bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine-Regulated Adrenocorticotropic Hormone Secretion in Lactating Rats: Functional Plasticity of Melanotropes
Authors: Oláh Márk , Fehér Pálma , Ihm Zsófia , Bácskay Ildikó , Kiss Timea , Freeman Marc E. , Nagy György M. , Vecsernyés Miklós
Published: July 2009

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and β-lipotropin in corticotropes of the anterior lobe, and to α-melanocyte-stimulating hormone (α-MSH) and β-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D2 type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence α-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E2)-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in α-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by α-methyl-p-tyrosine (αMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma α-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E2 animals. In lactating mothers, BRC was able to block ACTH responses induced by both αMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons.
Semaphorin3F Down-Regulates the Expression of Integrin αvβ3 and Sensitizes Multicellular Tumor Spheroids to Chemotherapy via the Neuropilin-2 Receptor in vitro
Authors: Zheng Chenhong , Zhou Qi , Wu Feng , Peng Qiuping , Tang Airong , Liang Houjie , Zeng Yanjun
Published: August 2009

Background: Multicellular resistance (MCR), i.e. decreased sensitivity to anticancer drugs compared with common monolayer cell (MC) cultures, depends partly on tumor cell-cell adhesion. Previous studies have shown that anti-adhesive therapies, including integrin αv, β1 and αvβ3 targeting, induced apoptosis and reversed the sensitivity of MCR. Methods: A model of three-dimensional cell culture was used to establish HT29 multicellular spheroid cells (MCS) and explore the effect of semaphorin3F (Sema3F) on integrin-mediated cell-cell interactions in MCS of a human colorectal adenocarcinoma cell line (HT29) and sensitization of HT29 MCS to 5-fluorouracil and oxaliplatin via a decrease in integrin αvβ3. Results: Elevated expression of Sema3F led to the up-regulation neuropilin-2 (Nrp2) receptor expression and the down-regulation of integrin αvβ3 expression. Furthermore, short interfering RNA of Nrp2 could reverse MCR. Conclusion: Our study demonstrates that Sema3F can sensitize MCR by decreasing integrin αvβ3 expression via the Nrp2 receptor.
Anticancer Activity and Differentially Expressed Genes in Head and Neck Cancer Cells Treated with a Novel Cyclin-Dependent Kinase Inhibitor
Authors: Shin Ho Cheol , Song Dal Won , Baek Won Ki , Lee Seong Ryong , Kwon Taeg Kyu , Lee Jinho , Park Sol Hee , Jang Byeong-Churl , Park Jong-Wook
Published: August 2009

Background: Cyclin-dependent kinases (CDKs) are involved in the regulation of the cell cycle and the growth of tumor cells. In this study, we investigated the antitumor effect and differentially expressed genes (DEGs) in head and neck cancer cells treated by a novel CDK inhibitor, 2-[1,1′-biphenyl]- 4-yl-N-[5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-1H-indazol-3-yl] acetamide (BAI). Methods: Cell growth was measured by XTT assay. Cell cycle and apoptosis were determined using flow cytometry. GeneFishing™ PCR was utilized to identify DEGs. Protein expression was analyzed by Western blot. Results: Exposure to BAI of 2 different head and neck cancer cell lines, AMC-HN4 and AMC-HN6, induced apoptosis in association with growth inhibition, cell cycle arrest, caspase-3 activation and cytochrome c release. Significantly, data from GeneFishing PCR experiments demonstrated 10 DEGs in AMC-HN6 cells treated with BAI. Some of these DEGs turned out to encode proteins with functions related to key cellular processes. Conclusions: These results indicate that BAI has strong anticancer activities on head and neck cancer cells, and the DEGs induced by BAI may become involved in BAI-induced cancer cell death.
Effects of Grepafloxacin on the Function of Human Polymorphonuclear Leukocytes and the Phosphorylation of p38 Mitogen-Activated Protein Kinase
Authors: Koshio Osamu , Ono Yasuo
Published: August 2009

Background: Some new quinolones (NQs) modulate polymorphonuclear leukocyte (PMN) functions. We investigated these effects on PMN functions at concentrations <10 μg/ml. Methods: Chemotactic activity and the production of reactive oxygen species (ROS) were measured using a 48-well chemotaxis chamber and by luminol-dependent chemiluminescence (CL) activity, respectively. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was measured by Western blot using specific antibodies to its phosphorylation sites. Results: Grepafloxacin (GPFX) at concentrations >5 μg/ml increased the chemotactic activity and ROS production of PMNs after stimulation with N-formylmethionyl-leucyl-phenylalanine (fMLP), whereas prulifloxacin (PUFX) showed no effect. In contrast to PUFX, GPFX at concentrations >1 μg/ml stimulated the phosphorylation of p38 MAPK. Conclusions: GPFX enhanced the chemotactic activity and ROS production of PMNs after stimulation with fMLP at concentrations <10 μg/ml. These effects of GPFX on PMNs could be in part due to the enhancement of p38 MAPK phosphorylation.
Eosinophils Utilize Multiple Chemokine Receptors for Chemotaxis to the Parasitic Nematode Strongyloides stercoralis
Authors: Stein Louis H. , Redding Kevin M. , Lee James J. , Nolan Thomas J. , Schad Gerhard A. , Lok James B. , Abraham David
Published: August 2009

