bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of protein allergenic potential in mice: dose–response analyses
Authors: Dearman R. J. , Stone S. , Caddick H. T. , Basketter D.A. , Kimber I. 
Published: November 2003

SummaryBackground
With the increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches for the characterization of the allergenic potential of proteins. Whereas immunogenicity is a common property of foreign proteins, including food proteins, relatively few are significant dietary allergens with the inherent capacity to provoke IgE antibody production and immediate‐type hypersensitivity responses.Objective
In order to evaluate an approach for the measurement of the allergenic potential of proteins, detailed dose–response analyses of humoral immune responses induced following systemic exposure of BALB/c strain mice to proteins known to differ in terms of sensitizing activity have been conducted.Results
Mice were exposed to a range of concentrations of ovalbumin, a major allergenic constituent of hen's egg, a purified peanut allergen, Arachis hypogea agglutinin, or to the milk allergen bovine serum albumin, and to materials considered to lack significant allergenicity: a crude potato protein extract and a purified potato protein, potato agglutinin. The specific IgE antibody was measured by homologous passive cutaneous anaphylaxis assay, and the specific IgG antibody was measured by enzyme‐linked immunosorbent assay. Each of the five proteins was immunogenic in mice, inducing IgG antibody responses at all doses tested, although there was some variation with respect to the vigour of IgG responses. Marked differences in the capacity of these proteins to induce IgE responses were observed, however, with relatively high‐titre IgE antibody provoked by all three allergens over the dose ranges examined, whereas the potato proteins stimulated low‐titre IgE antibody at the highest dose (10%) only. Importantly, differences in IgE antibody production have been observed against a background of equivalent immunogenicity (IgG antibody responses).Conclusion
The data presented here suggest that the measurement of antibody (IgE) responses in BALB/c mice appears to identify allergens accurately and to distinguish them from those materials that apparently lack allergenicity.
Early‐life exposure to antibacterials and the subsequent development of hayfever in childhood in the UK: case–control studies using the General Practice Research Database and the Doctors' Independent Network
Authors: Bremner S. A. , Carey I. M. , DeWilde S. , Richards N. , Maier W. C. , Hilton S. R. , Strachan D. P. , Cook D. G. 
Published: November 2003

SummaryBackground
Theoretically, antibacterial agents in early life might influence allergic sensitization in two ways: (i) as an indicator of infectious illness, they might be expected to protect against allergy; (ii) alternatively they might increase the risk through effects on the commensal bowel flora. Epidemiological evidence linking the prescription of antibacterial agents in early life to the subsequent development of hayfever is conflicting.Objective
To establish definitively whether an association exists between early‐life antibacterial exposure and childhood hayfever diagnosis.Methods
Nested case–control studies were based on birth cohorts of children identified within two large UK general practice databases of electronic patient records. One hundred and sixteen thousand and four hundred and ninety‐three children from 605 general practices were identified as being continuously registered from birth to at least age 5 years. Seven thousand and ninety‐eight cases were diagnosed with hayfever after the age of 2 years. One control per case was matched for practice, birth month, sex and still being registered on case diagnosis date. Odds ratios were derived from conditional logistic regressions within each database followed by pooling using a fixed‐effect model.Results
The pooled odds ratio for hayfever was 1.11, 95% CI (1.03–1.20) if exposed to antibacterials in the first year of life, 1.35 (1.25–1.46) in year 2 and 1.47 (1.37–1.59) in year 3. Adjusting for consultation frequency reduced these odds ratios to 0.92, 1.05 and 1.10, respectively. There was no evidence that broader spectrum antibacterials, exposure in any specific month of year 1 or in the grass pollen season influenced the risk of hayfever.Conclusion
These data exclude any important effect of antibacterial exposure in infancy on subsequent hayfever risk. Associations reported in earlier studies have likely been exaggerated through publication bias and by lack of control for the tendency of some families to consult frequently for a range of conditions.
Presentation of allergen in different food preparations affects the nature of the allergic reaction – a case series
Authors: Grimshaw K. E. C. , King R. M. , Nordlee J. A. , Hefle S. L. , Warner J. O. , Hourihane J. O.'B. 
Published: November 2003

