bluuebunny/crossref_metadata_2025 huggingface dataset:
Trichotillomania, Skin Picking Disorder, and Different Aspects of Impulsivity: A Systematic Review
Authors: Öğüt Çağrı , Öğüt Neslihan Demirel
Published: January 2023

Trichotillomania and skin picking disorder are psychiatric disorders with body-focused repetitive behaviors (BFRB). Impulsivity is considered to have a role in the etiology of BFRB. Various methods have been implemented to demonstrate different aspects of impulsivity due to its multidimensional construct. This systematic review aimed to synthesize existing studies to examine different aspects of impulsivity in BFRB. A systematic literature review was conducted in January 2021. Some original studies evaluating the relationship between impulsivity and trichotillomania or skin picking disorder were obtained. Twenty studies were examined after a systematic search of the MEDLINE database. The findings revealed that impulsivity was investigated using a self-report scale in five studies and behavioral tasks in 18 studies. Five studies reported higher trait impulsivity in BFRB with different self-report scales. Differences have been found in the urgency, motor, and attentional subscales. Eight studies measuring motor impulsivity (response inhibition) with behavioral tasks showed higher impulsivity in BFRB and its subgroups. Three studies evaluating cognitive impulsivity with behavioral tasks reported that BFRB is not related to reflection and decision-making impulsivity. However, functional alterations in BFRB patients fMRI, during a choice impulsivity task, were shown in one study only. Different aspects of impulsivity are associated with BFRB. The most commonly identified impairment with behavioral tasks, response inhibition impairment, is conceptually similar to the urgency and motor subscales determined by self-report scales. These results support the patients' self-reports and explain the patients' tendency to act rashly under an increasing sense of tension. However, further studies should be conducted to make a definite conclusion about cognitive impulsivity characteristics of BFRB patients.

[
Psychiatr Ann
. 2022;52(12):527–540.]
A robust study of the transmission dynamics of syphilis infection through non-integer derivative
Authors: Jan Rashid , Khurshaid Adil , Alotaibi Hammad , Inc Mustafa
Published: January 2023

One of the most harmful and widespread sexually transmitted diseases is syphilis. This infection is caused by the Treponema Palladum bacterium that spreads through sexual intercourse and is projected to affect $ 12 $ million people annually worldwide. In order to thoroughly examine the complex and all-encompassing dynamics of syphilis infection. In this article, we constructed the dynamics of syphilis using the fractional derivative of the Atangana-Baleanu for more accurate outcomes. The basic theory of non-integer derivative is illustrated for the examination of the recommended model. We determined the steady-states of the system and calculated the $ \mathcal{R}_{0} $ for the intended fractional model with the help of the next-generation method. The infection-free steady-state of the system is locally stable if $ \mathcal{R}_{0} < 1 $ through jacobian matrix method. The existence and uniqueness of the fractional order system are investigate by applying the fixed-point theory. The iterative solution of our model with fractional order was then carried out by utilising a newly generated numerical approach. Finally, numerical results are computed for various values of the factor $ \Phi $ and other parameters of the system. The solution pathways and chaotic phenomena of the system are highlighted. Our findings show that fractional order derivatives provide more precise and realistic information regarding the dynamics of syphilis infection.
Soldados romanos y vida conyugal en la epigrafía militar. Sobre la interpretación de los términos hospes/hospita
Authors: Gallego Franco Henar , López Casado Roberto
Published: January 2023

Los términos hospes/hospita presentan distintos significados en la epigrafía romana, relacionados en unos casos con la noción de extranjero, en otros con el hospedaje, e incluso con el concubinato. En este trabajo analizamos la presencia de estos vocablos en la epigrafía militar del Imperio romano, en la cual manifiestan una relación conyugal.
El modelo de la organización militar de Maŷrīṭ entre los siglos IX-XI
Authors: Malalana Ureña Antonio
Published: January 2023

Al margen de las investigaciones históricas precedentes, la primera intervención arqueológica en el recinto emiral de Madrid tendría lugar en 1972. Desde entonces sucesivas excavaciones han ido sumando datos, tanto sobre esta fortificación urbana, como de las puntuales reformas o de la construcción de originales perímetros defensivos, como la gran ampliación con un nuevo recinto en siglo XII. Ahora, después de cincuenta años, convendría poner orden a lo que sabemos, principalmente del ḥiṣn fundado por Muḥammad I, a mediados del siglo IX, y las siguientes actuaciones andalusíes, como el albacar o la atalaya taifa. Este artículo plantea una síntesis de dicha evolución a partir de la evidencia arqueológica.
Estudio descriptivo de la espada de guarnición de taza
Authors: Alejo Suescun Iker
Published: January 2023

Este trabajo pretende caracterizar la tipología de espada de guarnición de taza estableciendo su marco geográfico y temporal, así como definiendo las características básicas que permitan valorar su manejabilidad en base al estudio y medición de ejemplares históricos. Para ello se han examinado fuentes escritas, pictóricas y piezas museísticas, dando como resultado una recopilación de información de utilidad para futuros estudios de esta tipología de arma blanca o para la creación de réplicas fiables para el uso en esgrima histórica.
Open Access to Books – the Perspective of a Non-profit Infrastructure Provider
Authors: Ferwerda Eelco , Snijder Ronald , Stern Niels
Published: January 2023

