bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human mesenchymal stem cells alleviate bleomycin-induced pulmonary fibrosis in humanized mice
Authors: Ni Ke , Liu Ming , Zheng Jian , Wen Liyan , Chen Qingyun , Xiang Zheng , Lam Kowk-Tai , Liu Yinping , Chan Godfrey Chi-Fung , Lau Yu-lung , Tu Wenwei 
Published: January 2023

Abstract
Pulmonary fibrosis is a chronic disease characterized by progressive pulmonary function disruption and activity limitation, of which the pathogenesis and the effective therapy have not been elucidated. Although aberrant immune cell infiltration was found in the lung of patients with pulmonary fibrosis, the contribution of immune dysregulation in pulmonary fibrosis has not been confirmed in human. In order to directly investigate the role human immune response in pulmonary fibrosis in vivo, human periphery blood mononuclear cells (PBMC)-reconstituted humanized mice were used to establish bleomycin-induced pulmonary fibrosis model in this study. In addition, the suppressive efficacy of human bone marrow-derived mesenchymal stem cells (MSC) on pulmonary fibrosis were also evaluated based on this model. Here we found the abnormal activity of the human immune response in the lung prior to pulmonary fibrosis. Human MSC administration at the early stage could significantly modulate pulmonary human immune dysregulation, alleviate pulmonary damage, and improve lung function in humanized mice with pulmonary fibrosis. Furthermore, PD-L1 and indoleamine 2, 3-dioxygenase (IDO) were found to be involved in the immunomodulatory effect of human MSC on pulmonary fibrosis in humanized mice. This study demonstrates the relationship between human immune dysregulation and pulmonary fibrosis in humanized mice. It also suggests the therapeutic efficacy of human MSC for pulmonary fibrosis.
Sialic acid and Galectins mediate Xenogenic Neutrophil-Endothelial Adhesion
Authors: French Beth , Harris Donald , Laird Christopher , Burdorf Lars , Cheng Xiangfei , Feng Chiguang , Cross Alan S , Goldblum Simeon E , Vasta Gerardo R , Pierson Richard N , Azimzadeh Agnes M 
Published: January 2023

Abstract
Sialic acids (Sias) play multifarious roles in immunity, and likely contribute to inflammation seen in xenograft failure. The ‘net’ cellular sialyation state depends on many things including transient loss of Sia moieties with exposure of subterminal galactosyl structures (mediated by sialyltransferases and sialidases [neuraminidases]), which can function as receptors for extracellular lectins, such as galectins. Here, we report the role of Sias in modulating adhesion of human neutrophils (NΦ’s) to pig endothelial cells.
Human (hAECs) and pig (pAECs) aortic endothelial cells were pretreated with Clostridium perfringens neuraminidase (NA, to remove Sias), human tumor necrosis factor (hTNF, 25 ug/ml), or both. CalceinAM-labelled human NΦ’s were treated with rhIL-8, NA, or N-acetyllactosamine (LacNAc, a galectin inhibitor). NΦ adhesion was measured and expressed as percent adhesion.
NA treatment of AECs increased NΦ adhesion to pig (36.3% vs 22.4%) more than to human (24.2% vs 20.7%) AECs. NΦ adhesion was similarly increased by TNF activation of AECs in static and flow conditions. hIL-8 dramatically increased NΦ adhesion to pAECs (76.5%, p&lt;.001) and hAECs (45.3%, p&lt;.001), with the highest adhesion observed with NA-treated pAECs and hIL-8-activated NΦ’s. Pre-exposure of the NΦ’s to LacNAc prevented their galectin-mediated adhesion to galactose moieties exposed on the NA-treated pAECs (13.7%, p&lt;.0001).
In summary, AEC de-sialylation promotes xenogenic NΦ adhesion, an effect completely inhibited by pre-incubation of Nf’s with LacNAc. These results suggest the inhibition of sialidase activity or galectin binding as promising therapeutic approaches to limit inflammation in xenogeneic organ injury.
A Minimum Conditioning Protocol towards Transplantation Tolerance in NOD Mice by Mixed Hematopoietic Chimerism
Authors: Lin Jiaxin , Chan William F. N. , Anderson Colin C. 
Published: January 2023

