bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Psychological Stress in Inflammatory Bowel Disease: Quality Assessment of Methods of 18 Prospective Studies and Suggestions for Future Research
Authors: Cámara Rafael J.A. , Ziegler Roger , Begré Stefan , Schoepfer Alain M. , von Känel Roland
Published: August 2009

Background: Enquiries among patients on the one hand and experimental and observational studies on the other suggest an influence of stress on inflammatory bowel diseases (IBD). However, since this influence remains hypothetical, further research is essential. We aimed to devise recommendations for future investigations in IBD by means of scrutinizing previously applied methodology. Methods: We critically reviewed prospective clinical studies on the effect of psychological stress on IBD. Eligible studies were searched by means of the PubMed electronic library and through checking the bibliographies of located sources. Results: We identified 20 publications resulting from 18 different studies. Sample sizes ranged between 10 and 155 participants. Study designs in terms of patient assessment, control variables, and applied psychometric instruments varied substantially across studies. Methodological strengths and weaknesses were irregularly dispersed. Thirteen studies reported significant relationships between stress and adverse outcomes. Conclusions: Study designs, including accuracy of outcome assessment and repeated sampling of outcomes (i.e. symptoms, clinical, and endoscopic), depended upon conditions like sample size, participants’ compliance, and available resources. Meeting additional criteria of sound methodology, like taking into account covariates of the disease and its course, is strongly recommended to possibly improve study designs in future IBD research.
Identification of Novel Variants in the Cx29 Gene of Nonsyndromic Hearing Loss Patients Using Buccal Cells and Restriction Fragment Length Polymorphism Method
Authors: Wang Wen-Hung , Yang Jiann-Jou , Lin Yen-Chun , Yang Jen-Tsung , Chan Chien-Hui , Li Shuan-Yow
Published: August 2009

The crucial role of gap junctions, which are composed of connexin (Cx) protein, in auditory functions has been confirmed by numerous studies. Cx29 is a relatively new member of the Cx protein family. In this article, we report variants of the Cx29 gene in 253 unrelated Taiwanese patients with nonsyndromic hearing loss. Thirteen (5.14%) of the 253 patients had variants of Cx29. Five sequence changes (c.43C→G, c.230G→C, c.525T→G, c.781 + 62G→A and c.*2T→G) in the Cx29 gene were detected in the study, of which 3 (c.43C→G, c.230G→C and c.525T→G) were novel variants. One novel compound heterozygote missense variant, c.[43C→G(+) 230G→C], was identified in the Cx29 gene carried by 1 patient, and this variant appears to have been inherited from the mother’s chromosome. In addition, for diagnostic purposes, we developed a restriction fragment length polymorphism method using NaeI and StyI to identify c.43C→G and c.525T→G specific variants of the Cx29 gene, respectively. On the basis of the above results, we suggest that the c.[43C→G(+)230G→C] compound heterozygous variant of Cx29 may be a risk factor for the development of hearing loss in Taiwanese and that the restriction fragment length polymorphism method developed will be clinically useful in identifying variants of the Cx29 gene in patients with hearing loss.
Auditory Steady-State Evoked Responses for Preterm and Term Neonates
Authors: Ribeiro Flávia Martins , Carvallo Renata Mamede , Marcoux André M.
Published: August 2009

Hearing thresholds were estimated in normal-hearing term and preterm neonates of <35 weeks of age using multiple-stimulus auditory steady-state responses (ASSRs). The tresholds, expressed in decibel sound pressure level, at signal frequencies of 500, 1000, 2000 and 4000 Hz were 44.30 ± 9.88, 27.80 ± 6.79, 26.77 ± 6.09 and 32.87 ± 6.12 for the term group and 49.11 ± 9.44, 26.38 ± 6.59, 26.74 ± 7.57 and 35.90 ± 8.23 for the preterm group. Significant threshold differences were measured between the groups at 500 and 4000 Hz, while the thresholds at 1000 and 2000 Hz were similar. The signal and noise levels as well as signal-to-noise ratio of responses were also measured and found to be similar. These results indicate that ASSRs can be effectively measured with a similar signal-to-noise ratio in both groups, but that there is a significant maturational effect occurring during gestation at the level of structures which participate in the formation of the ASSR at 500 and 4000 Hz.
Diabetes, Cardiovascular Risk Factors and Idiopathic Sudden Sensorineural Hearing Loss: A Case-Control Study
Authors: Aimoni C. , Bianchini C. , Borin M. , Ciorba A. , Fellin R. , Martini A. , Scanelli G. , Volpato S.
Published: August 2009

Aims/Hypothesis: Idiopathic sudden sensorineural hearing loss (ISSNHL) represents an acute inner ear disorder with an overall incidence of 5–20/100000 individuals per year in western countries. No clear causes for this disease have been found so far, but cochlear ischemia has been hypothesized as one of the etiopathological mechanisms. The aim of our study was to assess the role of diabetes and traditional cardiovascular risk factors in the pathogenesis of ISSNHL. Materials/Methods: Case-control study of 141 patients (75 males/66 females) matched for age and gender. Cases were affected by ISSNHL, defined as a sudden hearing loss ≧30 dB, within 3 frequencies, developing over 72 h. The control group was composed of 271 sex- and age-matched subjects (142 males/129 females) who agreed to participate in this observational study and provided blood samples for laboratory investigations. Cardiovascular risk factors examined were: diabetes mellitus, smoking history, hypercholesterolemia, hypertriglyceridemia and hypertension. Results: On the univariate analysis, diabetes prevalence was higher in the ISSNHL group (15.6%) compared to controls (8.5%) (p = 0.03). Also hypercholesterolemia was significantly more frequent in the ISSNHL group compared to the control population. There were no statistically significant differences between the 2 populations concerning other cardiovascular risk factors. The risk of ISSNHL tended to increase as the number of cardiovascular risk factors increased (p for linear trend = 0.018). Conclusions: Our findings suggest that diabetes mellitus, hypercholesterolemia and a high burden of cardiovascular risk factors are associated with the risk of ISSNHL.
Does the Presence of Jaundice and/or a Lump in a Patient with Gall Bladder Cancer Mean that the Lesion Is Not Resectable?
Authors: Varma Vibha , Gupta Subash , Soin Arvinder Singh , Nundy Samiran
Published: August 2009

