bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remarks Concerning Landsteiner's Discovery of Isoagglutination and the Blood Groups, with Special Reference to a Paper by J. A. Kennedy
Authors: Zinsser Hans , Coca Arthur F. 
Published: January 2023

Abstract
In a preceding issue of this Journal there appeared a paper by Dr. J. A. Kennedy entitled “Isohemagglutination: The Work of Jan Janský with a Critical Analysis.” The paper was accepted by the Journal since it is the purpose of this publication to offer its columns freely for the discussion of controversial opinions in immunology. It was understood, however, that the Editors reserved the privilege of replying to statements which seemed, in their opinions, to be misinterpretations of facts. Since the paper of Dr. Kennedy questions the priority of Karl Landsteiner on the observation of isohemagglutination, the present note is published, the Editors believing that Dr. Kennedy is in error in this assertion.
In 1900, Landsteiner first observed serological, individual differences in human beings. In 1901, he described the three common groups, further laid the foundations for their scientific classification and for the serological recognition of these groups.
Note Concerning Differences Between the Clumping of Pseudoagglutination and that of Isoagglutination
Authors: Coca Arthur F. 
Published: January 2023

Abstract
In a paper by J. A. Kennedy that appeared in the preceding issue of this Journal, illustrations are reproduced from an article by Shattock, which apparently are considered by Kennedy as representing isoagglutination.
Since I disagree with this interpretation, believing the illustrations to be those of pseudoagglutination, and since I have had occasion to see how mistakes in blood-grouping can be made on account of confusing the two phenomena, it seems to be not superfluous to present side by side photographs of these two sorts of reactions (figs. 1 to 4).
One will see from these pictures that the two kinds of clumping differ sufficiently to permit, in general, a differentiation, which, as a rule, can be made easily by the use of the fact, first described by Shattock, that pseudoagglutination is prevented by slight dilution (1:2 or 1:3) of the serum.
Two features stand out in both of figures 1 and 2: first, the clumping, and secondly, the rouleaux, which are prominent—one may say characteristically so—at the periphery of the clumps.
Antigenic Value of Botulinum Toxoids Kept one Year at Ice Box Temperature
Authors: Graham Robert , Thorp Frank 
Published: January 2023

Summary
An antigenic decline in botulinum toxoids of 30 to 60 per cent over a period of one to twelve months was measured by the increased number of arbitrary units required to protect guinea pigs against lethal amounts of homologous toxins. None of the eleven toxoids that proved non-toxic in 1-unit doses later became toxic in the same amounts, notwithstanding an occasional toxoid inoculated pig died of intercurrent infection. Seven of eleven samples of botulinum toxins A, B, and C containing 0.3 to 0.9 per cent formalin became detoxified at 37° to 42°C. in one month. The remaining four of eleven samples required two to five months for detoxification. One sample (3826 A) retained its original antigenic properties for five months, another (3217 B) for three months, three for two months, and two for one month. Ten of the eleven toxoids were atoxic and antigenic in 2-unit doses at ten to twelve months of age. The rate of detoxification in botulinum toxoids by formalin and heat seemed uncorrelated with the longevity of the antigenic properties. One toxin with 20,000 guinea pig lethal doses per cubic centimeter required a longer period of time for detoxification than other toxins containing 10,000 guinea pig lethal doses per cubic centimeter. However no consistent difference in the rate of antigenic decline was observed between toxoids prepared from toxins containing 10,000 and 20,000 guinea pig lethal doses per cubic centimeter. The pH of eleven botulinum toxoids changed from an original titer of pH 7.6 in the inoculated mediums to an average of pH 6.7 in seven and one-half months.
Food Allergens
Authors: Vaughan Warren T. 
Published: January 2023

Abstract
While cutaneous testing for allergens has been of great aid in the study of the allergic disease, the tests not infrequently fail to identify the etiologic agent even when the case is manifestly allergic. Foods are less likely to give positive reactions than are pollens. Rowe (1) finds that frequently less than 50 per cent of those sensitive to a certain food give positive skin reaction to that food. Alexander (2) concludes that positive skin reactions are obtained in about 50 per cent of asthmatics. Several writers, including Schloss (3), O'Keefe (4), Spain (5), Eyermann (6), Dale and Thornburg (7), Rowe and Richet (8) have discussed the occurrence of specific food allergy in cases giving negative skin tests to these foods. Conversely it is a common observation that some foods, pollens and other allergens which give clear cut positive scratch or intradermal reactions do not cause allergic symptoms when the patient comes into contact with them through the normal channels.
On the Spontaneous Immunization of Rabbits to Vaccine Virus
Authors: Duran-Reynals F. 
Published: January 2023