This article describes the open access (OA) book platforms OAPEN Library and Directory of Open AccessBooks (DOAB), based on 1.the development and activities of OAPEN in the first ten years; 2. the underlying technical approach behind the platforms; 3. the current role of OAPEN and DOAB and future outlook.OAPEN started out as a project funded by the European Commission, and become a legal non-profit Dutch entity in 2011. It hosts, disseminates and preserves open access books. OA book publishing has been explored in several pilot projects. Its current collection contains over 24,000 documents. DOAB launched in 2012, inspired and supported by DOAJ. It became a legal non-profit Dutch entity in 2019, owned by the OAPEN Foundationand OpenEdition. It’s current collection contains close to 60,000 titles.The data model of both platforms  is optimised for a multilingual collection and supports funding information. Ingesting books has been optimised to support a wide array of publishers and the dissemination of books takes into account search engines; libraries and aggregators and other organisations. The usage has grown in the last years, to 1 million downloads per month.The future developments entail increased support of research funders with the establishment of a FunderForum and multi-year research into policy development. DOAB will invest more in bibliodiversity, by adding more emphasis on African and Asian countries. Also,DOAB will roll out its Peer Review Information Service for Monographs (PRISM).OAPEN and DOAB will continue to work on developing reliable infrastructures, policy development and quality assurance around open access books.
Analysing Roles of I4.0 Technologies in the Lean-Green Paradigm
Authors: Ram Prasad K.  , Nishal M.
Published: January 2023

In the recent trend, many manufacturing industries are looking to develop and optimise their operational excellence to match the raising complexity of integrating lean concept and Industrial 4.0 (I4.0). Through literatures of previous researchers, the authors can state that the lean principle and concept are the backbone for the industrial operational excellence which has been the primary objective across all sectors. Industry 4.0 has numerous technologies advanced to back up the process optimisation and supplement need for greener environment in industries. In this chapter, the study primarily focusses on exploring and identifying the best suited Industry 4.0 technologies, which can enhance lean and green paradigms in industry through which a clear pathway can be created for smooth transfer of technology within a system. Also, the authors have discussed the enhancement of lean tools by application of Industry 4.0 technologies and have developed a relationship matrix between Industrial 4.0 technologies and lean practices.
Technological Innovation Driven by Big Data
Authors: Naidu G. Taviti , Ganesh K. V. B. , Chellam V. Vidya , Praveenkumar S. , Dhabliya Dharmesh , Pramanik Sabyasachi , Gupta Ankur
Published: January 2023

Large-scale research evaluations, as well as the acquisition and analysis of massive amounts of data, in order to follow trends and models form the organization. As the world around us continues to change, many entrepreneurs are interested in learning how big data might help them enhance their businesses. While businesses have traditionally analyzed data, recent technical advancements have spawned new entrants and unlocked the potential of big data. The extent of the consequences of big data, according to an SNS research, is presently $57 billion and expected to rise further.
Consumers’ Knowledge, Attitudes, and Behavior Regarding Functional Food Products-A Survey from Selected Areas of Sri Lanka
Authors: Dias P. G. I. , Marapana R. A. U. J. , Rathnayaka R. M. U. S. K. , Gayathri S. M. D. S. , Anuradha N. G. D. , Kananke T. C. , Rathnayaka R. M. K. T. , Perera M. G. A. N. , Sabaragamuwa R. S. , Wickramaratne N. M.
Published: January 2023

Purpose: The purpose of this research is to assess the influence of demographical variables (gender, age, education level, study area, nature of residence, residential milieu, suffering from non-communicable diseases (NCDs), and monthly household income) on the consumption frequency of mostly available processed food products with health benefits (functional food products-FF) in Sri Lankan market. Consumers’ knowledge of the health-promoting ability of FF, attitude on FF choices, and behaviors on FF consumption were also analyzed.
Research Method: A questionnaire was completed by 303 individuals (60.40% females, 39.60% males, and 83.17% of the total having a diploma/degree) from the Western, Central, Southern, Sabaragamuwa, and Uwa provinces. Cronbach’s alpha coefficient assessed the reliability of the questionnaire and Pearson’s chi-squared test was used to examine the independence among qualitative variables. The Likert scale numbers were transformed to means and articulated the weights of the study variables. The Correlation analysis was carried out to find the association between Consumers' knowledge and attitudes regarding FF.
Findings: The age, education level, and NCDs of the respondents were significantly affected (p<0.05) in the FF consumption frequency of the selected sample. The population between the ages of 18-34 who have a diploma/degree and no NCDs was more likely to consume FFs. However, most of them have no clear idea and were not sure of the curing ability of FFs or their bioactive ingredients. They were not always thinking about healthiness while purchasing. Consumers' knowledge and attitudes regarding FF observed a positive correlation (P<0.01). The results showed that tea/herbal infusions were the most preferred FF type by the respondents. As per the responses, less awareness was a significant barrier to consuming FFs.
Research Limitations: The respondents in this study were biased toward the young age group with a diploma/degree.
Originality/Value: These findings provide valuable information concerning Sri Lankan consumers’ behavior and attitudes toward FF consumption. The knowledge can be utilized in future FF development processes.
A conceptual electrophoresis-mediated protein identification method by frictional coefficient during motion under electrical and magnetic interference
Authors: Senadheera Uvin Eksith , Jayasanka Jasintha
Published: January 2023