Background: The presence of jaundice or an abdominal lump in gall bladder cancer (GBC) is often translated to advanced and unresectable disease. We examined whether this was true. Methods: We retrospectively analysed 120 GBC patients, who had been operated on, for presenting symptoms, staging and resectability. The outcomes in patients with jaundice and/or an abdominal lump were compared with those who did not have these features. Early disease was represented by stages I and II, while stages III and IV represented advanced disease. Results: Sixty-eight patients (57%) presented with an abdominal lump and 62 (52%) had jaundice. An abdominal lump, jaundice or both were present in 89 patients (74%), of whom 78 (88%) had advanced disease, while 22 of the 31 patients (71%) with neither jaundice nor an abdominal lump had advanced disease. Forty-four patients (50%) with either or both of these features had R0 resections, while 20 patients (64%) with neither jaundice nor an abdominal lump had R0 resections. The presence of jaundice or an abdominal lump was significantly associated with advanced disease (p = 0.025), but not with unresectability (p = 1). Conclusions: Jaundice or an abdominal lump was present in 74% of the patients with GBC. While this represented advanced-stage cancer, it did not preclude resectability.
Mechanisms Underlying the Vascular Actions of Endothelin 1, Angiotensin II and Bradykinin in the Rat Carotid
Authors: Tirapelli Carlos R. , Bonaventura Daniella , Tirapelli Luis F. , de Oliveira Ana M.
Published: August 2009

The carotid artery has a pivotal role in the body since it supplies the head and neck with oxygenated blood. Alterations in the functional and structural integrity of these vessels can decrease blood flow to the brain. For this reason, it is important to understand how the carotid artery responds to various stimuli. The organ bath is a traditional experimental set-up that has been used extensively to investigate the (patho)physiology and pharmacology of in vitro tissue preparations including the rat carotid artery. Molecular biology developed from related fields such as biochemistry, genetics and biophysics is now considered an important tool for understanding physiological pathways in a variety of tissues. Several local and systemic factors regulate carotid reactivity, including vaso-active peptides, such as endothelin 1 (ET-1), angiotensin II (Ang II) and bradykinin (BK). These vaso-active peptides play a fundamental role in controlling the functional and structural integrity of the arterial wall and may be important in physiological processes and in pathological mechanisms underlying vascular diseases. In the rat carotid, these peptides induce vasoconstriction or relaxation by the release of endothelium-derived relaxing factors, such as nitric oxide and prostacyclin. Identification of such signal transduction processes is essential for understanding the mechanisms that regulate vascular smooth muscle cell function, both physiologically and pathophysiologically. The present review discusses the mechanisms of action, distribution of ET-1, Ang II and BK and their receptors in the rat carotid. With this purpose, data obtained in functional studies using classical pharmacological approaches as well as data obtained in molecular biology experiments are discussed.
Strength of Family History in Predicting Levels of Blood Pressure, Plasma Glucose and Cholesterol
Authors: Wandeler G. , Paccaud F. , Vollenweider P. , Waeber G. , Mooser V. , Bochud M.
Published: August 2009

Objective: Limited information is available on the quantitative relationship between family history and the corresponding underlying traits. We analyzed these associations for blood pressure, fasting blood glucose, and cholesterol levels. Methods: Data were obtained from 6,102 Caucasian participants (2,903 men and 3,199 women) aged 35–75 years using a population-based cross-sectional survey in Switzerland. Cardiovascular disease risk factors were measured, and the corresponding family history was self-reported using a structured questionnaire. Results: The prevalence of a positive family history (in first-degree relatives) was 39.6% for hypertension, 22.3% for diabetes, and 29.0% for hypercholesterolemia. Family history was not known for at least one family member in 41.8% of participants for hypertension, 14.4% for diabetes, and 50.2% for hypercholesterolemia. A positive family history was strongly associated with higher levels of the corresponding trait, but not with the other traits. Participants who reported not to know their family history of hypertension had a higher systolic blood pressure than participants with a negative history. Sibling histories had higher positive predictive values than parental histories. The ability to discriminate, calibrate, and reclassify was best for the family history of hypertension. Conclusions: Family history of hypertension, diabetes, and hypercholesterolemia was strongly associated with the corresponding dichotomized and continuous phenotypes.
Efficacy of Systemic Treatments for Moderate to Severe Plaque Psoriasis: Systematic Review and Meta-Analysis
Authors: Bansback Nick , Sizto Sonia , Sun Huiying , Feldman Steven , Willian Mary Kaye , Anis Aslam
Published: August 2009

