Biomedical subjects
S L Taylor
Publications and source records attributed to S L Taylor.
Somatic cell apoptosis markers and pathways in human ejaculated sperm: potential utility as indicators of sperm quality.
In this study we extended earlier work to determine whether sperm respond to somatic cell apoptotic stimuli and whether apoptotic phenotypes are significant indicators of human sperm quality. We evaluated ejaculated sperm from fertile donors and subfertile patients following purification of fractions of high and low motility. In unstimulated conditions, caspase enzymatic activity was higher in motile fractions from subfertile patients than in donors, and was higher in low motility fractions from both groups. Staurosporine, but not a Fas ligand or H2O2, significantly increased caspase activity, but only in high motility fractions. Procaspase-3, -7 and -9 and low levels of active caspase-3, -7 and -9 were identified by immunoblot analysis. Apoptosis-inducing factor (AIF) was present in all samples but poly ADP-ribose polymerase-1 (PARP-1) was not detected. Phosphatidylserine translocation was significantly increased only with H2O2 treatment. In ejaculates of both subfertile and fertile men, we demonstrated the presence and activation of several proteins that are key constituents of apoptosis-related pathways in somatic cells, which may serve as markers for sperm quality.
A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?
BACKGROUND: While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult. OBJECTIVE: A roundtable conference was convened to develop a consensus clinical protocol for low-dose challenge trials for the estimation of threshold doses for specific allergenic foods. METHODS: In May 2002, 20 clinical allergists and other interested parties were invited to participate in a roundtable conference to develop consensus of the key elements of a clinical protocol for low-dose challenge trials. RESULTS: A consensus protocol was developed. Patients with convincing histories of food allergies and supporting diagnostic evidence including past challenge trials or high CAP-RAST scores can be enrolled in low-dose challenge trials. Care must be taken with younger patients to assure that they have not outgrown their food allergy. An approach was developed for the medication status of patients entering such trials. Challenge materials must be standardized, for example, partially defatted peanut flour composed of equal amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish). Challenge materials must be appropriately blinded with sensory evaluation used to confirm the adequacy of blinding. A double-blind, placebo-controlled design should be used for low-dose challenge trials. Low-dose challenge trials would begin at doses of 10 microg of the allergenic food and would continue with doses of 100 microg and 1 mg followed by specific higher doses up to 100 mg depending upon the expert judgement of the physician; even higher doses might be applied to assure that the patient is indeed reactive to the particular food. A 30-min time interval would be used between doses, and reactive doses would be expressed as both discrete and cumulative doses. The goal of each challenge would be to develop objective symptoms; trials should not be discontinued on the basis of subjective symptoms only. Statistically, a minimum of 29 patients would be enrolled in low-dose challenge trials for each allergenic food because 0 reactors out of 29 patients at a particular dose allow the conclusion that there is 95% certainty that 90% of allergic individuals will not react to that dose. CONCLUSION: A consensus protocol was developed. Using this protocol, it will be possible to estimate threshold doses for allergenic foods, the lowest amount that elicits mild, objective symptoms in highly sensitive individuals.
Information provision for allergic consumers--where are we going with food allergen labelling?
As the current treatment for food allergy involves dietary exclusion of the problem food, information for food-allergic consumers provided on food labels about the nature of allergenic ingredients is important to the management of their condition. The members of an EU-funded networking project, InformAll, focusing on developing strategies for the provision of credible, reliable sources of information for food allergy sufferers, regulators and the food industry, have been considering these matters with respect to food labelling. This paper presents an overview of the genesis of the new EU directive on food labelling, its relevance to food-allergic consumers and the problems that might arise if precautionary labelling becomes more widespread in response to concerns regarding inadvertent allergen contamination in foods. International efforts to define threshold levels of allergens able to trigger a reaction coupled with validated allergen detection methods are essential if the food industry is to implement effective hazard control procedures and address the problems of cross-contact allergens without devaluing the information provided to consumers on food labels.
Five cases of non-typhoidal Salmonella endovascular infection.
