bluuebunny/crossref_metadata_2025 huggingface dataset:
Tenocyte responses to mechanical loading in vivo: A role for local insulin‐like growth factor 1 signaling in early tendinosis in rats
Authors: Scott Alexander , Cook Jill L. , Hart David A. , Walker David C. , Duronio Vincent , Khan Karim M.
Published: February 2007

Objective

To investigate tenocyte regulatory events during the development of overuse supraspinatus tendinosis in rats.

Methods

Supraspinatus tendinosis was induced by running rats downhill at 1 km/hour for 1 hour a day. Tendons were harvested at 4, 8, 12, and 16 weeks and processed for brightfield, polarized light, or transmission electron microscopy. The development of tendinosis was assessed semiquantitatively using a modified Bonar histopathologic scale. Apoptosis and proliferation were examined using antibodies against fragmented DNA or proliferating cell nuclear antigen, respectively. Insulin‐like growth factor 1 (IGF‐1) expression was determined by computer‐assisted quantification of immunohistochemical reaction. Local IGF‐1 signaling was probed using antibodies to phosphorylated insulin receptor substrate 1 (IRS‐1) and ERK‐1/2.

Results

Tendinosis was present after 12 weeks of downhill running and was characterized by tenocyte rounding and proliferation as well as by glycosaminoglycan accumulation and collagen fragmentation. The proliferation index was elevated in CD90+ tenocytes in association with tendinosis and correlated with increased local IGF‐1 expression by tenocytes and phosphorylation of IRS‐1 and ERK‐1/2. Both apoptosis and cellular inflammation were absent at all time points.

Conclusion

In this animal model, early tendinosis was associated with local stimulation of tenocytes rather than with extrinsic inflammation or apoptosis. Our data suggest a role for IGF‐1 in the load‐induced tenocyte responses during the pathogenesis of overuse tendon disorders.
Primary necrotizing lymphocytic central nervous system vasculitis due to perforin deficiency in a four‐year‐old girl
Authors: Moshous Despina , Feyen Oliver , Lankisch Petra , Schwarz Klaus , Schaper Jörg , Schneider Marion , Dilloo Dagmar , Laws Hans‐Jürgen , Schwahn Bernd C. , Niehues Tim
Published: February 2007

We report the case of a 4‐year‐old girl who presented with headaches, ataxia, and visual disturbances. Cranial magnetic resonance imaging showed multiple supra‐ and infratentorial lesions with peripheral contrast enhancement and central necrosis. Brain biopsy revealed necrotizing lymphocytic vasculitis of undetermined etiology. Perforin expression was found to be significantly reduced in the patient's peripheral blood cells, and sequence analysis of the patient's perforin gene showed a compound heterozygous state with 1 nonsense mutation and 2 missense alterations in exon 2. Central nervous system (CNS) vasculitis was thus attributed to the perforin deficiency, and the patient was successfully treated by transplantation of stem cells from an HLA‐identical brother. The findings described herein indicate that, even in the absence of classic non‐neurologic symptoms of hemophagocytic lymphohistiocytosis, measurement of perforin expression should be one of the diagnostic tests used to identify the cause of unexplained CNS vasculitis, since this may have profound implications regarding therapy.
Bradykinin potentiates cytokine‐induced prostaglandin biosynthesis in osteoblasts by enhanced expression of cyclooxygenase 2, resulting in increased RANKL expression
Authors: Brechter Anna Bernhold , Lerner Ulf H.
Published: February 2007

Objective

Bradykinin (BK) stimulates bone resorption in vitro and synergistically potentiates interleukin‐1 (IL‐1)–induced bone resorption and prostaglandin (PG) formation, suggesting that kinins are important in inflammation‐induced bone loss. The present study was undertaken to study 1) the role of the kinin B1 and B2 receptors in the synergistic interaction with IL‐1 and tumor necrosis factor α (TNFα), 2) the molecular mechanisms involved in synergistic enhancement of PG formation, and 3) the effects of kinins on cytokine‐induced expression of RANKL, RANK, and osteoprotegerin (OPG) (the latter being crucial molecules in osteoclast differentiation).

Methods

Formation of PGs, expression of enzymes involved in arachidonic acid metabolism, and expression of RANKL, RANK, and OPG were assessed in the human osteoblastic cell line MG‐63 and in mouse calvarial bones. The role of NF‐κB and MAP kinases was studied using pharmacologic inhibitors.

Results

PGE2formation and cyclooxygenase 2 (COX‐2) protein expression were induced by IL‐1β and potentiated by kinins with affinity for the B1 or B2 receptors, resulting in PGE2‐dependent enhancement of RANKL. The enhancements of PGE2formation and COX‐2 were markedly decreased by inhibition of p38 and JNK MAP kinases, whereas inhibition of NF‐κB resulted in abolishment of the PGE2response with only slight inhibition of COX‐2.

Conclusion

Kinin B1 and B2 receptors synergistically potentiate IL‐1– and TNFα‐induced PG biosynthesis in osteoblasts by a mechanism involving increased levels of COX‐2, resulting in increased RANKL. The synergistic stimulation is dependent on NF‐κB and MAP kinases. These mechanisms might help to explain the enhanced bone resorption associated with inflammatory disorders, including that in rheumatoid arthritis.
Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance
Authors: Wu Tianfu , Xie Chun , Bhaskarabhatla Madhavi , Yan Mei , Leone Amanda , Chen Su Sin , Zhou Xin J. , Putterman Chaim , Mohan Chandra
Published: February 2007

Objective

Currently, proteinuria is viewed as the earliest indicator of renal disease in immune‐mediated nephritis. The objective of this study was to determine whether additional mediators may be excreted in the urine during immune‐mediated nephritis, using an experimental model with a well‐defined disease course.