Aims: To compare the efficacy of psoriasis treatments through a systematic literature review and meta-analysis. Methods: Randomized controlled trials evaluating the Psoriasis Area and Severity Index (PASI) were identified and assessed for quality. PASI responses were modeled using a mixed-treatment comparison, which enabled the estimation of the relative effectiveness of several treatments. Sensitivity analyses were performed. Results: Twenty-two trials were included. Tumor necrosis factor (TNF) inhibitors were most likely to achieve PASI 75, with a mean relative risk (RR) of 15.57 (95% CI 12.46–19.25) versus mean RRs of 9.24 (95% CI 5.33–13.91) for systemic and 5.65 (95% CI 3.74–7.97) for T-cell therapies. Infliximab (81%) and adalimumab (71%) had greater probabilities of achieving PASI 75 than etanercept (50%). Dosage was an important determinant of outcome. Conclusions: TNF inhibitors were more effective than T cell agents; adalimumab and infliximab were more effective than systemic therapies and etanercept. Evidence-based comparisons support patient and physician decisions.
Antibodies to Purified Protein Derivative in Different Immunoglobulin Classes in the Diagnosis of Tuberculosis in Man
Authors: Radin Robert C. , Zeiss Raymond , Phair John P.
Published: August 2009

The sera of patients with active tuberculosis (TB) and sera from control groups were assayed for IgG, IgA, secretory IgA, IgM and IgE antibody activity to purified protein derivative (PPD) using the enzyme-linked immunosorbent assay. Patients with active TB clearly had higher levels of IgG antibody activity to PPD antigen than did healthy patients who were skin test positive or negative. There was a clear separation between the diseased and healthy groups. Similar, but not as marked increases were seen in IgA and secretory IgA antibody activity in diseased patients. No correlation between the presence of disease and antibody levels were found with IgM, and no IgE antibodies were found. The method presented is a rapid reproducible assay using commercially available materials, and may offer a clinically useful test for the diagnosis of TB.
Expression of FcIgG Receptors on Cultured Fetal Rat Brain Cells
Authors: Aanderud Sylvi , Lillehaug Johan , Tønder Olav , Laerum Ole Didrik
Published: August 2009

The expression of FcIgG receptor (FcR) was studied during various stages of growth and subculturing of: (1) fetal rat brain cells (FBC); (2) FBC during in vitro neoplastic transformation after a transplacental pulse of the alkylating carcinogen ethylnitrosurea in vivo, and (3) an established neoplastic brain tumor cell line. Hemadsorption of antibody-coated sheep erythrocytes was used for the detection of FcR-positive cells. Such cells were not detected in cryostat sections of fetal rat brains, but in primary cultures of FBC 1 day after the explantation. FcR-positive cells were present throughout the logarithmic-growth phase. When reaching confluency after 5–7 days in culture, FcR-positive cells could not be detected. In the secondary cultures the occurrence of FcR-positive cells showed a similar variation related to growth: The growth-related receptor was also present on cells growing into arteficial defects in confluent cultures, while the resting cells in the same cultures were FcR-negative. With further subculturing the cells became epithelioid and slowly growing without FcR. Morphologically induced differentiation of such epithelioid cells by 12-O-tetra-decanoyl phorbol-13-acetate did not change the FcR expression. We did not detect any change in the receptor expression related to the malignant transformation, and the malignant cell line was FcR-negative. Expression of FcR on FBC undergoing malignant transformation therefore seems to be mainly connected to the mode of growth (log-phase versus confluence).
Effects of Hydrocortisone and Protein Synthesis Inhibitors on FcIgG Receptors on Cultured Fetal Rat Brain Cells
Authors: Aanderud Sylvi , Lillehaug Johan , Matre Roald
Published: August 2009

The in vitro effect of protein synthesis inhibitors on FcIgG receptor (FcR) expression was studied in secondary cultures of fetal rat brain cells (FBC). Hemadsorption of antibody-coated sheep erythrocytes was used for the detection of FcR-positive cells. The addition of actinomycin D 0.5 and 2.5 μg/ml or cycloheximide 1.0 and 5.0 μg/ml to the growth medium did not change the FcR activity after 4 and 12 h. When the cells were cultured in medium containing hydrocortisone 10––6 and 10––7M for 1, 2 or 3 days, the number of FcR-positive cells increased markedly. Confluent cultures of FBC and FBC undergoing in vitro neoplastic transformation were FcR negative. Hydrocortisone did not induce FcR activity in these cultures. The results indicate that the persistence of FcR on cultured FBC is not dependent on de novo protein synthesis. Hydrocortisone seems to prolong the period of FcR expression in FcR-positive cells.
Histopathology of Delayed-Onset Hypersensitivities in Contact-Sensitive Guinea Pigs
Authors: Godfrey H.P. , Phillips Mildred E. , Askenase P.W.
Published: August 2009

We have studied the specificity of macroscopic responses and the corresponding cellular infiltrates in Giemsa-stained, glycol methacrylate embedded tissue sections of delayed skin reactions elicited by contact sensitizers, homologous and heterologous hapten-protein conjugates, and tuberculin (PPD) in guinea pigs. The animals were sensitized with contact sensitizers emulsified in Freund’s complete adjuvant and tested at 19 days and, after repeated contact testing with homologous sensitizer, at 48 days after sensitization. At both times, all delayed reactions contained numerous mononuclear cells. The reactions elicited by contact sensitizer or hapten-protein conjugate also contained significant numbers of basophils which were lacking in PPD reactions. Contact reactions were highly specific macroscopically and microscopically while reactions elicited by conjugates displayed considerable macroscopic and microscopic cross-reactivity. The greater cross-reactivity of conjugate-elicited reactions compared to contact reactions may reflect differences in mechanism of initiation or mediation of these two reactions.
Release of Eosinophil Chemotactic Leukotriene from Neutrophils of Patients with Pseudo-Allergic Reactions
Authors: Czarnetzki Beate M.
Published: August 2009

