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Biomedical subjects

S Lowe

Publications and source records attributed to S Lowe.

At least 19 recordsLinked to original sources
PubMed2006

Odour emissions from anaerobic piggery ponds. 1. Results of a three season, 14-month survey.

Odour emission rates were measured for seven different anaerobic ponds treating piggery wastes at six to nine discrete locations across the surface of each pond on each sampling occasion over a 14-month period. Emission rate values varied between ponds, between seasons for the same pond and even for the same pond on different days of a sampling week. Average seasonal emission rates ranged from 7.9 to 46.5OU/m(2)s, while average emission rates ranged from 16.0 to 29.0OU/m(2)s. Factors potentially responsible for the variability in emission rates were investigated, including air and pond liquor temperatures, time of day of sample collection, season and the impact of a prolonged drought.

Animals↗
PubMed2006

Odour emissions from anaerobic piggery ponds. 2: improving estimates of emission rate through recognition of spatial variability.

Odour emission rates were measured for seven different anaerobic ponds treating piggery wastes at six to nine discrete locations across the surface of each pond on each sampling occasion over a thirteen month period. Significant variability in emission rates were observed for each pond. Measurement of a number of water quality variables in pond liquor samples collected at the same time and from the same locations as the odour samples indicated that the composition of the pond liquor was also variable. The results indicated that spatial variability was a real phenomenon and could have a significant impact on odour assessment practices. Considerably more odour samples would be required to characterise pond emissions than currently recommended by most practitioners, or regulatory agencies.

Animals↗
PubMed2006

Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report.

As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas Ligand (FasL). As an important note, and in contrast to somatic cell therapy trials, there are no reported deaths due to therapeutic vector administration in any cancer gene therapy trial. That said, from our studies and from the published literature, the issue of gene delivery remains the major obstacle to successfully employing gene therapy for cancer treatment. Numerous laboratories are studying this with many different approaches. My co-workers and I have focused on the delivery issue by using various approaches that address tumor targeting and transgene expression. In addition, we are focusing on enhancing tumor cell killing via the bystander effect and through use of small molecules to enhance bystander activity.

Adenoviridae↗
PubMed2006

p53 tumor suppressor protein regulates the levels of huntingtin gene expression.

The p53 protein is a transcription factor that integrates various cellular stress signals. The accumulation of the mutant huntingtin protein with an expanded polyglutamine tract plays a central role in the pathology of human Huntington's disease. We found that the huntingtin gene contains multiple putative p53-responsive elements and p53 binds to these elements both in vivo and in vitro. p53 activation in cultured human cells, either by a temperature-sensitive mutant p53 protein or by gamma-irradiation (gamma-irradiation), increases huntingtin mRNA and protein expression. Similarly, murine huntingtin also contains multiple putative p53-responsive elements and its expression is induced by p53 activation in cultured cells. Moreover, gamma-irradiation, which activates p53, increases huntingtin gene expression in the striatum and cortex of mouse brain, the major pathological sites for Huntington's disease, in p53+/+ but not the isogenic p53-/- mice. These results demonstrate that p53 protein can regulate huntingtin expression at transcriptional level, and suggest that a p53 stress response could be a modulator of the process of Huntington's disease.

Animals↗
PubMed2005

Sentinel node biopsy should be supplemented by axillary sampling in patients with small breast cancers.

Axillary clearance provides important prognostic information but is associated with significant morbidity. Sentinel node biopsy can provide staging .141 patients with node negative early breast cancers-tumour size less than 1.5 cm measured clinically or by imaging had guided axillary sampling (sentinel lymph node biopsy in combination with axillary sampling). Four node axillary sampling improved the detection rate of axillary node metastases by 13.6% as compared to blue dye sentinel node biopsy alone. Positive sampled nodes strongly indicated the likelihood of further metastatic being revealed by axillary dissection (67%). Negative sampled nodes in combination with a positive sentinel node biopsy were associated with a much lower rate of further nodal involvement in the axillary clearance (8%).

Journal Article↗
PubMed2004

Bisphosphonate infusions: patient preference, safety and clinic use.