The incidence of human non-typhoidal Salmonella (NTS) infection has increased in many countries. Endovascular infection is one of the most serious forms of extraintestinal infection. Five patients with NTS endovascular infection treated at Middlemore Hospital, Auckland, New Zealand, are presented here. All persons with NTS bacteraemia who are older than 50 years and have a risk of atherosclerosis should be evaluated for possible endovascular infection.
Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation.
Numerous case reports describe patients with previously documented immunity developing active hepatitis B virus (HBV) infection after transplantation. However, the risk of reactivation of HBV under long-term immunosuppression in hepatitis B core antibody (HBcAb)-positive, hepatitis B surface antigen (HBsAg)-negative transplant recipients has not been clearly described. Herein, we present a long-term follow-up for 49 HBcAb-positive, HBsAg-negative recipients (27 liver, 18 kidney, 4 pancreas) transplanted between June 1996 and April 2001. Among these, 37 recipients (76%) were HBsAb positive at transplantation. Immunosuppression consisted of various antibody induction regimens in 20 (41%) of the recipients with either tacrolimus (33 [67%])- or cyclosporine (16 [33%])-based maintenance immunosuppression. The incidence and duration of HBV prophylaxis was not significant. No patient received hepatitis B immunoglobulin (HBIG) before or after transplantation. Additionally, only two patients received lamivudine, which was started post transplant without clinical indication. The mean length of follow-up was 3.1+/-1.4 years. At the last follow-up, overall patient and graft survival were 98% and 96%, respectively. Patient survival was 96% in liver, 100% in kidney, and 100% in pancreas transplant recipients. The graft survival for each organ type was 93% in liver, 100% in kidney, and 75% in pancreas transplant recipients at the end of follow-up. There was no incidence of HBV reactivation defined as recurrence of HBsAg and/or HBV DNA positivity. These data suggest that the risk of reactivation of HBV in HBcAb-positive, HBsAg-negative transplant recipients under immunosuppression is negligible, regardless of immunosuppressive regimen, lamivudine prophylaxis, or HBsAb status. These patients should have access to transplantation as they enjoy excellent patient and graft survival rates.
Evaluation of the health aspects of methyl paraben: a review of the published literature.
Methyl paraben (CAS No. 99-76-3) is a methyl ester of p-hydroxybenzoic acid. It is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics for over 50 years. Methyl paraben is readily and completely absorbed through the skin and from the gastrointestinal tract. It is hydrolyzed to p-hydroxybenzoic acid, conjugated, and the conjugates are rapidly excreted in the urine. There is no evidence of accumulation. Acute toxicity studies in animals indicate that methyl paraben is practically non-toxic by both oral and parenteral routes. In a population with normal skin, methyl paraben is practically non-irritating and non-sensitizing. In chronic administration studies, no-observed-effect levels (NOEL) as high as 1050 mg/kg have been reported and a no-observed-adverse-effect level (NOAEL) in the rat of 5700 mg/kg is posited. Methyl paraben is not carcinogenic or mutagenic. It is not teratogenic or embryotoxic and is negative in the uterotrophic assay. The mechanism of cytotoxic action of parabens may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation. Parabens are reported to cause contact dermatitis reactions in some individuals on cutaneous exposure. Parabens have been implicated in numerous cases of contact sensitivity associated with cutaneous exposure; however, the mechanism of this sensitivity is unknown. Sensitization has occurred when medications containing parabens have been applied to damaged or broken skin. Allergic reactions to ingested parabens have been reported, although rigorous evidence of the allergenicity of ingested paraben is lacking.
Evaluation of an automated screening assay for von Willebrand disease type 2N.
Evaluating the factor VIII (FVIII) binding activity of von Willebrand factor (VWF) is an important step in the diagnostic work-up of families affected by apparent mild haemophilia A. In von Willebrand's disease (VWD) type 2N (Normandy), mutations at the N-terminal end of the mature VWF subunit gene prevent the binding of FVIII. Individuals heterozygous for type 2N VWD are generally asymptomatic. Homozygotes and compound heterozygotes present with a clinical picture which mimics haemophilia A, with a markedly reduced FVIII : C activity and VWF within the normal range, but instead of exhibiting X-linked inheritance they show an autosomal recessive inheritance pattern. The distinction between haemophilia A and VWD type 2N has important implications for therapy and genetic counselling. We present a highly specific enzyme-linked immunosorbent assay screening method for the Normandy variant, which measures VWF : FVIII binding activity in parallel with VWF antigen, using monoclonal capture and detection antibodies. The assay is fully automated using a robotic microtitre plate processor, requiring minimal user intervention and providing the capacity to screen large numbers of patients.