SummaryBackground
Characterization of fatal and non‐fatal reactions to food indicates that the majority of reactions are due to the ingestion of prepared foods rather than the non‐processed allergen. In an ongoing study that used a double‐blind placebo‐controlled food challenge to investigate peanut allergy and clinical symptoms, the observed reaction severity in four of the first six subjects was greater than anticipated. We hypothesized that this was due to differences in the composition of the challenge vehicle.Objective
The aim was to investigate whether the severity of observed challenge reactions would be repeated on re‐challenge with a lower fat challenge vehicle.Methods
Peanut‐allergic subjects were re‐challenged with a lower fat recipe after reacting more severely than was anticipated to an initial peanut challenge. Similar challenge vehicle recipes were used, the only difference being the lower fat content (22.9% compared with 31.5%). The peanut content of the two recipes was analysed using RAST inhibition studies and ELISA tests.Results
Three of four subjects reacted to much smaller doses of peanut protein on re‐challenge (mean dose equivalence – 23 times less peanut) with the lower fat recipe. RAST inhibition showed that neither recipe altered epitope recognition. The higher fat recipe required twice as much peanut to cause 50% inhibition. ELISA detected far lower levels of peanut in the higher fat recipe (220 000 parts per million (p.p.m.)) than in the lower fat recipe (990 000 p.p.m.).Conclusion
The fat content of a challenge vehicle has a profound effect on the reaction experienced after allergen ingestion. This is another factor to be considered in assessing the risk of certain foods to food‐allergic consumers and adds another dimension to clinical, research and regulatory practice.
Age at bacille Calmette–Guérin vaccination and risk of allergy and asthma
Authors: Bager P. , Rostgaard K. , Nielsen N.M. , Melbye M. , Westergaard T. 
Published: November 2003

SummaryBackground
It has been proposed that early age at bacille Calmette–Guérin (BCG) vaccination protects against the development of allergy.Objective
To study whether early age at BCG vaccination was associated with a decreased risk of atopy, allergic rhinitis, and asthma compared to BCG vaccination at later ages in childhood.Methods
The occurrence of atopy, allergic rhinitis, and asthma was studied in nearly 2000 women participating in the Danish National Birth Cohort study. Detailed information on age at BCG vaccination (age 0–15 years) was available from school health records. Atopic status was assessed serologically by a specific response to 11 common inhalant allergens using serum samples obtained from the women during the period 1997–2001. Information on allergic rhinitis and asthma was available from telephone interviews.Results
Approximately 85% of the women had been BCG‐vaccinated. Age at BCG vaccination was not associated with risk of atopy, allergic rhinitis, or asthma. The odds ratio of atopy, allergic rhinitis, and asthma associated with being vaccinated during the first year of life was 1.05 (95% CI 0.71–1.56), 1.42 (95% CI 0.85–2.36), and 1.71 (95% CI 0.91–3.20), respectively, compared with being vaccinated at the age of 7 years. Adjustment for birth cohort, sibship size, age of the woman's mother at birth, and social class in childhood did not affect the results.Conclusion
Our findings suggest that age at BCG vaccination in childhood does not influence the development of allergy or asthma.
Intranasal exposure to a damp building mould, Stachybotrys chartarum, induces lung inflammation in mice by satratoxin‐independent mechanisms
Authors: Leino M. , Mäkelä M. , Reijula K. , Haahtela T. , Mussalo‐Rauhamaa H. , Tuomi T. , Hintikka E.‐L. , Alenius H. 
Published: November 2003