Methods

Urine samples from mice with anti–glomerular basement membrane (anti‐GBM) antibody–induced experimental nephritis were screened using a focused immunoproteome array bearing 62 cytokines/chemokines/soluble receptors. Molecules identified through this screening assay were validated using an enzyme‐linked immunosorbent assay. One of these molecules was further evaluated for its pathogenic role in disease, using antibody‐blocking studies.

Results

Compared with B6 and BALB/c mice, in which moderately severe immune‐mediated nephritis develops, the highly nephritis‐susceptible 129/Sv and DBA/1 mice exhibited significantly increased urinary levels of vascular cell adhesion molecule 1 (VCAM‐1), P‐selectin, tumor necrosis factor receptor I (TNFRI), and CXCL16, particularly at the peak of disease. Whereas some of the mediators appeared to be serum derived early in the disease course, local production in the kidneys appeared to be an important source of these mediators later in the course of disease. Both intrinsic renal cells and infiltrating leukocytes appeared to be capable of producing these mediators. Finally, antibody‐mediated blocking of CXCL16 ameliorated experimental immune nephritis.

Conclusion

These studies identified VCAM‐1, P‐selectin, TNFRI, and CXCL16 as a quartet of molecules that have potential pathogenic significance; the levels of these molecules are significantly elevated during experimental immune nephritis. The relevance of these molecules in spontaneous immune nephritis warrants investigation.
Purchasing decisions in non‐traditional households: the case of lesbian couples
Authors: Wilkes Robert E. , Laverie Debra A.
Published: February 2007

Extant research on family purchase behavior has focused almost exclusively on heterosexual couples. This exploratory study of non‐traditional households shows that lesbian couples are strongly egalitarian in decision behavior for a wide range of products and services. Perceptions about relative influence of each partner in these dyads are increasingly congruent as the decision process progresses. Findings demonstrate the inapplicability of two concepts long associated with family research, that is, power and relative resource theory, in lesbian couples. Instead, gender dynamics and equity play dominant roles in these relationships.

Copyright © 2007 John Wiley & Sons, Ltd.
A Water Molecule in the Stereospecificity Pocket of Candida Antarctica Lipase B Enhances Enantioselectivity towards Pentan‐2‐ol
Authors: Léonard Valérie , Fransson Linda , Lamare Sylvain , Hult Karl , Graber Marianne
Published: February 2007

The effect of water activity on enzyme‐catalyzed enantioselective transesterification was studied by using a solid/gas reactor. The experimental results were compared with predictions from molecular modelling. The system studied was the esterification of pentan‐2‐ol with methylpropanoate as acyl donor and lipase B from Candida antarctica as catalyst. The data showed a pronounced water‐activity effect on both reaction rate and enantioselectivity. The enantioselectivity increased from 100, at water activity close to zero, to a maximum of 320, at a water activity of 0.2. Molecular modelling revealed how a water molecule could bind in the active site and obstruct the binding of the slowly reacting enantiomer. Measurements of enantioselectivity at different water‐activity values and temperatures showed that the water molecule had a high affinity for the stereospecificity pocket of the active site with a binding energy of 9 kJ mol−1, and that it lost all its degrees of rotation, corresponding to an entropic energy of 37 J mol−1 K−1.
A Kinetic Model for Nanocrystal Morphology Evolution
Authors: Xu Xiangxing , Liu Feng , Yu Kehan , Huang Wei , Peng Bo , Wei Wei
Published: February 2007

A kinetic model is developed with the goal of understanding and predicting the morphology evolution of nanocrystals in nonequilibrium growth conditions. The model is based on the assumption that under such conditions, different crystal planes have different kinetic parameters. This model focuses on the morphology‐developing stage and is successfully related to the nucleation process and other crystal evolution mechanisms. It is believed to be a universal model and is applied to discuss the morphology evolution of CdSe nanocrystals, including the aspect ratio, injection schemes, ligands effect and morphology distribution.
Association between the HLA haplotype and the TCR‐Vβ repertoire of anti‐hCMV specific memory T‐cells in immunocompetent healthy adults
Authors: Rodriguez‐Caballero Arancha , Garcia‐Montero Andres C. , Almeida Julia , Balanzategui Ana , Munoz‐Criado Santiago , Orfao Alberto
Published: February 2007

Background:

Despite the key role of memory T‐cells specific for human cytomegalovirus (hCMV) in protecting against hCMV‐reinfection early after immunodeficiency episodes, the precise characterization and definition of the essential components of a protective CD4 T‐cell response still remain to be established.

Methods:

We analyzed by flow cytometry hCMV‐specific immune responses driven by peripheral blood antigen‐presenting cells (APC) and CD4 memory T‐cells at both the cellular and soluble levels, and their cooperation in priming and sustaining the effector function of specific CD8 T cells in adult healthy individuals using a hCMV whole viral lysate stimulatory model.