Abstract
It has been shown in previous publications (1, 2) that in the testicle, especially, and also to some degree in certain other organs, there exists a factor which is capable of greatly augmenting the lesions produced by viruses and bacteria. In the course of experiments designed to test the possibility of neutralizing this factor by an antitesticular serum, a number of rabbits were given repeated injections of testicle extract subcutaneously, intravenously and intraperitoneally. As a control, others were similarly injected with spleen extract. In the course of testing the effects of the resultant sera on the factor of testicle extract, it was observed that in certain instances not only was the enhancing power of testicle extract neutralized, but the vaccine virus used in the test was inactivated. An examination was made into this unexpected result.
ADAM17-deficient mast cells exhibit decreased IgE-mediated activation due to impaired Lyn phosphorylation.
Authors: Luker Andrea , Conrad Daniel 
Published: January 2023

Abstract
Allergies and asthma are common ailments that are on the rise globally. Mast cells play a direct role in the signs and symptoms commonly displayed by allergic patients. The family of A Disintegrin And Metalloproteinases (ADAMs) are involved in regulating many cellular processes by cleaving surface receptors, ligands, and signaling molecules. We sought to determine the role of ADAM17 in mast cell activity. Using inhibitor-based and genetic knockout studies, loss of ADAM17 reduced mast cell degranulation. This resulted in decreased cytokine and histamine release. ADAM17MC−/− mice exhibited less severe IgE-mediated passive systemic anaphylaxis, while no difference was seen when initiated by exogenous histamine. We previously showed that ADAM17 forms a protein complex with the signaling molecule Lyn. Upon cross-linking, ADAM17−/− mast cells have reduced Lyn phosphorylation which affects downstream signaling events. ADAM17 may play a role in apical FcɛRI signaling through interactions with Lyn.
MicroRNA-146a is a negative regulator of IL-33 stimulated mouse mast cells.
Authors: Taruselli Marcela T. , Qayum Amina Abdul , Ryan John J. 
Published: January 2023

Abstract
Interleukin 33 (IL-33) is an inflammatory cytokine that promotes allergic disease by activating ILC2, Th2 cells, and mast cells. IL-33 is increased in asthmatics, and its blockade suppresses asthma-like inflammation in mouse models. The IL-33 receptor, ST2, shares signaling cascades with the TLR family, but homeostatic control of ST2 function is poorly understood. MicroRNA-146a (miR-146a) is induced by LPS and suppresses TLR4 signaling in macrophages. Therefore, we explored whether miR-146a has a role in IL-33 signaling. IL-33 induced cellular and exosomal miR-146a expression in mouse bone marrow derived mast cells (BMMC). Induction required MyD88, Akt, and NFκB, since antagonizing these pathways decreased miR-146 expression. BMMC transfected with a miR-146a antagomir or derived from miR-146a KO mice showed enhanced cytokine expression in response to IL-33, suggesting that mir46a is a negative regulator of IL-33-ST2 signaling. Our data further suggest that miR-146a may act by targeting IRAK proteins, because mir146a KO BMMC have increased IRAK1 and IRAK4 expression. These results support the hypothesis that miR-146a is a feedback regulator of IL-33-mediated mast cell functions associated with allergic disease.
Characterization of the phenotype of the connective tissue mast cell knockout Mcpt5Cre
+
;Rosa(DTA) mice in the lung
Authors: Cohen Jonathan 
Published: January 2023

