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Biomedical subjects

J A Harrison

Publications and source records attributed to J A Harrison.

At least 19 recordsLinked to original sources
PubMed2006

Expression and localization of VEGF-C and VEGFR-3 in glioblastomas and haemangioblastomas.

Primary human brain tumours account for approximately 2% of all cancers. High levels of expression of vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor, are linked to poor prognosis. In contrast, the potential role in human brain tumour biology of newer VEGF family members, VEGF-C and VEGF-D, both of which are lymphangiogenic factors, is poorly understood. In the present study, the expression of all VEGFs (VEGF-A, -B, -C, and -D) and their receptors (VEGFR-1, -2, and -3) has been assessed in 39 primary human brain tumours. The well-established findings were confirmed with VEGF-A. Surprisingly, however, VEGF-C and VEGF-D, as well as VEGFR-3, were expressed in some tumour types such as haemangioblastomas and glioblastomas, despite their lack of lymphatic vessels. VEGF-C and VEGFR-3 transcripts were localized to the tumour palisade around necrotic areas in glioblastomas and were evenly distributed throughout haemangioblastomas. VEGF-C protein was localized by immunohistochemistry to the palisade layer in glioblastomas. More than 50% of VEGF-C-positive cells also expressed the intermediate-stage inflammatory macrophage marker CD163; however, a significant proportion of VEGF-C-positive cells were CD163-negative. These data demonstrate the presence of molecules, primarily described as regulators of lymphangiogenesis, in normal human brain and brain tumours that are devoid of lymphatics. Their localization in macrophages points to a role in tumour-associated inflammation.

Biomarkers, Tumor↗
PubMed2006

Lymphatic vessel density in the neoplastic progression of Barrett's oesophagus to adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma is an aggressive neoplasm with poor prognosis as a result of early lymph node metastasis. AIMS: To measure lymphatic vessel density (LVD) in the neoplastic progression from Barrett's metaplasia to adenocarcinoma and determine whether LVD can predict the risk of cancer. In addition, to correlate LVD with lymph node metastasis and assess whether LVD could be used as a prognostic indicator for outcome or survival. METHODS: LVD and microvascular density (MVD) were assessed after immunohistochemical staining of vessels in Barrett's metaplasia, dysplasia, and adenocarcinoma tissues and were correlated with clinicopathological features. RESULTS: LVD was significantly reduced in adenocarcinoma, being half that seen in normal stomach/oesophagus or metaplasia/dysplasia. LVD did not correlate with tumour grade, stage, or clinical outcome; however, patients who had either lymph node metastasis or invasion of tumour cells into peritumorous lymphatic vessels had a significantly worse overall survival. MVD was also assessed as a prognostic marker; its increase appeared to be linked more with the development of Barrett's metaplasia than adenocarcinoma. CONCLUSIONS: The reduction in lymphatic vessel numbers was not useful for determining disease outcome in the patient group studied. It is the entry of tumour cells into pre-existing peritumorous lymphatic vessels that confers a significantly worse overall survival.

Adenocarcinoma↗
PubMed2006

Denitrification across landscapes and waterscapes: a synthesis.