Results:

Overall, activated T‐cells showed a heterogeneous phenotype, with a marked predominance of CD45RA−/CCR7+/− memory CD4+ T‐cells. Despite this, cytoplasmic expression of granzyme B was found in both the CD45RA+/effector and CD45RA−/memory T‐cell compartments of the two major CD4+ and CD8+ activated T‐cell subpopulations, further confirming the presence of circulating antigen experienced cytotoxic CD4+ T cells in hCMV‐seropositive individuals. Moreover, we observed that both CD4+ and CD8+ hCMV‐specific T‐cells included relatively restricted numbers of TCR‐Vβ family members. Interestingly, we found a significant association between some HLA Class II and Class I haplotypes and the presence of specifically expanded TCR‐Vβ clones of anti‐hCMV T cells.

Conclusions:

These results indicate that hCMV‐specific memory T‐cells are phenotypically heterogeneous, their TCR‐Vβ repertoire shaped through the interaction between hCMV epitopes and the HLA haplotype. © 2007 Clinical Cytometry Society.
The European Water Framework Directive and economic valuation of wetlands: the restoration of floodplains along the River Elbe
Authors: Meyerhoff Jürgen , Dehnhardt Alexandra
Published: February 2007

This paper concerns the economic valuation of riparian wetlands ecological services within the European Water Framework Directive (WFD). The directive is an integrated approach to river basin management in Europe and aims at achieving a good water status for both surface and ground water. It introduces economic analysis as a core part of the development of integrated river basin management plans. However, to date the WFD has not clearly stated to what extent wetlands should be used for the achievement of environmental objectives, or what scope the economic analysis should have. Our study of the river Elbe shows that riparian wetlands provide significant benefits that should be considered in river basin management decisions. To neglect these benefits would lead to biased cost–benefit analysis results and might therefore misguide the decision‐making process. Copyright © 2007 John Wiley & Sons, Ltd and ERP Environment.
The somatic generation of immune recognition
Authors: Jerne N. K.
Published: February 2007

Antibody specificity is determined by structural v‐genes that code for the amino acid sequences of the variable regions of antibody polypeptide chains. The present hypothesis proposes that the germ‐cells of an animal carry a set of v‐genes determining the combining sites of antibodies directed against a complete set of a certain class of histocompatibility antigens of the species to which this animal belongs. The evolutionary development of this set of v‐genes in phylogeny is traced back to the requirements for cell to cell recognition in all metazoa. The hypothesis leads to a distinction between two populations of antigen‐sensitive cells. One population consists of cells forming antibodies against foreign antigens; these lymphocytes have arisen as mutants in clones descending from lymphocytic stem cells which expressed v‐genes belonging to the subset (subset S) coding for antibody against histocompatibility antigens that the individual happens to possess. The other population consists of allograft rejecting lymphocytes that express v‐genes of the remaining subset (subset A) coding for antibody against histocompatibility antigens of the species that the individual does not possess. The primary lymphoid organs are viewed as mutant‐breeding organs. In these organs (e. g. in the thymus), the proliferation of lymphocytes expressing the v‐genes of subset S and the subsequent suppression of the cells of these “forbidden” clones, leads to the selection of mutant cells expressing v‐genes that have been modified by spontaneous random somatic mutation. This process generates self‐tolerance as well as a diverse population of antigen‐sensitive cells that reflects antibody diversity. The proliferation in the primary lymphoid organs of lymphocytes expressing v‐genes of subset A generates the antigen‐sensitive cell population that is responsible for allo‐aggression.

The theory explains how a functional immune system can develop through a selection pressure exerted by self‐antigens, starting during a period in early ontogeny that precedes clonal selection by foreign antigens. The hypothesis provides explanations for the variability of the N‐terminal regions of antibody polypeptide chains, for the dominant genetic control of specific immune responsiveness by histocompatibility alleles, for the relative preponderance of antigen‐sensitive cells directed against allogeneic histocompatibility antigens, for antibody‐idiotypes, for allelic exclusion, for the precommitment of any given antigen‐sensitive lymphocyte to form antibodies of only one molecular species and for the cellular dynamics in the primary lymphoid tissues.
Dose response and induction of tolerance to the synthetic antigen (T,G)‐A–L in adult rabbits
Authors: Sela M. , Fuchs Sara , Maron Ruth , Gertner Bela
Published: February 2007

The immunogenicity of the synthetic multichain polypeptide (T,G)‐A–L in rabbits was investigated under a variety of conditions. The polymer led to antibody production with as little as four micrograms in complete Freund's adjuvant per immunization. The pattern of antibody formation as a function of time varied from dose to dose, the highest initial response corresponding to the lowest dose administered. The synthetic polypeptide was immunogenic also when incorporated in an alum precipitate, but not when injected intravenously in buffered saline. Tolerance to (T,G)‐A–L was produced in adult rabbits upon intravenous injection.
Two allotypic specifities of rat immunoglobulin
Authors: Armerding D.
Published: February 2007

Two allotypic specificities (W‐1 and SD‐1) of rat immunoglobulin are described. These allotypic specificities are detected by a passive hemagglutination assay. Both specificities are located on the L‐chains of rat immunoglobulin and were found to be present in both IgG2 and IgM. The gene loci controlling the allotypic determinants are inherited in a simple Mendelian fashion. Rats of 27 different strains tested possessed either the W‐1 or the SD‐1 specificity.
Immunological unresponsiveness of genetically thymusless (nude) mice
Authors: Kindred Berenice
Published: February 2007