Streptococcus iniae inhibition of apoptosis of nonspecific cytotoxic cells: a mechanism of activation of innate immunity in teleosts.
Nonspecific cytotoxic cells (NCC) may provide innate anti-bacterial resistance against Streptococcus iniae infections in tilapia. The mechanism of immunity would be elaboration and release of various cytokines, augmentation of inflammation and amplification of increased antigen processing. To investigate bacterial regulation of NCC function, 2 different processes of cellular pathology were examined: apoptosis and necrosis. Different isolates of S. iniae from diseased teleosts, a dolphin and a human were tested. All isolates were examined for their ability to produce apoptosis and/or necrosis on freshly purified tilapia NCC and on a tilapia continuous cell line (i.e. TMB-8 cells). Two different isolates (9033 and 173) inhibited the outer membrane expression of phosphatidylserine (PS) by NCC, an early sign of apoptosis. This occurred at 4 h post-treatment and lasted throughout the 24 h treatment period. All other isolates either did not differ from control levels or produced a small increase in PS expression by NCC. The early reduction in PS expression occurred concomitantly with increased necrosis associated with nonspecific DNA fragmentation. Two-color flow cytometry (Annexin-V vs propidium iodide staining) demonstrated the specificity of Annexin-V binding. Experiments were also done to determine the effects of S. iniae on TMB-8 cells. Treated TMB-8 cells did not produce appreciable Annexin-V binding. Compared to the ATCC strain, 9033 produced high levels of necrosis-associated DNA fragmentation of TMB-8 cells at 4 and 8 h post-treatment. These data indicated that different isolates of S. iniae may regulate NCC anti-bacterial resistance by causing reduced levels of programmed cell death (PCD), increased necrosis and associated enhancement of inflammatory responses. Understanding the relevance of these bacterial effects on NCC may be an important consideration in the evaluation of isolates used in vaccine/ bacterin production.
Pneumococcal bacteraemia and opportunities for prevention.
AIMS: Despite availability of active antimicrobial agents for its treatment, the mortality from pneumococcal bacteraemia (PB) may reach 30% to 40% in high-risk groups. Greater vaccine use may reduce the incidence of PB. The aim of this study was to determine the proportion of patients with PB who had indications for, but had not received, pneumococcal vaccination. METHODS: From December 1998 to March 2000, all episodes of PB in adults in four Auckland hospitals were followed prospectively. Underlying disease, outcome, and pneumococcal vaccination history were recorded. RESULTS: 96 patients had PB: the median age was 63 years, range 16 to 93 years. 42 (44%) were > or = 65 years. The relative risk (RR) of acquiring PB for Maori and Pacific Island people was more than two times that of both European and other ethnic groups: RR 2.3 (95% CI 1.5 - 3.6) and 2.4 (1.6 - 3.8), respectively. The most common presentation was pneumonia; 84 (88%), of which 74 (88%) were community acquired. Five (5%) patients had meningitis. The overall mortality was 18%. Eleven (11%) pneumococcal isolates had intermediate susceptibility to penicillin and six (6%) were resistant. 69 (72%) patients had one or more condition for which pneumococcal vaccination is recommended but only two (2%) patients had received it. 82 (85%) patients were infected with serotypes included in the current pneumococcal vaccine. CONCLUSIONS: Most adult patients with PB have underlying medical conditions for which vaccination is recommended but only rare patients get vaccinated. Emerging antimicrobial resistance is a further incentive to increase the use of pneumococcal vaccination. Greater use of pneumococcal vaccine will probably require a change in its funding status, similar to the current policy for influenza vaccine. It may also be appropriate to consider targeted use of the vaccine in Maori and Pacific Island people given their higher rates of disease.
Infection of orthopedic prostheses after Staphylococcus aureus bacteremia.