SummaryBackground
Stachybotrys chartarum is a damp building mould and a potent toxin producer that has been related to serious cases of respiratory health problems. However, the direct link between exposure and health symptoms has not been established.Objective
To examine the mechanism by which exposure to spores of satratoxin producing and non‐producing S. chartarum strains induce inflammatory responses in murine lungs.Methods
BALB/c mice were intranasally exposed for 3 weeks to spores of a satratoxin‐producing and a non‐producing S. chartarum strain. Inflammatory cell infiltration was characterized from bronchoalveolar lavage (BAL) fluid. Cytokine and chemokine mRNA expression in lung tissue was measured with real‐time PCR. Bronchial responsiveness to methacholine (MCh) was determined by whole‐body plethysmography and serum antibody levels by ELISA.Results
A dose‐dependent increase in monocytes, neutrophils and lymphocytes was observed in BAL fluid after intranasal (i.n.) instillation of S. chartarum spores. There was no difference in the BAL between exposure to the satratoxin‐producing and the non‐producing strains. Infiltration of inflammatory cells was associated with an induction of pro‐inflammatory cytokine (IL‐1β, IL‐6 and TNF‐α) and chemokine (CCL3/MIP‐1α, CCL4/MIP‐1β and CCL2/MCP‐1) mRNA levels in the lungs. Interestingly, CXCL5/LIX was the only chemokine that showed significantly higher mRNA levels after exposure to the satratoxin‐producing strain compared with the non‐producing strain. MCh‐induced bronchial responsiveness was not altered significantly after mould instillation. Moreover, no significant increase in total or specific IgE, IgG2a and IgG1 antibody levels were found after S. chartarum exposure.Conclusion
These results indicate that lung inflammation induced by i.n. instillations of S. chartarum spores is regulated by the induction of pro‐inflammatory cytokines and leucocyte‐attracting chemokines. The data also imply that S. chartarum‐derived components, other than satratoxins, are mediating the development of this inflammatory response.
Molecular diagnosis of von Hippel‐Lindau disease in a kindred with a predominance of familial phaeochromocytoma
Authors: Garcia Arnald , Matias‐Guiu Xavier , Cabezas Rosa , Chico Ana , Prat Jaime , Baiget Montserrat , De Leiva Alberto 
Published: November 2003

OBJECTIVE To study the presence of germline mutations in the von Hippel‐Lindau gene (vhl ) in a kindred with a predominance of familial phaeochromocytoma in order to confirm the diagnosis of von Hippel‐Lindau disease (VHLD) as well as to identify asymptomatic members.DESIGN DNA extracted from peripheral blood was amplified by the polymerase chain reaction using oligonucleotide primers corresponding to exon 3 of the vhl gene. Specific mutations in codon 238 were screened by restriction endonuclease digestion of PCR products with Msp I. The results were confirmed by DNA sequence analysis.PATIENTS Two generations of a family consisting of 15 individuals were studied.RESULTS A germline missense point mutation at codon 238 of the vhl gene (CGG → TGG; Arg → Trp) was detected in all patients with phaeochromocytoma and in only one of the asymptomatic family members.CONCLUSION Mutational analysis of the vhl gene in patients with familial phaeochromocytoma may permit specific diagnosis of von Hippel‐Lindau disease, and is a good method for the identification of asymptomatic individuals at risk of von Hippel‐Lindau disease.
Ovarian hyperthecosis, diabetes and hirsuties in post‐menopausal women
Authors: Barth J. H. , Jenkins M. , Belchetz P. E. 
Published: November 2003

OBJECTIVE We describe four patients with ovarian hyperthecosis and the effects of gonadotrophin releasing hormone on clinical and metabolic variables.DESIGN Open out‐patient study.PATIENTS Four women presented with post‐menopausal hirsuties. They had significant hair growth across the chest, upper back and shoulders. Three had histologically proven ovarian hyperthecosis and a fourth had large ovaries visualized on ultrasound. All four women had pronounced risk factors for vascular disease; hypertension, hyperlipidaemia and glucose intolerance, and three had already developed symptomatic vascular disease.RESULTS Gonadotrophin releasing hormone agonist therapy resulted in significant reduction in plasma androgens and cosmetic reduction in hair growth but had no effect on hyperlipidaemia.CONCLUSION The post‐menopausal women described in this report were clinically considered to have hyperandrogenism due to the pathological pattern of marked body hair over the upper trunk. Treatment with GnRH was very effective at reducing the severity of the hirsuties.The post‐menopausal women with hyperthecosis in this report had a high prevalence of cardiovascular disease. Since hyperandrogenism and insulin are considered risk factors for cardiovascular disease in premenopausal women with polycystic ovaries, we discuss the possible relationship between insulin and the post‐menopausal ovary.
Influence of endogenous cholinergic tone and growth hormone‐releasing peptide‐6 on exercise induced growth hormone release
Authors: Nooitgedagt Aldert , Koppeschaar Hans P. F. , De Vries Wouter R. , Sidorowicz Anna , Klok Lammert J. , Dieguez Carlos , Mallo Federico 
Published: November 2003

