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1.  Contribution of solid fuel, gas combustion or tobacco smoke to indoor air pollutant concentrations in Irish and Scottish homes 
Indoor air  2011;22(3):212-223.
There are limited data describing pollutant levels inside homes that burn solid fuel within developed country settings with most studies describing test conditions or the effect of interventions. This study recruited homes in Ireland and Scotland where open combustion processes take place. Open combustion was classified as coal, peat or wood fuel burning, use of a gas cooker or stove, or where there is at least one resident smoker. 24-hour data on airborne concentrations of particulate matter less than 2.5 microns in size (PM2.5), carbon monoxide (CO), endotoxin in inhalable dust and carbon dioxide (CO2), together with 2–3 week averaged concentrations of nitrogen dioxide (NO2) were collected in 100 houses during the winter and spring of 2009–2010.
The geometric mean of the 24-hour time-weighted-average (TWA) PM2.5 concentration was highest in homes with resident smokers (99μg/m3 – much higher than the WHO 24-hour guidance value of 25 μg/m3. Lower geometric mean 24-hour TWA levels were found in homes that burned coal (7 μg/m3) or wood (6 μg/m3) and in homes with gas cookers (7 μg/m3). In peat-burning homes the average 24-hourPM2.5 level recorded was 11 μg/m3. Airborne endotoxin, CO, CO2 and NO2 concentrations were generally within indoor air quality guidance levels.
doi:10.1111/j.1600-0668.2011.00755.x
PMCID: PMC3573694  PMID: 22007695
indoor; pollution; solid-fuel; biomass; environmental tobacco smoke; homes; health
2.  Locomotor Networks are Targets of Modulation by Sensory Transient Receptor Potential Vanilloid 1 and Transient Receptor Potential Melastatin 8 Channels 
Neuroscience  2009;162(4):1377-1397.
It is well recognized that proprioceptive afferent inputs can control the timing and pattern of locomotion. C and Aδ afferents can also affect locomotion but an unresolved issue is the identity of the subsets of these afferents that encode defined modalities. Over the last decade, the transient receptor potential (TRP) ion channels have emerged as a family of non-selective cation conductances that can label specific subsets of afferents. We focus on a class of TRPs known as ThermoTRPs which are well known to be sensor receptors that transduce changes in heat and cold. ThermoTRPs are known to help encode somatosensation and painful stimuli, and receptors have been found on C and Aδ afferents with central projections onto dorsal horn laminae. Here we show, using in vitro neonatal mouse spinal cord preparations, that activation of both spinal and peripheral transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential melastatin 8 (TRPM8) afferent terminals modulates central pattern generators (CPGs). Capsaicin or menthol and cooling modulated both sacrocaudal afferent (SCA) evoked and monoaminergic drug-induced rhythmic locomotor-like activity in spinal cords from wild type but not TRPV1-null (trpv1−/−) or TRPM8-null (trpm8−/−) mice, respectively. Capsaicin induced an initial increase in excitability of the lumbar motor networks, while menthol or cooling caused a decrease in excitability. Capsaicin and menthol actions on CPGs involved excitatory and inhibitory glutamatergic mechanisms, respectively. These results for the first time show that dedicated pathways of somatosensation and pain identified by TRPV1 or TRPM8 can target spinal locomotor CPGs.
doi:10.1016/j.neuroscience.2009.05.063
PMCID: PMC2880570  PMID: 19482068
TRP; mouse spinal cord; locomotor rhythm; CPG; capsaicin; menthol
3.  Prostate cancer treated by anti-androgens: is sexual function preserved? 
British Journal of Cancer  2000;82(2):283-290.
This paper reports on results of the EORTC protocol 30892, an open, prospective, randomized study of 310 patients with previously untreated metastatic prostate cancer with favourable prognostic factors who were treated by either flutamide (FLU) or cyproterone acetate (CPA) monotherapy. The final analysis with regard to the main end points, time to progression and survival are still pending. Final results related to the evaluation of sexual functioning prior to and under treatment are reported here. Of 310 randomized patients 294 were eligible for evaluation within this side study. The median age was 71 years (range 48–85). Potential risk factors related to age, general health and prostate cancer were evaluated. For evaluation of sexual functions a five-item questionnaire was used which was administered by the investigator. The protocol allowed time dependent observations at 3-monthly follow-up visits. Sexual functioning was dependent on age but not on prostate cancer-related parameters. Sexual functions at entry were similar within the two treatment groups, spontaneous (nightly) erections and sexual activity were seen in 43–51% and 29–35% of cases. Under treatment, sexual functions under FLU and CPA declined slowly with median times of 12.9 and 5.8 months versus 13.7 and 8.9 months respectively for spontaneous erections and sexual activity. Eventually, with an average observation time in excess of 2 years, loss of spontaneous erections and of sexual activity occurred in 80% versus 92% and in 78% versus 88% of men under FLU versus CPA treatment respectively. None of these differences reached statistical significance. Maintenance of potency under treatment with FLU as reported in the literature is not confirmed in this study. However, loss of sexual functions under monotherapy with both antiandrogens is slow and 10–20% of men retain sexual activity after 2–6 years of treatment. This observation can be exploited in new treatment schemes and is likely to lead to improved quality of life. The advantage of FLU in time and total preservation of sexual functions is statistically not significant and must be balanced against the side effects of FLU and other pure antiandrogens, which may exceed those of CPA especially with respect to gynaecomastia. Hepatic toxicity may limit the long-term use of both drugs. © 2000 Cancer Research Campaign
doi:10.1054/bjoc.1999.0916
PMCID: PMC2363280  PMID: 10646878
prostate cancer; anti-androgens; sexual function
4.  Soluble forms of the adhesion molecule E-cadherin in urine. 
Journal of Clinical Pathology  1995;48(2):179-180.