Protein Identification (PI) based on conventional Mass Spectrometry (MS) is prone to errors. These errors are a result of the inability to solubilize the protein, interference of detergents, usage of wrong protease enzymes, inability to cleavage of the target protein by proteases, and interference of endogenous or exogenous contaminant molecules and calibrants. Conventional Mass Spectrometric PI is solely based on ionization and mass trajectory of protein in a vacuum. Therefore, it is crucial to develop and modify the existing technique not to be entirely dependent on the ionization and mass of the protein molecule in a vacuum. Other than the mass and an overall electrostatic charge of a protein, characteristic steric hindrance on a protein while travelling through a Polyacrylamide Gel matrix, can be used for accurate identification of proteins in Mass Spectrometry. A concept for a modified Mass Spectrometric method based on a Polyacrylamide Gel platform, to utilize the steric hindrance and friction coefficient of the moving protein under the influence of electric field and magnetic fields is proposed in the article. The theoretical approach of the concept is based on the laws of motion, electrical fields, electromagnetism, and Fleming's Left Hand Rule. In this concept, on a Polyacrylamide Gel platform, in an electric field, protein is accelerated to a constant velocity characteristic of the protein introduced to a magnetic field where the radius of the circular trajectory and ratio of mass and overall surface charge of the accelerated protein is measured. This article directs attention to the modificati on of Mass Spectrometry to improve reliability and accuracy in protein identification.
Host Response to Tumor-Associated Fetal Antigens
Authors: Salinas F. A. , Hanna M. G.
Published: January 2023

We have evaluated the contribution of the host response with respect to transplantation immunity to tumor-associated fetal antigens by a colony-forming unit technique with fetal liver test cells as the source of fetal colony-forming units (FCFU). To measure host immunity we evaluated the effect of immunization with tumor cells on the development of fetal colonies in spleens of immunized, irradiated recipients. It could be demonstrated that immunization with syngeneic (plasmacytoma, MSV-BALB/3T3), allogeneic (EL4), or xenogeneic (SV40 hamster) tumor cells was capable of generating a host response in BALB/c recipients that was at least cytostatic to adoptively transplanted fetal liver cells.

In an in vitro modification of the FCFU assay, fetal liver cells were first incubated with serum from mice hyperimmunized with fetal liver cells or plasmacytoma cells and then transplanted into irradiated recipients. Colony-forming ability was reduced in both cases, indicating that humoral antibody is an effective component in the host response to tumor-associated fetal antigens. A marked suppression of FCFU was also observed with transplanted fetal liver cells that had been incubated with sensitized lymphocytes (lymphocytes from mice immunized with fetal liver cells or plasmacytoma cells).

Maternal immunity to transplanted syngeneic fetal liver cells was also evaluated by the in vivo FCFU assay. A strong, short-lived postpartal immunity was seen in primiparous females; a weak immunity was seen after second litters but was detectable only several weeks postpartum; and a strong immunity, which increased as a function of time, was seen after five or more litters.
Limit-dilution analysis of weak influenza-immune T cell responses associated with H-2Kb and H-2Db.
Authors: Allouche M , Owen J A , Doherty P C
Published: January 2023

A limiting-dilution analysis has been made of influenza-immune cytotoxic T lymphocyte (CTL) response patterns associated with H-2Kb and H-2Dd in the B10.A(5R), and H-2Kk and H-2Db in the B10.A(2R) and B10.A(4R) recombinant mouse strains. In previous in vivo experiments the H-2Kb allele has been shown to be associated with low responsiveness or nonresponsiveness, whereas Db-restricted influenza-specific responses were found to be weak in recombinant strains that possessed the Kk allele. Influenza-immune CTL restricted to the more "dominant" H-2Dd and H-2Kk alleles were found consistently when primed T cells were restimulated in vitro under limiting-dilution conditions. Precursors were present at frequencies of at least twice background levels (lysis of normal targets) in the great majority of experiments, performed with or without added helper factors. The H-2Kb- and H-2Db-restricted responses were much more variable and, for H-2Kb but not for H-2Db, were completely absent when the culture medium did not contain added interleukin preparations. Even so, experiments in which individual microcultures were tested on more than one target demonstrated conclusively both that H-2Kb-restricted CTL can be generated under limiting-dilution conditions and that most, if not all, of these T cells do not cross-react with influenza virus presented in the context of H-2Dd. The characteristics of these "weak" responses are thus that they are more help dependent and show evidence of greater variability between individual mice than the "dominant" CTL clones do.
Role of syngeneic Ia+ accessory cells in the generation of allospecific CTL responses.
Authors: Weinberger O , Germain R N , Springer T , Burakoff S J
Published: January 2023

Under conditions in which antigen dose is suboptimal, the recognition of Ia determinants is a necessary component of the generation of allospecific CTL responses. With monoclonal anti-Ia antibodies used as blocking reagents, it is demonstrated that the recognition of alloantigens may proceed via two pathways. Alloantigens can be recognized in the context of syngeneic Ia determinants in a similar fashion to conventional antigens. If, however, the Ia+ cells are removed from the responder population, the generation of such responses involves the recognition of allogeneic Ia determinants directly. A non-T, non-B, adherent accessory cell was identified as the critical syngeneic Ia+ cell required for CTL responses in these cultures.
Studies on the clonal origin of human B cell leukemia using monoclonal anti-idiotype antibodies.
Authors: Mayumi M , Kubagawa H , Omura G A , Gathings W E , Kearney J F , Cooper M D
Published: January 2023