Possible alterations in the release of eosinophil chemotactic leukotrienes (ECL) were studied with leukocytes from 14 patients with chronic urticaria due to pseudo-allergic reactions (PAR) and from 14 healthy volunteers. Patients tended to release less ECL, and inhibition of ECL release was more marked in the presence of cyclooxygenase and lipoxygenase inhibitors. The latter compounds did not cause ECL secretion by themselves. Increased release of lipoxygenase products of arachidonate metabolism from blood leukocytes is therefore an unlikely cause for PAR.
The Release of Histamine from Rat Mast Cells by Chymotrypsin
Authors: Nials A.T. , Vardey C.J. , Skidmore I.F.
Published: August 2009

The release of histamine from rat peritoneal mast cells induced by α-chymotrypsin and that induced by antigen have characteristics in common. The kinetics of histamine release initiated by the two agents are similar. Both α-chymotrypsin and antigen release histamine in the absence of extracellular calcium, phosphatidyl serine enhances the release, and disodium cromoglycate inhibits both reactions. In contrast, extracellular α-chymotrypsin does not induce histamine release from cells isolated from fragments of human lung, human basophils, histamine-containing cells lavaged from the bronchial lumen of the rhesus monkey, fragments of human lung and fragments of guinea pig lung.
Perfluorocarbon Enhancement of Heterologous Red Cell Survival: A Reticuloendothelial Block Effect?
Authors: Castro Oswaldo , Reindorf Carl A. , Socha Wladyslaw W. , Rowe Arthur W.
Published: August 2009

The intravascular survival of human erythrocytes transfused to primate animals was prolonged by infusing the recepients with a perfluorocarbon red cell substitute (Fluosol DA). This effect is probably due to transient block of the animals’ reticuloendothelial system by the perfluorocarbon emulsion. Perfluorocarbon compounds could be used to study the role of reticuloendothelial function in the immune destruction of red cells.
Decrease of E and EA but Not EAC Rosette Formation after Incubation of Blood Lymphocytes in Cerebrospinal Fluid
Authors: Næss A.
Published: August 2009

Peripheral blood lymphocytes (PBL) were incubated in autologous cerebrospinal fluid (CSF) or Hanks’ balanced salt solution (HBSS) for between 5 and 60 min at 37 °C. Incubation in CSF caused an increase in cell death as measured by trypan blue inclusion. Incubation in CSF also resulted in a decreased percentage of E and EA rosette-forming cells (RFC) – but not of EAC-RFC – as compared with preincubation levels. Incubation in HBSS did not cause significant changes in rosette formation. Although incubation in CSF resulted in decreased E and EA rosette formation by PBL, lymphocytes isolated from CSF showed increased E and EAC rosette formation as compared with PBL.
Determination of Antibodies to Partially Purified Aspergillus Antigens by an Enzyme-Linked Immunosorbent Assay
Authors: Schønheyder H. , Andersen P.
Published: August 2009

A total of 75 sera from 17 patients with pulmonary aspergillosis and 58 controls were investigated by ELISA for IgG antibodies against different antigen fractions of Aspergillus fumigatus. Somatic antigen obtained by homogenization of young hyphi was fractionated on a Sephadex G-200 column, and 11 antigen fractions (I-XI) were prepared. Antibodies to fractions I-XI were detected in sera from patients with aspergillosis, whereas antibodies in sera from control patients and healthy blood donors were directed against only 7 fractions (I-VII). Antibodies against fraction VIII with an approximate molecular weight of 70,000 appeared to be of high diagnostic significance for pulmonary aspergillosis.
Antibodies against Polyethylene Glycol Produced in Animals by Immunization with Monomethoxy Polyethylene Glycol Modified Proteins
Authors: Richter Ary Wolfgang , Åkerblom Eva
Published: August 2009

Antibodies to polyethylene glycol (PEG) were raised in rabbits by immunization with monomethoxy polyethylene glycol modified ovalbumin (OA), bovine superoxide dismutase (SOD), and ragweed pollen extract (Rag), given in Freund’s complete adjuvant (FCA). Immunogenicity depended on the nature of the protein and the degree of modification. With modified OA, in the presence of FCA, the majority of animals showed an anti-PEG response. With modified SOD and Rag only a small proportion of animals responded. In the absence of FCA, modified OA, given s.c, did not elicit any anti-PEG antibody response in rabbits and only a weak response in mice. PEG of Mw 10,000 and 100,000 given in FCA was found nonimmunogenic in rabbits, and PEG of Mw 5.9 × 106, given s.c. to mice, showed no or very poor immunogenic properties. Gel diffusion, heterologous passive anaphylaxis and passive hemagglutination were used to demonstrate anti-PEG antibodies raised to PEG-modified proteins. Specificity was confirmed by hapten inhibition of precipitation, inhibition of passive hemagglutination and cross-reactivity tests. PEG of Mw ≥ 4,000 produced specific precipitates, smaller molecules acted as monovalent haptens. From hapten inhibition of precipitation by PEG of Mw 300 it appears that the antigenic determinant of PEG may be a sequence of 6–7 -CH2CH2O-units. Anti-PEG antibodies can be used analytically. By gel diffusion, Peg was detected in minimal concentrations of 0.1–1 μg/ml. The clinical relevance of these findings with regard to therapy with PEG-modified enzymes and allergens in humans remains to be established.
Effect of BSA on Ca2+ Influx in Mast Cells Stimulated by Ovalbumin
Authors: Tanizaki Yoshiro , Townley Robert G.
Published: August 2009

To examine the effect of bovine serum albumin (BSA) on the cell surface of mast cells, we measured 45Ca influx in mast cells from actively sensitized rats, and in cells passively sensitized in vitro with IgE-containing serum before or after BSA purification. Mast cells from actively sensitized rats showed a marked increase in 45Ca uptake after stimulation by ovalbumin. The uptake of 45Ca by mast cells passively sensitized before separation through BSA was also increased in response to ovalbumin. Variation in 45Ca uptake increased in the cells sensitized after separation. We did not observe a significant increase in 45Ca uptake in mast cells incubated with inactivated or normal serum compared to that of unstimulated cells.
Autoantibodies to Tamm-Horsfall Protein in Acute and Chronic Hepatitis
Authors: Lindberg Johan , Fasth Anders , Norkrans Gunnar , Nilsson Lars-Åke
Published: August 2009