The adhesion molecule E-cadherin is essential for maintaining epithelial intercellular adhesion. Loss or reduced expression of E-cadherin has been related to invasive behaviour in a wide range of carcinomas. Using immunoblotting techniques, the existence of multiple soluble forms of E-cadherin was demonstrated in urine from healthy volunteers and patients with benign urinary tract disorders or bladder cancer. The existence of soluble forms of E-cadherin in the urine may reflect shedding from the urinary tract epithelium as part of the normal turnover of this molecule. The possibility that enhanced shedding may contribute to the loss of E-cadherin expression/function in malignancy is discussed.
Images
PMCID: PMC502407  PMID: 7745120
5.  cis-Acting signals involved in termination of vesicular stomatitis virus mRNA synthesis include the conserved AUAC and the U7 signal for polyadenylation. 
Journal of Virology  1997;71(11):8718-8725.
We investigated the cis-acting sequences involved in termination of vesicular stomatis virus mRNA synthesis by using bicistronic genomic analogs. All of the cis-acting signals necessary for termination reside within the first 13 nucleotides of the 23-nucleotide conserved gene junction. This 13-nucleotide termination sequence at the end of the upstream gene comprises the tetranucleotide AUAC, the tract containing seven uridines (U7 tract), and the intergenic dinucleotide (GA), but it does not include the downstream gene start sequence. Data presented here show that upstream mRNA termination is independent of downstream mRNA initiation. Alteration of any nucleotide in the 13-nucleotide sequence decreased the termination activity of the gene junction and resulted in increased synthesis of a bicistronic readthrough RNA. This finding indicated that the wild-type gene junction has evolved to achieve the maximum termination efficiency. The most critical position of the AUAC sequence was the C, which could not be altered without complete loss of mRNA termination. Reducing the length of the wild-type U7 tract to zero, five, or six U residues also totally abolished mRNA termination, resulting in exclusive synthesis of the bicistronic readthrough mRNA. Shortening the wild-type U7 tract to either five or six U residues abolished VSV polymerase slippage during readthrough RNA synthesis. Since neither the U5 nor U6 template was able to direct mRNA termination, these data imply that polymerase slippage is a prerequisite for termination. Evidence is also presented to show that in addition to causing polymerase slippage, the U7 tract itself or its poly(A) product constitutes an essential signal for mRNA termination.
PMCID: PMC192336  PMID: 9343230
6.  Role of the intergenic dinucleotide in vesicular stomatitis virus RNA transcription. 
Journal of Virology  1997;71(3):1794-1801.
To investigate the role played by the intergenic dinucleotide sequence of the conserved vesicular stomatitis virus (VSV) gene junction in modulation of polymerase activity, we analyzed the RNA synthesis activities of bicistrionic genomic analogs that contained either the authentic N/P gene junction or gene junctions that had been altered to contain either the 16 possible dinucleotide combinations, single nucleotide intergenic sequences, or no intergenic sequence at all. Quantitative measurements of the amounts of upstream, downstream, and readthrough mRNAs that were transcribed by these mutant templates showed that the behavior of the viral polymerase was profoundly affected by the nucleotide sequence that it encountered as it traversed the gene junction, although the polymerase was able to accommodate a remarkable degree of sequence variation without altogether losing the ability to terminate and reinitiate transcription. Alteration or removal of the intergenic sequence such that the U tract responsible for synthesis of the upstream mRNA poly(A) tail was effectively positioned adjacent to the consensus downstream gene start signal resulted in almost complete abrogation of downstream mRNA synthesis, thus defining the intergenic sequence as an essential sequence element of the gene junction. Many genome analogs with altered intergenic sequences directed abundant synthesis of a readthrough transcript without correspondingly high levels of downstream mRNA, an observation inconsistent with the shunting model of VSV transcription, which suggests that polymerase molecules are prepositioned at gene junctions, awaiting a push from upstream. Instead, the findings of this study support a model of sequential transcription in which initiation of downstream mRNA can occur only following termination of the preceding transcript.
PMCID: PMC191248  PMID: 9032308
7.  Prostate-specific membrane antigen: evidence for the existence of a second related human gene. 
British Journal of Cancer  1995;72(3):583-588.