The clonal origin of an IgA1 kappa B cell leukemia in a 71-year-old man (WF) was examined using a monoclonal anti-Id antibody and a panel of monoclonal anti-VH antibodies. Immunofluorescent studies revealed that all surface IgA1 kappa + leukemic cells in WF's blood and 10% of the IgM+ B cells in his bone marrow expressed the WF Id. Three percent of the IgA1 kappa + leukemic cells in blood also expressed gamma-chains in their cytoplasm. Approximately 0.1%, 1%, and 10% of bone marrow mononuclear cells, respectively, expressed mu-chains, gamma-chains, and alpha-chains in their cytoplasm, but no detectable light chains or surface immunoglobulins. These mu, gamma, and alpha-positive cells had the convoluted nucleus and narrow cytoplasm characteristic of normal mu+ pre-B cells. Sequential isotype switching among this unusual pre-B population was indicated by co-expression of mu-chains and alpha-chains by 11% and 63%, respectively, of the gamma pre-B cells. These pre-B cells and the surface alpha-chains and cytoplasmic gamma-chains of the leukemic B cells were reactive with one of four monoclonal anti-VH antibodies. The data suggest malignant transformation of the clone before isotype switching, and also imply light chain precommitment at the pre-B cell level of differentiation.
Target specificity and cell surface structures involved in the human cytolytic T lymphocyte response to endothelial cells.
Authors: Clayberger C , Uyehara T , Hardy B , Eaton J , Karasek M , Krensky A M
Published: January 2023

Two long-term cytolytic T lymphocyte (CTL) lines derived from the peripheral blood lymphocytes (PBL) of a single donor were analyzed for target specificity and involvement of cell surface molecules in CTL-target interactions. One line, AH2, was generated after stimulation with B lymphoblastoid cells. Cytolysis by these cells was restricted to targets expressing the appropriate HLA-A2 specificity and was blocked by mAb recognizing CD2, CD3, CD8, LFA-1, and LFA-3. The second line, AE1, was generated after stimulation with cultured endothelial cells derived from human newborn preputial microvessels. These CTL lysed all human target cells tested, except autologous cells and the Class I negative cell line Daudi. In addition, mAb specific for CD2, CD3, and CD8 did not affect cytolysis. Anti-LFA-1 and -LFA-3 mAb blocked cytolysis of B lymphoblastoid targets but not endothelial targets. These results indicate that some CTL utilize as yet uncharacterized cell surface structures for CTL-target interactions.
Lymphocyte recognition of lymph node high endothelium. VII. Cell surface proteins involved in adhesion defined by monoclonal anti-HEBFLN (A.11) antibody.
Authors: Rasmussen R A , Chin Y H , Woodruff J J , Easton T G
Published: January 2023

Lymphocyte entry into lymph nodes (LN) and Peyer's patches (PP) occurs specifically at high endothelial cell venules (HEV). We previously isolated a high endothelial binding factor (HEBFLN) from rat lymph that blocked the lymphocyte binding sites of HEVLN but not HEVPP. In this study, mouse monoclonal anti-HEBFLN antibody (A.11) was used to investigate rat lymphocyte surface structures mediating adhesion to high endothelium. The A.11 antigen was expressed on the majority of thoracic duct lymphocytes (TDL), spleen, LN, PP cells, but was only detected on few (1 to 10%) thymus and bone marrow cells (indirect immunofluorescence). The treatment of TDL with the A.11 IgG blocked their ability to bind to HEVLN. This effect was specific, inasmuch as A.11 antibody did not block lymphocyte binding to HEVPP, and an anti-leukocyte-common antigen monoclonal antibody, OX1, did not block lymphocyte binding to HEVLN. In addition, the A.11 antigen isolated from the lymph and detergent lysates of TDL by antibody affinity chromatography had the capacity to block the lymphocyte binding sites of HEVLN but not HEVPP. Immunoprecipitation studies revealed that the A.11 antibody recognized the radioiodinated surface membrane proteins of TDL and TDL-derived T cells and B cells, which resolved with SDS-PAGE autoradiography into three polypeptides with relative m.w. of approximately 135,000, 63,000, and 40,000. We conclude that the A.11 antigen is a component of the lymphocyte surface recognition structure that mediates adhesion to high endothelial cells of rat peripheral lymph nodes.
Specificity of the T cell receptor: two different determinants are generated by the same peptide and the I-Ak molecule.
Authors: Allen P M , Matsueda G R , Haber E , Unanue E R
Published: January 2023

The determinants recognized by two I-Ak-restricted hen egg-white lysozyme-specific T cell hybridomas were differentiated with a series of truncated or substituted peptides. The 10mer 52-61 was the smallest peptide that was immunogenic for both T cells. This peptide differed by a single residue, Leu56, from the corresponding autologous lysozyme peptide, which was nonimmunogenic. The addition of amino acids to the amino terminus of 52-61 increased the immunogenicity of the peptides for 3A9 T cells and decreased the immunogenicity for 2A11 T cells. By deleting or diiodinating Tyr53, the resulting peptides were rendered totally nonimmunogenic. In contrast, the 3-NO2-Tyr derivative was fully immunogenic for the 3A9 cells but completely nonimmunogenic for the 2A11 cells. Thus, two different, but very similar, determinants were generated by the same HEL peptide and the I-Ak molecule.
Analysis of T cell activation requirements with the use of alloantigens or an anti-clonotypic monoclonal antibody.
Authors: Hua C , Boyer C , Guimezanes A , Albert F , Schmitt-Verhulst A M
Published: January 2023