OBJECTIVE The neuroendocrine mechanisms of exercise‐induced GH release remain incompletely understood. In this study we have investigated the influence of endogenous cholinergic tone and growth hormone‐releasing peptide‐6 (GHRP‐6) on exercise induced GH release.DESIGN Analysis of responses of serum GH to administration of pyridostigmine (PD, 120 mg, orally) or GHRP‐6 (100 μg, i.v.), to exercise alone, and to the combinations of PD plus exercise or GHRP‐6 plus exercise. An indirect estimation of the secretory pattern of GH was calculated by the deconvolution technique. Exercise was performed on a bicycle ergometer with a 20‐minute workload near the individual lactate threshold of 4 mmol/l. The five tests were performed in random order after an overnight fast, and at least 3 days apart.SUBJECTS Eleven healthy, non‐obese male subjects (age 23.9 ± 0.3 years, body mass index 23 ± 0.7 kg/m2, VO2 max: 52.4 ± 2.0 ml/min/kg body weight; mean ± SEM) participated in this study.MEASUREMENTS Serial blood samples from an indwelling catheter were taken before, during and after exercise for analysis of GH (IRMA), lactate (YSI 2300) and haematocrit (micromethod).RESULTS Irrespective of the tests, peak values of GH were found between the 18th and 26th minute. The secretory pattern showed differences between the tests. Exercise alone induced relatively short lasting peaks of medium amplitude, whereas PD induced long lasting peaks with low amplitudes. PD plus exercise showed additive effects on the amplitude of GH peaks. GHRP‐6 induced long lasting peaks with high amplitude, and GHRP‐6 plus exercise also had additive effects on the amplitude.CONCLUSIONS The increase in frequency and amplitude of GH peaks, which occurred during the GHRP‐6 plus exercise, indicates that exercise‐induced GH release is not mediated through an increment in the release of an endogenous GHRP‐6‐like ligand, favouring the possibility that exercise‐induced GH release is mediated through an increase in endogenous GHRH release.
Insulin‐like growth factor‐binding protein‐2 in patients with prostate carcinoma and benign prostatic hyperplasia
Authors: Ho P. Jean , Baxter Robert C. 
Published: November 2003

OBJECTIVE Insulin‐like growth factor‐binding protein (IGFBP)‐2 is a major prostatic IGFBP and may be involved in regulating prostate growth. Patients with prostate carcinoma (PC) have elevated serum IGFBP‐2 levels which correlate with the specific PC marker, prostate‐specific antigen (PSA). The aims of this study were to investigate whether elevated serum IGFBP‐2 is unique to PC or also occurs in benign prostatic hyperplasia (BPH), to examine the relations among age, PSA and IGFBP‐2 levels, and to examine longitudinal changes in serum IGFBP‐2 with PSA in prostate carcinoma.DESIGN AND PATIENTS Sixteen patients (61–83 years) with inoperable PC attending the oncology unit at a tertiary referral hospital were studied. Some serum samples were obtained retrospectively while the majority were collected prospectively over 13 months of treatment. The patients with PC were compared to 8 patients (66–73 years) with histologically proven BPH and 7 male control subjects (61–82 years) with no known prostate abnormality.MEASUREMENTS A new IGFBP‐2 RIA was developed. Serum PSA (by EIA), and IGFBP‐2, IGFBP‐3, IGF‐I and IGF‐II (by RIA) were measured in all subjects, and serially in patients with PC.RESULTS Serum IGFBP‐2 was significantly higher in PC with high PSA (560 ± 66 μg/l, n = 12) than PC with normal PSA (292 ± 65 μg/l, n = 4, P = 0.02), BPH (364 ± 61 μg/l, P = 0.03) and controls (367 ± 44 μg/l, P = 0.04). Mean IGFBP‐2 in BPH was not different from controls. IGFBP‐2 and PSA were signi‐ ficantly correlated with age (r = 0.543 and r = 0.433 respectively) and with each other even when the age effect was removed. Serum IGFBP‐2 and PSA levels changed concordantly in all 7 PC patients who had serial sampling. Serum IGF‐II but not IGF‐I or IGFBP‐3 was higher in PC and BPH than in controls (PC 332 ± 23 μg/l), BPH 359 ± 26μg/l vs controls 241 ± 37 μg/l;  P = 0.03 and 0.02 respectively).CONCLUSIONS Serum IGFBP‐2 levels are uniquely elevated in active prostate carcinoma but not in benign prostatic hypertrophy. In PC, serum IGFBP‐2 levels closely parallel those of PSA and probably reflect tumour burden. The relation between PSA and IGFBP‐2 is partially independent of their individual relations with age. Although serum IGFBP‐2 is less sensitive than PSA in PC, it may have adjunctive value in the management of prostate carcinoma.
Demonstration of thyroid stimulating activity within H chain fragments of TSAb‐IgG by protease digestion and reduction
Authors: Kouki Tsuyoshi , Inui Takehiro , Hachiya Takashi , Okabe Hidetoshi , Ochi Yukio , Kajita Yoshihiro 
Published: November 2003