Prostate-specific membrane antigen (PSM) is a glycoprotein recognised by the prostate-specific monoclonal antibody 7E11-C5, which was raised against the human prostatic carcinoma cell line LNCaP. A cDNA clone for PSM has been described. PSM is of clinical importance for a number of reasons. Radiolabelled antibody is being evaluated both as an imaging agent and as an immunotherapeutic in prostate cancer. Use of the PSM promoter has been advocated for gene therapy applications to drive prostate-specific gene expression. Although PSM is expressed in normal prostate as well as in primary and secondary prostatic carcinoma, different splice variants in malignant tissue afford the prospect of developing reverse transcription-polymerase chain reaction (RT-PCR)-based diagnostic screens for the presence of prostatic carcinoma cells in the circulation. We have undertaken characterisation of the gene for PSM in view of the protein's interesting characteristics. Unexpectedly, we have found that there are other sequences apparently related to PSM in the human genome and that PSM genomic clones map to two separate and distinct loci on human chromosome 11. Investigation of the function of putative PSM-related genes will be necessary to enable us to define fully the role of PSM itself in the development of prostatic carcinoma and in the clinical management of this malignancy.
Images
PMCID: PMC2033874  PMID: 7669565
8.  Dipstick haematuria: its association with smoking and nonsteroidal anti-inflammatory drugs. 
Of 1015 men over the age of 60, 125 (12.3%) were found to have dipstick haematuria on a single test. Analysis of smoking history revealed a 1.6 fold increased incidence of dipstick haematuria in current smokers as compared with ex-smokers and non-smokers. The relationship with bladder cancer and smoking is discussed. Several commonly used drugs, including nonsteroidal anti-inflammatory preparations, have been implicated as a cause of urinary tract bleeding. In this study of 1015 men over the age of 60, no association was found between the presence of dipstick haematuria and the intake of aspirin, other nonsteroidal anti-inflammatory drugs or warfarin.
PMCID: PMC1292557  PMID: 2325056
9.  Dipstick haematuria and bladder cancer in men over 60: results of a community study. 
BMJ : British Medical Journal  1989;299(6706):1010-1012.
OBJECTIVE--To investigate the prevalence and relevance of dipstick haematuria in a group of men in the community. DESIGN--Prospective study of elderly men invited to attend a health centre for urine screening as part of a health check. SETTING--An inner city health centre in Leeds. SUBJECTS--578 Of 855 men aged 60-85 responding to an invitation to participate. INTERVENTIONS--The subjects had their urine tested with a dipstick (Multistix) for the presence of blood and then tested their urine once a week for the next 10 weeks. Those with one or more positive test results were offered full urological investigation. MAIN OUTCOME MEASURE--The prevalence of urological disease in those subjects with dipstick haematuria. RESULTS--78 Men (13%) had dipstick haematuria on a single test and a further 54 (9%) had evidence of dipstick haematuria when testing their urine once a week during a subsequent 10 week period. Investigation of 87 men disclosed urological disease in 45, including four with a bladder tumour and seven with epithelial dysplasia. CONCLUSION--Dipstick haematuria is a common incidental finding in men over 60 and is associated with appreciable urological disease. The introduction of less invasive methods of investigation, particularly flexible cystoscopy and ultrasonography, has made investigation of these patients simple and safe and makes screening for bladder cancer in the community more feasible.
PMCID: PMC1837876  PMID: 2511941
10.  Prevalence of chlamydial infection in acute epididymo-orchitis. 
Genitourinary Medicine  1987;63(1):16-18.
The prevalence of sexually transmitted infection was studied in 40 men presenting with acute epididymo-orchitis in Leeds. Chlamydia trachomatis infection was identified in 13 of 29 men (45%) aged under 35 years. Neisseria gonorrhoeae was isolated from four of these 13 men with chlamydial urethritis. C trachomatis was isolated from the urethra of only one of 11 men (9%) aged over 35. Appreciable bacteriuria was found in six of these 11 men (55%). Noting details of sexual history and screening for sexually acquired pathogens is advocated in younger men with acute epidiymo-orchitis.
PMCID: PMC1193999  PMID: 3817820
12.  Treatment of acute scrotal pain. 
PMCID: PMC1441247  PMID: 6426650
14.  The effects of reinforcement on the modification, maintenance, and generalization of social responses of mental patients1 
Social greeting responses of three withdrawn, chronic schizophrenics were experimentally modified. Initially, none of the subjects spoke to an experimenter. Prompts and cigarette reinforcement were employed to produce increases in the rates of greetings. Then, the prompts were faded so that the greetings came under the control of the presence of the experimenter. Reversal and subsequent reinforcement procedures were employed to demonstrate that the responses were controlled by their consequences. Next, the schedule of cigarette reinforcement was leaned out so that greetings continued to occur in the absence of cigarette reinforcement. However, low or zero rates of greetings occurred in the presence of a second experimenter. Five new experimenters employed the prompting, fading, reinforcement, and schedule-leaning procedures. Subsequently, all subjects emitted appropriately high rates of greetings in the presence of the second experimenter. Without further application of the experimental procedures, greetings were still occurring in the presence of both the first and second experimenters almost three months later.
doi:10.1901/jaba.1968.1-307
PMCID: PMC1311017  PMID: 16795189

Results 1-15 (15)