H-2Kb-specific alloreactive cytotoxic T lymphocyte (CTL) clones, which secrete macrophage-activating factor (MAF) in response to antigen, were used to study the antigenic and physiologic parameters for T cell-antigen receptor (Ti)-mediated activation. When H-2Kb was presented on untreated, formaldehyde (FOR)-fixed cells, or liposomes, optimal stimulation in the absence of co-factors was obtained only with the untreated cells. FOR cells, which were efficient inhibitors of CTL-target cell interactions for the CTL clones studied, had a greatly reduced activating capacity. Phorbol myristic acetate (PMA), which alone had no activating effect on the CTL clones, acted in synergy with FOR cells, restoring an unimpaired H-2Kb-dependent activation for some CTL clones. H-2Kb-liposomes were not stimulatory even in the presence of PMA and/or splenic feeder cells. For one H-2Kb-specific CTL clone (KB5-C20), activation was studied with the use of an anti-clonotypic (anti-Ti) monoclonal antibody (mAb), Désiré-1. By using this immunoglobulin (Ig) G2a mAb or its F(ab')2 or Fab fragments, it was observed that the association constant of the IgG2a (4.7 X 10(9) M-1) for KB5-C20 was 30-fold higher than that of the Fab fragment, whereas the molar concentration of mAb required to inhibit 50% of the H-2Kb-specific CTL activity of clone KB5-C20 was 70-fold to 90-fold higher for the Fab fragment than for the IgG2a (1 to 5 X 10(-10) M). It was also observed that activation as measured by MAF secretion of clone KB5-C20 was obtained by using the divalent IgG2a mAb or its F(ab')2 fragment at 10(-9) M to 10(-8) M in the absence of any added co-factor or feeder cells, whereas a 500-fold higher molar concentration of the Fab fragment only induced very low levels of MAF secretion. Also, in the presence of PMA, the mAb-mediated activation of MAF secretion by clone KB5-C20 was increased, but Fab-induced activation never resulted in high titers of MAF. We conclude that the intrinsic "affinity" of the H-2Kb-Ti interaction is probably so low for the Ti of clone KB5-C20 that efficient activation by H-2Kb is obtained only when multivalency is achieved on H-2Kb-expressing cells, and possibly when molecules on the T cells such as Lyt-2 and LFA-1 stabilize the interactions.(ABSTRACT TRUNCATED AT 400 WORDS)
A mutation in a non-MHC murine cell surface antigen detectable by cytotoxic T lymphocytes.
Authors: Rinchik E M , Amos D B
Published: January 2023

During the course of screening new T-H-2 region congenic strains of mice constructed from the C57BL/6 and B6-H-2k strains, a new cell surface polymorphism, designated dtc-1, was identified by cell-mediated lympholysis techniques. The dtc-1 antigen can be found on both Con A- and LPS-stimulated lymphoblasts, peritoneal macrophages, and SV40-transformed mouse embryo fibroblasts. Lysis of dtc-1+ targets by CTL is H-2Dk restricted. All inbred strains tested are dtc-1+, with the exception of the B6-H-2k strain, which is dtc-1-, and several congenic strains directly derived from B6-H-2k. Because B6/Boy and AKR/Boy, the parents of the B6-H-2k strain, are dtc-1+, the dtc-1- phenotype may be the result of mutation in the locus specifying the cell surface molecule that carries this antigen. Segregation analysis of the dtc-1+/dtc-1- polymorphism demonstrated that this locus is not linked to T or H-2. The dtc-1 antigen thus identifies yet another cell surface polymorphism and adds another immunologically defined genetic marker to the murine genome. Furthermore, the dtc-1 system indicates the need for reevaluation and restandardization of congenic strains of mice derived from the B6-H-2k congenic strain.
Two major human allergenic sites on ragweed pollen allergen antigen E identified by using monoclonal antibodies.
Authors: Olson J R , Klapper D G
Published: January 2023

