cat during Normal Development and after Visual Cortex Ablation

The short-term metabolic response of immature retinal ganglion cells to destruction of their target cells in the dorsal lateral geniculate nucleus (dLGN) was assessed in newborn cats. Retrograde degeneration of virtually all dLGN cells was induced by ablation of the 13 contiguous areas of visual cortex on the day of birth. The metabolic response of retinal ganglion cells to this loss of target cells in dLGN was determined by exposing the ganglion cell layer to tritiated uridine, a precursor of RNA. Control measurements were made from unoperated littermates. Following sectioning and processing of the retinae from both groups of kittens for autoradiography, silver grain densities overlying the cellular profiles in the ganglion cell layer were calculated. These calculations revealed levels of uridine incorporation at Postnatal Day 4 in both groups of kittens significantly higher than at either Postnatal Day 2 or 7, but no significant differences between the two groups on any day examined. These results show that the level of RNA synthesis in retinal ganglion cells increases temporarily during the first postnatal week and that this synthesis is unaffected by the death of target cells in the dLGN. The temporary increase may be related to the establishment of synaptic connections on retinal ganglion cells by their afferent bipolar and amacrine neurons in the inner nuclear layer.     

Protein antigen-monoclonal antibody contact sites investigated by limited proteolysis of monoclonal antibody-bound antigen: protein "footprinting"

This study describes the use of limited proteolysis of monoclonal antibody (mAb)-bound antigens in the analysis of the two measles virus surface glycoproteins. This approach is dubbed protein "footprinting" in analogy with DNA "footprinting." Protein footprinting was superior to competitive-binding assays and as good as in vitro mAb-selected variant analysis in differentiating among mAbs with various specificities to a given protein. Proteolytic digestion of the antigen prior to mAb binding drastically reduced mAb binding resulting in poor differentiation among mAbs. In contrast, protein footprinting showed that some mAbs retained the ability to immunoprecipitate such fragments. Thus footprinting could be used for localization of mAb epitopes on a protein and proved also to be an effective means of distinguishing among mAb-selected variants differing in single epitopes. Conformational changes caused by heat-denaturation or the binding of anti-antibody to an antigen-antibody complex could also be detected by footprinting.     

Renal clearance and protein binding of melphalan in patients with cancer

Summary The renal clearance of melphalan and the fraction unbound in plasma were determined after intravenous infusion of 5 mg/m² over 5 min in nine patients with cancer to obtain information regarding the mechanism of renal handling of melphalan. Four of the patients underwent bone marrow transplantation and also received an IV dose of 220 mg/m². Total melphalan clearance after the 5 mg/m² dose ranged from 66.0 to 272 ml/min per m²; the percentage of the dose excreted unchanged in urine, from 2.5% to 92.8%; renal clearance, from 4.1 to 188 ml/min per m²; the fraction unbound in plasma, from 0.0598 to 0.460; and t_1/2, from 39.4 to 84.3 min. Unbound melphalan clearance and renal clearance calculated from the unbound fraction in plasma for each patient ranged from 441 to 3356 ml/min per m² and 15 to 961 ml/min per m² respectively and were not related to serum albumin, serum creatinine or creatinine clearance. The percentage of the dose exctreted and melphalan renal clearance were not related to urine flow. There was evidence of active secretion of melphalan in the kidney an possible reabsorption. There were no significant paired differences in melphalan disposition between the high- and low-dose studies. Highly variable renal clearance involving active secretion may contribute in part to large interpatient differences in the total plasma clearance of melphalan in patients with cancer.This study was supported by a grant from The Queen Elizabeth Hospital Research Foundation     

Aspects of three dimensional reconstruction for a multi ring positron tomography

An important feature of multi ring positron tomographs is the inter plane septa, the purpose of which is to reduce random and scattered coincidences. In general, such septa also eliminate the coincidence lines of response between pairs of detectors more than one ring apart. The operation of a camera without septa must result in an increase not only in the true coincidence rate, but also in the singles, and therefore in the dead time and randoms rate, and in the scattered coincidences. A configuration option in the coincidence hardware of the 8 ring, 15 slice ECAT 931/08-12 enables a full set of 64 sinograms to be acquired when the septa are removed. The detector normalisation and transmission data for studies with the septa out can be obtained using a rotating pin source. To take maximum advantage of the additional signal, the emission data must be reconstructed using a fully three dimensional reconstruction algorithm. This paper presents an analysis of some phantom studies acquired without septa and reconstructed in three dimensions. The results are compared with data acquired with septa for the same phantoms imaged under similar conditions. It is found that, with the septa removed, the signal to noise for a uniform, 20 cm diameter cylinder improves by a factor of 2.8 in the centre of the field of view, whereas in regions distant from the centre in the axial direction, the signal to noise decreases due to the increase in scatter and randoms. An improvement in signal to noise is observed in 6 cm of the 10 cm axial length of the tomograph.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)     

The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones

LIM kinase 1 (LIMK1) controls important cellular functions such as morphogenesis, cell motility, tumor cell metastasis, development of neuronal projections, and growth cone actin dynamics. We have investigated the role of the RING finger protein Rnf6 during neuronal development and detected high Rnf6 protein levels in developing axonal projections of motor and DRG neurons during mouse embryogenesis as well as cultured hippocampal neurons. RNAi-mediated knock-down experiments in primary hippocampal neurons identified Rnf6 as a regulator of axon outgrowth. Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons. Rnf6 is functionally linked to LIMK1 during the development of axons, as the changes in axon outgrowth induced by up- or down-regulation of Rnf6 levels can be restored by modulation of LIMK1 expression. Thus, these results assign a specific role for Rnf6 in the control of cellular LIMK1 concentrations and indicate a new function for the ubiquitin/proteasome system in regulating local growth cone actin dynamics.     

Comparison of the morphology of three coronaviruses

Summary The morphology of three coronaviruses; avian infectious bronchitis virus strain Connecticut (IBV Conn), human coronavirus strain 229E (HCV 229E) and mouse hepatitis virus strain 3 (MHV3), were examined by negative staining. Significant differences were found in the sizes of the three coronaviruses. Furthermore, three types of surface projection of the same lengths, but varying widths and morphology, were observed. Both IBV Conn and HCV 229E had bulbous projections characteristic of coronaviruses, although the projections of HCV 229E were somewhat thinner than those of IBV Conn. On the other hand, MHV3 particles had thin, cone-shaped surface projections, that were completely unlike typical coronavirus projections. The significance of these results is discussed.With 3 Figures     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.