Protective innate immunity to the nematode Strongyloides stercoralis requires eosinophils in the parasite killing process. Experiments were performed to determine if an extract of S. stercoralis would trigger eosinophil chemotaxis, and to then compare the chemotactic migration response, including second messenger signals and receptors, to those mechanisms triggered by host chemoattractants. Eosinophils undergo both chemotaxis and chemokinesis to soluble parasite extract in transwell plates. Pretreatment of eosinophils with pertussis toxin, a G protein-coupled receptor inhibitor, inhibited migration of the eosinophils to the parasite extract. Likewise, blocking PI3K, tyrosine kinase, p38 and p44/42 inhibited eosinophil chemotaxis to parasite extract. Furthermore, CCR3, CXCR4 or CXCR2 antagonists significantly inhibited eosinophil chemotaxis to the parasite extract. Molecular weight fractionation of parasite extract revealed that molecules attracting eosinophils were present in several fractions, with molecules greater than 30 kDa being the most potent. Treating the extract with proteinase K or chitinase significantly inhibited its ability to induce chemotaxis, thereby demonstrating that the chemoattractants were both protein and chitin. Therefore, chemoattractants derived from parasites and host species stimulate similar receptors and second messenger signals to induce eosinophil chemotaxis. Parasite extract stimulates multiple receptors on the eosinophil surface, which ensures a robust innate immune response to the parasite.
Effect of Metal Allergens on Thymocytes from Unsensitized Guinea Pigs: A Comparative Light and Electron Microscopic Study
Authors: Nordlind K. , Thyberg J.
Published: August 2009

In the present investigation we studied the effects of different metal allergens on cell counts, dye exclusion, and fine structure of unsensitized guinea pig thymocytes cultured in vitro for up to 96 h. At concentrations which inhibit DNA synthesis of lymphoid cells, the metal salts most often caused cell degeneration as judged by dye exclusion test and electron microscopy. DNA synthesis stimulating concentrations of mercuric chloride gave an increase in the percentage of viable cells. Absolute cell counts were not changed with either DNA synthesis inhibiting or stimulating concentrations. The importance of using different methods in investigating effects of metal allergens on lymphocytes in vitro is pointed out.
Production of Migration Inhibitory Factor by Listeria-Immune Mouse T Lymphocytes, but not B Lymphocytes
Authors: Kearns Robert J. , Campbell Priscilla A.
Published: August 2009

Antigens and B cell mitogens have been reported to induce migration inhibition factor (MIF) production by mouse B cells. Immune resistance to the intracellular bacterium, Listeria monocytogenes is thought to involve T cells, but not B cells. Since Listeria-derived components are B cell, but not T cell mitogens, it was important to determine whether these materials could stimulate secretion of the lymphokine, MIF by T cells, B cells, or both. Thus populations of whole, unfractionated spleen cells, obtained from normal and Listeria-immune BDF1 mice, were cultured with or without 100 μg/ml of Listeria intracellular product (LIP). The culture supernatants obtained 24 h later were assayed for MIF activity using the in vitro macrophage migration inhibition assay. Data obtained show that immune T lymphocytes release MIF in response to specific Listeria antigens, but that spleen B cells from immune and normal mice, obtained as immune, nylon-wool-adherent cells treated with anti-T-cell serum plus complement, are not capable of releasing MIF. This suggests that release of lymphokines by Listeria-immune or normal B cells stimulated with Listeria-derived antigens and mitogens is unlikely to contribute to resistance against Listeria in vivo.
Effects of Fibrinogen Fragment and Proteolytic Enzyme on the Immune System in Mice
Authors: Ahlstedt S. , Hessel B. , Nilsson B.S. , Sohl-Åkerlund A. , Wedel I. , Widström O.
Published: August 2009

The immunomodulating ability of fibrinogen fragment (Hol-DSK) and proteolytic enzyme with fibrinolytic activity from Aspergillus oryzae was analysed in CBA/Ca, C57B1, C3H/HeJ and NMRI mice. Suppressive effects on the blastogenic response to mitogens were noted. No consistent suppressive effect, but sometimes an enhancing one, was recorded on the antibody responses to protein antigens. Administration of Hol-DSK or proteolytic enzyme shortly after the immunization resulted in a slight inhibition of the development of delayed hypersensitivity to picryl chloride in C57B1 but not in CBA mice. When similar administration was done simultaneously with administration of the challenging antigen of picryl chloride or sheep red blood cells in immunized mice, significant impairment of the delayed-type hypersensitivity reaction was noted. The modulating effects by Hol-DSK did not alter the in vitro bacteriocidal effects of peritoneal exudate cells from mice on Escherichia coli.
Effect of Antihistamins (H1 and H2), Cortisone and Beta-Adrenergic Stimulator on Murine Contact Sensitivity and Histamine Metabolism
Authors: Olafsson Jon H. , Granerus Göran , Roupe Gösta
Published: August 2009

A study on the influence of histamine receptor blockade, beta-adrenergic stimulation and cortisone on murine cutaneous inflammation and histamine metabolism has been performed. Cortisone was found to reduce the inflammation and urinary histamine excretion while histamine receptor blockade and beta-adrenergic stimulation did not influence the reaction. A good correlation existed between inflammation and urinary histamine excretion in all experiments. Contact sensitivity in the mouse was not found to be transferable with serum indicating that humoral antibodies play no essential role in this reaction in the mouse. On the basis of these results it is suggested that basophils might participate in murine contact sensitivity.
Factors in the Sera of Tumor-Bearing Mice Modifying the Charge of Immune Cells
Authors: Vaillier D. , Vaillier J.
Published: August 2009