Murine monoclonal antibodies specific for antigen E (AgE), the major allergen isolated from short ragweed pollen, have been produced and characterized. These monoclonal antibodies, when coupled to Sepharose and used as immunoadsorbents, specifically bound AgE when a crude pollen extract was passed through the column. Three antigenic sites (A, B, and C) on AgE were identified by using five of these monoclonal antibodies in both inhibition and double-bind solid-phase ELISA. These three antigenic sites appear to be nonoverlapping and nonrepeated, that is, present only once on each AgE molecule. Site C on AgE could readily be bound by the monoclonal antibody specific for that site, but only when AgE was in solution or "presented" by an anti-site A or anti-site B antibody. Site C appears to be only marginally available for binding when AgE is directly adsorbed to polyvinyl chloride microtiter wells. The majority of monoclonal antibodies isolated after immunization of BALB/c mice were specific for site A on AgE. In addition, the binding to AgE of pooled BALB/c polyclonal, hyperimmune antisera against AgE was blocked approximately 80% by a monoclonal antibody directed against site A, but was only blocked approximately 20% by an anti-site B monoclonal antibody. This suggests that site A on AgE is the predominant antigenic site in the BALB/c immune response and that site B represents a less dominant site. The binding of IgE in pooled human serum from ragweed-allergic individuals is blocked approximately 50% by a monoclonal antibody directed to site A on AgE and also approximately 50% by a monoclonal antibody directed against site B. A series of individual human short ragweed allergic antisera also showed significant, although varied, inhibition of IgE binding to AgE by both anti-site A and anti-site B monoclonal antibodies. Simultaneous addition of anti-site A and anti-site B was somewhat additive and inhibited up to 80% of the binding of human IgE specific for AgE. The conclusion from these data is that site A and site B defined by two murine monoclonal antibodies represent two very major allergenic sites in the human response to this molecule.
Interferon-gamma, mitomycin C, and cycloheximide as regulatory agents of MHC class II-associated invariant chain expression.
Authors: Rahmsdorf H J , Harth N , Eades A M , Litfin M , Steinmetz M , Forni L , Herrlich P
Published: January 2023

The murine and human major histocompatibility complex class II-associated invariant chain genes are expressed in mature B cells and in antigen-presenting cells. Several pre-B cell lines and fibroblasts do not naturally contain invariant chain mRNA. Expression is inducible, however, by interferons and other agents interfering with proliferation. Mitomycin C induces the transcription of the gene in pre-B cells, but not in fibroblasts. Interferon-gamma acts in both types of cells. Cycloheximide inhibits the induction of the invariant chain mRNA by interferon-gamma, suggesting that protein synthesis is required. In fact, cycloheximide itself increases the transcriptional rate at the invariant chain gene, suggesting the existence of a labile repressor or an indirect action through cycloheximide arrest of the cell cycle. Lipopolysaccharide (LPS) activation of B lymphocytes causes a rapid decrease of the invariant chain mRNA level and of the amount of invariant chain protein due to rapid turnover. Also class II alpha and beta mRNA expression decreases after LPS treatment. The decrease of invariant chain protein is accompanied by increased surface expression of alpha and beta. The murine invariant chain gene transfected into human fibroblasts is regulated by the same agents and the same dose of agents as is the endogenous gene. The differentiation marker invariant chain thus seems to be transcribed from a gene that is accessible to regulation even in nonlymphoid cells and the expression of which is linked to states of nonproliferation. The sequence responsible for these responses is contained within the cloned genomic fragment and is conserved between mouse and man.
Identification of IL-6 as a T cell-derived factor that enhances the proliferative response of thymocytes to IL-4 and phorbol myristate acetate.
Authors: Hodgkin P D , Bond M W , O'Garra A , Frank G , Lee F , Coffman R L , Zlotnik A , Howard M
Published: January 2023

Thymocytes undergo a vigorous proliferative response when stimulated with a combination of IL-4 and PMA. We have found that conA-induced supernatants from a number of Th cell clones could enhance the level of IL-4/PMA-induced proliferation of unseparated thymocytes 0.5- to 2-fold and of peanut agglutinin-positive thymocytes 2- to 10-fold. These supernatants did not contain IL-2 or IFN-gamma, and the enhancing activity could be chromatographically separated from IL-3, -4, -5, and granulocyte/macrophage CSF. The possibility that the thymocyte enhancement factor contained in these supernatants was IL-6 was suggested when murine rIL-6 was found to have similar activity. Further evidence for the identity of these two factors was obtained when an IL-6 assay, based on plasmacytoma growth, was used to test column fractions showing thymocyte enhancement. All fractions active in the thymocyte enhancement assay also had activity in the plasmacytoma growth assay. These observations suggest that the thymocyte-stimulating activity present in the T cell supernatants was due to IL-6.
Onchocerca volvulus. Monoclonal anti-idiotype antibody as antigen signal for the microfilaricidal cytotoxicity of diethylcarbamazine-treated platelets.
Authors: Cesbron J Y , Hayasaki M , Joseph M , Lutsch C , Grzych J M , Capron A
Published: January 2023

Over the past 35 yr, diethylcarbamazine (DEC) has been the most widely used agent for the treatment of filarial diseases, particularly in onchocerciasis. The microfilaricidal action of DEC has been recently shown to be mediated by blood platelets with the additional triggering of a filarial excretory Ag (FEA). This FEA could be detected by using mAb in the serum of infected patients. By using one mAb (IA2(23] directed against Onchocerca volvulus and recognizing circulating Ag (Ab1), we purified by affinity chromatography the target molecule of IA2(23) (an O. volvulus glycoprotein recognized by IA2(23) mAb). This compound had a dose-dependent effect on the cytotoxic action of DEC-treated platelets. We subsequently produced an anti-idiotype mAb to Ab1 (Ab2), and considered the possibility of replacing the O. volvulus glycoprotein recognized by IA2(23) mAb by Ab2. Ab2 was selected according to its ability to inhibit the binding of radioiodinated Ab1 to the filarial target Ag. It induced the production of anti-O. volvulus antibodies (Ab3) in rats. At a constant concentration of DEC platelets, the addition of increasing amounts of Ab2 led to a dose-dependent cytotoxic effect against parasite larvae. Experiments performed with Ab2 on detergent solubilized surface proteins of platelets identified four bands of Mr 18, 26, 43.5, and 100 kDa, supporting the idea of the presence of binding sites on the platelets for a FEA required for the microfilaricidal cytotoxicity of DEC-treated platelets.
Novel mechanism for Trypanosoma cruzi-induced suppression of human lymphocytes. Inhibition of IL-2 receptor expression.
Authors: Beltz L A , Sztein M B , Kierszenbaum F
Published: January 2023

