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Biomedical subjects

Paul Gibbs

Publications and source records attributed to Paul Gibbs.

18 recordsLinked to original sources
PubMed2006

Cadmium availability to wheat grain in soils treated with sewage sludge or metal salts.

Grain Cd concentrations were determined in wheat (Triticum aestivum L.) grown in 1999, 2001 and 2003, at six sludge cake field experiments. Three of these sites also had comparisons with Cd availability from metal amended liquid sludge and metal salts. Grain Cd concentrations in all years and at all sites were significantly linearly correlated with NH4NO3 extractable Cd and soil total Cd (P<0.001). Soil extractability was greater in the liquid sludge and metal salt experiments than in the cake experiments, as were grain Cd concentrations. Across all the sites, NH4NO3 extractable soil Cd was no better at predicting grain Cd than soil total Cd. Stepwise multiple linear regression analysis showed that soil total Cd, pH and organic carbon were the only significant (P<0.001) variables influencing wheat grain Cd concentrations, explaining 78% of the variance across all field experiments (1408 plots). This regression predicted that the current UK soil total Cd limit of 3 mg kg(-1) was not sufficiently protective against producing grain above the European Union (EU) grain Cd Maximum Permissible Concentration (MPC) of 0.235 mg Cd kg(-1) dry weight, unless the soil pH was > 6.8. Our predictions show that grain would be below the MPC with > 95% confidence with the proposed new EU draft regulations permitting maximum total Cd concentrations in soils receiving sludge of 0.5 mg kg(-1) for soils of pH 5-6, 1 mg kg(-1) for soils of pH 6-7, and 1.5 mg kg(-1) for soils of pH > or = 7.

Cadmium↗
PubMed2006

Recombinant C fragment of botulinum neurotoxin B serotype (rBoNTB (HC)) immune response and protection in the rhesus monkey.

Botulinum neurotoxin B (BoNTB) is a distinct protein subtype of a family of neurotoxins with the potential for use in biological warfare or terrorist attacks. This study is one in a series evaluating the immunogenicity and protective effects of recombinant vaccines against the different subtypes of botulinum toxin. The recombinant subunit vaccines encoding the C fragment portion ( approximately 50 kDa) of the toxins are produced in the yeast, Pichia pastoris. In this study, groups of rhesus monkeys were vaccinated with three doses (1 and 5microg per dose) of rBoNTB(H(c)) vaccine. Total and neutralizing antibody titers were determined at various times during and postvaccination. Two groups of vaccinated monkeys plus non-vaccinated controls were actively challenged with B toxin by aerosol exposure. All monkeys receiving vaccine were protected from the toxin and no clinical signs of disease were observed, while controls displaying classic signs of botulism succumbed to the toxin challenge. Two additional groups of monkeys receiving the same vaccine regiment as the first two groups had significant levels of circulating neutralizing antibody titers up to 24 months postvaccination. This non-human primate study demonstrated the short- and long-term immunity afforded by the rBoNTB(H(c)) vaccine.

Animals↗
PubMed2006

Liver transplantation in an adult with sclerosing cholangitis due to Langerhans cell histiocytosis.

Sclerosing cholangitis due to Langerhans cell histiocytosis (LCH) is a rare cause of end-stage liver disease, seen mainly in children. Only a few adult cases have been reported worldwide. Liver transplantation may be a viable treatment option for what is otherwise an irreversible condition. We describe a 65-year-old female with LCH who developed severe sclerosing cholangitis with jaundice, intractable pruritus and peritoneal disease. She underwent orthotopic liver transplantation with complete amelioration of symptoms and remained well 14 months following her operation. Explant histology confirmed LCH involvement with an associated extensive sclerosing cholangitis. Symptomatic LCH cholangiopathy is an emerging indication for liver transplantation in adults.

Aged↗
PubMed2005

Compromised lymphocytes infiltrate hepatocellular carcinoma: the role of T-regulatory cells.