The mean electrophoretic mobility (EPM) of normal C3H spleen cells is significantly slackened (by approximately 15%) when the cells are incubated for 0.5 h at 37 °C with serum from slow-growing tumors (VMM2 and VMM1 tumors). On the contrary, it is not modified when the cells are incubated with serum from fast-growing tumors (RV2 or VFM1 tumors). VMM2 serum heated at 56°C induces the same phenomenon. Incubation at 4°C with VMM2 serum does not induce any change in spleen cell EPM. VMM2 and VMM1 sera seem to be essentially active on T cells. Indeed, no effect is observed with cells from ‘nude’, thymectomized, bone marrow-reconstituted C3H mice, or with the B cell-enriched fraction after nylon wool separation of normal spleen cells. A significant EPM decrease is only observed after serum incubation with the T cell-enriched fraction. Polyacrylamide gel electrophoresis shows that these sera exhibit an increase in the content of different protein groups. These phenomena suggest that the reduction of negative charge of lymphocytes after interaction with some tumor sera (VMM2 and VMM1 sera) might help establish tumor cell-lymphocyte contact and thus explain the slow growth rate of these VMM2 and VMM1 tumors.
Detection of IgE Antibodies in Onchocerciasis Using a Semi-Purified Fraction from Dipetalonema viteae Total Antigen
Authors: Ouaissi Ali , des Moutis J. , Cornette J. , Pierce R. , Capron A.
Published: August 2009

A Dipetalonema viteae extract was separated by gel filtration on ACA 34 Ultrogel into four fractions (A, B, C and D). The allergenic activity of the D. viteae extract and its various fractions was assayed by the passive cutaneous anaphylaxis (PC A) test in rats using mouse sera obtained from Balb/c mice transplanted with D. viteae. The PCA reaction showed that fraction B was the most potent allergenic fraction of the D. viteae extract. By the radioallergosorbent test (RAST) the use of fraction B coupled to CNBr-activated paper discs showed elevated binding of IgE antibodies in onchocerciasis human sera. A comparative study demonstrated the efficiency of the above fraction in the RAST technique in distinguishing between Onchocerca volvulus-infected patients and those infected with other human filarial worms or other helminth parasites. The binding of IgE to fraction B was confirmed by the radioimmunoelectrophoresis and radio-double diffusion methods using an 125I anti-human IgE. Since D. viteae antigens are more readily obtainable than those of O. volvulus, a further purification of fraction B to improve its specificity for the detection of IgE antibodies in human onchocerciasis is warranted.
Attempt to Infect the Nine-Banded Armadillo with Treponema pallidum
Authors: Wicher Konrad , Kalinka Carolyn , Walsh Gerald P.
Published: August 2009

10 nine-banded armadillos were infected by various routes with Treponema pallidum, Nichols strain. The animals did not demonstrate visible lesions but 4/7 animals responded with increasing titers of treponemal antibodies. Cardiolipin antibodies were not detected.
Regulation of Lymphocyte Transformation by Components Identified in Ultrafiltrates Prepared from Leukocyte Extracts
Authors: Sakatsuji Kikukazu , Gottlieb Arthur , Inui Jiro , Ohno Tomohiko , Nakamine Hirokazu , Nishimoto Yukio , Kawaguchi Yoshiaki , Saito Koji
Published: August 2009

Leukocyte components which can inhibit or enhance the uptake of 3H-thymidine by peripheral lymphocytes can be prepared by ultrafiltration of leukocyte extracts followed by gel filtration on Sephadex G-10. A potent inhibitor of lymphocyte transformation is present in an ultrafiltrate fraction having a nominal molecular weight of 5,000–10,000. Three other components having inhibitory, and one component having enhancing, activity on lymphocyte transformation were found in an ultrafiltrate fraction having a molecular weight less than 5,000. The inhibitory components in the latter were principally derived from polymorphs and inhibited both T and B lymphocyte proliferation. Enhancing components were mainly derived from mono-nuclear cells and augmented the proliferation of T cells only.
Cerebrospinal Fluid Granulocytes in Bacterial Meningitis Have E Receptors
Authors: Næss A.
Published: August 2009

Cerebrospinal fluid (CSF) granulocytes from 4 patients with bacterial meningitis were tested for rosette formation with sheep erythrocytes (E), a standard assay for T lymphocytes. CSF granulocytes from all patients formed E rosettes, although to a varying degree (66, 63, 17 and 2%, respectively). E rosettes could not be demonstrated with granulocytes from peripheral blood from the patient with 66% E-rosette-forming granulocytes in the CSF.
Comparative Studies on Tree-Pollen Allergens
Authors: Vik H. , Lillehaug J.R.
Published: August 2009

The structural changes as due to thermal denaturation of antigens and allergens of birch pollen produced by gel filtration chromatography were studied by circular dichroism, RAST inhibition and immunoelectrophoretic techniques. Results of circular dichroism showed that both BV3 and BV4 contained 20–25% alfa-helix, while BV45 consists of beta-pleated sheet and random coil. Fractions BV3 and BV4 lost about 50% of their native tertiary structures when heated at 100oC for 3 h. The number of antigenic lines found in the CIE plates for the heat-treated fractions was reduced as well. The CRIE preparations showed unchanged radio-staining for the heated BV3 fraction (correlated to the untreated BV3 fraction). For the BV4 fraction a diminished radiostaining was observed. A reduction of 8-fold and 4-fold of the IgE binding capacity was observed in RAST inhibition for fractions BV3 and BV4, respectively after heating. The purified fraction BV45 showed 50% decrease in CD absorption after heating to 100°C for 1 h. The CIE pattern of the heated fraction gave a single precipitate line and the area under the precipitate line was reduced as compared to the unheated fraction. The CRIE plate showed reduced intensity of radiostaining. Skin prick tests and PK tests confirmed the reduced allergenicity of the heated fractions. These findings confirm the relative thermostability of the allergens in birch pollen. However, heating infers irreversible changes on the tertiary structure of the molecules, and these structural changes can be correlated to a quantitative reduction of allergenic reactivity.
BL-5255 II: Effects on Release and Smooth Muscle Activity of Mediators of Immediate Hypersensitivity Reactions
Authors: Reed, III Frederick C. , Newball Harold H. , Siminoff Paul
Published: August 2009