Abstract
Mast cells are roughly grouped as resident connective tissue mast cells (CTMCs) and mucosal mast cells which are recruited to mucosal epithelia during inflammation. Although mast cells are known to play critical roles in allergic lung inflammation, little is known about the specific function of pulmonary CTMCs under any condition. To investigate their function, we employed Mcpt5Cre+; Rosa(DTA) transgenic mice to eliminate cells that ever expressed Mcpt5, a classic marker of CTMCs. Unexpectedly, we discovered that the lungs of these mice contained an increased number of mast cells, likely mucosal mast cells. In addition, we found spontaneous inflammation characterized by recruitment of neutrophils and eosinophils, elevated il-33 expression, mucus overproduction and excessive collagen in the airway. Inflammation was detected as early as postnatal day 21 but resolved around 2–3 months of age. In contrast, other tissues that normally have abundant CTMCs, such as the skin and intestine, present no baseline phenotypes in Mcpt5Cre+;Rosa(DTA) mice. These findings suggest a tissue-specific role of CTMCs in maintaining tolerance in the lung, potentially by inhibiting the recruitment of pro-inflammatory mucosal mast cells. Further, in conflict with previous findings that the Mcpt5Cre line specifically targets CTMCs, lineage labeling using Mcpt5Cre+;Rosa(TmRed) mice revealed the presence of TmRed reporter in CTMCs and a small subset of other leukocytes in the lung. While these leukocytes are being mapped, the already identified cell types are unlikely to contribute to the baseline phenotype of Mcpt5Cre+;Rosa(TmRed) mice. Our ongoing studies aim to determine the role of CTMCs in establishing immune tolerance.
Follicular Regulatory T cells Positively Regulate Follicular Helper T Cells, Germinal Center B Cells and IgE Response in Peanut Allergic Mice
Authors: Xie Markus Ming , Liu Hong , Dent Alexander 
Published: January 2023

Abstract
Food allergy remains a major health problem in developed countries such as United States. However, the immunological mechanisms that control peanut allergy are largely unknown. In an oral sensitization food allergy model using peanut protein and cholera toxin (PCT), we found mice (Bcl6FC: FOXP3cre Bcl6 fl/fl) deficient in follicular T regulatory (Tfr) cells had lower follicular helper T (Tfh) cells and germinal center B (GCB) cells after two challenges. The decrease in Tfh/GCB cells was seen in both mesenteric Lymph Node and spleen responses. In this two-challenge model, peanut specific IgE, IgG1 and IgA antibody (Ab) responses were sharply decreased in Bcl6FC mice compared with wild type (WT) ones. However, after eight PCT challenges, Tfh and GCB cells were similar in Bcl6FC mice compared with WT, and peanut specific IgE was elevated in the absence of Tfr cells. We also show that Tfh/GCB cells are required for IgE production in this food allergy model. In mice with Blimp1-deficiency in T regulatory (Treg) cells (Blimp1FC: FOXP3cre Blimp1 fl/fl), Tfr, Tfh and GCB cells were significantly higher compared with WT or Bcl6FC mice while Treg derived IL-10 was much lower. Peanut specific Ab responses trended lower in Blimp1FC mice after two PCT challenges. Our data presented here is the novel evidence showing a positive regulation of Tfh/GCB cells and IgE response by Tfr cells, and suggest that a key regulatory pathway of Tfh/GCB cells and IgE response involves IL-10 production by Tfr cells. Supported by The AAI Careers in Immunology Fellowship Program.
Pam3CSK4 Induces B Cells to Release FasL+ Killer Exosomes That Suppress Allergic Asthma
Authors: Lundy Steven K. , Yang Jennifer , Taitano Sophina , van der Vlugt Lucien 
Published: January 2023

Abstract
We have previously shown that mouse B lymphocytes can express Fas ligand (FasL) on their cell surfaces and can kill peptide antigen-specific T helper cells. In humans, FasL protein produced by human B cells was exclusively found intracellularly on the surface of exosomes. In the current study we determined that mouse B cells are a major source of FasL+ exosomes, as well as contributing significantly to the Granzme B+ exosome pool. The major B cell subsets in the spleen and lungs that produced FasL and Granzyme B were marked by CD9 and/or CD107a expression. We tested a panel of toll-like receptor ligands in combination with anti-IgM and CD40 ligand for their ability to activate killer function in purified mouse B cells. The TLR2 ligand Pam3CSK4 was a potent inducer of surface FasL expression and FasL+ exosome release from B cells. Using a mouse model of OVA-specific allergic airways disease, we showed that transfer of Pam3CSK4-induced B cell-derived exosomes diminished total numbers of eosinophils and CD4+ T cells in the bronchoalveolar lavage fluid (BAL). Lung TH cell apoptosis was higher in the mice that received exosome transfer. Lung cells produced less IL-4 and IL-5 upon restimulation with OVA in the exosome-treated mice. Effects of Pam3CSK4-induced exosomes on BAL cell infiltration, TH cell apoptosis and cytokine production were all diminished when exosomes were derived from mice with a functional mutation of the FasL gene. These data indicate a potential role for B cell-derived killer exosomes in control of allergic airways disease.
Syndecan-1 (CD138) Regulates Competition Between Antibody Secreting Cells for Survival
Authors: Fooksman David R. , McCarron Mark 
Published: January 2023