Denitrification is a critical process regulating the removal of bioavailable nitrogen (N) from natural and human-altered systems. While it has been extensively studied in terrestrial, freshwater, and marine systems, there has been limited communication among denitrification scientists working in these individual systems. Here, we compare rates of denitrification and controlling factors across a range of ecosystem types. We suggest that terrestrial, freshwater, and marine systems in which denitrification occurs can be organized along a continuum ranging from (1) those in which nitrification and denitrification are tightly coupled in space and time to (2) those in which nitrate production and denitrification are relatively decoupled. In aquatic ecosystems, N inputs influence denitrification rates whereas hydrology and geomorphology influence the proportion of N inputs that are denitrified. Relationships between denitrification and water residence time and N load are remarkably similar across lakes, river reaches, estuaries, and continental shelves. Spatially distributed global models of denitrification suggest that continental shelf sediments account for the largest portion (44%) of total global denitrification, followed by terrestrial soils (22%) and oceanic oxygen minimum zones (OMZs; 14%). Freshwater systems (groundwater, lakes, rivers) account for about 20% and estuaries 1% of total global denitrification. Denitrification of land-based N sources is distributed somewhat differently. Within watersheds, the amount of land-based N denitrified is generally highest in terrestrial soils, with progressively smaller amounts denitrified in groundwater, rivers, lakes and reservoirs, and estuaries. A number of regional exceptions to this general trend of decreasing denitrification in a downstream direction exist, including significant denitrification in continental shelves of N from terrestrial sources. Though terrestrial soils and groundwater are responsible for much denitrification at the watershed scale, per-area denitrification rates in soils and groundwater (kg N x km(-2) x yr(-1)) are, on average, approximately one-tenth the per-area rates of denitrification in lakes, rivers, estuaries, continental shelves, or OMZs. A number of potential approaches to increase denitrification on the landscape, and thus decrease N export to sensitive coastal systems exist. However, these have not generally been widely tested for their effectiveness at scales required to significantly reduce N export at the whole watershed scale.

Agriculture↗
PubMed2004

Use of hand-held laser scanning in the assessment of facial swelling: a preliminary study.

A new generation lightweight, hand-held, laser surface scanner (FastSCAN) was validated and clinically evaluated for the assessment of postoperative facial swelling. The potential sources of error-scanner error, registration error, and repositioning and movement error were established for laser scans of a mannequin head and seven volunteers. For the mannequin head the mean (S.D.) volume of the simulated swelling was 12.5 (0.5) cm3. The measurement error was therefore about 4%, and reflected the error in scanned data and in surface registration. Among the volunteers, repositioning of the head introduced additional errors of up to 7.6 cm3 (mean 1.8 cm3), illustrating the additional influence of variable positions. We then scanned 20 patients (9 women and 11 men, age range 18-26) before and 2 days after, third molar removal. The external, facial soft tissue volume changes were calculated for both left and right sides (range 0.2-64.3 cm3). The main source of inaccuracy was again variability of position. Despite this, the FastSCAN proved to be a simple, accurate, and non-invasive method of measuring postoperative changes in volume in the external, soft tissues of the face. Minimising variability in position by using more precise positioning techniques will increase the accuracy of this technique and is a focus for future work.

Adolescent↗
PubMed2004

Review of the role of alcohol in drowning associated with recreational aquatic activity.

OBJECTIVE AND DESIGN: To assess the role of alcohol in drowning associated with recreational aquatic activity by reviewing the English language literature published up to October 2003. RESULTS: Alcohol is widely used in association with recreational aquatic activity in the United States, but there is minimal information regarding the extent of use elsewhere. A priori and anecdotal evidence suggests that alcohol is an important risk factor for drowning associated with recreational aquatic activity. Specific studies provide good evidence supporting this, but the extent of increased risk associated with alcohol use, and the attributable risk due to alcohol use, is not well characterised. Drowning appears to be the overwhelming cause of death associated with recreational aquatic activity with alcohol detected in the blood in 30%-70% of persons who drown while involved in this activity. The few relevant studies on degree of increased risk suggest persons with a blood alcohol level of 0.10 g/100 ml have about 10 times the risk of death associated with recreational boating compared with persons who have not been drinking, but that even small amounts of alcohol can increase this risk. The population attributable risk seems to be in the range of about 10%-30%. CONCLUSIONS: Alcohol consumption significantly increases the likelihood of immersions resulting in drowning during aquatic activities. However, more information is required if appropriate prevention activities are to be planned, initiated, and evaluated. This includes better information on alcohol use, and attitudes to alcohol use, in association with recreational aquatic activity, and the nature and extent of increased risk associated with alcohol use. Evaluation of interventions is also needed.

Accident Prevention↗
PubMed2001

Crystallization and X-ray diffraction measurements on recombinant molbindin, MopII, from Clostridium pasteurianum.