We prospectively evaluated 53 patients with prosthetic joints and 27 patients with other orthopedic prosthetic devices who developed Staphylococcus aureus bacteremia (SAB). After exclusion of patients with primary postoperative infections, the risk of a prosthesis becoming infected by means of hematogenous seeding after SAB was 34% (15 of 44 patients) for prosthetic joints and 7% (1 of 15 patients) for other orthopedic prostheses.
Postmarketing surveillance of new food ingredients: results from the program with the fat replacer olestra.
Market introduction of savory snacks containing olestra offered an opportunity to evaluate the safety of olestra in a free-living population and thereby compare the outcome to the previously established safety profile determined in clinical trials in which subjects were required to eat predetermined amounts at prescribed intervals. Therefore, a multifaceted postmarketing surveillance program was designed to evaluate consumer experience and safety of olestra in the marketplace. Customer comments were solicited through toll-free telephone numbers. Collected data were evaluated by both internal and external medical experts. About 10% of toll-free telephone calls reported health effects, most of which were gastrointestinal (GI) in nature. Clinical studies were designed and conducted to determine potential GI effects under the range of consumption patterns reported by toll-free calls. Health effects reported were those found commonly in the general population and analyses of the data found no biological reason to conclude that serious or meaningful health effects were the result of olestra consumption.
Safety assessment of propyl paraben: a review of the published literature.
Propyl paraben (CAS no. 94-13-3) is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics for over 50 years. It is an ester of p-hydroxybenzoate. Propyl paraben is readily absorbed via the gastrointestinal tract and dermis. It is hydrolyzed to p-hydroxybenzoic acid, conjugated and the conjugates are rapidly excreted in the urine. There is no evidence of accumulation. Acute toxicity studies in animals indicate that propyl paraben is relatively non-toxic by both oral and parenteral routes, although it is mildly irritating to the skin. Following chronic administration, no-observed-effect levels (NOEL) as high as 1200-4000 mg/kg have been reported and a no-observed-adverse-effect level (NOAEL) in the rat of 5500 mg/kg is posited. Propyl paraben is not carcinogenic, mutagenic or clastogenic. It is not cytogenic in vitro in the absence of carboxyesterase inhibitors. The mechanism of propyl paraben may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation. Sensitization has occurred when medications containing parabens have been applied to damaged or broken skin. Parabens have been implicated in numerous cases of contact sensitivity associated with cutaneous exposure, but high concentrations of 5-15% in patch testing are needed to elicit reaction in susceptible individuals. Allergic reactions to ingested parabens have been reported, although rigorous evidence of the allergenicity of ingested paraben is lacking.
The role of natural color additives in food allergy.
A critical evaluation of the available information demonstrates that reactions to natural color additives are rare. Studies of turmeric and carotenoid pigments administered in mixtures with other food colorings failed to definitely identify reactions to either color additive. For carotenoids, the one case report of an adverse reaction was not conclusive. An anaphylactic reaction to saffron does suggest an IgE-mediated reaction, but the high use of saffron as compared with this single report of an adverse reaction suggests that sensitivity to saffron is extremely rare. Numerous reports of reactions to grapes or grape products have been reported in the literature, but no reports of sensitivities to grape skin extract or grape color extract were found. In rare cases, annatto dye may provoke a severe, adverse reaction in individuals with an uncommon hypersensitivity, and may aggravate the symptoms of patients suffering from recurrent urticaria. In its long history of use, there has been only one reported case of anaphylaxis resulting from the ingestion of annatto. Studies designed to investigate the role of annatto in recurrent urticaria sufferers were limited due to the absence of double-blind challenge and placebo controls. A number of cases of adverse reactions to carmine following ingestion have been reported in the literature. These adverse reactions suggest an IgE-mediated hypersensitivity. In many of the reported cases, the cause of sensitization to carmine was topical exposure from the use of carmine-containing cosmetics or occupational exposure to carmine and not from ingestion of carmine-containing foods and beverages. Following sensitization, affected individuals would be sensitive to carmine and the amounts present in foods and beverages could elicit allergic reactions. It is not known whether all individuals with carmine sensitivity induced through topical use are sensitive to the ingestion of carmine in foods. However, reactions to carmine solely because of ingestion are likely to be exceedingly rare due to the low use levels of carmine in foods and beverages. Despite their widespread use in food products, few reports of allergic reactions following ingestion have been reported for the majority of natural color additives. It is concluded that the ingestion of natural color additives presents a very low risk of provoking adverse reactions.