Abstract
Long-lived antibody secreting cells (LLASCs) are critical immune effector cells constitutively secreting high affinity antibody providing prophylaxis against infections. In contrast to live attenuated viruses which can provide lifelong immunity, protein-based vaccines are known to poorly induce LLASCs, often requiring multiple boosting to generate sufficient antibody titer. The factors that control LLASC production are poorly understood, but are critically important for all humoral-based vaccines. Survival of LLASCs is chiefly mediated by soluble cytokines, such as APRIL in the BM, and IL-6 in secondary lymphoid tissues. After immunization, antibody secreting cells (ASCs) express variable levels of CD138, and its function was unclear, since it can bind 100+ proteins, and CD138−/− mice have no overt phenotype. However, we have discovered a direct role for CD138 for potent antibody responses, by controlling ASC maturation and survival after immunization via cytokine signaling. LLASCs express the highest level of CD138 among all cells, in comparison to newly minted ASCs, which express intermediate levels of CD138. We propose that high expression of CD138 provides LLASCs with higher binding and accumulation of IL-6 and APRIL, which are limiting, leading to a competitive advantage over new ASCs for survival.
Role of Astrocyte Activation in Experimental Cerebral Malaria
Authors: Tunon-Ortiz Arnulfo B.N. , King Thayer P. , Mimche Patrice N. , Lamb Tracey J. 
Published: January 2023

Abstract
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum (Pf) with a high lethality rate. Key features at the cellular and molecular level are endothelial cell (EC) activation, blood-brain barrier (BBB) dysfunction, pro-inflammatory cytokine signaling, and sequestration of infected red blood cells (iRBCs). While research on malaria as a peripheral infection is extensive, there is still much left to investigate in terms of its neuropathological progression. Astrocytes are cells that maintain the stability of the BBB, yet nothing is known about their role in maintaining the BBB during cerebral malaria. In the mouse model of experimental cerebral malaria (ECM), we have used flow cytometry to determine that astrocytes in the cerebellum and frontal cortex of mice infected with Plasmodium berghei ANKA (PbA) are both activated at 6 days PI, a time-point correlated with breakdown of the BBB. Furthermore, EphA2, a receptor tyrosine kinase, is upregulated in malaria and plays a critical role in BBB disruption. We show increases in EphA2 densities on astrocytes in ECM. The implications of these data for BBB disruption in cerebral malaria will be discussed.
Endogenous cannabinoid, anandamide mitigates acute lung injury by altering the microbiome and metabolome profile in the gut-lung axis with the induction of an anti-inflammatory response
Authors: Sultan Muthanna Ali , Nagarkatti Prakash , Ngarkatti Mitzi 
Published: January 2023