Clostridium pasteurianum carries three genes termed mopI, II and III encoding three molbindin isoforms, one of which has been cloned, the gene product expressed in high yield and crystallized using the hanging-drop vapour-diffusion method. Well ordered monoclinic crystals in two different crystal forms, both with space group C2, were obtained in the presence and absence of Na(2)MoO(4) and Na(2)WO(4). Ligand-bound MopII crystallized with polyethylene glycol (PEG) 400 as a precipitant, whereas apo MopII required PEG 6000. High-resolution diffraction data were collected for ligand-bound MopII structures using synchrotron radiation to 1.8 and 1.6 A resolution for the molybdate and tungstate complexes, respectively. Data were collected on apoMopII crystals to a resolution of 1.8 A in-house.

Bacterial Proteins↗
PubMed2001

Hydrolase and sialyltransferase activities of trypanosoma cruzi trans-sialidase towards NeuAc-alpha-2,3-gal-Gal-beta-O-PNP.

NeuAc-alpha-2,3-Gal-beta-O-PNP has been synthesised and its ability to act as a substrate for the hydrolase and transferase activities of Trypanosoma cruzi trans-sialidase have been investigated. The turn-over of this compound shows marked differences from the behaviour of NeuAc-MU. In addition, distinct differences in the action of T. cruzi trans-sialidase and Clostridium perfringens neuraminidase on NeuAc-alpha-2,3-Gal-beta-O-PNP were apparent.

Clostridium perfringens↗
PubMed2001

The involvement, understanding and attitudes of dietitians towards research and audit.

AIM: To investigate the involvement of dietitians in research and audit and to assess their understanding of and attitudes towards these activities. METHODS: A postal questionnaire was used to investigate the knowledge, attitude towards and involvement in research and audit of State Registered Dietitians practising in the National Health Service (NHS) in the UK. RESULTS: A response rate of 64% was achieved. Few respondents (15%) were currently involved in research, although more (65%) were currently involved in audit. Involvement in audit rose significantly with increasing grade and managerial responsibility. Dietitians qualifying more recently were more likely to believe that their college training prepared them to undertake research, but felt less confident about undertaking audit. Experience of audit made respondents more confident about auditing their work and improved their belief that they understood audit terminology. Higher grade dietitians were more likely to see audit as an important part of their role than were their more junior colleagues. Understanding of the terms 'research' and 'audit' was poor, although 48% of respondents identified the link between the two activities. Perceived constraints to involvement in research and audit were identified. CONCLUSION: The present level of involvement of dietitians in research and audit activities falls below that recommended in the BDA's (1997a) National Professional Standards for Dietitians Practising in Healthcare. This study identifies factors that influence dietitians' involvement in, understanding of and attitudes towards research and audit and recommends ways of increasing their involvement in these activities.

Adult↗
PubMed2001

Home-style beef jerky: effect of four preparation methods on consumer acceptability and pathogen inactivation.

The safety of homemade jerky continues to be questioned. Producing a safe product that retains acceptable quality attributes is important. Lethality of Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes as well as consumer acceptability and sensory attributes of jerky prepared by four methods were examined. Preparation methods were drying marinated strips at 60 degrees C (representing a traditional method), boiling strips in marinade or heating in an oven to 71 degrees C prior to drying, and heating strips in an oven after drying to 71 degrees C. A 60-member consumer panel rated overall acceptability. A 10-member descriptive panel evaluated quality attributes. Samples heated after drying and samples boiled in marinade prior to drying had slightly higher acceptability scores but were not statistically different from traditional samples. Although the four treatments were significantly different in color (P = 0.0001), saltiness (P = 0.0001), and texture (P = 0.0324), only texture appeared to influence overall consumer acceptability. Microbial challenge studies subjecting the pathogens to the four treatments showed a 5.8-, 3.9-, and 4.6-log reduction of E. coli O157:H7, L. monocytogenes, and Salmonella, respectively, even with traditional drying. Oven treatment of strips after drying was shown to have the potential to reduce pathogen populations further by approximately 2 logs. In conclusion, a safer, yet acceptable home-dried beef jerky product can be produced by oven-heating jerky strips after drying.

Animals↗
PubMed2000

Tetanus toxin fragment C expressed in live Salmonella vaccines enhances antibody responses to its fusion partner Schistosoma haematobium glutathione S-transferase.