Mice homozygous for the nude mutation completely lack a thymus. Their response to antigenic stimulus is very poor. They do produce a small amount of hemolysing antibody in response to sheep red blood cells but significant hemagglutinating antibody, or antibody against bacteriophage T4 could not be demonstrated and they did not reject allogeneic skin grafts.
The carrier effect in the secondary response to hapten‐protein conjugates. IV. Uptake of antigen in vitro and failure to obtain cooperative induction in vitro
Authors: Britton S. , Mitchison N. A. , Rajewsky K.
Published: February 2007

Uptake of antigen in the cooperative adoptive secondary response of mice to hapten‐protein conjugates was examined. Spleen cells from donors primed with bovine serum albumin (BSA) took up 4‐Hydroxy‐5‐iodo‐3‐nitro‐phenacetyl(NIP)‐BSA in vitro, as judged by their subsequent ability to induce a response to NIP in cooperation with NIP‐ovalbumin‐primed spleen cells. Competitive inhibition by BSA could be demonstrated, indicating that uptake occured onto specific receptors. The antibody‐forming‐cell‐precursor population also could take up conjugates in vitro.

Allogeneic helper and antibody‐forming‐cell‐precursors were incubated together under conditions likely to support cooperative induction of the secondary response and then transferred into hosts alloimmune to the helper cells. Under these conditions the response did not proceed after the transfer. It is likely therefore that continuous cooperation is required in order to support a full response.
The carrier effect in the secondary response to hapten‐protein conjugates. V. Use of antilymphocyte serum to deplete animals of helper cells
Authors: Mitchison N. A.
Published: February 2007

Treatment of mice primed with bovine serum albumin, chicken γ‐globulin or keyhole limpet hemocyanin with rabbit anti‐mouse lymphocyte serum (ALS) depresses the secondary response, and particularly the adoptive secondary response, to these antigens. If, however, the transferred cells are boosted with NIP (4‐hydroxy‐5‐iodo‐3‐nitro‐phenacetyl‐) or DNP (2,4‐dinitrophenyl‐) conjugates of the protein with which they had been primed, their ability to make an anti‐protein response can be partially restored by adding cells primed against the hapten. Such hapten‐primed cells can be obtained, for example, by immunization with the hapten conjugated to another carrier. These helper cells can therefore be regarded as hapten‐specific.

DNP‐specific helper cells can be obtained, as expected, from lethally‐irradiated thymocyte‐repopulated, FDNB (2,4‐dinitrofluorobenzene) skin‐painted donors.

Hapten‐specific helper cells can be demonstrated in guinea pigs according to the same principle. As in mice, there is no correlation between helper activity and antibody‐forming‐cell‐precursor activity in terms of anti‐hapten antibody.

ALS suppression spares the secondary response to high doses of conjugate, suggesting that this type of response is helper‐independent; it also indicates that the loss of carrier‐effect obtainable with high doses of conjugate cannot be attributed to the operation of hapten‐specific helper cells.

These ALS experiments strengthen the evidence for the identification of helper cells in the adoptive secondary response to conjugates as thymus‐derived lymphocytes mediating cellular immunity. The case for this identity is summarized in the discussion.
Immunological properties of synthetic sugar‐polypeptide conjugates. Effect of N‐Lauroyl‐glucosamine residues on immunogenicity
Authors: Rüde E. , Meyer‐Delius Margot , Gundelach Maria‐Luise
Published: February 2007

Several mono‐ and disaccharides were tested for their capacity to enhance the immunogenicity of a weakly immunogenic synthetic polypeptide. For this purpose the sugars were attached to the side chains of multichain poly‐DL‐alanine as O‐glycosides of serine. Some of the conjugates were essentially non‐immunogenic in rabbits while others, like the unsubstituted polypeptide, were relatively weak immunogens. Antibodies elicited by the latter were directed almost entirely against the serine glycoside residues. Thus, the sugars contributed to the antigenic specificity of the respective conjugate, but were not very efficient in enhancing its immunogenicity.

In further experiments, the effect of lipids on the immunogenicity of sugar‐polypeptide conjugates was studied. In addition to the usual sugars, N‐lauroyl‐glucosaminyl‐serine residues were incorporated into the polymers. In all cases, this led to an increase in immunogenicity, which may be due, in part, to the fact that these polymers were highly aggregated. However, in addition to aggregation, a more specific effect of the N‐lauroyl‐glucosamine groups appears to be involved. In most of the polymers the N‐lauroyl‐glucosaminyl‐serine residues also functioned as determinant groups and it could be shown that for the interaction with antibody the fatty acid residue plays an essential role.
Allotypic markers of rabbit IgM
Authors: Kelus A. S. , Pernis B.
Published: February 2007

Five different allotypic specificities called Ms1 to Ms5 were identified in rabbit sera by agar gel precipitation with the use of antisera developed in the same species.

Immunoelectrophoresis and investigation of purified immunoglobulin classes have shown that these allotypes are on IgM molecules.

The cellular localization of these allotypes has been studied by immunofluorescence on rabbit plasma cells; numerous double‐staining experiments with different antisera have confirmed the presence of these allotypes in IgM synthesizing plasma cells.

One allotype, Ms3, has been shown to be strictly limited to the IgM plasma cells containing the b locus allotype As4, while for allotypes Ms4 and Ms5 the expression in plasma cells appeared to be connected with the expression of the a locus allotypes. This last condition also applied to allotype Ms6, an IgM allotype which was demonstrated by the immunofluorescence studies only.