Abstract
Stable mixed hematopoietic chimerism is a robust method for inducing donor specific tolerance. However, its clinical application is dampened by the toxicity of current recipient conditioning regimens. We previously showed an irradiation-free mixed chimerism protocol in diabetes prone NOD mice is achievable with antibodies to T cells and CD40L together with busulfan and high dose rapamycin. We sought to generate a more clinically feasible chimerism protocol and tested the hypothesis that more efficient recipient T cell depletion would eliminate the need for anti-CD40L (known to cause thromboembolism in humans) and rapamycin.
We preconditioned NOD mice with donor specific transfusion from fully mismatched mice (d −10), cyclophosphamide (CYP) (d −8), antibodies against CD90 and/or CD4 + CD8 (d −6, −1, 4, 9, 14), busulfan (d −1) and donor bone marrow transplant (d 0). Flow cytometry was used to detect chimerism.
Mixed chimerism was induced in 33/45 NOD mice. Stable chimerism with multilineage donor cells was maintained in 21/33 recipients. Loss of chimerism could be predicted by a lower early level of chimerism at d 4, 9 or 14. Inclusion of αCD90 mAb, busulfan and CYP was critical for chimerism induction. With anti-CD90 17/23 mice became stable chimeras. 5/5 chimeric mice accepted skin from bone marrow donors but rejected skin from MHC-matched and minor antigen mismatched donors. The loss of anti-donor Vβ11+ T cells and anti-recipient Vβ17+ T cells in stable chimeric mice indicated the establishment of chimerism involves clonal deletion.

Conclusion
A protocol causing rapid and robust recipient T cell depletion generated chimerism without the need for anti-CD40L or rapamycin in tolerance induction resistant NOD mice.
Upregulation of IL-33 protects against chronic allograft rejection
Authors: Turnquist Heth Roderick , Liu Quan , Mathews Lisa , Dai Helong , Lucas Anna , Zhang Zhongqiang , Lott Jeremy , Matta Benjamin M , Watkins Simon 
Published: January 2023

Abstract

Background
IL-33 is a broadly expressed, but poorly understood IL-1 cytokine. After lung and muscle injury, immunoregulatory and tissue reparative functions of IL-33 have been suggested. Yet, pro-inflammatory IL-33 properties are known. How endogenous IL-33 shapes outcomes after of solid organs transplant is an important, but unanswered question.

Methods
Mouse heterotopic heart transplant (HTx) models of both acute [BALB/c (H2d) to WT or Il33−/− B6 (H2b)] and chronic rejection [Il33+/+ or Il33−/− bm12 (H2bm12) to WT or Il33−/− B6 mice] were utilized. Cytokines were quantitated in transplant and naïve heart tissues by qRT-PCR and Western blot. HTx were evaluated microscopically following staining with H&E, Trichrome or IHC. IL-33+ cell types within the HTx were identified by confocal. Splenocytes were analyzed by flow cytometry. IL-33 quantities were determined in clinical samples from pediatric HTx (n=39) recipients.

Results
Acute and chronic rejection, and surgery increased HTx IL-33 levels in mice. BALB/c IL-33+HTx cells were predominantly CD45− cTnI− vimentin+ with subsets of α-SMA+ Desmin+ or CD31+ cells. Clinical samples displayed increases in IL-33 during acute rejection. IL-33 was protective during both acute and chronic rejection in mice. At 100 days post HTx, Il33−/− Bm12 grafts displayed dramatically increased chronic rejection-associated fibrosis and vessel disease, especially in Il33−/−recipients. A lack of IL-33 was associated with increased HTx immune infiltrates as well as decreased systemic and local Treg levels.

Conclusion
Our data support an unappreciated, yet critical role for upregulated IL-33 in heart allograft protection, particularly during alloimmune responses causing chronic rejection.
Clonal Deletion and Anergy Play Dominant Role To Achieve Immune Tolerance After Reduced Intensity Unrelated Donor Cord Blood Transplantation (UCBT)
Authors: Chen Xiaohua , Hill Memphis , Szabolcs Paul 
Published: January 2023