GOALS OF WORK: We set out to assess the preference of patients with common cancers involving bone receiving intravenous bisphosphonate therapy for either pamidronate (P) or zoledronic acid (Z) and their preference for the location of the infusion (clinic or home). We also aimed to monitor these patients' renal safety, and to compare their time in clinic to receive P and Z infusions. PATIENTS AND METHODS: Enrolled in the study were 184 patients, and all received initial infusions of Z (so any first infusion reactions did not confound preferences for P). For their second and third infusions, patients were randomized to receive Z then P or P then Z, and questioned on their preferences. For up to 1 year they continued on Z infusions every 3-4 weeks, while their renal safety was monitored. Where practical, later infusions were given at home (rather than in the clinic) and patients questioned on their preferred infusion location. In a convenience subset of 43 patients, clinic use for Z and P infusions was also measured by timing infusions and other procedures. MAIN RESULTS: Of 144 patients who received a third infusion, 138 responded to questions on bisphosphonate preference, and of these 138, 92% (127) preferred Z to P, because shorter infusions caused less disruption to their day. Only 12% of eligible patients (16/138) received home infusions, but 13/14 questioned preferred this location. Among 184 patients, 19 episodes of renal impairment were noted, mostly owing to disease progression (e.g. obstructive uropathy), with none linked to Z therapy. The mean clinic time taken to receive Z and any concomitant therapy was about half that for P (78 vs 161 min). CONCLUSIONS: Cancer patients prefer shorter bisphosphonate infusions-and at home, where practical. Regular Z 4 mg infusions appear to be safe in these patients, with routine monitoring of serum creatinine. Using Z rather than P could save busy cancer centres time and improve patient satisfaction.

Adult↗
PubMed2003

Causes of sediment toxicity to Mytilus galloprovincialis in San Francisco Bay, California.

Since the San Francisco Regional Monitoring Program (RMP) sampling began, elutriate samples prepared with sediment from the Grizzly Bay monitoring station have been consistently toxic to bivalve larvae (Mytilus galloprovincialis). An investigation into the cause of toxicity was initiated with a Phase I Toxicity Identification Evaluation (TIE) using bivalve embryos. TIE results and chemical analyses of elutriate samples suggested that divalent metals were responsible for the observed toxicity. Following the initial characterization of trace metals as toxicants, additional TIEs were performed on elutriates prepared from three additional Grizzly Bay samples collected between 1997 and 2001. Additional TIEs included ethylenediamine tetraacetic acid (EDTA) treatments in a sediment-water interface (SWI) exposure system, and the use of a cation exchange column with serial elution of sample fractions with hydrochloric acid of increasing normality. EDTA significantly reduced toxicity in overlying water in the SWI system. The cation exchange column reduced both toxicity and concentrations of trace metals, and serial elution of the column added back both toxicity and specific metals contained in individual acid fractions. Chemical analyses of three elutriate samples demonstrated copper concentrations were within the range toxic to bivalves. Results of Phase I TIEs, additional Phase II treatments, SWI exposures, and metals analyses indicate the potential for metal toxicity in sediments from this estuarine site. When combined with the results of standard TIE methods, a solid-phase cation extraction and elution approach identified copper as the most probable cause of toxicity.

Animals↗
PubMed2001

A novel mammalian receptor for the evolutionarily conserved type II GnRH.

Mammalian gonadotropin-releasing hormone (GnRH I: pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) stimulates pituitary gonadotropin secretion, which in turn stimulates the gonads. Whereas a hypothalamic form of GnRH of variable structure (designated type I) had been shown to regulate reproduction through a cognate type I receptor, it has recently become evident that most vertebrates have one or two other forms of GnRH. One of these, designated type II GnRH (GnRH II: pGlu-His-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2), is conserved from fish to man and is widely distributed in the brain, suggesting important neuromodulatory functions such as regulating K+ channels and stimulating sexual arousal. We now report the cloning of a type II GnRH receptor from marmoset cDNA. The receptor has only 41% identity with the type I receptor and, unlike the type I receptor, has a carboxyl-terminal tail. The receptor is highly selective for GnRH II. As with the type I receptor, it couples to G(alpha)q/11 and also activates extracellular signal-regulated kinase (ERK1/2) but differs in activating p38 mitogen activated protein (MAP) kinase. The type II receptor is more widely distributed than the type I receptor and is expressed throughout the brain, including areas associated with sexual arousal, and in diverse non-neural and reproductive tissues, suggesting a variety of functions. Surprisingly, the type II receptor is expressed in the majority of gonadotropes. The presence of two GnRH receptors in gonadotropes, together with the differences in their signaling, suggests different roles in gonadotrope functioning.

Amino Acid Sequence↗
PubMed2001

Creation of a new transgene cloning site near the right ITR of Ad5 results in reduced enhancer interference with tissue-specific and regulatable promoters.

Tissue-specific transgene expression is a valuable research tool and is of great importance in delivering toxic gene products with adenovirus vectors to tumors. Limiting cytotoxic gene expression to the target cells is highly desirable. While a number of successful applications of tissue- and tumor-specific gene expression using Ad vectors has been reported, cloning of some promoters into Ad vectors resulted in modulation or loss of tissue specificity. This phenomenon is likely the result of the interaction of E1A enhancer (and possibly other Ad sequences) with the promoter cloned in the E1 region. We have compared performance parameters of prostate-specific and tet-regulatable promoters in plasmids containing the terminal repeat sequences of Ad5 with or without the E1A enhancer. Subsequently, adenoviral vectors were constructed containing identical expression units either in the E1 region or near the right ITR, and tested in several cell lines. Here, we report that promoters placed near the right ITR of Ad5 retain higher selectivity and lower background expression in both plasmid and adenovirus vectors. We confirm that the E1A enhancer can interfere with the desired activity of nearby promoters, and describe an alternative transgene insertion site for construction of Ad vectors.