The levels of antibodies of the IgG, IgA and IgM class against the Tamm-Horsfall glycoprotein (anti-THP) were determined in 108 patients with the following diagnoses: acute hepatitis A, acute hepatitis B, acute hepatitis non-A non-B, chronic hepatitis B, chronic hepatitis non-A non-B and chronic autoimmune hepatitis. The mean levels of antibodies of the IgM class were higher in all types of hepatitis than in healthy controls, while the mean levels of anti-THP of the IgA and IgG class were increased in acute hepatitis B only. 13 of 20 patients (65%) with acute hepatitis B exhibited increased levels of anti-THP of the IgA class compared to 6–18% of the patients in the other categories. The increased levels of anti-THP of the IgA class could not be attributed to elevated serum IgA but instead were correlated with the levels of serum aminotransferase. The possible impact of this particular association of anti-THP with acute hepatitis B is discussed.
Detection of Antibodies Interacting with Glycosaminoglycan Polysulfate in Patients Treated with Heparin or Other Polysulfated Glycosaminoglycans
Authors: Wolf H. , Nowack H. , Wick G.
Published: August 2009

A new method has been developed for the demonstration of the antibody nature of a factor occurring in some patients during treatment with heparin or other polysulfated glycosaminoglycans (GAGPS). So far, antibodies reacting with GAGPS, except heparin, have not been described. We used heparin- or GAG PS-coated normal blood group·thrombocytes for the detection of suspected antibodies. After addition of patients’ plasma or serum to a suspension of purified heparin- or GAGPS-coated platelets, agglutination was determined microscopically. In indirect immunofluorescence, positive staining of agglutinated platelets was observed with fluorescein isothiocyanate anti-Ig and anti-IgG conjugates, but not with anti-IgA or anti-IgM, with one exception in which IgM antibodies were also involved. Binding of complement was also shown using a tetramethylrhodamin isothiocyanate-labelled anti-C3 conjugate in double-staining experiments. Fibronectin could be excluded as a possible factor responsible for thrombocyte agglutination.
Suppression of Contact Sensitivity by IgG1 Antihapten Antibody
Authors: Katayama I. , Nishioka K.
Published: August 2009

Sera obtained from guinea pigs sensitized with 2,4-dinitrofluorobenzene (DNFB) showed suppressive activity on the migration inhibitory factor (MIF) production by the lymph node cells obtained from DNFB-contact-sensitized guinea pigs. A similar suppressive effect was achieved by the sera of 2,4,6-trinitro-chlorobenzene- (TNCB-)sensitized guinea pigs. The suppressive factor in the sera was found to be IgG1 antihapten antibody. It suppressed MIF production dose-dependently during a period between 3 h before and 1 h after the antigen stimulation. Pretreatment of macrophages with IgG1 antihapten antibody abolished the MIF production of the lymph node cell. The antibody lost its suppressive activity after splitting off its Fc portion, and pretreatment of macrophages with Fc fragments of normal IgG1 interfered with the action of the IgG1 antibody. Therefore, the IgG1 antihapten antibody in the sera of contact-sensitized guinea pigs acted on macrophages through its Fc portion to inhibit MIF production by lymph node cells.
Antigen Presentation by Macrophages from Adult Thymectomised Mice
Authors: Schon-Hegrad M.A. , Holt P.G.
Published: August 2009

Recent claims that macrophages from adult thymectomised mice fail to mature to a stage where they can ‘present’ antigen were examined. Comparisons were made between the capacity of antigen-pulsed peritoneal exudate macrophages from adult thymectomised and normal mice to elicit both primary and secondary lymphoproliferative responses in vitro, and to prime lymph node cells for antigen-specific recruitment in vivo. Macrophages from thymectomised donors were partially deficient in their capacity to activate naive or immune T-cells in vitro but were nevertheless capable of emitting a significant immunogenic signal. These results suggest partial, but not absolute T-cell regulation of the immunogenic function(s) of exudate macrophage populations.
Inhibition of Lymphoid Cell DNA Synthesis by Metal Allergens at Various Concentrations
Authors: Nordlind K.
Published: August 2009

Metal allergen concentrations inhibiting lymphoid cell DNA synthesis were tested on short-time cultured nonadherent and nonseparated thymic and splenic cells. With all tested metal allergens, the DNA-synthesis-inhibiting effect was more marked for nonadherent compared to nonseparated splenic cells. In thymocytes, a stronger inhibition of nonadherent cells was seen after addition of mercuric chloride. A protective or modifying role of adherent cells towards inhibiting or toxic effects of metal allergens in vitro is postulated.
Storage and Turnover of Histamine, 5-Hydroxytryptamine and Heparin in Rat Peritoneal Mast Cells in vivo
Authors: Wingren Urban , Wasteson Åke , Enerbäck Lennart
Published: August 2009