The observations performed are consistent with the hypothesis that allotype Ms3 is in fact an allotype of the κ‐light chains which is expressed only when these chains are part of an IgM molecule, while allotypes Ms4, Ms5 and Ms6 are true markers of the μ‐chain. This hypothesis is also supported by absorption experiments performed with separated heavy and light chains of rabbit IgM.
Studies on the relation between the fifth component of complement and anaphylatoxinogen
Authors: Vogt W. , Lufft Elke , Schmidt Gisa
Published: February 2007

Preparations of anaphylatoxinogen obtained from rat serum contain the fifth component of complement in an hemolytically active state. Conversely, crude C5 preparations of hog serum release anaphylatoxin (AT) on incubation with the AT‐forming cobra enzyme. The ratio between the C5 content and the amount of anaphylatoxinogen does not remain constant during the preparation of anaphylatoxinogen.

By incubation of rat plasma with zymosan, consumption of C5 and production of AT proceed simultaneously.

When instead of zymosan, aggregated human γ‐globulin is used as complementbinding agent, the two processes can be differentiated. Though a considerable portion of C5 is inactivated, only a small amount of AT is formed. Subsequent incubation with zymosan releases the full amount of AT.

During incubation of hog serum with labeled guinea pig C5 and yeast, i. e. under classical conditions of AT formation in serum by contact activation, a labeled basic peptide is cleaved from the added C5. Its behavior on chromatography is rather similar to but not entirely identical with hog serum AT. Probably the same split product is obtained by treatment of labeled C5 with the cobra enzyme.

It is concluded that (1) C5 appears to be the precursor of AT, i.e. anaphylatoxinogen, (2) the hemolytic activity of C5 is not essential for the release of the AT moiety and (3) the process of AT release is only partially identical with the reaction of utilization of C5 in immune hemolysis.
C1 inactivator protein complexed with albumin in plasma from a patient with angioneurotic edema
Authors: Laurell Anna‐Brita , Mårtensson Ulla
Published: February 2007

An abnormal protein, antigenically identical with C1 inactivator and belonging electrophoretically to the α1‐globulins was found in plasma and serum from a patient with angioneurotic edema. Treatment of the pathological protein with 2‐mercaptoethanol or with neuraminidase followed by analysis with antigen‐antibody crossed electrophoresis showed that the protein was a complex of C1 inactivator and albumin. The patient's serum and plasma was found to contain also a C1 inactivator protein migrating with α2‐globulin but somewhat faster than normal C1 inactivator. Neither the α2‐ nor the α1‐C1 inactivator inhibited the hydrolyzing effect of C1 on N‐acethyl‐L‐tyrosine ethyl ester.
Cell cooperation in antibody induction. The susceptibility of helper cells to specific lethal radioactive antigen
Authors: Roelants G. E. , Askonas Brigitte A.
Published: February 2007

Irradiated mice were reconstituted with syngeneic spleen cells from mice immunized with 2,4‐Dinitrophenyl(DNP)‐ovalbumin or Maia squinado hemocyanin (MSH) and challenged with DNP‐MSH. In this hapten‐carrier system MSH primed cells showed the expected helper activity for an anti‐DNP response. As previously shown for another system by Mitchison and Raff, the helper activity of MSH‐primed cells could be attributed to thymus‐derived (T) lymphocytes since it was suppressed by anti‐Θ serum and complement.

Susceptibility of helper activity to lethal radioactive antigen was tested. MSH‐primed cells were incubated with [125I] MSH of high specific activity, a treatment known to suppress antibody secreting precursor cells. Cell transfer experiments were carried out using two doses of cells. With a low dose transfer (5 × 106 cells), [125I]MSH treatment suppressed the helper activity of MSH cells specifically indicating that thymus‐derived lymphocytes must have antigen specific receptors and are susceptible to killing by radioactive antigen. However, after transfer of a large number (25 × 106) of cells treated with [125I] MSH, helper activity was still present although the anti‐MSH antibody forming capacity was completely suppressed. This finding and the effect of anti‐Θ treatment demonstrate the dissociation of T and B lymphocyte function.

The observation that a large dose of MSH‐primed cells retained its helper function after radioactive antigen treatment could be attributed to an excess of MSH specific helper cell activity in spleen cells primed with MSH. Limiting cell dilution experiments have shown that as few as 106 MSH‐primed cells are sufficient to exert full helper activity in this system. Thus more than 96% of the helper cells would need to be killed by lethal radioactive antigen to suppress the helper effect of 25 × 106 cells.

The analysis of the anti‐MSH response showed that memory in the T cell population was not sufficient to obtain a secondary response and that memory in the B lymphocyte population was also required.
Inhibition of the immune response of mouse spleen cells to sheep erythrocytes in vitro by anti‐immunoglobulin sera
Authors: Sjöberg O. , Greaves M.
Published: February 2007

The effect of anti‐immunoglobulin sera on the antibody response of both non‐sensitized and sensitized mouse spleen cells in vitro has been studied. Antisera to immunoglobulin Fab gave almost complete inhibition of both IgM and IgG responses. Antisera to IgM suppressed the IgM but not the IgG response and conversely antisera to IgG classes caused some suppression of the IgG response but did not reduce the IgM response. These results have been discussed in terms of the nature of receptor molecules on lymphocytes responsible for recognition of antigen.
Quantitative studies on antigenic recognition. II. Kinetics of the recognition event
Authors: Ramseier H.
Published: February 2007

Recognition of transplantation antigens by immunocompetent rat or mouse cells was measured quantitatively by determinations of a product of antigenic recognition (PAR). This product is present in supernatants of in vitro cultures of lymphoid cell mixtures from genetically dissimilar normal animals and also in those of cells from specifically presensitized animals and donor‐type cellular antigens.