Co-culture of blood forms of Trypanosoma cruzi, the causative agent of Chagas' disease, with human PBMC impaired the capacity of T lymphocytes to express surface receptors for IL-2. This effect was evidenced by marked reductions in both the proportion of Tac+ cells and the density of Tac Ag on the surface of the positive cells, determined by flow cytometry. The extent of the inhibition increased with parasite concentration. Under optimal or suboptimal conditions of stimulation with either PHA or monoclonal anti-CD3, specific for an epitope of the T3-Ti human T cell Ag receptor complex, the presence of T. cruzi curtailed the capacity of T lymphocytes to proliferate and express Il-2R but did not affect IL-2 production. Furthermore, the addition of exogenous IL-2 did not restore the responsiveness of suppressed human lymphocytes but did when mouse lymphocytes were used instead. Therefore, unlike mouse lymphocytes, human lymphocyte suppression by T. cruzi did not involve deficient IL-2 production and was accompanied by impaired IL-2 utilization. Co-culture of human monocytes/macrophages with suppressive concentrations of T. cruzi increased IL-1 production, and the parasite did not decrease IL-1 secretion stimulated by a bacterial LPS. Therefore, the suppression of IL-2R expression and lymphoproliferation is not likely to have been an indirect consequence of insufficient IL-1 production due to infection of monocytes or macrophages. We have shown that suppression of human lymphocyte proliferation by T. cruzi is not caused by nutrient consumption, absorption of IL-2, lymphocyte killing, or mitogen removal by the parasite. Therefore, these results uncover a novel suppressive mechanism induced by T. cruzi, involving inhibited expression of IL-2R after lymphocyte activation and rendering T cells unable to receive the IL-2 signal required for continuation of their cell cycle and mounting effective immune responses.
Trans-activation of class II (I-A alpha) gene by I-A beta gene transfection using bovine papilloma virus as a shuttle vector system.
Authors: Fukushima J , Tani K , Atsumi Y , Hamajima K , Kawamoto S , Okuda K
Published: January 2023

We have engineered a bovine papilloma virus to carry the class II MHC (A beta d) gene. The recombinant plasmid was introduced into various mouse B cell hybridomas by co-transfecting with the neomycin-resistance gene. Several transfectants which received only the beta-chain gene of I-Ad, expressed I-Ad proteins on the cell surface. Their presence was determined by direct immunofluorescence and by Northern blot hybridization as well as RNA dot blot hybridization. These I-Ad molecules could induce IL-2 production in I-Ad restricted T cell hybridomas. When I-Ad molecules are expressed on the cell surface of the transfectants, they become fully active in inducing the I-Ad restricted T cell response. The original B cell hybridomas used for transfection possessed the alpha and beta chain genes of the I-Ad molecule but there are no transcripts of these genes in the cell. We suppose that many copies of the transfected beta-chain gene or its product may also induce production of cellular alpha-chain gene products and thereby induce expression of the I-Ad molecule on the cell surface.
Age-related variation in the proportion and activity of murine liver natural killer cells and their cytotoxicity against regenerating hepatocytes.
Authors: Itoh H , Abo T , Sugawara S , Kanno A , Kumagai K
Published: January 2023

We investigated the distribution of liver NK cells in mice of various ages and their cytotoxicity against regenerating hepatocytes. Liver NK cells were identified by asialo GM1 antibody in mononuclear cell suspension from the liver, whereas NK activity was assayed against YAC-1 target cells. Mononuclear cells in the liver consisted of more than 25% NK cells with potent NK activity in C3H/He mice, 8 wk of age. The strain-specific distribution (C3H/He greater than C57BL/6 greater than DBA/2) of liver NK cells was the same as those in the spleen and blood. The proportion of liver NK cells and the level of NK activity in C3H/He mice were further demonstrated to vary depending on age, in that both the proportion and the function were generated at 4 wk of age, reached a maximum between the 6th and 8th wk, and then rapidly decreased around the 9th wk. The appearance of an increased number of NK cells in the liver seemed to coincide with the slowing of the rapid increase of murine liver weight. We then investigated whether liver NK cells mediated their cytotoxicity against regenerating hepatocytes. Both specific 51Cr-release assay and single cell cytotoxicity assay demonstrated that liver NK cells were significantly cytotoxic against regenerating hepatocytes in partially hepatectomized liver, but to a lesser extent against normal hepatocytes in resting liver. Morphologic study revealed that normal liver predominantly consisted of hepatocytes with binuclei (greater than 60%) but that regenerating liver mainly consisted of hepatocytes with a single nucleus (greater than 70%). One-nucleus hepatocytes were more susceptible to the cytotoxicity of liver NK cells. A comparative study of restoration kinetics of the liver weight and the number of liver NK cells after partial hepatectomy also showed a unique relationship. These results raise the possibility that liver NK cells might be responsible for regulating hepatocyte growth.
Identification of suppressor T cells in virgin non-responder spleen cells responsible for primary unresponsiveness to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).
Authors: Pierce C W , Sorensen C M , Kapp J A
Published: January 2023