The biogenic amines and heparin of rat peritoneal mast cells were labelled in vivo by the injection of amine precursors (3H-histidine and 3H-5-hydroxytryptophan) and 35S-sodium sulfate. Uptake of label was rapid, probably reflecting the synthesis of new granule material, but the elimination was slow. Half-lives of radiolabelled histamine (23 days) and 5-hydroxytryptamine (5-HT; 25 days) did not differ statistically from that of heparin (35 days). The slow elimination rates suggest that mast cell secretion is of little biological significance under normal conditions but are well compatible with the idea that mast cell function is related to secretion evoked by appropriate immunological stimuli. It further permitted an analysis of the amine storage by repeated injections of unlabelled 5-HT. A 15-fold increase in 5-HT content was obtained while the total amine content remained constant. The uptake of 5-HT was balanced by a reduction of histamine in a molar 1:1 ratio. A displacement of histamine by 5-HT was further indicated by increased elimination rate of radiolabelled histamine in response to 5-HT injections. The results support previous binding studies in vitro and indicate that histamine and 5-HT are bound to identical storage sites in the mast cell granules.
Increased ‘T Lymphocyte’ Bearing Fc Receptors for IgG in Pregnancy
Authors: Ong Khing S. , Grieco Michael H. , Goel Zarina
Published: August 2009

T cell subpopulations as defined by E rosette formation and Fc receptors for immunoglobulins were determined, using ox red blood cells coated with the IgG or IgM fraction of rabbit anti-ox red blood cells antibody to form rosettes with the peripheral blood lymphocytes of 18 pregnant females and 12 healthy non-pregnant females. It was shown that the TG cell population in the pregnant females is significantly increased as compared to those in the nonpregnant controls (mean ± SEM %TG cells: 18 ± 1.2 vs. 9.6 ± 0.7; p < 0.001). By using peripheral blood from normal nonpregnant subjects it was also shown that To cells suppressed one-way mixed lymphocyte reactions (mean ± SEM suppression: 23 ± 7.2; p < 0.01). These findings suggest that the TG cell population may exert a suppressor function on the immune response to alloantigens and act in concert with other humoral factors to protect the fetus from rejection.
Formation of Biologically Inactive Polymers is Responsible for the Thermal Inactivation of Rat IgE
Authors: Rousseaux-Prévost Roselyne , Rousseaux Jean , Bazin Hervé , Biserte Gérard
Published: August 2009

The structural changes induced by heating rat IgE at 56 °C and relationship with loss of cytotropic activity were examinated in the present study. Circular dichroism spectrum of IgE heated at 56 °C showed irreversible changes in the peptide bond spectral regions: increase in β-sheet structure, but no significant modifications in the aromatic side chain region. Thus, circular dichroism studies did not suggest important perturbations of the tertiary structure of the IgE molecule. Parallel studies with F(ab’)2-ε fragment did not show significant alterations of either peptide bond or aromatic side chain spectral regions. Analysis of IgE heated at 56 °C by polyacrylamide gradient gel electrophoresis showed the presence of large amounts of polymeric material. Polymerization of IgE was found to increase with time of heating at 56 °C and to depend on protein concentration; polymerization was decreased at temperatures lower than 56 °C. A relationship between loss of cytotropic activity and the proportion of polymeric material in the heated IgE solutions was observed. Isolated polymeric molecules produced by heating showed considerable decrease in cytotropic activity whereas monomer isolated from heated IgE was found biologically active. The ability to form polymers is an intrinsic property of the carboxy-terminal domains Cε3 and Cε4, as the F(ab′)2-ε fragment did not polymerize upon heating at 56°C. A model of thermal inactivation of rat IgE is proposed in which aggregation of the carboxy-terminal domains of the ε-chain does not allow interaction of these domains with the monovalent IgE receptor of mast cells.
Antiallergic Activity of Nylidrin Hydrochloride (RHC 3432-A)
Authors: Khandwala A. , Coutts S.M. , Weinryb I.
Published: August 2009

Nylidrin (RHC 3432-A) has been investigated for its antiallergic activity in three in vitro models. Nylidrin was an effective inhibitor of IgE-mediated release of histamine from passively sensitized rat peritoneal mast cells and human basophils, and of IgG1-mediated release of histamine from passively sensitized guinea pig lung slices. The inhibition of the release of histamine by nylidrin in all three models was not antagonized by propranolol, indicating that nylidrin does not inhibit histamine release via stimulation of β-adrenergic receptors. Isoproterenol and epinephrine were effective as inhibitors of the release of histamine only from guinea pig lung while salbutamol and terbutaline had no effect on immunologic release of histamine in all three models. Detailed comparative studies with disodium cromoglycate (DSCG) indicated that the mechanism of action of nylidrin in the rat mast cell model is different from that of DSCG.
RHC 3024: Antiallergic Activity in vitro and Comparison with Disodium Cromoglycate and Other Antiallergic Agents
Authors: Khandwala Atul , Coutts Stephen M. , Dally-Meade Vernetta , Jariwala N. , Huang Fu-Chih
Published: August 2009

RHC 3024 has been investigated for its antiallergic activity in three in vitro models of anaphylaxis. We have also compared its activity profile in these models with that of disodium cromoglycate (DSCG) and other antiallergic agents. As an inhibitor of antigen-induced release of histamine from rat mast cells RHC 3024 was 4 times more potent than DSCG. In the same model the activity profile of RHC 3024 was identical to that of DSCG in the following respects: loss of inhibitory activity with increasing preincubation time, reversibility of the inhibition, tachyphylaxis and cross-tachyphylaxis to each other and inability to inhibit histamine release stimulated by Ca++ ionophore, dextran/phosphatidyl serine and compound 48/80. Both drugs had no effect in the other two models, IgG1-mediated histamine release from guinea pig lung and anti-IgE-induced histamine release from human basophils. We conclude: (1) RHC 3024 is a potent inhibitor of mediator release with a mechanism of action similar to that of DSCG, M&B 22,948, PRD-92-Ea and AH-7725 and (2) the in vitro activity profiles of proxicromil, doxantrazole, ICI 74,917 and WY-16,922 are different from DSCG and RHC 3024.
Conditions for the Enhancing Effect of Protease Inhibitors on the Concanavalin A Induced Thymidine Response of Murine Lymphocytes
Authors: Hammann K.P. , Scheiner O. , Raile A. , Schulz T. , Schopf R.E. , Peters H. , Erdei A. , Dierich M.P.
Published: August 2009