BL-5255 inhibited release of preformed mediators from passively sensitized mast cells in the rat peritoneal cavity, chopped monkey lung or human lung tissue. The compound failed to block rat cutaneous reactions elicited by histamine or serotonin. It exhibited weak to no ability, depending on the mediator employed, to block contraction of isolated guinea pig ileum or tracheal tissue. At concentrations of 1 μM or greater, BL-5255 itself was contractile to the ileum but not to the quiescent or submaximally contracted trachea. The compound relaxed spontaneously contracting rabbit jejunum muscle but at doses not likely to be achieved in vivo. Phosphodiesterase activities in extracts of rat and human lung were inhibited at concentrations greater than those required to inhibit mediator release.
Regulation of Lymphocyte Responses in Cancer Patients
Authors: Tsuru S. , Nomoto K. , Aiso S. , Ogata T. , Zinnaka Y.
Published: August 2009

The gangliosides compose a major portion of the surface membrane structure of the lymphocytes and their expression may relate with functional properties of different lymphocyte subpopulations. In the present study, the binding of the ganglioside GM1 to the human peripheral blood mononuclear cells (PBMC) and their effects on the lymphocyte function were examined. Cholera toxin (CT) was used as an indicator for detection of GM1 on the cell surface. It was shown that the exogenous GM1 binds to normal PBMC and inhibits proliferative responses in vitro by various mitogens (Con A, PHA, PWM). It was also revealed that more than 18 h is required to induce unresponsiveness of lymphocytes by preincubation with GM1, even though GM1 bound very rapidly (10–30 min) to lymphocytes. Some intracellular event may be needed to induce unresponsive state of the lymphocytes by GM1 binding. Moreover, the number of CT binding lymphocytes and the amount of CT bound to each cell showed to increase in the cancer patients. These results suggest that the increase of GM1 in the serum and the lymphocyte surface may be one of the mechanisms of suppressed lymphocyte responsiveness in the various pathological states especially in the cancer patients.
Studies on the Paul-Bunnell Antigen-Antibody System
Authors: Morito Takao , Kano Kyoichi , Milgrom Felix
Published: August 2009

By means of double-diffusion precipitation tests in agarose gel with selected infectious mononucleosis (IM) sera, an antigen was detected in sera of patients with syphilis and leprosy. Of 378 syphilis sera tested 39 (10.3%) and of 36 leprosy sera 7 (19.4%) gave positive results. Sera of patients with various other diseases were negative. This antigen was demonstrable in sera of patients with both early and late syphilis and was shown to be unrelated to cardiolipin. Absorption studies of the IM sera with bovine and sheep erythrocytes and guinea pig tissues revealed that this antigen was identical with or closely related to the previously described B antigen of the Paul-Bunnell (P-B) antigenic complex and distinct from heterophile antigens of Hanganutziu-Deicher (H-D) and of Forssman specificity. However, 2 of 89 syphilis sera without the P-B antigen were shown to contain antigen(s) of H-D specificity. None of the syphilis or the leprosy sera contained P-B antibodies, but H-D antibodies were found in 13% of syphilis sera.
Time Course of Morphometric Changes after Acute Allergic Bronchoconstriction in the Guinea Pig
Authors: Baumal R. , Hooi C. , McAvoy D. , Broder I.
Published: August 2009

Experimental allergic bronchoconstriction was induced in guinea pigs by passive sensitization with a standard dose of homologous antiserum followed by challenge with aerosolized antigen. Lungs were removed from animals at intervals of up to 6 days thereafter, and several parameters of the reaction were assessed morphometrically by comparison with lungs from unsensitized guinea pigs. We determined all changes in volume of the lung tissue resulting from fixation through to the preparation of histologic sections, but no significant differences were observed between the time course subgroups. The size of both large and small airways was assessed by a point-counting technique, as well as by measurement of the percentage of the diameter of the airways contributed by the mean thickness of the muscular layer. Maximal bronchoconstriction was observed morphometrically to correspond with the peak of a response as determined clinically by the use of a strain gauge around the chest. This was followed by a return to normal of the airway size. The number of mast cells and eosinophils around large and small airways, around branches of the pulmonary artery and in random fields of the lung parenchyma was tabulated. The maximal decrease in mast cells was seen in animals which died immediately following challenge, but the numbers were not restored to the control level even in animals which had survived for 6 days. The greatest increase in eosinophil response occurred in lungs obtained 10 min following challenge. This model will be of value in determining the effects at the tissue level of pharmacological inhibitors of this reaction.
The Use of Particle Counting Immunoassay (PACIA) for the Titration of Specific Antibodies
Authors: Magnusson C.G.M. , Djurup R. , Weeke B. , Masson P.L.
Published: August 2009