Studies on kinetic aspects of PAR formation were done employing immunological one‐way reactions in which one of the partners of the cell mixtures was of parental and the other of appropriate F1 hybrid origin.

The degree of recognition, as measured by the amount of PAR discernible, depended on many factors. Duration of contact of competent cells and recognizable antigen in relation to antigenic specificity, particularly the degree of incompatibility, had a marked effect. The process was also influenced by the number of cells participating, by this number and the time of cocultivation, and by whether recognizing cells were from animals sensitized to transplantation antigens or from normal animals. The different tempos of antigenic recognition could be used to demonstrate specificity of the response.

Formation of PAR appeared to be a process regulated by an inhibitory substance. The action of an inhibitor could be demonstrated and shown to be species specific, but not strain specific. Suggestive evidence is presented for the view that the regulatory influence of the inhibitor is at the level of PAR formation.
Genetics of the immune response. I. The immune response to the phage fd in high and low responding inbred strains of mice
Authors: Kölsch E. , Diller Eva , Weber G. , Davies A. J. S.
Published: February 2007

The immune response to the bacteriophage fd has been analyzed in several inbred strains of mice.

The inactivation curve of bacteriophage fd by specific antisera follows initially first order kinetics and finally levels off gradually. The strength of the antisera has been characterized primarily by the velocity constant K of the inactivation kinetics. Two other methods, endpoint and plateau determination, have been used for the analysis of selected problems.

The threshold dose for priming for a secondary response varies widely among the strains tested. Low responding strains have a hundred‐ to thousandfold higher threshold dose than high responding strains. High responsiveness is dominant over low responsiveness in genetical analysis and inherited as a single dominant trait. The dose for an optimal response in high and low responders lies within the same range at about 1 × 109 fd/g body weight. Further increase of the priming dose leads in all except one strain to a suppression of the response probably due to partial high zone paralysis. One strain of mice, CBA/MH, shows a dose response curve different from the others. No suppression of the response with high priming doses is found.

The cooperating role of thymus derived cells and of macrophages has been tested. The previous uptake of antigen by macrophages probably prevents induction of high zone paralysis. No evidence has been found for macrophages being responsible for high and low responsiveness. The immune response to phage fd is strongly thymus dependent. The response of animals lacking thymic influence is below the response of low responders.
Immunological unresponsiveness against the 4‐Hydroxy‐3,5‐dinitro‐phenacetyl (NNP) hapten in different lymphoid cell populations
Authors: Möller Erna , Sjöberg O. , Mäkelä O.
Published: February 2007

Mice which received repeated injections of the hapten 4‐hydroxy‐3,5‐dinitro‐phenacetyl (NNP) conjugated to BSA showed a reduced immune response to NNP when challenged with NNP coupled to heterologous red blood cells.

The antibody secreting cell response was more depressed than the response of cells capable of specifically binding the antigen. The data are consistent with the assumption that the unresponsive state was more pronounced in the thymus derived cell population than in the bursa‐equivalent lymphoid cell population.
Impairment of humoral antibody response in neonatally thymectomized and irradiated chickens
Authors: Iványi J. , Salerno A.
Published: February 2007

The recovery of humoral antibody responsiveness in chickens following sub‐lethal irradiation at hatching is thymus‐dependent: the antibody response to 5 × 107 or 5 × 109 sheep erythrocytes between 2 and 6 weeks was significantly suppressed in thymectomized‐irradiated chickens in comparison with irradiated controls. An impairment of response to human serum albumin was observed only with a low dose of antigen (0.5 mg/kg), but not with 100 mg/kg. Both hemagglutinating (mainly IgM) and antigen‐binding (mainly IgG) antibodies were affected. The secondary response to both antigens was also inhibited.
Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide
Authors: Teitelbaum Dvora , Meshorer A. , Hirshfeld T. , Arnon Ruth , Sela M.
Published: February 2007

Three random basic copolymers of amino acids were tested for their effect on experimental allergic encephalomyelitis (EAE). One of these copolymers denoted as Cop 1, composed of alanine, glutamic acid, lysine and tyrosine, with a molecular weight of 23 000, showed a marked suppressive effect on the disease. The intravenous administration of Cop 1 in physiological saline, as late as 5 days following the challenge with the disease‐inducing dose of the basic encephalitogenic protein, reduced the clinical incidence of EAE from 64% in the control group to 22%; the histological lesions were also decreased both in prevalence and in severity. The suppressive effect on the disease attained by the synthetic copolymer is of the same order of magnitude as that previously reported for the basic encephalitogen.

The effect of the copolymers appears to be specific, since neither an acidic amino acid copolymer, nor unrelated basic proteins, had any protective action. On the other hand, a second batch of Cop 1 showed activity identical to that of the first batch. The potential applicability of this non‐encephalitogenic and non‐immunosuppressive material is discussed.
Detection of homocytotropic antibody associated with a unique immunoglobulin class in the bovine species
Authors: Hammer D. K. , Kickhöfen B. , Schmid Thersilla
Published: February 2007

Homocytotropic antibodies capable of sensitizing calf skin were demonstrated in serum of cows as early as 7 to 9 days following antigenic stimulation with rabbit serum albumin. In addition, the antibody was present in colostrum of the immunized dam and was taken up by the intestine of the newborn calf as an intact molecule. Skin‐sensitizing activity was also detected in calf urine after uptake of colostrum. Evidence is presented for an anamnestic response, suggesting the existence of an immunological memory for the formation of skin‐sensitizing antibodies. The homocytotropic antibody was shown to be heat labile and sensitive to treatment with 2‐mercaptoethanol. Time course studies revealed that homocytotropic antibodies persist in calf skin for at least 8 weeks.