Hepatocellular carcinoma (HCC) has a poor prognosis with limited therapeutic options. We propose that local immune responses in patients with HCC are held in check by tumor-infiltrating CD4(+)CD25(+) T-regulatory lymphocytes (T(reg) cells), which suppress the activity and proliferation of effector CD4(+) and CD8(+) T cells. The phenotype and cell cycle status of tumor-infiltrating lymphocytes (TILs) in HCC were analyzed via immunohistochemistry of sections from patients undergoing surgery for HCC and via flow cytometry of peripheral blood mononuclear cells and TILs isolated from patients with HCC. Circulating and tumor-infiltrating T-cell function and activation status were assessed via proliferation and flow cytometry. More than 96% of TILs were quiescent as measured via Mcm-2 or Ki-67 expression, while less than 10% of CD8(+) T cells expressed perforin or granzyme B. CD4(+)CD25(+) T(reg) cells comprised 8.7% (1.4-13.8) of TILs and always exceeded the proportion in distant nontumor tissue (2.4% [1.5-5.6]; P = .014). T(reg) cells isolated from HCC suppressed proliferation of autologous circulating CD4(+)CD25(-) cells and perforin expression and proliferation of autologous CD8(+) T cells. The proportion of circulating T(reg) cells in patients with HCC was similar in healthy controls (7.2% [1.2-23.3] and 9.2% [1.6-30.2], respectively), but the proportion of circulating T(reg) cells that were also transforming growth factor beta1(+) was elevated in HCC compared with controls (55.5% [8.2-73.9] and 2.0% [0-4.9], respectively; P = .003). In conclusion, TILs are compromised and contain a subpopulation of suppressive CD4(+)CD25(+)Foxp3(+) T(reg) cells. Functional deletion of tumor-infiltrating T(reg) cells could enhance tumor-specific immunotherapy.

CD4-Positive T-Lymphocytes↗
PubMed2004

Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation.

BACKGROUND: The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation. METHODS: Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined. RESULTS: Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD. CONCLUSIONS: Donor lymphocyte macrochimerism was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation.

Aged↗
PubMed2004

Target selection in designing pasteurization processes for shelf-stable high-acid fruit products.

This study is focused on the search for targets and criteria for the design of pasteurization processes for high-acid shelf-stable fruit products, such as juices, nectars, pastes, purees, concentrates, jams, jellies, etc. First, an overview of pasteurization is presented and then, frequently used targets for pasteurization processes are reviewed Enzymes naturally present in fruits, in decreasing order of heat resistance, were pectinesterase, peroxidase, and polyphenoloxidase, and they may be used as pasteurization targets. The heat resistance of each enzyme is strongly dependent on its fruit origin. The most heat resistant micro-organisms capable of spoiling high acid fruit products include ascospores of Neosartorya fischeri, Byssochlamys nivea, Talaromyces flavus, Eupenicillium javanicum, and Byssochlamys fulva moulds, as well as bacterial spores of Clostridium butyricum, Bacillus coagulans, and Bacillus megaterium. These micro-organisms, spores, and enzymes were, in general, less heat resistant than the spores of a particular spoilage micro-organism named Alicyclobacillus acidoterrestris, which has been causing problems in the fruit industry. Therefore, the use of Alicyclobacillus acidoterrestris spores as a reference micro-organism in the design of pasteurization processes for high-acid shelf-stable fruit products is suggested.

Food Microbiology↗
PubMed2004

Acute graft versus host disease following liver transplantation: the enemy within.

This article reviews acute graft vs. host disease (GVHD) as a complication of orthotopic liver transplantation (OLT). The incidence, presentation, clinical course and outcome of GVHD after OLT are summarized and the pathogenesis is discussed, drawing parallels with GVHD after allogeneic haematopoietic stem cell transplantation. Risk factors for GVHD after OLT are examined and the potential role of donor lymphocyte macrochimerism in the recipient peripheral blood as a diagnostic aid for GVHD is discussed. Finally, treatment of GVHD after OLT is reviewed with particular emphasis on the potential role of some of the newer biological agents.