Abstract
The mechanism of immune tolerance after successful hematopoietic stem cell transplantation is not fully understood. Both central (clonal deletion) and peripheral (anergy, Treg, Tr1) mechanisms are conceivable and may even coexist. In this study, we set up serial experiments to test for the presence and relative contribution of these mechanisms after HLA-mismatched UCBT in the GvH direction.
Nine patients (age 1m to 9y) were transplanted and enrolled on a clinical trial (NCT01852370). Five immunocompetent patients were off immunosuppression therapy (IST) with no GVHD, while 4 had either limited or recently resolved GvHD and were still on IST when studied. Donor T cell chimerism was a median 97%. Purified T cells responses to host APCs were measured by MLR (3HTdR) and CTL reaction (Europium assay), along with cytokine secretion profiling (Bioplex). Host-reactive T cell clones were tracked with TCRVβ repertoire by ImmunoSEQ® (Adaptive Biotech). In tolerant patients, there was no significant MLR or CTL response towards host APC. Similarly, cytokine profiles revealed non-responsiveness while T cells responded vigorously to 3rd party APC by all assays. Recipient-specific T cell clones that were identified from infused UCB stimulated by host APC pre-UCBT became undetectable. There was no indication of Treg or Tr1 cell involvement in sustaining tolerance as deletion by IL-2 immunotoxin or IL-10R blockade was unable to “break” tolerance. However, low dose IL-2 (5U/mL) was able to restore some proliferation (S.I.=19; p=0.05) and IL-13, IFNγ, TNFα secretion, but in lesser degree in comparison to 3rd party responses (S.I.=112). In summary, clonal deletion and anergy contribute to immune tolerance after UCBT with deletion being dominant.
Prevention of acute graft-versus-host disease by anti-human OX40L monoclonal antibody
Authors: Tripathi Trivendra , Yin Wenjie , Kim Renee , Xue Yaming , Zurawski Sandy , Hanabuchi Shino , Liu Yong-Jun , Oh SangKon , Joo HyeMee 
Published: January 2023

Abstract
Graft-versus-host disease (GVHD) is one of the major hurdles for the success of solid organ and bone marrow transplantation. Numerous strategies to control alloreactive donor T cell responses have been used in the clinic with limited success. In this study, we investigated the effectiveness of anti-human OX40L monoclonal antibody (ahOX40L) in the prevention and treatment of acute GVHD (aGVHD) in a human xenogeneic model. NOD/SCID/γc−/−NOD.Cg-PrkdcscidIl2rgtm1Sug/Jic mice were transplanted with human PBMCs. Animals were treated with ahOX40L or control antibody either when human PBMCs were inoculated or at the onset of aGVHD. Clinical manifestations and immune profiles of human lymphocytes were monitored over time. ahOX40L treatment significantly alleviated disease severity and prolonged survival in both preventative and therapeutic models. Serological examination of circulating human PBMCs over the course of aGVHD revealed that ahOX40L treatment controls proliferation of CD45+CD3+ T cells, particularly CD8+ T cell expansion, resulting in an increased CD4+/CD8+ T cell ratio. In addition, ahOX40L treatment greatly reduced the infiltration of OX40-expressing CD3+ T cells in the target organs. In line with this, T cells in mice treated with ahOX40L decreased expression of tissue homing receptors. We further observed that ahOX40L treatment significantly down-regulated IL-21 and TNFα but increased IL-10 expression by T cells. Importantly, ahOX40L treatment was more effective in reducing aGVHD-associated mortality compared with neutralizing IL-21, TNFα or IL-21 plus TNFα. Altogether, our data support the clinical development of ahOX40L for the prevention and treatment of aGVHD.
Correct and Incorrect Methods of Performing the “Daily Titrations” for the Wassermann Reaction and Other Forms of Complement Fixation
Authors: Ottenberg Reuben 
Published: January 2023

Abstract
The strength of guinea pigs complement varies greatly. There are in general two different methods employed by different workers to compensate for this varying potency in determining doses of complement and amboceptor for use in the Wassermann reaction as well as in complement fixation with bacterial antigens. These methods are (1) keeping the dose of complement constant and varying the dose of amboceptor from day to day according to the varying strength of the complement, and (2) keeping the dose of amboceptor constant and varying the dose of complement from day to day according to its varying strength. The fact does not seem to have been recognized that these two procedures represent entirely different things and produce different results.
None of the authors gives any reason for adopting the one or the other procedure.
A Study of Two Hundred and Ninety Post Mortem Wassermann Reactions
Authors: Graves Stuart 
Published: January 2023

Abstract
The diagnostic value of the Wassermann test for syphilis performed on sera from human blood taken post mortem has been the subject of investigation and discussion for the last ten years. Practically all published reports on the work have been made in Germany. The first to carry out this research, Much and Fraenkel (1) and Pick and Proskauer (2), concluded that the Wassermann reaction gave reliable results when done on post mortem blood and that the results confirmed the prevailing comprehension of fibrous meso-arteritis, aneurism of the aorta, etc., as syphilitic lesions. Later investigators, on the contrary, arrived at different conclusions. Beside others, Krefting (3), de Besche (4) and Von Bruck (5) decided against the employment of the Wassermann reaction on post mortem blood because they found a very considerable number of positive reactions in cases where not the slightest probability of the existence of syphilis was apparent.
A Comparative Study of Different Methods of Performing the Wassermann Test for Syphilis
Authors: Smith J. Wheeler , MacNeal Ward J. 
Published: January 2023