Adenoviridae↗
PubMed2000

Development of the Handicap Assessment and Resource Tool (HART).

An important determinant of whether people can live in community settings is the absence of significant handicap. People with considerable disabilities can live without handicap if they have adequate supports. Handicap, rather than disability, limits peoples' residence options. Disability assessment tools are commonly used to guide where people can live--these assess neither the resources available nor the personal-care handicap present. The Handicap Assessment and Resource Tool (HART) was designed to provide information about the personal-care issues (clothing, hygiene, nutrition, mobility, safety, residence and supports) relevant to choice of residence. The HART was tested by occupational therapists who are frequently expected to provide recommendations regarding disabled clients' residence options. It is a client-centred tool that addresses key occupational performance components of personal care. Pilot testing in hospital and community settings shows the HART is a comprehensive and practical tool that is acceptable to users and clients.

Activities of Daily Living↗
PubMed1999

Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports.

OBJECTIVE: To receive and collate reports of death or major complications of transfusion of blood or components. DESIGN: Haematologists were invited confidentially to report deaths and major complications after blood transfusion during October 1996 to September 1998. SETTING: Hospitals in United Kingdom and Ireland. SUBJECTS: Patients who died or experienced serious complications, as defined below, associated with transfusion of red cells, platelets, fresh frozen plasma, or cryoprecipitate. MAIN OUTCOME MEASURES: Death, "wrong" blood transfused to patient, acute and delayed transfusion reactions, transfusion related acute lung injury, transfusion associated graft versus host disease, post-transfusion purpura, and infection transmitted by transfusion. Circumstances relating to these cases and relative frequency of complications. RESULTS: Over 24 months, 366 cases were reported, of which 191 (52%) were "wrong blood to patient" episodes. Analysis of these revealed multiple errors of identification, often beginning when blood was collected from the blood bank. There were 22 deaths from all causes, including three from ABO incompatibility. There were 12 infections: four bacterial (one fatal), seven viral, and one fatal case of malaria. During the second 12 months, 164/424 hospitals (39%) submitted a "nil to report" return. CONCLUSIONS: Transfusion is now extremely safe, but vigilance is needed to ensure correct identification of blood and patient. Staff education should include awareness of ABO incompatibility and bacterial contamination as causes of life threatening reactions to blood.

Blood Component Transfusion↗
PubMed1999

Laser-induced fluorescence (LIF) recognition of the structural composition of porcine heart valves.

Reconstruction and replacement of heart valves with grafts fro pig tissue is a common procedure. However, bioprosthetic valves wear out in a shorter time span than mechanical valves. Bioprosthetic valve structure may contribute to degenerative changes that lead to valve failure. There is, at present, no method to examine the structure of a tissue valve prior to implant. Laser-induced fluorescence (LIF) of natural fluorophores is an elegant method developed for the detection of tumors, dermal lesions and atherosclerosis. We have studied LIF as a potential diagnostic technique for analysis of valvular tissue. Using excimer laser excitation, we examined natural fluorescence recorded from porcine aortic, mitral and pulmonary valves. All three valve outflow surface tissue layers are less fluorescent at 390-450 nm than the inflow layers. Immunohistochemical analysis of collagen I and elastin content in inflow and outflow surface layers of all three valves correlated well with LIF intensities and dI/d lambda values at selected wavelengths. In conclusion, the differences observed in emitted LIF from valve surface layers are found to correlate well with diversity in the structural protein content. The LIF spectroscopic measurements may provide an appropriate tool for examination of tissue valve structure prior to use for implantation.

Animals↗
PubMed1999

Glucolipsin A and B, two new glucokinase activators produced by Streptomyces purpurogeniscleroticus and Nocardia vaccinii.

During the screening of the natural products for their ability to increase the activity of glucokinase by relieving inhibition by long chain fatty acyl CoA esters (FAC), two novel compounds, glucolipsin A (1) and B (2) were isolated from the butanol extracts of Streptomyces purpurogeniscleroticus WC71634 and Nocardia vaccinii WC65712, respectively. The structures of these two compounds were established by spectroscopic methods and chemical degradation. Glucolipsin A (1) and B (2) relieved the inhibition of glucokinase by FAC with RC50 values of 5.4 and 4.6 microM.

Disaccharides↗