The immunoglobulin class associated with homocytotropic activity was enriched from appropriate antisera by salt precipitation, DEAE‐cellulose chromatography and gel filtration on Sephadex G‐200 columns. The final preparation was still capable of sensitizing calf skin for positive PCA reactions using a minimum dose of 0.009 μg N. The homocytotropic activity of the vinal fraction could not be removed by antibodies specific for the IgG class, but was completely blocked by antibodies against the fraction enriched in homocytotropic activity. The immunoglobulin class associated with skin‐sensitizing activity possesses antigenic determinants which are lacking in μ‐, α‐, and γ‐chains. The results indicate that the homocytotropic activity in the bovine species is associated with a unique immunoglobulin class analogous to human IgE.
Reconstitution of a thymus cell‐deprived immune system by syngeneic and allogeneic thymocytes in vitro
Authors: Schimpl Anneliese , Wecker E.
Published: February 2007

Mouse spleen cell suspensions deprived of their T cells by treatment with anti‐Θ‐serum and complement exhibit a drastically reduced immune response to sheep red blood cells in vitro. Syngeneic thymocytes generally fail to reconstitute the system. A full response can, however, be obtained by the addition of thymocytes from syngeneic mice pretreated with hydrocortisone, or by the addition of allogeneic thymocytes.
The secretion of a Bence‐Jones type light chain from a mouse plasmacytoma
Authors: Melchers F.
Published: February 2007

A mouse myeloma light chain is synthesized by MOPC 41A myeloma plasma cells as the only immunoglobulin chain. After being synthesized the light chain migrates through different subcellular structures of plasma cells in a way very similar to that of other immunoglobulins: from rough membranes into smooth membranes of the endoplasmic reticulum and from there out of the cells. Radioactive mannose, galactose and fucose are incorporated into MOPC 41 A cells at rates and in amounts comparable to other immunoglobulin‐producing tumor plasma cells, indicating that no large pools of these sugars exist inside these cells. However, intracellular as well as secreted MOPC 41 A light chains do contain very little, if any, radioactivity stemming from these sugars. It is concluded that MOPC 41 A light chain is secreted with less than 0.1 residues of either mannose, galactose or fucose, and that the intracellular form of the light chain contains less than 0.2 residues of either of these sugars. Since an intracellular pool of free glucosamine cannot be ruled out, it remains to be seen whether MOPC 41 A light chain is also devoid of N‐acetyl‐glucosamine residues. The results are discussed in relation to hypotheses which postulate that addition of carbohydrate residues is requisite for transport and secretion of immunoglobulins.
Competition of antigens during induction of low zone tolerance
Authors: Liacopoulos P. , Couderc J. , Gille M. F.
Published: February 2007

Induction of low zone tolerance in mice after injection of either ultracen‐trifuged BGG or low doses of BSA was accompanied by competition of these antigens with immunization to the unrelated antigen OVA, although this competitive effect was less and of shorter duration as compared to the inhibitory effect observed during induction of high zone tolerance with either pneumococcal S III polysaccharide or high doses of BSA. Conversely, medium immunizing doses of BSA resulted in hyperimmunization to both BSA and the test antigen OVA.

These results suggest that tolerance is induced through the same mechanism in the low as in the high zone of antigen dosage. A scheme is proposed in order to explain the induction of low and high zone tolerance which postulates that a characteristic quantitative antigen‐to‐cell ratio determines the induction of either tolerance or immunization.
Studies on antibody avidity at the cellular level. Effects of immunological paralysis and administered antibody
Authors: Andersson B. , Wigzell H.
Published: February 2007

The avidity of antibodies produced by single cells has been studied using inhibition of hemolytic plaque formation by free antigen as a test system. The effect of a paralyzing injection of antigen into mice immunized with heterologous albumins was studied. After a lag period of approximately two days the number of plaque‐forming cells (PFC) decreased in the paralyzed mice. The PFC that remained in the paralyzed animals released antibodies with a low avidity for the antigen as compared to control PFC. The impact of an injection of antibody into immune mice was then studied. A reduction in the number of PFC was found in the antiserum suppressed animals. The remaining PFC released antibody of a relatively high avidity for the antigen. The data support the concept of a similar binding constant for the cell‐associated antibody‐like receptor operating in induction of immunity and paralysis and the antibody released from the cell after stimulation.
The asynchronous development of immunological memory in helper (T) and precursor (B) cell lines
Authors: Cunningham A. J. , Sercarz E. E.
Published: February 2007

A simple method is described for distinguishing helper (T) and precursor (B) immunological memory: it depends on the sequential use of 2 cross‐reacting antigens for priming and challenge. Using cow and sheep erythrocytes, we have followed the asynchronous development of helper and precursor memory.

Helper (T) memory is optimal 4 – 6 days after a wide range of antigen doses (2 × 104 –2 × 109 red blood cells). It reaches rather higher levels after very small injections, but persists longer after high doses.