Tetanus toxoid has been used widely as an adjuvant. The atoxic fragment C from tetanus toxin (TetC) is potently immunogenic when expressed in Salmonella vaccine strains and has been used as a fusion partner for antigens (Ag). However, there has been no formal comparison of the immunomodulatory impact of TetC on its fusion partners. In this study, we have addressed this important issue. The protective 28-kDa glutathione S-transferase (GST) from Schistosoma haematobium (Sh28GST) was expressed either as a fusion to TetC or as the full-length Sh28GST alone in a nonvirulent aroA-attenuated strain of Salmonella enterica serovar Typhimurium. The Sh28GST proteins were soluble and stably expressed in Salmonella, as evaluated by Western blotting with TetC and/or Sh28GST antisera. Mice were immunized orally with a single dose of the live recombinant Salmonella. The constructs were stable in mice but, dramatically, only the strain expressing the TetC-Sh28GST fusion elicited significant antibody (Ab) responses directed against Sh28GST as determined by enzyme-linked immunosorbent assay. An analysis of the isotype profiles showed that these mice also produced anti-Sh28GST immunoglobulin A and GST-neutralizing assays revealed high levels of neutralizing Abs in sera. These are important correlates of protection in schistosomiasis. In addition, stimulation of spleen cells from immunized mice with Sh28GST Ag showed that both strains, expressing Sh28GST alone or the TetC-Sh28GST fusion, were able to stimulate the secretion of Th1-related cytokines (gamma interferon and interleukin 2) to comparable levels. Thus, TetC has modulated the immune responses generated against its fusion partner, Sh28GST, by markedly enhancing the Ab responses elicited. These results have important implications in the rational development of live vaccines.

Adjuvants, Immunologic↗
PubMed1999

The role of the C-terminal domain in the inhibitory functions of tissue factor pathway inhibitor.

Tissue factor pathway inhibitor (TFPI) inhibits the activity of coagulation factors VIIa and Xa through Kunitz domains, thereby inhibiting the activity of tissue factor. However, it has been shown that the C-terminal of this inhibitor is essential for the maximal anticoagulant activity of TFPI. We have investigated the endogenous ability of the C-terminal of TFPI to influence coagulation. A synthetic peptide corresponding to residues 254-265 within the C-terminal of TFPI was prepared and shown to be capable of inhibiting tissue factor pathway by preventing the activation of factor VII. Mutational analysis of the peptide revealed the identity of the key lysine residues.

Amino Acid Sequence↗
PubMed1999

Interleukin 18 contributes to host resistance and gamma interferon production in mice infected with virulent Salmonella typhimurium.

Spleen and peritoneal macrophages obtained from innately resistant A/J mice released low levels of interleukin 18 (IL-18) upon infection with Salmonella typhimurium C5 RP4. Incubating the cells with recombinant gamma interferon (rIFN-gamma) enhanced IL-18 production. A/J mice treated in vivo with anti-IL-18 antibodies showed impaired resistance to infection, with increased bacterial loads in the liver and spleen. Administration of rIL-18 could protect A/J mice from challenge with a lethal dose of virulent salmonellae, with a dramatic reduction in bacterial numbers in the tissues. rIL-18 administration did not ameliorate the disease in IFN-gamma-R-/- mice. IL-18 proved to be required for IFN-gamma production by mouse splenocytes from conventional, scid, and rag-1(-/-) mice; in vivo IL-18 neutralization caused a decrease in circulating IFN-gamma levels. Thus, IL-18 is a key factor in early host resistance to Salmonella and probably acts via IFN-gamma.

Animals↗
PubMed1998

Single photon infrared emission spectroscopy: a study of IR emission from UV laser excited PAHs between 3 and 15 micrometers.