Summary
In a group of 110 syphilitic individuals in various stages of the disease, the cholesterin-reinforced antigen with incubation at 37°C. gave 58.2 per cent, the simple antigen at 37°C., 32.2 per cent, and the simple antigen at 8°C., 77.1 per cent of positive tests. In a group of 43 patients, probably syphilitic, the first method yielded 65.9 per cent, the second 36.3 per cent and the third method 75.0 per cent of positive fixations. In a group of 59 patients, probably not syphilitic, the first method yielded 40.0 per cent, the second 1.6 per cent and the third 5.0 per cent of positive tests. In a group of 265 non-syphilitic patients, tests by all methods were negative throughout.
Studies in Anaphylaxis
Authors: Weil Richard 
Published: January 2023

Abstract
It may now be regarded as a well established fact that cellular antibody alone is responsible for the reaction known as acute anaphylactic shock. There are, however, certain other manifestations of anaphylaxis which are with difficulty explained upon that basis, and on this account many conservative workers incline to the belief that under certain circumstances circulating antibody may also play an important part in the production of the symptoms. At first sight it might not appear to be a matter of great consequence whether the interaction between antigen and antibody takes place within the cells, or in the fluids of the body. Such, however, is far from the fact. The humoral theory requires the assumption of an intermediary toxic product, a hypothetical anaphylatoxin, which secondarily affects the cells. The cellular theory does not require such an hypothesis.
Immunochemistry of the Proteins of Horse Dander
Authors: Wodehouse R. P. 
Published: January 2023

Summary and Conclusions
From horse dander there can be dissolved out with weak alkali a large amount of protein matter. Part of this can be precipitated by neutralization with HCl, and if this is treated with 95 per cent alcohol the major portion, the “alkali metaprotein,” remains undissolved, while a very much smaller portion, the “alcohol soluble protein,” is dissolved by the alcohol. Of the protein substance that is not precipitated by neutralization by HCl a portion, the “heat coagulated protein,” can be precipitated by boiling, when the reaction is slightly acid. After this is removed there still remains in the solution another protein, the “hair peptone.”
Pure keratin was also prepared from the hair and from this a peptone, “keratin peptone,” was prepared by hydrolysing with HCl.
When tested by means of the skin reaction the four proteins dissolved out from the dander by dilute alkali showed distinctly different anaphylactogenic properties and they are likewise different from the serum.
Pure keratin is inactive towards horse asthmatics; so, also, is a peptone prepared by acid hydrolysis from it.
From this it is concluded that there are, besides keratin, at least four proteins present in horse dander and that these are not decomposition products of keratin.
Immunologic Studies in Typhus Exanthematicus
Authors: Olitsky Peter K. 
Published: January 2023

Abstract
Before discussing the results of immunologic studies made in typhus exanthematicus, the relationship of the B. typhi-exanthematici to this disease will be briefly stated.
Up to the present time, this organism has been recovered from the blood of patients suffering from typhus fever endemic or epidemic in the various parts of the world—the United States, Serbia, Bulgaria, Russia and Mexico. It has also been recovered from the blood and spleen of animals, guinea-pigs and monkeys, injected with infectious typhus-fever blood. It has been isolated from typhus-infected lice. It has not been recovered from numerous nontyphus patients, nor from tissues of normal animals, nor from “normal” (nontyphus) lice.
In regard to positive blood cultures in human and experimental typhus fever in animals, the organism can be recovered during the entire febrile period of the disease. It is also found in greatest numbers during the early stages of the disease, especially the chill, and more often in severe than in mild cases.
Rôle of Hepatic Tissues in the Acute Anaphylactic Reaction
Authors: Manwaring W. H. , Crowe Harold E. 
Published: January 2023