Precursor (B) memory requires a large amount of antigen for optimal development (2 × 107 – 2 × 109 red blood cells). It increases for at least 2 months after priming. B‐memory cells defined by the cross‐reactive criterion are insensitive to anti‐theta serum but require the presence of T cells for their effective stimulation by antigen. Precursor memory does not appear to be carried by the antibody‐forming cells themselves. It is more sensitive to irradiation damage than T memory.

Memory of either kind leads to increased production of both IgM and IgG antibody‐forming cells. Helper memory cells seem to be able to interact with virgin B cells in the normal spleen.
Intercellular communication in cell‐mediated cytotoxicity. Fluorescein transfer between H‐2d target cells and H‐2b lymphocytes in vitro
Authors: Sellin D. , Wallach D. F. H. , Fischer H.
Published: February 2007

Fluorescein permeable junctions occur infrequently between unsensitized C57BL/6 lymphocytes (H‐2b) and DBA/2 mastocytoma cells (H‐2d), but the incidence of such junctions increases significantly with lymphocytes from animals sensitized against the mastocytes. The mastocytoma cells were labeled intracellularly with fluorescein using permeant (non‐fluorescent) fluorescein dipropionate which is hydrolyzed to free fluorescein within the cells; they were additionally stained with neutral red.

As an in vitro model of cell‐mediated cytotoxicity the Brunner system was used in which close contact is a prerequisite of cell lysis. With contacts of aggressor cells to targets fluorescein permeable junctions were found in 17 out of 23 experiments, or 168 times, when sensitized spleen cells from female C57BL mice took part in the reaction. This incidence is significantly greater than in control experiments with normal spleen cells, when fluorescein permeable junctions were observed only 28 times and in only 9 out of 23 experiments.
Lymphocytes in human immunodeficiency states: a study of membrane‐associated immunoglobulins
Authors: Siegal F. P. , Pernis B. , Kunkel H. G.
Published: February 2007

The peripheral blood lymphocytes from fourteen patients with various types of immunodeficiency states were studied with respect to surface immunoglobulins by the fluorescent antibody technique. The results obtained ranged from a complete absence of immunoglobulin‐bearing lymphocytes in certain patients to normal levels in others. Serial determinations in each patient gave similar results. Three male children with the X‐linked form of the disease and very low serum immunoglobulins had no lymphocytes that stained for immunoglobulins. However, two brothers and a third boy who presumably also had this type of disease, had immunoglobulin‐bearing lymphocytes in the low normal range. Of special interest was an adult female patient with a thymoma who showed no such lymphocytes. Patients with the common variable type of immunodeficiency all had some staining lymphocytes numbering from a very few to within the normal range.

The findings indicate that this approach provides important information regarding the basic defects in certain of these patients, and various hypotheses are proposed.
An immunofluorescence study on the specificity of antibodies synthesized in separate cells after the administration of an immunogen with double specificity
Authors: Hijmans W. , Schuit Henrica R. E. , Teiko Y. , Schechter I.
Published: February 2007

The question whether cells can synthesize antibodies with two specificities was studied in lymph nodes of rabbits. The immunogen was poly‐D L ‐ alanylated human serum albumin which possesses distinct antigenic specificities. Tests were carried out with antibodies, conjugated to fluorescein and rhodamine, directed against the poly‐alanine and the protein moieties of the immunogen. Onwards the 20th postimmunization day, no cells with double specificity were detected.
Studies on the induction of antibody synthesis against sulfanilic acid in rabbits. 1. Effect of the number of hapten molecules introduced in homologous protein on antibody synthesis against the hapten and the new antigenic determinants
Authors: Rubin B.
Published: February 2007

The present experiments were carried out in order to elucidate further the following three questions:

Is there any difference in “helper activity” between the diazotized rabbit serum albumin (RSA) molecule and the bovine γ‐globulin (BGG) molecule in the induction mechanism of antibody synthesis to sulfanilic acid (Sulf) in rabbits?

Is there an optimal hapten density on a homologous carrier molecule for induction of and maximum antibody synthesis against sulfanilic acid?

Does the hapten density affect the expression of, and antibody synthesis against the new antigenic determinants introduced through the haptencoupling reaction?

Carrier antibody titers against diazotized RSA and BGG in the rabbits were significantly different when measured between day 7 and day 30, the BGG titer being higher. Thus, the higher anti‐Sulf antibody response observed in rabbits challenged with Sulf10 BGG compared to the anti‐Sulf response to Sulf11 RSA can presumably be related to a higher immunogenicity and thereby a more effective “helper” property of the BGG molecule.

Anti‐Sulf antibody titers of similar magnitude were observed when using Sulf11 ‐, Sulf23 ‐, and Sulf40 RSA as immunogens, Sulf4 RSA elicitating a somewhat lower anti‐Sulf response. The anti‐Sulf antibodies produced against the different SulfRSA conjugates showed increasing proportions of 19 S antibodies with increasing hapten density.

Antibody synthesis against new antigenic determinants was observed when using Sulf4‐, and Sulf11 RSA as immunogens, not observed when using Sulf23, and Sulf40 RSA. This finding was in agreement with the in vitro reactivity of the SulfRSA conjugates against sheep anti‐RSA: Sulf4 and Sulf11 RSA reacted with anti‐RSA, Sulf23, and Sulf40 RSA did not. These results are discussed on the basis of the cellular cooperation hypothesis, and multivalent binding of high density conjugates onto antibody‐forming precursor cells is proposed as a mechanism alternative to cellular cooperation.