Age Factors↗
PubMed2004

Protein extraction and comparison of stain protocols for analysis of two-dimensional electrophoresis gels.

Protein extraction and the proteome of Lactobacillus delbrueckii subsp. bulgaricus were studied using different stains. The reversible silver staining technique was shown to be more sensitive than the irreversible silver stain. Coomassie colloidal was demonstrated to be as sensitive as reversible silver stain; however, the Coomassie colloidal blue solution developed a higher background and for sample preparation was more time-consuming.

Bacterial Proteins↗
PubMed2003

Notch ligation by Delta1 inhibits peripheral immune responses to transplantation antigens by a CD8+ cell-dependent mechanism.

Notch signaling plays a fundamental role in determining the outcome of differentiation processes in many tissues. Notch signaling has been implicated in T versus B cell lineage commitment, thymic differentiation, and bone marrow hematopoietic precursor renewal and differentiation. Notch receptors and their ligands are also expressed on the surface of mature lymphocytes and APCs, but the effects of Notch signaling in the peripheral immune system remain poorly defined. The aim of the studies reported here was to investigate the effects of signaling through the Notch receptor using a ligand of the Delta-like family. We show that Notch ligation in the mature immune system markedly decreases responses to transplantation antigens. Constitutive expression of Delta-like 1 on alloantigen-bearing cells renders them nonimmunogenic and able to induce specific unresponsiveness to a challenge with the same alloantigen, even in the form of a cardiac allograft. These effects could be reversed by depletion of CD8+ cells at the time of transplantation. Ligation of Notch on splenic CD8+ cells results in a dramatic decrease in IFN-gamma with a concomitant enhancement of IL-10 production, suggesting that Notch signaling can alter the differentiation potential of CD8+ cells. These data implicate Notch signaling in regulation of peripheral immunity and suggest a novel approach for manipulating deleterious immune responses.

Animals↗
PubMed2003

The foot-and-mouth disease epidemic of 2001 in the UK: implications for the USA and the ""war on terror".

While there is no evidence to suggest that the recent epidemic of foot-and-mouth disease (Fmd) in the Uk and its subsequent spread to continental Europe were caused by bioterrorism, the extent of the epidemic shows that Fmd could be a very powerful weapon for a bioterrorist wishing to cause widespread disease in livestock and economic disruption for the targeted country. This paper describes the epidemic. It then examines the contentious issues that arose through the use of extensive slaughter to control the epidemic and explores how, in turn, the concerns of society are being translated into a radical change in policy within the European Union with respect to the control of Fmd and other foreign animal diseases. The crisis generated by the Fmd epidemic in Europe in 2001 provides many lessons to be learned for the US and highlights the need for creative thinking in research and teaching within colleges of veterinary medicine to more effectively address the threat of epidemic diseases under the "new world order." There is general agreement that the veterinary profession in the US plays a unique role in protecting the nation against epidemic livestock diseases, whether caused naturally or through bioterrorism. The profession also has a significant role in protecting the public's health, since several epidemic diseases of animals, such as rift valley fever, are zoonotic. However, improved financial support at the federal and state levels is urgently needed to support epidemic-diseases research and teaching in colleges of veterinary medicine.

Animals↗
PubMed2002

Mapping of antibody responses to the protective antigen of Bacillus anthracis by flow cytometric analysis.

BACKGROUND: Knowledge of the target and functional capability of the antibody response against an antigen provides more specific and relevant information about protective immunity than measuring the total amount of antibody produced against an antigen. METHODS: Using flow cytometry, a competitive assay has been created for measuring the antibody response against important epitopes of an antigen. Monoclonal antibodies (mAbs) against the protective antigen (PA) component of Bacillus anthracis are available that neutralize the activity of lethal toxin (LeTx). Flow cytometric analysis revealed that these mAbs bind PA conjugated to polystyrene latex microspheres. RESULTS: Unlabeled mAbs against PA competed with fluorescent mAbs that bind the homologous epitope but not with fluorescent mAbs that bind heterologous epitopes. Four-parameter logistic models were developed for measuring the antibody response against two epitopes of PA. Sera from anthrax-vaccinated rabbits inhibited the binding of fluorescent mAbs to either epitope; the degree of inhibition correlated with the dilution of sera. CONCLUSIONS: The response in the rabbit sera to either epitope on PA depended on the dose of vaccine administered to the rabbits. No inhibition was seen with sera from control animals. With no species-specific components, this assay could be adapted readily for comparing responses between species.