Abstract
Staphylococcus Enterotoxin B (SEB) is a superantigen that can activate ~30% of T cells. Inhalation of SEB can lead to toxic shock syndrome and death. We have shown that anandamide (AEA) is effective in ameliorating SEB-induced ALI. Cross-talk between microbiome through the gut-lung axis (GLA) can influence the immune and respiratory functions. In the current study, we found that AEA treatment alleviated SEB-induced ALI in mice by alteration in the microbiome and the metabolome profile especially short-chain fatty acid (SCFA) production in the GLA. Sequencing of the V3–V4 region of 16S rRNA of colon, cecal flushes and lungs was performed and analysis showed that AEA treatment led to a significant increase, starting from the phylum level in Bacteroidetes until genus Aldercreutzia. Mass Spectrometric (MS) analysis revealed that there was a significant increase in the SCFAs in AEA treatment group, especially iso-butyrate, which may be responsible for induction of T regulatory cells (T regs). Flow cytometry data showed that AEA increased CD4+FOXP3+ in the lung compared to vehicle-treated SEB-induced disease group. Our study also showed that AEA treatment significantly decreased the infiltration of inflammatory cells in the lungs. Furthermore, AEA treatment led to a significant decrease in gut and lung leakage, and pro-inflammatory cytokines (IL-2 and TNFα) while increasing anti-inflammatory cytokines (IL-10). Collectively, these data suggest that AEA ameliorates ALI and prevents leakage through modulation of microbiome profile and the metabolome in the GLA while promoting an anti-inflammatory response to include induction of Tregs and decrease in pro-inflammatory cytokines.
Microbiota Regulation of Pro-atherogenic Phagocytes − Separating Metabolic and Inflammatory Mechanisms.
Authors: Eshghjoo Sahar , Ding Yufang , Hunt Carrie , Jayaraman Arul , Alaniz Robert Christopher 
Published: January 2023

Abstract
A significant hallmark of the chronic inflammatory disease, atherosclerosis, is the accumulation of pro-inflammatory M1-like macrophages (macs) and dendritic cells (DCs) in coronary arteries that respond to pro-atherogenic stimuli and fail to digest lipids that contribute to the formation of foam cells in atherosclerotic plaques. Mechanisms that reduce Mac/DC inflammation, increase lipid degradation, and prevent foam cell formation are likely to decrease progression of atherosclerosis. Mechanisms that regulate autophagy in macs and DCs will likely reveal targets for the prevention of atherosclerosis.
Mouse models of high-fat diets demonstrate a link between microbiota composition and the development of obesity, diabetes, and atherosclerosis through several mechanisms best demonstrated by the microbiota-dependent production of TMAO that promotes atherosclerosis.
We have identified a tryptophan-derived microbiota metabolite, indole, that has novel immunomodulatory properties. This strong association between obesity, inflammation, and the microbiota has led us to the hypothesis that microbiota-derived metabolites in the GI tract might regulate dietary saturated fat-induced inflammation. To test this hypothesis, we generated bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs) and tested the effects of indole on these cells in the context of saturated fatty acid-induced inflammation. We investigated pro-inflammatory cytokine production, M1 macrophage development, and metabolic flux. Here, we demonstrate that indole reduces saturated fatty acid-derived inflammation in BMDCs and BMDMs and regulates metabolic programming of phagocytes by inducing autophagy on a level similar to rapamycin.
VCAM-1 might be a potential angiogenic biomarker for Metal-on-Metal prosthetic device and FSH-induced inflammation
Authors: Wood Steven C. , Jamison Joshua 
Published: January 2023

Abstract
Follicle stimulating hormone (FSH) rises in peri-menopausal women and remains elevated during menopause. Bone loss, previously attributed to estrogen, may be due to direct effect of FSH. On this background of decorticated bone, hips are replaced due to fractures or osteoarthritis. Metal-on-metal (MoM) hips replacements were developed as they were thought to be longer lasting and robust implants. However, in women, they are failing at a significantly higher rate when compared to men. Failure modes include pain, device loosening due to osteolysis and exuberant blood vessel formation resulting in pseudotumor formation. Recent work from our lab has demonstrated the molecular interaction of the wear particles from MoM with immune cells and the release of inflammatory and pro-angiographic factors such as IL-1b, TNF-a and IL-8. Therefore we hypothesize that binding of monocytes to the endothelium induced via FSH and MoM wear particles should stimulate angiogenesis that would increase detectable inflammatory biomarkers. Vascular inflammatory markers were investigated with FSH and MoM particle stimulation of endothelial cells and bound monocytes. From these data, soluble VCAM-1 protein levels increased during monocyte-endothelial co-culture induced by FSH and MoM wear particle co-stimulation. FSH stimulation was also associated with increased monocyte binding and endothelial tube thickness. These data indicate that FSH promotes vascular endothelial cell cohesion and monocyte recruitment, which may lead to increased VCAM-1 expression towards combined MoM wear particle and FSH stimulation. Our findings suggest that sVCAM-1 may be a biomarker of pseudotumor formation elicited by MoM wear particles in women with elevated FSH.