Incorporation of [3H]-thymidine – [3H]-TdR – into concanavalin A (Con A) stimulated murine splenocytes and thymocytes was found to be enhanced by addition of certain concentrations of phenyl-methyl-sulfonylfluoride (PMSF), di-isopropylfluorophosphate (DFP), N-α-tosyl-L-lysyl-L-chloromethylketone (TLCK), and soybean trypsin inhibitor (SBTI). No enhancement could be observed when mononuclear cells of the peripheral blood were used, and a medium enhancement when thymocytes were applied. Furthermore, no enhancing effect of the protease inhibitors (PI) on the Con A response of murine splenocytes could be observed within the first 24 h of the culturing period. DFP, PMSF, and TLCK enhanced the Con A response to a similar degree, whereas SBTI was less effective. DFP and SBTI proved to be also effective when they were added after 15–24 h to the Con A cultures, if the cultures were harvested 48 h later. Removal of adherent and phagocytic spleen cells or reduction of the concentration of spleen cells shifted the effective DFP concentration to lower concentrations, whereas addition of adherent spleen cells caused a shift of the enhancing DFP amounts to higher concentrations. The data presented suggest that the enhancing effect of PI on the T cell response depends on the concentration of PI, the time of culturing and incubation, the PI used the origin of the stimulated cells, and especially on the number of adherent and phagocytic cells. These findings might explain – at least in part – the different results on the effect of PI on the T cell response obtained in the past.
Distribution of IgM-, IgG-, and IgA-Positive Cells in Lymphatic Organs of Normo- and Dysgammaglobulinemic UM-B19 Chickens
Authors: Hoffmann-Fezer G. , Lösch U.
Published: August 2009

Lymphatic organs of normo- and dysgammaglobulinemic chickens were studied by immunohistochemical methods concerning IgM-, IgG-, and IgA-positive cells. IgM- and IgA-positive lymphocytes and plasmacytic cells are similarly distributed in dys- and normogammaglobulinemic chickens. Follicles of the bursa of Fabricius contain cortical lymphocytes weakly and medullar lymphocytes distinctly stained by anti-IgM, as well as some larger irregularly shaped cells with intensely labeled cytoplasm. In spleen, periellipsoid lymphocytes, some red pulp lymphocytes, and varying numbers of plasmacytic cells are also distinctly labeled by anti-IgM. IgA-positive lymphocytes are not present in the bursa of Fabricius, but the bursal medulla is populated by some irregular, mostly longish cells with cytoplasmic IgA reaction. Spleen contains a few IgA-labeled lymphocytes and plasmacytic cells. The only difference between normo- and dysgammaglobulinemic chickens is found in IgG-positive cells, which are absent in permanently dysgammaglobulinemic chickens. The results from dysgammaglobulinemic chickens show that IgA can also be produced in untreated chickens lacking IgG synthesis and suggest that the theory of an IgM → IgG → IgA sequence is unlikely.
Enhancement of IgE Antibody Production by Ovalbumin Aerosol in Mice
Authors: Imai Toru , Shimizu Fujio , Fujimaki Hidekazu , Watanabe Naohiro
Published: August 2009

The effect of aerosolized ovalbumin (OA) on the induction of IgE antibody production was investigated in BALB/c mice. Enhancement of anti-OA IgE antibody production was obtained after the administration of 10 μg OA in mice preexposed to 1% aerosolized OA for 6 or 30 min, and after the administration of 1 μg OA in mice preexposed to aerosolized OA for 30 min. IgE antibody production could also be induced by preexposure to aerosolized OA at a concentration as low as 0.1%. A carrier effect was observed by preexposure to aerosolized OA using a hapten-carrier system. In the latter system, whole body irradiation (200 R) could not enhance IgE response, suggesting that irradiation-sensitive suppressor T cells might be generated in insufficient amount or not at all by aerosolized OA. Preexposure to aerosolized dinitrophenol-OA could not enhance anti-dinitrophenol IgE response. These results suggest that the exposure to aerosolized antigen primed preferentially T helper cells.
IgE on Rat Pleural and Peritoneal Mast Cells; Relation to Serum IgE
Authors: van Toorenenbergen A.W. , van Swieten P. , Aalberse R.C.
Published: August 2009

Brown Norway rats were immunized with trinitrophenylated ovalbumin (TNP-OVA). TNP-specific and total IgE in serum and in acid eluates of pleural and peritoneal mast cells were determined by radio-immunoassay. The IgE load of peritoneal mast cells was significantly higher than the IgE load of pleural mast cells. 8–9 days after immunization, the ratio specific/total IgE for cell-bound IgE was smaller than this ratio for free circulating IgE. The composition of IgE on mast cells that were isolated 8–9 days after immunization was better reflected by the composition of serum IgE on the day before isolation than by the composition of serum IgE at the time of isolation of the mast cells. Therefore, we conclude that (1) IgE on mast cells is not in rapid equilibrium with free circulating IgE, and (2) the composition of IgE on mast cells lags at least 1 day behind that of serum IgE.
Comparative Studies on Tree-Pollen Allergens
Authors: Vik H. , Elsayed S. , Apold J.
Published: August 2009