Particle counting immunoassay (PACIA) is shown to be a suitable nonradioisotopic method for the titration of anti-phospholipase A2 antibodies in the sera from honeybee venom-desensitized patients. The sensitivity of the method is equal to the RAST-IgG with a correlation coefficient between the two methods of r = 0.94. Within-day and between-day precisions were 2.5 and 9.2%, respectively. The main advantages of PACIA are: (i) the use of easily prepared non-radioactive reagents having a shelf-life of at least 1 year at ––20°C; (ii) partial automation; (iii) calibration with antisera of animal origin, and (iv) the possibility of allergen standardization of honeybee venom extracts.
Airway Response to Leukotriene D4 in Rhesus Monkeys
Authors: Patterson Roy , Harris Kathleen E. , Smith Lewis J. , Greenberger Paul A. , Shaughnessy Martha A. , Bernstein Peter R. , Krell Robert D.
Published: August 2009

We studied the effect of leukotriene D4 (LTD4) given by aerosol challenge on asthmatic and normal monkeys. The response to LTD4 occurred within 2 min., was prolonged at higher concentrations, was reversed by epinephrine, and more closely resembled an antigen response than a histamine response. Since LTD4 concentrations of 30–100 μg/ml produced a response similar to 2–20 mg/ml of histamine, the LTD4 was 300–900 times as potent as histamine on a molar basis. Thus, LTD4, which appears to reproduce an antigen-induced response in rhesus monkeys, may be a mediator of allergic asthma in these animals.
Adjuvant Effects of a Crystalline Silica on IgE and IgG1 Antibody Production in Mice and Their Prevention by the Macrophage Stabilizer Poly-2-Vinylpyridine N-Oxide
Authors: Mancino D. , Buono G. , Cusano M. , Minucci M.
Published: August 2009

A crystalline silica (standard quartz DQ12 with particle size <5μm) is able to stimulate in Balb/c mice the production of IgE and IgG1 antibody to a single 1-μg dose of ovalbumin. The adjuvant effects of silica on both IgE and IgG1 antibody production are prevented by pretreatment of animals with poly-2-vinylpyridine N-oxide, a polymer that protects macrophages from the well-documented toxic effects of silica. These results indicate that adjuvanticity of silica is, at least partly, correlated to the damage induced on macrophages.
Specific Antibody Responses in Rats and Mice after Daily Immunization without Adjuvant
Authors: Ahlstedt S. , Björkstén B.
Published: August 2009

We have previously devised an immunization protocol to obtain IgE antibody formation in mice without the use of adjuvants. In this communication the observations were confirmed using several antigens and various routes of administration. The studies were also extended to rats. Subcutaneous (s.c.) administration to rats of 100-ng doses of trinitrophenylated human serum albumin (TNP-HSA) in 10-day periods resulted in production of IgE antibodies as determined with the RAST using antirat IgE. Higher antigen doses resulted in lower IgE antibody responses. Intranasal (i.n.) or peroral (p.o.) exposure of rats did not result in any IgE antibody responses. Exposure to antigen by the s.c. and i.n. route but not p.o. administration induced IgG, IgM and IgA antibody responses in rats as recorded with the enzyme-linked imunosorbent assay (ELISA). Several different antigens were given to CBA/Ca mice, i.e. penicilloylated bovine gammaglobulin (PO-BGG), FITC-conjugated dog serum albumin (FITC-DSA) or timothy pollen extract. All the antigens induced boosterable IgE antibody responses as determined with RAST utilizing antimouse IgE. Antibodies of IgG isotype were also recorded after such immunizations, whereas only low IgM and no IgA antibody titers were found in serum employing ELISA. After similar daily administration of antigen by the p.o. or i.n. route of antigen at doses from 102 to 105 ng, IgG antibody responses but no IgE antibodies were found. Intranasal administration of 106 ng induced some IgE and IgA antibodies. A single p.o. administration of 4 × 107 ng of antigen induced an antibody response of the IgG class. Pretreatment of animals with 4 × 107 ng of PO-BGG orally prior to the 10-day periods of s.c. injections suppressed the IgE antibody responses by 80% but enhanced the IgG antibody response. It was concluded that IgE antibody responses can be induced in rats and mice by daily s.c. administration of small doses of a variety of antigens without the use of any adjuvants. Antibody responses of the other isotypes may also be raised by such immunization. Intranasal and p.o. administration is less efficient in this respect, possibly requiring much higher antigen doses. The protocol for s.c. immunization appears to be suitable for studies of the regulation of an allergic immune response.
Increase of Mucosal Mast Cells in the Jejunum of Patients Infected with Trichinella spiralis
Authors: Gustowska Leokadia , Ruitenberg E.J. , Elgersma Anneke , Kocięcka Wanda
Published: August 2009

The mast cell response in the mucosa and connective tissue of 36 jejunal biopsies of patients with clinically diagnosed trichinellosis, teniasis and lambliasis has been studied. Biopsy material was fixed in standard formalin or Carnoy’s fixative, enabling differentiation between mucosal mast cells (MMC) and connective tissue mast cells (CTMC). With both fixatives CTMC could equally well be recognized. With Carnoy’s fixative an additional population of mast cells (MMC) could be visualized both in the mucosa and the connective tissue. In the mucosa small mucosal mast cells were observed as well. Compared to the numbers of mast cells in the mucosa and the connective tissue of teniasis and lambliasis patients, the number of mast cells in trichinellosis patients only visualized using Carnoy’s fixative was markedly higher. It was concluded that also in man trichinellosis is accompanied by an increase of cells with MMC characteristics. Further studies are needed to clarify the morphological and histochemical features of these cells and their possible role in this parasitic infection.
Local and Systemic Factors Regulating Mucosal Mast Cells
Authors: Pitts Rosanne M. , Mayrhofer Graham
Published: August 2009

