Is it possible to determine use of hospice palliative care services by matching hospice and cancer registry data?

Population-based studies investigating access to palliative care often use death in a hospice as a proxy for service use. We linked data from a large South London hospice to Thames Cancer Registry (TCR) data to determine whether patients who received hospice services differed from those who did not. We matched hospice data for 2474 cancer patients dying between 2000 and 2006, while resident within a restricted catchment area, to TCR data for residents in this area. During matching 14.2% (n = 352) of hospice patients were excluded due to differing key dates or addresses. In addition, 5.6% (n= 175) of residents initially defined as not receiving hospice services were recorded as dying in a hospice in the TCR dataset. The problems of overlapping catchment areas and of defining patients receiving services meant we could not adequately determine use of hospice services. This method might be applied more successfully to non-urban hospices, primary care trusts or larger regions.

Novel intercellular communication system in Escherichia coli that confers antibiotic resistance between physically separated populations.

AIMS: To determine whether intercellular signalling can occur between physically separated populations of Escherichia coli. METHODS AND RESULTS: Intercellular signalling between physically discrete populations of E. coli BL21 was analysed in bi-partite Petri dishes. Transfer of a growth-promoting signal resulted in induction of resistance to the antibiotic ampicillin. Optimal expression of the signal occurred when the signalling population was established as a bacterial lawn for 24 h. This represented an entry into the stationary phase of growth, as indicated by the expression profile of the RNA polymerase subunit sigma38 (sigmaS; sigma S). The growth-promoting effect was also observed when E. coli DH5alpha (luxS-) was used as the signalling population. Preventing passage of air between the two populations resulted in a complete cessation of the growth-promoting effect. CONCLUSIONS: A growth-promoting signal occurs between physically separated cultures of E. coli. The exact nature of the signal remains to be determined but does not involve the production of autoinducer-2 from the luxS gene. Signal transmission is likely to involve airborne transfer of a signal species. SIGNIFICANCE AND IMPACT OF THE STUDY: Intercellular signalling systems exist in bacteria that enable antibiotic resistance to be conferred between physically separated populations.

Illusory perceptions of space and time preserve cross-saccadic perceptual continuity.

When voluntary saccadic eye movements are made to a silently ticking clock, observers sometimes think that the second hand takes longer than normal to move to its next position. For a short period, the clock appears to have stopped (chronostasis). Here we show that the illusion occurs because the brain extends the percept of the saccadic target backwards in time to just before the onset of the saccade. This occurs every time we move the eyes but it is only perceived when an external time reference alerts us to the phenomenon. The illusion does not seem to depend on the shift of spatial attention that accompanies the saccade. However, if the target is moved unpredictably during the saccade, breaking perception of the target's spatial continuity, then the illusion disappears. We suggest that temporal extension of the target's percept is one of the mechanisms that 'fill in' the perceptual 'gap' during saccadic suppression. The effect is critically linked to perceptual mechanisms that identify a target's spatial stability.

Development of a neuronal pressure sensor.

Neuronal sensory systems are capable of performing very complex signal processing functions. Reconstruction of such sensory systems in vitro should enable whole-cell biological sensors to be generated that possess inherent signal processing capabilities. In this paper, the results of preliminary investigations to produce a mechanosensory neuronal network are presented. An in vitro network of rat dorsal root ganglion neurons has been produced on a microelectrode plate revealing an interesting rhythmical pattern of spontaneous discharges. This periodic activity has been shown to be disrupted following the application of a static pressure to the cell culture. These results indicate that neuronal networks represent a practical system that may be used for the development of intelligent, whole-cell, biological sensors.

Induction of calreticulin expression in response to amino acid deprivation in Chinese hamster ovary cells.

The role of calreticulin as a stress-induced molecular chaperone protein of the endoplasmic reticulum is becoming more apparent. We characterize here the induction of calreticulin in response to complete amino acid deprivation in Chinese hamster ovary cells. Amino acid deprivation caused a 4-fold increase in calreticulin protein levels over a period of 4-10 h. In addition to an overall increase in protein levels, the glycosylation of calreticulin was increased. This glycosylation event was blocked by tunicamycin and was not required for the increase in calreticulin protein levels. Immunofluorescence studies localized calreticulin to the ER of CHO cells, and no significant change was observed after amino acid deprivation. Northern-blot analysis showed that calreticulin mRNA levels were increased approx. 10-fold in response to complete amino acid deprivation. The response was sensitive to actinomycin D and alpha-amanitin, implying that regulation is primarily at the level of transcription. These results are similar to the large increases in asparagine synthetase mRNA observed in response to amino acid deprivation, but the amino acid-deprivation-response element identified to be involved in asparagine synthetase induction is absent from the calreticulin promoter.

Induction of the stress protein Grp75 by amino acid deprivation in CHO cells does not involve an increase in Grp75 mRNA levels.

The induction of the stress protein Grp75 in response to amino acid deprivation of Chinese Hamster Ovary cells was characterised using a specific monoclonal antibody. A 2-fold increase in the Grp75 protein content occurred over a period of 5-10 h after incubation of the cells in amino acid-free medium. A partial induction was obtained when either all non-essential amino acids or all essential amino acids were omitted from the medium indicating a broad-specificity response. Deletion of the single amino acids tryptophan, histidine or phenylalanine from otherwise complete medium also produced a partial induction of the protein. The increase in the level of Grp75 was completely blocked by cycloheximide, but only partially blocked by the inhibitors of mRNA synthesis actinomycin D and alpha-amanitin. A specific cDNA probe for Grp75 was generated by PCR and used to quantify mRNA levels. No increase in Grp75 mRNA was observed during the induction of the protein indicating that the primary regulation of Grp75 expression was not at the transcriptional level. These results contrast with the large increase in asparagine synthetase mRNA which has been shown to occur during amino acid deprivation, and indicate that cells respond to this form of stress by more than one mechanism.

NLP-1: a DNA intercalating hypoxic cell radiosensitizer and cytotoxin.

The 2-nitroimidazole linked phenanthridine, NLP-1 (5-[3-(2-nitro-1-imidazoyl)-propyl]-phenanthridinium bromide), was synthesized with the rationale of targeting the nitroimidazole to DNA via the phenanthridine ring. The drug is soluble in aqueous solution (greater than 25 mM) and stable at room temperature. It binds to DNA with a binding constant 1/30 that of ethidium bromide. At a concentration of 0.5 mM, NLP-1 is 8 times more toxic to hypoxic than aerobic cells at 37 degrees C. This concentration is 40 times less than the concentration of misonidazole, a non-intercalating 2-nitroimidazole, required for the same degree of hypoxic cell toxicity. The toxicity of NLP-1 is reduced at least 10-fold at 0 degrees C. Its ability to radiosensitize hypoxic cells is similar to misonidazole at 0 degrees C. Thus the putative targeting of the 2-nitroimidazole, NLP-1, to DNA, via its phenanthridine group, enhances its hypoxic toxicity, but not its radiosensitizing ability under the present test conditions. NLP-1 represents a lead compound for intercalating 2-nitroimidazoles with selective toxicity for hypoxic cells.