A comparative electrophoretic and autoradiographic analysis of the different fractions of birch pollen crude extract was performed. This extract included a minimum of 17 reproducible and distinct antigens located in the gel filtration fractions BV2–BV4. Only one of these precipitates had the ability to bind IgE, as demonstrated by immunoelectrophoretic and autoradiographic techniques using several poly- and monospecific rabbit antibodies. The allergenicity of the different fractions was examined in vitro by RAST and RAST inhibition, and in vivo by passive cutaneous transfer and skin prick tests. The data suggested that Betula verrucosa pollen extract contains a group of isoallergens with related antigenicity but with variable molecular sizes. The findings have also confirmed the presence of identical antigenic properties of the previously isolated pI 5.18 and BV45 as deduced from their immunoelectrophoretic and autoradiographic studies.
Carrier Requirement for Development of Acute Experimental Hypersensitivity Pneumonitis in the Rabbit
Authors: Butler J.E. , Richerson H.B. , Swanson P.A. , Suelzer M.T. , Kopp W.C.
Published: August 2009

Fluorescein isothiocyanate (FITC) conjugated to protein carriers was used to explore carrier dependence in an established rabbit model of acute hypersensitivity pneumonitis (HSP). Rabbits were immunized via toepads with either FITC-ovalbumin (OA) or FITC-human γ-globulin (HGG) in complete Freund’s adjuvant, and were aerosol challenged with homologous or heterologous conjugates 30 days later. Only those rabbits challenged with the homologous carrier developed acute HSP, despite the presence of comparable levels of anti-FITC antibodies in the sera of all groups. These findings indicate a strict carrier dependence in the pathogenesis of HSP in this model and provide further evidence that the mechanism of inflammation depends upon a cellular immune response.
Allergens of Alternaria: Further Characterization of a Basic Allergen Fraction
Authors: Budd T.W. , Kuo C.Y. , Cazin, Jr. J. , Yoo T.J.
Published: August 2009

A basic allergen fraction isolated from Alternaria extracts by preparative flat-bed gel isoelectric focusing (as previously reported) was subjected to further characterization. The fraction was chromatographed on a Sephadex G-25 column and exhibited two major peaks, the first of which was allergenic and the second of which was nonallergenic but caused a precipitate to form when added to a mixture of sodium dodecyl sulfate (SDS) (1 %) and trichloroacetic acid (5%). SDS-PAGE indicated that the allergen component of the basic fraction migrated at about the same rate as insulin (5.8 kdaltons). Both G-25 peaks were carbohydrate rich with a proteinxarbohydrate ratio (by weight) of 1:4.5 and 1:5.8 for peak 1 and peak 2 respectively. Heat (100°C for 10 min) and enzyme digestion (trypsin, α-chymotrypsin and pepsin) did not reduce the RAST inhibition values for peak 1 or the original basic fraction. The basic fraction did not bind human IgE specific for birch pollen indicating that the RAST inhibition and IgE (Alternariaspecific) binding to radioimmunoelectrophoresis plates was not due to nonspecific binding of IgE. We conclude that the allergenicity of the basic fraction is due to a small molecule that is predominantly carbohydrate in nature and is a major allergen of Alternaria.
Antigen Release from Thermoactinomyces vulgaris by Lysozyme Treatment
Authors: Ojanen Tarja H. , Naukkarinen Anita H.M. , Katila Marja-Leena , Terho Erkki O. , Mäntyjärvi Rauno A.
Published: August 2009

Lysozyme treatment was used to release antigenic material from Thermoactinomyces vulgaris, one of the microbes associated with farmer’s lung. Lysozyme caused degradation of the murein layer visualized as changes and disappearance of the bacterial morphology in scanning electron microscopy. Enrichment of different antigenic components in the lysozyme extract and in the cell residue, respectively, was detected by immunoprecipitation. When lysozyme extract and cell residue antigens were used in enzyme-linked immunosorbent assay to test sera of farmer’s lung patients and control persons, it became evident that there was no significant difference between the reactions against the two antigens. However, a number of sera reacted preferentially against one or the other of the two antigens.
Activation of the Complement System and Accumulation of Hemoglobin-Haptoglobin Complexes in Plasma during an Adverse Reaction to Penicillin Treatment
Authors: Brandslund I. , Svehag S.-E. , Teisner B. , Petersen Hyltoft
Published: August 2009

A patient treated with penicillin intravenously developed a serum sickness-like reaction. Classical pathway complement (C) activation was indicated by quantitation of the split products C3c and C3d as well as demonstration of C4 conversion. Circulating immune complexes could, however, not be detected by the solid-phase C1q and PEG-precipitation methods. A concomitant accumulation of circulating hemoglobin-haptoglobin complexes and a marked fall in serum-fibronectin concentrations suggested saturation of the reticuloendothelial system. The plasma became a deep-red color, and a diffuse intravascular coagulation followed. The patient recovered completely upon discontinuation of penicillin administration.
In vitro Generation of Mast Cell-Like Cells from Human Peripheral Mononuclear Phagocytes
Authors: Czarnetzki Beate M. , Krüger Gabriele , Sterry Wolfram
Published: August 2009

An in vitro culture method, previously shown to induce the transformation of rat macrophages to mast cells, has been adapted to humans. Adherent peripheral human blood mononuclear cells were cultured in a medium supplemented with 30% L-cell supernatant and 30% horse serum. During the first week of culture, the cells were phagocytic (80%), lacked histamine, were not metachromatic and stained faintly for naphthol-AS-D-chloroacetate esterase, primarily in a paranuclear location. During the first 2 weeks of culture, the cells grew in size, synthesized DNA, became nonadherent and developed cytoplasmic chloroacetate esterase staining which was strongly positive in 50–60% of the cells during the third week. Intracellular histamine levels increased steadily during culture, and electron-dense metachromatic cytoplasmic granules were present during the third week. Human peripheral blood mononuclear cells contain therefore a subpopulation of cells that can differentiate into mast cells-like cells under specific in vitro culture conditions.