The contributions of local and systemic factors to the regulation of mucosal mast cells and globule leukocytes have been examined in the rat. Nippostrongylus brasiliensis has been used to provide a potent immunological stimulus for mucosal mast cell hyperplasia and the roles of intestinal and extraintestinal sensitization observed by comparison of the gut mast cell responses to larval and adult worm infestations. Systemic effects of adult worm infestations have been examined in isolated Thiry-Vella loops of intestine. It is concluded that the extraintestinal phase of larval infestation is not obligatory for a gut mast cell response and that mast cell hyperplasia and globule leukocyte formation are not dependent on direct contact with the parasite or its products. The dissemination of the mast cell response and the general significance of the results are discussed.
Use of Dialyzed Venoms in the Radioallergosorbent Test
Authors: Wypych John I. , Abeyounis John , Müller Ulrich R. , Reisman Robert E.
Published: August 2009

Optimal concentrations of honeybee, hornet and yellow jacket venoms were used in the radioallergosorbent test (RAST) before and after dialysis. RASTtiters in the majority of sera from insect-allergic patients increased significantly with the dialyzed yellow jacket and hornet venom-coupled discs. Of 26 sera which had negative RASTs with crude venom, 20 became positive with dialyzed venom. No change in RAST results was found with crude and dialyzed honeybee venom. The low molecular weight component in the vespid venoms removed by dialysis had no specific activity in RAST inhibition experiments, suggesting nonspecific blocking of binding sites. These results indicate the importance of the appropriate antigen preparation coupled to discs in the RAST.
Antiallergic Activity Profiles in vitro of RHC 3164 and Related Compounds
Authors: Khandwala A. , Van Inwegen R. , Coutts S. , Dally-Meade V. , Jariwala N. , Huang F. , Musser J. , Brown R. , Loev B. , Weinryb I.
Published: August 2009

A series of 26 compounds belonging to the chemical class of (1,2,4)triazolo(4,3-a)-quinoxaline-1,4-diones have been investigated for their antiallergic activities in 3 in vitro models of anaphylaxis. Effects of these and other known antiallergic agents on cyclic nucleotide phosphodiesterases (cNUC-PDE) from purified rat mast cells have also been investigated. 18 compounds were potent (I50 ≤ 45 μM) inhibitors of antigen-induced release of histamine (AIR) from rat mast cells (RMC), 3 compounds inhibited anti-IgE-induced release of histamine from human basophils (I50 ≤ 25 μM) and none of the compounds significantly affected AIR from guinea pig lung slices. 13 of the compounds were more potent than theophylline as inhibitors of cyclic AMP-PDE and/or cyclic GMP-PDE from RMC. Parallel concentration-response curves for the inhibition of cyclic AMP-PDE and cyclic GMP-PDE indicated that these compounds probably interact with enzyme in the same manner. Paired regression analysis of the I50 values for inhibition of AIR and cNUC-PDE from RMC by these compounds revealed no statistically significant correlation between the inhibition of AIR and inhibition of cyclic AMP-PDE or cyclic GMP-PDE. We conclude: (1) some of these compounds are potent inhibitors of immunologic release of histamine from RMC with an in vitro activity profile similar to that of DSCG, and (2) inhibition of cyclic AMP or cyclic GMP hydrolysis by cNUD-PDE by these compounds, DSCG, and 6 known antiallergic agents is not the biochemical mechanism by which they inhibit AIR from RMC.
In vitro Effect of Panax Ginseng on Phytohaemagglutinin-Induced Lymphocyte Transformation
Authors: Chong S.K.F. , Brown H.A. , Rimmer E. , Oberholzer V. , Hindocha P. , Walker-Smith J.A.
Published: August 2009

The effect of hydrocortisone or Panax ginseng, and/or a combination of hydrocortisone and Panax gingseng on phytohaemagglutinin (PHA-P)-induced transformation of peripheral blood lymphocytes were studied in 4 normal healthy adult volunteers. Increasing concentrations of Panax ginseng 0.16–1.60 μg ml––1 caused a dose-related inhibition of PHA-P transformation of lymphocytes. A combination of 500 μg ml––1 hydrocortisone and 0.80 μg ml––1 Panax ginseng produced a greater suppression of PHA-P stimulation than either drug used alone. This suggests that Panax ginseng has a steroid-like effect in vitro, and may have a potentiating effect with hydrocortisone on T-cell-mediated immunity.
Non-IgG1 Nature of Cutaneous Basophil Hypersensitivity Factor in Contact Sensitivity
Authors: Katayama Ichiro , Nishioka Kiyoshi , Nishida Kenju , Doi Toshiaki
Published: August 2009

It was recently demonstrated that there was a specific activity to induce basophil-rich skin reaction in the sera of contact-sensitized guinea pigs (CBH factor, CBH-F). In the in vitro chemotactic assay system, CBH-F was shown to have weak basophil chemotactic activity but enhanced its activity in the presence of corresponding antigen(s). Furthermore, basophil chemotaxis in reaction to the antigen(s) was observed when the cells were preincubated with CBH-F. It worked mainly for Percoll-separated bone marrow basophils but not for oil-induced peritoneal macrophages. Immunological analysis revealed that CBH-F was a protein with a small molecular weight (MW 4–6 × 104) with an antigen binding site and isoelectric point of between 4.5 and 5.0. It did not show any characteristics of IgG1 or IgG2 on immunoadsorbent column and immunoelectrophoresis. Enzyme treatment with insoluble trypsin eliminated the chemotactic activity but this was not the case with neuraminidase treatment.
IgG Subclasses of Anti-HBs Antibodies in Vaccinated and Nonvaccinated Individuals and in Anti-HBs Immunoglobulin Preparations
Authors: Skvaril F. , Joller-Jemelka Helene
Published: August 2009