OBJECTIVE Whether or not the distribution of biologically active fragments in TSAb‐IgG molecules parallels antigen‐binding activity in other anti‐thyroidal antibodies was examined.DESIGN Both the thyroid stimulating (TS) activity (cAMP production in thyroid cells) and TSH binding inhibition (TBI) activity (determined by TSH receptor assay) were examined by measuring the reduction in TSAb‐IgG followed by gel‐filtration on Sephadex G‐100. Two forms of IgG were separated from TSAb‐IgG by column chromatography using Protein L‐Sepharose (specifically binds to κ chain). The IgG(κ) was reduced with dithiothreitol (DTT) and the unbound fraction (UF) (the free heavy (H) chain) and the bound fraction (BF) (the free κ chain and the non‐reduced IgG(κ)) were separated using Protein L‐Sepharose. The Fab fragment was separated by Protein A‐Sepharose after papain hydrolysis of TSAb‐IgG, then separated into two Fab(κ) and Fab(λ) forms by Protein L‐Sepharose. The Fd fragment (or fragment containing Fd) was prepared from Fab(κ) by DTT reduction followed by Protein L column.RESULTS The free H chain fraction showed TS and TBI activity, but neither anti‐thyroglobulin (Tg) nor anti‐thyroid peroxidase (TPO) antibody activities. The free light (L) chain was not biologically active. Similar TS and TBI activities were found not only in IgG(κ) and IgG(λ) but also in the Fab(κ) and Fab(λ) fractions. Fd fragment that was not contaminated with free κ chain had TS and weak TBI activities.CONCLUSIONS The thyroid stimulating activity in 5 TSAb‐IgG samples was found in IgG (κ), IgG (λ), Fab (κ), Fab (λ), H chain and Fd separated by papain digestion and reduction. These results showed that TSAb was polyclonal and that the Fd fragment was important as the biologically active site.
Effects of hyperthyroidism and radioactive iodine given to ablate the thyroid on the composition of whole stimulated saliva
Authors: Ford Henry , Johnson Lesley , Purdie Gordon , Feek Colin 
Published: November 2003

OBJECTIVE For many years there has been speculation about possible damage to the salivary glands following administration of ablative doses of radioactive iodine for treatment of hyperthyroidism. We have investigated the changes that occur in the composition of saliva in hyperthyroidism and after the administration of an ablative dose of radioactive iodine to hyperthyroid subjects.DESIGN The study consisted of two parts: first, a comparison of a group of hyperthyroid patients with a group of normal subjects with regard to the concentration or activity of 10 constituents of saliva; second, measurement of those constituents 3–42 weeks after administration of 370 MBq of radioactive iodine to a group of hyperthyroid subjects.PATIENTS Saliva specimens from 38 untreated out‐patients with hyperthyroidism due to Graves' disease or toxic nodular goitre were studied to evaluate the effects of hyperthyroidism and the results were compared with a group of 93 normal subjects. Seventy‐one samples of saliva from 26 patients with persistent hyperthyroidism were collected and analysed 3–42 weeks after radioactive iodine administration.MEASUREMENTS The flow rate; the concentrations of total protein, iodine, calcium, urate, phosphate, potassium and immunoglobulin A; and the activities of N‐acetylglucosaminidase, lysozyme and lactate dehydrogenase were measured.RESULTS In hyperthyroidism the salivary flow rate and the concentrations of urate and potassium were significantly (P<0.05) increased and the concentrations of total protein, calcium and lactate dehydrogenase activity significantly decreased compared to the control group. After radioactive iodine was administered, significant positive trends were observed in the concentrations of total protein, N‐acetylglucosaminidase and immunoglobulin A. These trends were independent of the free T3 levels obtained from the same specimens.CONCLUSIONS Hyperthyroidism leads to a number of changes in salivary composition. For most of the salivary components measured no significant changes were observed 3–42 weeks after administration of 370 MBq of radioactive iodine to patients with persistent hyperthyroidism. The relatively small positive trends in the concentrations of total protein, N‐acetylglucosamidase activity and immunoglobulin A may have been due either to changes in thyroid status or to the effects of radiation on the salivary glands, or both.