Summary
The liver of a normal guinea-pig, repeatedly perfused with a mixture of foreign protein and defibrinated normal or anaphylactic blood, produces little or no change in the toxicity of the perfusion mixture on subsequent tests with isolated anaphylactic lungs.
The liver of an anaphylactic guinea-pig, similarly perfused, usually renders the perfusion fluid almost completely non-toxic for these lungs.
This reduction in toxicity is not due to the presence of anaphylactic humoral elements, but to a specific functional action of the fixed hepatic cells.
The reduction in toxicity is not due to a removal or destruction of the foreign protein in the perfusion fluid.
Evidence points to the explosive formation or liberation of vaso-dilator and broncho-dilator substances by the sensitized liver cells.
A New Method for Making Wassermann Antigens from Normal Heart Tissue
Authors: Neymann Clarence A. , Gager Leslie T. 
Published: January 2023

Summary
The antigenic value and anticomplementary and hemolytic properties of the various lipoids of beef heart have been investigated. It was found that lecithin is the only substance of the primary ether extract of dried pulverized beef heart that had any antigenic value, and that the most important substance as regards antigenic value occurs in the secondary alcohol extract and is a diaminomonophosphatide. On this basis of solubilities new methods for making antigens have been described.
Studies on the “Toxins” of Hemolytic Streptococci
Authors: Ando K. 
Published: January 2023

Summary
One can differentiate between toxins of value x and 2x if satisfactory numbers of volunteers are available. The ordinary Dick toxin, though usually very stable, may deteriorate under some unknown condition, while dried toxin may retain its full specific activity for a long period of time. Nucleoprotein in the ordinary toxin may cause some confusion in the results of the Dick test. For the standardization of the Dick toxin it is not enough to determine its skin units; its nucleoprotein content must also be considered, the unsuitableness of a toxin containing blood element being taken for granted. It is recommended to adopt a purified toxin free from nucleoprotein and reduced to the dry condition as a standard toxin. The fact that a qualitative difference between toxins produced by various strains, while it is not marked, nevertheless surely exists, indicates the need of further careful comparison of various toxins as to the potency of their toxicity and especially their antigenic activity before the selection of a toxin as the international standard.
Comparative Study of the Anaphylactic and Tuberculin Types of Hypersensitiveness
Authors: Dienes L. 
Published: January 2023

Summary
Tuberculous guinea pigs sensitized with egg white and also with various other antigens often die after intraperitoneal injection in a protracted shock which is similar in many respects to the tuberculin shock. It is of special significance that a strong hemorrhagic reaction develops around the tuberculous lesion. This hemorrhagic reaction is not the result of the special sensitiveness of the lesion, it might be present in any inflammatory area without regard to the origin of the inflammation.
The eggwhite shock differs in two points from the tuberculin shock. The symptoms often begin to develop early after the injection, and in the early phases of the reaction and in the slight reactions usually a drop of temperature is present. These differences are probably connected with the presence of the usual anaphylactic sensitiveness after treatment with eggwhite. When the latter is associated with the tuberculin sensitiveness, the tuberculin shock often presents the same temperature curve and early onset of symptoms as the eggwhite shock.
The capacity to react with severe protracted shock develops later after the treatment than either the tuberculin type of skin sensitiveness or anaphylaxis. We observed it only in actively sensitized guinea pigs, and our experiments to transfer it passively remained unsuccessful. The different manifestations of the hypersensitive condition develop in a large measure independently from each other. The independence of the severe protracted shock from the anaphylactic shock is shown also by the observation that the desensitization to the acute anaphylactic shock does not interfere with the development of the severe protracted shock.
The severe protracted eggwhite shock and tuberculin shock are probably analogous processes; but without a more thorough understanding of the physiologic mechanism of the reaction this conclusion must be regarded as only provisory.
Diphtheria Toxoid. Preparation and Dosage
Authors: Povitzky Olga R. , Jackson Erla , Eisner Minnie 
Published: January 2023

Abstract
Under the old nomenclature the term “toxoid” meant a slightly toxic diphtheria toxin which was used instead of toxin-antitoxin in some cases for immunization against diphtheria (1). At present Ramon's “Anatoxin” and “Toxoid” are synonymous terms in this country. Under the regulation of the Hygienic Laboratories of the Public Health Service “toxoid” or “anatoxin” should not possess any toxicity.
Detoxification shall be so complete that five human doses given subcutaneously in guinea pigs weighing 300 grams will cause no signs of diphtheria poisoning, including paralysis at any time during a period of thirty days.
The minimum antigenic requirements are put down as follows:
The original toxin from which the toxoid is made shall have an L + dose of not more than 0.20 cc. or an m.l.d. of not more than 0.0025 cc.
At least ten guinea pigs weighing 270 to 320 grams shall receive subcutaneously the initial human dose.