Animals↗
PubMed2002

Comparative efficacy and immunogenicity of Q fever chloroform:methanol residue (CMR) and phase I cellular (Q-Vax) vaccines in cynomolgus monkeys challenged by aerosol.

Preliminary evidence gathered in rodents and livestock suggested that a phase I chloroform:methanol residue (CMR) extracted vaccine was safe and efficacious in protecting these animals from challenge with the obligate phagolysosomal pathogen (Coxiella burnetii). Prior to the initiation of phase II studies in human volunteers, we compared, in non-human primates (Macaca fascicularis), the efficacy of CMR vaccine with Q-Vax, a licensed cellular Australian Q fever vaccine that has been demonstrated to provide complete protection in human volunteers. Vaccine efficacy was assessed by evaluating thoracic radiographs and the presence of fever and bacteremia in monkeys challenged by aerosol with Coxiella burnetii. Changes in blood chemistries, hematology, behavior and pulmonary function were also examined. CMR, whether administered in single 30 or 100 microg doses or two 30 microg subcutaneous doses, gave equivalent protection in vaccine recipients as a single 30 microg dose of Q-Vax. In addition, vaccination resulted in significant, although temporary, increases in specific antibody titers against C. burnetii phases I and II antigens. The C. burnetii CMR vaccine may be an efficacious alternative to cellular Q fever vaccines in humans.

Administration, Inhalation↗
PubMed2002

Antibody response to a delayed booster dose of anthrax vaccine and botulinum toxoid.

We evaluated the prevalence and concentration of serum antibodies 18-24 months after primary inoculation with anthrax and botulinum vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with anthrax vaccine and/or botulinum toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm. Subjects were vaccinated with the licensed anthrax vaccine, adsorbed (AVA) and pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective antigen (PA) IgG antibody was measured in serum using an immunocapture enzyme-linked immunosorbent assay (ELISA). A mouse neutralization test was used to determine the titer of Clostridium botulinum type A antitoxin in serum samples. The prevalence of anti-PA IgG was 30% in individuals 18-24 months after priming with one, two or three doses of AVA. After boosting, 99% of volunteers had detectable anti-PA IgG; only two individuals failed to respond. The prevalence of antibodies against botulinum toxin type A was 28% 18-24 months after initial priming. Following boosting, 99% of volunteers had serum titers >0.02IU/ml, and 97% responded with titers > or =0.25IU/ml. Systemic reactions to booster vaccinations could not be specifically ascribed to one or the other vaccine, but were generally mild and of brief duration. Forty-five percent of volunteers reported one or more systemic reactions over the course of 7 days. Injection site reactions of any kind occurred in 25% of AVA recipients and in 16% of PBT recipients; persistence of local reactions beyond 7 days was infrequent. While the kinetics and durability of immune responses must be studied, these findings suggest that booster doses of anthrax vaccine and botulinum toxoid sufficient to stimulate a robust anamnestic response may be given at times distant from receipt of the primary inoculations.

Adult↗
PubMed2002

Anthrax vaccine: immunogenicity and safety of a dose-reduction, route-change comparison study in humans.