T cell subsets that regulate antibody responses to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) in mice that are Ir gene non-responders have been further characterized. We previously defined several T cell subsets in GAT-primed non-responder mice. The Lyt-2+ suppressor-effector T cells suppress responses to GAT and GAT complexed to methylated BSA (GAT-MBSA). The Lyt-1+ cell population is complex and can be separated into I-J- Th cells, which support responses to GAT and GAT-MBSA. After priming, the Lyt-1+, I-J+ cell population contains suppressor-inducer cells that activate precursors of suppressor-effector cells to suppress responses to GAT and GAT-MBSA as well as Ts cells that directly inhibit responses to GAT but not GAT-MBSA. By contrast, the Lyt-1+ cells from virgin mice contain only cells that directly suppress responses to GAT but not GAT-MBSA. The major question addressed in the present studies was whether the Lyt-1+, I-J+ Ts cells in virgin and primed mice and the suppressor-inducer cells in GAT-primed mice were functionally and serologically distinct subsets. The studies used mAb and panning procedures to separate cell populations and inhibition of PFC cell responses to functionally define the activity of the cell populations. We used the following two mAb that were raised by immunizing rats with GAT-specific suppressor factors: 1248A4.10 (known to react with suppressor-inducer cells) and 1248A4.3, another reagent from the same fusion. Lyt-1+ cells from virgin spleens contained Ts cells that were A4.10-, A4.3+ and no suppressor-inducer T cells, whereas Lyt-1+ cells from GAT-primed spleens contained Ts cells that were A4.10-, A4.3+ as well as A4.10+, A4.3- suppressor-inducer cells. Thus, the Lyt1+, I-J+ cell subset can be divided into two functionally and serologically distinct subsets, direct Ts cells (1248A4.3+), which suppress responses to GAT but not GAT-MBSA, and GAT-primed suppressor-inducer T cells (1248A4.10+).
Co-dominant restriction by a mixed-haplotype I-A molecule (alpha k beta b) for the lysozyme peptide 52-61 in H-2k x H-2b F1 mice.
Authors: Moreno J , Adorini L , Hämmerling G J
Published: January 2023

Helper (CD4+) T lymphocytes recognize protein Ag as peptides associated to MHC class II molecules. The polymorphism of class II alpha- and beta-chains has a major influence on the nature of the peptides presented to CD4+ T lymphocytes. For instance, T cell responses in H-2k and H-2b mice are directed at different epitopes of the hen egg lysozyme (HEL) molecule. The current studies were undertaken with the aim of defining the role of mixed haplotype I-A (alpha k beta b and alpha b beta k) molecules in T cell responses to HEL in (H-2k x H-2b)F1 mice, as well as the nature of the immunogenic peptides of HEL recognized in the context of I-A alpha k beta b and I-A alpha b beta k. A series of HEL-reactive T cell lines and hybridomas derived from MHC class II heterozygous (C57BL/6 x C3H F1) mice were established. Their responsiveness to HEL and synthetic HEL peptides was analyzed with the use of L cells transfected with either I-A alpha k beta b or I-A alpha b beta k as APC. Out of 28 clonal T cell hybridomas tested, 13 (46%) only responded to HEL presented by I-A alpha k beta b, 11 (40%) by I-A alpha b beta k (and to a minor extent I-A alpha k beta k), only 4 (14%) were primarily restricted by I-Ak, and none by I-Ab. All the I-A alpha k beta b-restricted T cell hybridomas responded to the HEL peptide 46-61 and to its shorter fragment 52-61, even at concentrations as low as 0.3 nM. As this determinant has been previously defined as immunodominant for I-Ak but not for I-Ab mice, these results suggest a role for the I-A alpha k chain in the selection and immunodominance of HEL 52-61 in H-2k mice. The fine specificity of I-A alpha k beta b-restricted T cell hybridomas for a series of different HEL peptides around the sequence 52 to 61 suggests that peptide 52-61 binds to I-A alpha k beta b with higher affinity than to I-A alpha k beta k. The peptides recognized in the context of I-A alpha b beta k and I-A alpha k beta k were not identified.
Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor.
Authors: Callahan K M , Fort M M , Obah E A , Reinherz E L , Siliciano R F
Published: January 2023

The propensity of HIV-1 to undergo sequence variation, particularly in the envelope glycoprotein gp120, complicates vaccine development and may enable the virus to evade ongoing immune responses in infected individuals. We present here a molecular analysis of the effects of this variability on human T cell recognition of HIV-1 gp120. Synthetic peptides representing a defined CD4+ human T cell epitope in gp120 were used to survey gp120 molecules from various HIV-1 strains for the capacity to be recognized in the context of a single human MHC molecule, DR4. Variation affected recognition at two levels. For some strains, variation in this epitope was sufficient to alter the interaction of Ag receptors on gp120-specific human T cell clones with peptide-DR4 complexes on APC. In the case of two strains, the natural variation was sufficient to prevent the critical initial interaction between the relevant gp120 peptides and DR4 on the APC. However, these strains were highly divergent from the reference strain. Thus it is encouraging to note that the range of natural sequence variation in this T cell epitope falls, for the most part, within the range of peptide sequences that can be accommodated by the relevant human MHC molecule.