IgG subclasses in anti-HBs antibodies in sera from 9 vaccinated (H-B-Vax, Merck, Sharp & Dohme) individuals and from 18 individuals with naturally acquired anti-HBs were characterized in enzyme-linked immunosorbent assay with monoclonal subclass-specific antibodies. Also eight hyperimmune immunoglobulin preparations from five producers were investigated. In vaccinated persons, the activity was predominantly present in IgG1 and IgG4 subclass. Various combinations of subclasses in anti-HBs antibodies were found in persons after recovery from hepatitis B and in immunoglobulin preparations. The serum concentration of subclasses does not reflect the subclass profiles of the anti-HBs antibody.
Differentiation of Chronic Lymphocytic Leukemia from Reactive Lymphocytosis by the Mouse Red Cell Rosette Assay
Authors: Howard Donald R. , Wicken Judith , Nishiyama Ronald
Published: August 2009

The differential diagnosis of chronic lymphocytic leukemia (CLL) from other neoplastic and nonneoplastic lymphocytoses may be difficult, even when optimal clinical and laboratory data are available. The mouse red cell (M) rosette assay has been valuable in distinguishing normal and lymphomatous lymphocytes from those of CLL. Not yet tested is the ability of this test to separate reactive (benign) lymphocytes from morphologically similar but neoplastic cells of CLL. In the present study, lymphocytes of 58 subjects with CLL, reactive lymphocytosis, and healthy controls were evaluated for M rosette formation, in addition to the usual B and T cell markers. Lymphocytes from patients with CLL showed a marked increase in the ability to form M rosettes in comparison to those from normal controls and patients with reactive lymphocytosis. The formation of M rosettes was a more reliable marker for CLL than surface membrane immunoglobulin.
Defective Cell-Mediated Immunity in Lipoid Nephrosis
Authors: Matsumoto Koichi , Osakabe Kotaro , Katayama Hisashi , Okano Kikuo , Hatano Michinobu
Published: August 2009

Cell-mediated immunity (CMI) was studied in 28 patients with biopsy-proven lipoid nephrosis (LN). The LN patients with nephrotic syndrome (NS) had a significant depression in CMI, characterized by impaired delayed hypersensitivity skin reactivity to purified protein derivative (PPD), depressed local graft-versus-host reaction (GVHR), decreased proportion of T lymphocytes and diminished lymphocyte transformation to phytohemagglutinin (PHA). Concanavalin A (Con A)-induced suppressor cell activity (SCA) was found to be significantly increased in LN patients with NS compared to that in normal individuals. In contrast, the mean levels of CMI and SCA studied in LN patients in remission and in patients with chronic mesangial proliferative glomerulonephritis (CGN) did not differ from normal subjects. Our findings support the notion that at least in some LN patients with the NS, activated suppressor cells are present and possibly account for their decreased CMI.
Comparative Actions of Biologic and Synthetic Leukotrienes on Isolated Human Bronchus and Rat Mast Cells
Authors: Hanna Christopher J. , Johnston Mark E. , Bach Michael K. , Rokach Joshua , Schellenberg Robert
Published: August 2009

The effects of biologically prepared leukotriene C4 (LTCb) and leukotriene D4 (LTDb), obtained from rat monocytes stimulated with the calcium ionophore A23187, were compared with those of chemically synthetized leukotrienes (LTCS and LTDS) using two in vitro systems. All four leukotriene preparations (10––10 to 6 × 10––6M) showed equal activity upon human bronchi, inducing slow, sustained contractions. LTCb alone (10––7 to 6.9 × 10––7M) elicited histamine release and enhanced compound 48/80-induced release in a dose-dependent manner from rat mast cells. In contrast, LTDb alone was without effect but inhibited release caused by 48/80. FPL 55712 failed to block the LTCb and LTDb effects on the release process. The synthetic leukotrienes neither caused histamine release nor modulated 48/80-induced release from rat mast cells. We conclude that biologic and synthetic leukotrienes exhibit comparable contractile activity on isolated human bronchi but only biologic preparations modulate histamine release by previously unappreciated substances that isolate with the biologic leukotrienes.
Platelet Augmentation of IgE-Dependent Histamine Release from Human Basophils and Mast Cells
Authors: Knauer Kent A. , Kagey-Sobotka Anne , Adkinson, Jr. Franklin , Lichtenstein Lawrence.M.
Published: August 2009

A factor(s) from human platelets enhances IgE-mediated histamine release from human basophils and mast cells. This effect is directly related to the platelet number; at physiological platelet/leukocyte ratios (40:1), the enhancement was 66 ± 11 %. Platelet stimulation by thrombin more than doubled the enhancement, to 172 ± 10% at 40:1. Mast cell release was also enhanced by platelets although the magnitude was more limited (86 ± 13% at 40:1 with thrombin). Direct basophil/platelet contact was unnecessary in that platelet supernatants were fully active; a direct platelet factor/basophil interaction is suggested, however, by the fact that basophils purified 100-fold with respect to other leukocytes were enhanced by the platelet factors. The appearance of platelet-enhancing activity is associated with the release of an alpha-granule marker (PF4) rather than with products of arachidonic acid metabolism (thromboxane B2). The platelet factor(s) responsible for these effects are not dialyzable, are heat stable and do not appear to be identical to PF4 or platelet-derived growth factor (PDGF). Since anti-IgE-stimulated basophils cause PF4 release and this correlates with the release of enhancing factor, we suggest that a pro-inflammatory feed forward relationship exists. Together with our previous data showing that platelets are activated in vivo during antigen challenge of allergic asthmatic subjects, these results suggest that platelets may be important in modulating IgE-mediated allergic reactions in man.
Effect of the Calcium Ionophore A23187 and Aspirin on Histamine Release in vitro from Leukocytes of Aspirin-Intolerant Donors
Authors: Bochner Bruce S. , Thomas Larry L. , Godnik Lucille , Samter Max
Published: August 2009