Anthrax vaccine adsorbed (AVA), an effective countermeasure against anthrax, is administered as six subcutaneous (SQ) doses over 18 months. To optimize the vaccination schedule and route of administration, we performed a prospective pilot study comparing the use of fewer AVA doses administered intramuscularly (IM) or SQ with the current schedule and route. We enrolled 173 volunteers, randomized to seven groups, who were given AVA once IM or SQ; two doses, 2 or 4 weeks apart, IM or SQ; or six doses at 0, 2, 4 weeks and 6, 12, and 18 months (control group, licensed schedule and route). IM administration of AVA was associated with fewer injection site reactions than SQ administration. Following the first SQ dose of AVA, compared to males, females had a significantly higher rate of injection site reactions such as erythema, induration and subcutaneous nodules (P<0.001). Reaction rates decreased with a longer dose interval between the first two doses. The peak anti-PA IgG antibody response of subjects given two doses of AVA 4 weeks apart IM or SQ was comparable to that seen among subjects who received three doses of AVA at 2-week intervals. The IM route of administering this aluminum hydroxide adsorbed vaccine is safe and has comparable peak anti-PA IgG antibody levels when two doses are administered 4 weeks apart compared to the licensed initial dose schedule of three doses administered 2 weeks apart. A large pivotal study is being planned by the Centers for Disease Control and Prevention to confirm these results.

Adult↗
PubMedDate not supplied

Hepatic expression of IL-15 mRNA is associated with liver graft acceptance.

BACKGROUND: Acute allograft rejection continues to be a major cause of morbidity following organ transplantation. The aim of this study was to investigate the local expression of a range of immunomodulatory molecules which may be mediating rejection of, or tolerance to, liver allografts. METHODS: RNA was extracted from 31 protocol liver biopsies taken 7-10 days post-transplantation, reverse transcribed and screened by a sensitive RT-PCR for a wide range of cytokines and other immunomodulatory molecules. The mRNA profile of each biopsy was subsequently related to the histological and clinical status of the graft. Samples of RNA isolated from activated leukocytes and T cell clones, and from normal liver, were used as controls to compare to the 'immunological snapshot' obtained from the biopsies. RESULTS: Presence of tumour necrosis factor-alpha, fas ligand, granzyme B and perforin mRNA in most of the liver biopsies reflected the occurrence of cell-mediated immune reactions. However, the expression of only one cytokine, interleukin-15 (IL-15), was significantly more frequent in allografts that showed no histological or biochemical signs of rejection during the early post-transplant period. Using an in vitro model it was demonstrated that recombinant IL-15 expands tenfold the number of CD3(+)CD56(+) (natural T; NT) cells from peripheral blood mononuclear cells cultures. Conditioning with IL-15 also increased cytotoxic activity of lymphocytes against leukaemic target cells. CONCLUSIONS: Although considerable evidence for cell-mediated immunity was shown for all liver allografts, the only clinical association was for IL-15 mRNA expression and graft acceptance. An in vitro model suggested that IL-15 may be enhancing the numbers and the activity of local regulatory cells, in particular resident NT cells in the liver, which may have a role in killing activated lymphocytes such as graft-reactive host T cells.

Adjuvants, Immunologic↗
PubMedDate not supplied

Effects of various sugars added to growth and drying media upon thermotolerance and survival throughout storage of freeze-dried Lactobacillus delbrueckii ssp. bulgaricus.

The aim of this research effort was to investigate the role of various sugar substrates in the growth medium upon thermotolerance and upon survival during storage after freeze-drying of Lactobacillus bulgaricus. Addition of the sugars tested to the growth medium, and of these and sorbitol to the drying medium (skim milk) was investigated so as to determine whether a relationship exists between growth and drying media, in terms of protection of freeze-dried cells throughout storage. The lowest decrease in viability of L. bulgaricus cells after freeze-drying was obtained when that organism was grown in the presence of mannose. However, L. bulgaricus clearly survived better during storage when cells had been grown in the presence of fructose, lactose or mannose rather than glucose (the standard sugar in the growth medium). A similar effect could not be observed in terms of thermotolerance; in this case, the growth medium supplemented with lactose was found to yield cells bearing the highest heat resistance. Supplementation of the drying medium with glucose, fructose, lactose, mannose or sorbitol led in most cases to enhancement of protection during storage, to a degree that was growth medium-dependent.

Adaptation, Physiological↗