Carotenoid content, physicochemical, and sensory qualities of deep-fried carrot chips as affected by dehydration/rehydration, antioxidant, and fermentation.
Carrot slices were subjected to one of the following experiments prior to deep-frying: (A) dehydration/rehydration, (B) soaking in different antioxidants, and (C) fermentation with/without blanching. There were no significant differences (P > or = 0.05) in carotenoid contents among carrot chips treated with/without dehydration. Soaking in sodium metabisulfite resulted in the highest carotenoid content and lightness (L), redness (a), and yellowness (b) values among the antioxidant treatments. Fermentation without blanching significantly decreased (P < 0.05) carotenoid content, vitamin A activity, and fat content. Dehydration and fermentation with blanching significantly increased (P < 0.05) the lightness (L), redness (a), and yellowness (b) values of the chips. Dehydration/rehydration, but not antioxidant and fermentation, significantly decreased (P < 0.05) the water activity of the chips. The textural values of carrot chips prepared using sodium metabisulfite, without dehydration and without fermentation, were the lowest among other treatments which suggests the crispiest. Carrot chips prepared using sodium metabisulfite, without dehydration and without fermentation, had the highest carotenoid content and retention, and the highest overall acceptability score.
Ingredient and labeling issues associated with allergenic foods.
Foods contain a wide range of food ingredients that serve numerous technical functions. Per capita consumer exposure to most of these food ingredients is rather low with a few notable exceptions such as sugar and starch. Some food ingredients including edible oils, hydrolyzed proteins, lecithin, starch, lactose, flavors and gelatin may, at least in some products, be derived from sources commonly involved in IgE-mediated food allergies. These ingredients should be avoided by consumers with allergies to the source material if the ingredient contains detectable protein residues. Other food ingredients, including starch, malt, alcohol and vinegar, may be derived in some cases from wheat, rye or barley, the grains that are implicated in the causation of celiac disease. If these ingredients contain gluten residues, then they should be avoided by celiac sufferers. A few food ingredients are capable of eliciting allergic sensitization, although these ingredients would be classified as rarely allergenic. These ingredients include carmine, cochineal extract, annatto, tragacanth gum and papain. Food manufacturers should declare the presence of allergenic food ingredients in the ingredient listings on product labels so that allergic consumers can know to avoid these potentially hazardous products.
Will genetically modified foods be allergenic?
Foods produced through agricultural biotechnology, including such staples as corn, soybeans, canola, and potatoes, are already reaching the consumer marketplace. Agricultural biotechnology offers the promise to produce crops with improved agronomic characteristics (eg, insect resistance, herbicide tolerance, disease resistance, and climatic tolerance) and enhanced consumer benefits (eg, better taste and texture, longer shelf life, and more nutritious). Certainly, the products of agricultural biotechnology should be subjected to a careful and complete safety assessment before commercialization. Because the genetic modification ultimately results in the introduction of new proteins into the food plant, the safety, including the potential allergenicity, of the newly introduced proteins must be assessed. Although most allergens are proteins, only a few of the many proteins found in foods are allergenic under the typical circumstances of exposure. The potential allergenicity of the introduced proteins can be evaluated by focusing on the source of the gene, the sequence homology of the newly introduced protein to known allergens, the expression level of the novel protein in the modified crop, the functional classification of the novel protein, the reactivity of the novel protein with IgE from the serum of individuals with known allergies to the source of the transferred genetic material, and various physicochemical properties of the newly introduced protein, such as heat stability and digestive stability. Few products of agricultural biotechnology (and none of the current products) will involve the transfer of genes from known allergenic sources. Applying such criteria provides reasonable assurance that the newly introduced protein has limited capability to become an allergen.
Allergic reactions after ingestion of erythritol-containing foods and beverages.
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