Single-photon infrared emission spectroscopy (SPIRES) has been used to measure emission spectra from polycyclic aromatic hydrocarbons (PAHs). A supersonic free-jet expansion has been used to provide emission spectra of rotationally cold and vibrationally excited naphthalene and benzene. Under these conditions, the observed width of the 3.3-micrometers (C-H stretch) band resembles the bandwidths observed in experiments in which emission is observed from naphthalene with higher rotational energy. To obtain complete coverage of IR wavelengths relevant to the unidentified infrared bands (UIRs), UV laser-induced desorption was used to generate gas-phase highly excited PAHs. Lorentzian band shapes were convoluted with the monochromator-slit function in order to determine the widths of PAH emission bands under astrophysically relevant conditions. Bandwidths were also extracted from bands consisting of multiple normal modes blended together. These parameters are grouped according to the functional groups mostly involved in the vibration, and mean bandwidths are obtained. These bandwidths are larger than the widths of the corresponding UIR bands. However, when the comparison is limited to the largest PAHs studied, the bandwidths are slightly smaller than the corresponding UIR bands. These parameters can be used to model emission spectra from PAH cations and cations of larger PAHs, which are better candidate carriers of the UIRs.

Argon↗
PubMed1998

Interleukin-12 is required for control of the growth of attenuated aromatic-compound-dependent salmonellae in BALB/c mice: role of gamma interferon and macrophage activation.

The attenuated S. typhimurium SL3261 (aroA) strain causes mild infections in BALB/c mice. We were able to exacerbate the disease by administering anti-interleukin-12 (IL-12) antibodies, resulting in bacterial counts in the spleens and livers of anti-IL-12-treated mice that were 10- to 100-fold higher than the ones normally observed in premortem mice; yet the animals showed only mild signs of illness. Nevertheless, they eventually died of a slow, progressive disease. Mice infected with salmonellae become hypersusceptible to endotoxin. We found that IL-12 neutralization prevented the death of infected mice following subcutaneous injection of lipopolysaccharide. Granulomatous lesions developed in the spleens and livers of control animals, as opposed to a widespread infiltration of mononuclear cells seen in the organs of anti-IL-12-treated mice. In the latter (heavily infected), salmonellae were seen within mononuclear cells, indicating an impairment of the bactericidal or bacteriostatic ability of the phagocytes in the absence of biologically active IL-12. Gamma interferon (IFN-gamma) levels were reduced in the sera and tissue homogenates from anti-IL-12-treated mice compared to those in control animals. Furthermore, fluorescence-activated cell sorter analysis on spleen cells showed that IL-12 neutralization impaired the upregulation of I-Ad/I-Ed antigens on macrophages from infected mice. Inducible nitric oxide synthase and IFN-gamma mRNA production was down-regulated in anti-IL-12-treated mice, which also showed an increased production of IL-10 mRNA and a decrease in nitric oxide synthase activity in the tissues. Administration of recombinant IFN-gamma to anti-IL-12-treated mice was able to restore host resistance, granuloma formation, and expression of major histocompatibility complex class II antigens in F4/80(+) and CD11b+ spleen cells.

Animals↗
PubMed1998

Survival of Escherichia coli O157:H7 in ground beef jerky assessed on two plating media.

Recent outbreaks of food-borne illness due to Salmonella spp. in beef jerky and Escherichia coli O157:H7 in venison jerky, coupled with the fact that a variety of preparation methods and dying procedures abound, raise concern over the safety of processed meat products made in the home. The potential of injured bacterial cells to regain the ability to cause illness is a particular threat with pathogens such as E. coli O157:H7, which is believed to have a low infectious dose. This study examined the efficacy of various methods of jerky preparation in reducing populations of E, coli O157:H7 in ground beef jerky and compared the recovery rate of E. coli O157:H7 on two selective plating media, modified sorbitol MacConkey agar (MSMA) and modified eosin methylene blue agar (MEMB). Populations of E. coli O157:H7 in both heated and unheated samples exhibited a greater decline during drying when a nitrite and salt cure mix was added during jerky preparation. When recovery of E. coli O157:H7 on MSMA and MEMB was compared, a trend toward slightly higher recovery rates with MEMB was observed. On the basis of these results, MEMB is a suitable alternative to MSMA for the recovery of E. coli O157:H7 from heated and dried meat samples similar to beef jerky.

Animals↗