In vitro histamine release from leukocytes of 10 aspirin-intolerant donors in response to the calcium ionophore A23187 and aspirin was compared to that of controls. Incubation with A23187 induced a concentration-dependent histamine release from leukocytes of all donors. At 0.1 and 0.2 μg/ml A23187, release from leukocytes of aspirin-intolerant donors was significantly less (p < 0.01) than that of controls. Preincubation with aspirin failed to alter spontaneous or A23187-stimulated histamine release. Leukocytes of aspirin-intolerant donors do not demonstrate an enhanced sensitivity to histamine release stimulated by aspirin or A23187.
Lymphocyte-Induced Macrophage Cytotoxicity
Authors: Pels Elisabeth , De Weger Roelof A. , Den Otter Willem
Published: August 2009

T cells obtained from C57BL (H-2b) mice, that were immunized against allogeneic SL2 (H-2d) tumor cells, were able to produce a factor with the capacity to render macrophages cytotoxic. The factor producing T cells were of the Lyt 1+2+ phenotype. The factor was only produced by the T cells after triggering in vitro by SL2 cells or other cells with H-2d antigens. The macrophages armed with the factor only killed tumor cells with H-2d antigens. The factor was absorbed from the supernatant by macrophages and by cells bearing H-2d antigens but not by other cells. This showed that the factor has an affinity for macrophages and the specific sensitizing alloantigen. Therefore, the specificity of the lymphocytes is the same as the specificity of the factor and the factor-armed macrophages. The factor produced by the Lyt 1+2+ T cells is therefore the specific macrophage arming factor.
Proliferation of Mouse Lymphocytes to Rye Grass Pollen Extract: Effect of Inflammatory Exudate Cells
Authors: Cook R.M. , Moran D.M.
Published: August 2009

The ability of inflammatory peritoneal exudate cells to modify a murine lymphoproliferative response to rye grass pollen extract was investigated. Popliteal and mesenteric lymph node cells from Balb/c mice immunised with either aqueous rye or rye grass emulsified in complete Freund’s adjuvant were co-cultured with 2 × 103–105 macrophage or polymorphonuclear neutrophil (PMN)-enriched exudate cells. There was a dose-dependent increase in the response to rye grass antigen with increasing numbers of PMN. A similar enhancement was seen with up to 104 macrophages per culture; higher numbers were inhibitory. Lymph node cells from rye grass or ovalbumin-immune mice that had been challenged with a combination of sensitising antigen plus 107 PMN gave an increased antigen-specific response in vitro. Neither antigen alone, PMN nor a mixture of PMN plus heterologous antigen was active. Adoptive transfer of a similar number of peritoneal macrophages plus antigen was also without effect. These results are in accord with the suggestion that cells obtained from acute inflammatory lesions can directly influence the activity of immunocompetent lymphocytes.
IgA Antibody Produced by Local Presentation of Antigen in Orally Primed Rats
Authors: Cox Donald S. , Muench David
Published: August 2009

The effect of the introduction of antigen by gastric intubation on the locally stimulated mammary gland IgA antibody (Ab) response was examined. Rats receiving a particulate DNP antigen by gastric intubation prior to injection in the vicinity of the mammary glands (MGV) demonstrated increased levels of IgA Ab in milk. Soluble DNP antigen introduction by gastric intubation did not lead to increased IgA Ab levels in milk. Prior administration of either form of DNP antigen by gastric intubation did not affect the IgG response. Only those rats receiving particulate DNP antigen by intubation demonstrated salivary IgA Ab. Particulate forms of antigen administered by intubation can provide a means of increasing the locally induced IgA response at a secretory site.
IgG Antibodies to Purified Aspergillus fumigatus Antigens Determined by Enzyme-Linked Immunosorbent Assay
Authors: Schønheyder H. , Andersen P.
Published: August 2009

IgG antibodies to three purified Aspergillus fumigatus antigens were determined by enzyme-linked immunosorbent assay (ELISA) in sera from 26 patients with definite pulmonary aspergillosis (group 1), 23 patients with suspected pulmonary aspergillosis (group 2), 8 patients with precipitating antibodies to A. fumigatus of undetermined clinical significance (group 3), and 113 healthy blood donors (group 4). With a 470,000-dalton antigen fraction ELISA values exceeded the upper range of group 4 (0.72) in 92, 91 and 13% of cases in groups 1, 2 and 3, respectively. With a 250,000-dalton antigen fraction the figures were 96, 78 and 13%, respectively (upper range of group 4 = 0.25). With an antigen fraction of 25,000–50,000 daltons the figures were 96, 65 and 13%, respectively (upper range of group 4 = 0.18). In 48 of 49 cases of definite or suspected aspergillosis (groups 1 + 2) ELISA values with at least one antigen exceeded the upper range of controls (group 4). It appears that antibody determination with these three antigen fractions may have a high diagnostic sensitivity.