bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-1-antichymotrypsin inhibits the NADPH oxidase-enzyme complex in phorbol ester-stimulated neutrophil membranes.
Authors: Kilpatrick L , McCawley L , Nachiappan V , Greer W , Majumdar S , Korchak H M , Douglas S D 
Published: December 2022

Abstract
The generation of superoxide anion and release of granule contents are essential to the bactericidal function of neutrophils, but may also contribute to host tissue damage during inflammation. In previous studies (J. Immunol. 146:2388), we have demonstrated that the acute phase reactant alpha-1-antichymotrypsin (ACT), a potent inhibitor of the serine protease cathepsin G, also suppresses superoxide anion generation. The inhibitory effect of ACT was not directly linked to its antiproteolytic activity and may reflect interaction at a site other than its reactive loop. To further characterize the mechanism of inhibition, we investigated the direct effects of ACT on the NADPH oxidase enzyme complex and the signaling pathways that regulate motivation of the respiratory burst. We present evidence that ACT does not intefer with agonist-stimulated calcium mobilization or translocation and activity of protein kinase C. ACT was an effective inhibitor of superoxide anion generation in membrane preparations isolated from PMA-activated cells. These results support the notion that ACT is acting on a component of the active assembled NADPH oxidase complex. Thus, ACT may have an important role in regulation of specific aspects of the inflammatory processes and the modulation of toxic oxygen-based host tissue damage.
Detection of alveolar macrophage-derived IL-1 beta in asthma. Inhibition with corticosteroids.
Authors: Borish L , Mascali J J , Dishuck J , Beam W R , Martin R J , Rosenwasser L J 
Published: December 2022

Abstract
This study investigated alveolar macrophage function in asthma as assessed by the presence and source of the cytokine IL-1 beta. Bronchoalveolar lavage (BAL) fluid and cell pellets were obtained at 4 a.m. from a cohort of asthmatic subjects. Normal subjects were used as controls. Asthmatic BAL fluid contained 57.0 +/- 5.9 pg/ml of IL-1 beta as determined by ELISA. No IL-1 beta could be identified in the BAL fluid of the control group. This IL-1 represented synthesis by cells of the airway as assessed by the presence of IL-1 beta-specific mRNA transcripts in the BAL cell pellets. Inasmuch as IL-1 beta transcripts are known to be present for only a short time period after activation (approximately 0.5 to 16 h), the presence of transcripts represents recent cellular activation. Using the technique of in situ hybridization, IL-1 beta transcripts were found to be located exclusively within alveolar macrophages, and a mean of 40 +/- 14% of alveolar macrophage were activated at the time of the lavage. Corticosteroids are known to be efficacious in the treatment of asthma. Administration of a single 50-mg dose of prednisone at 3 p.m. resulted in diminished IL-1 beta protein concentration in the BAL fluid (28.3 +/- 5.7 pg/ml; p &lt; 0.01 compared to baseline) and completely abrogated IL-1 beta mRNA expression. In summary, these studies demonstrate that IL-1 beta is synthesized within the airways by alveolar macrophage and suggest that IL-1 beta may be a mediator of asthma. Inhibition of IL-1 beta may be an additional mechanism for the efficacy of corticosteroids in the treatment of asthma.
Development of murine lupus in CD4-depleted NZB/NZW mice. Sustained inhibition of residual CD4+ T cells is required to suppress autoimmunity.
Authors: Connolly K , Roubinian J R , Wofsy D 
Published: December 2022

Abstract
Chronic administration of anti-CD4 mAb prevents autoimmune disease in NZB/NZW F1 (B/W) mice. This may be due either to CD4 cell depletion or to inhibition of CD4 cell function. To evaluate the relative importance of these mechanisms, we devised a system in which the consequences of cell depletion could be analyzed independent of the inhibitory effects of chronic mAb therapy. This was accomplished by performing adult thymectomy before mAb administration. Specifically, female B/W mice underwent thymectomy or sham thymectomy at age 6 wk, followed at age 3 mo by a short course of either anti-CD4 (2 mg/wk for 3 wk) or saline. Treatment with anti-CD4 depleted 90% of circulating CD4 cells, but a small subpopulation (10%) of CD4 cells was refractory to depletion. In non-thymectomized mice, the CD4 population gradually reconstituted after cessation of therapy. In contrast, in thymectomized mice, recovery of CD4 cells was prevented by the absence of the thymus. Despite the striking reduction in CD4 cells in thymectomized mice, severe autoimmune disease developed, with autoantibody levels, proteinuria, and mortality comparable with non-thymectomized, nondepleted controls. The unexpected development of lupus nephritis in thymectomized, CD4-depleted B/W mice suggested that the thymus might be required to achieve the benefits of therapy with anti-CD4. To exclude this possibility, we demonstrated that chronic therapy with anti-CD4 prevents autoimmunity in thymectomized B/W mice. These findings imply that: 1) substantial depletion of CD4 T cells is not sufficient to suppress autoimmunity; 2) suppression of autoimmunity requires sustained functional inhibition of CD4 T cells; and 3) a small subpopulation of CD4 cells that is refractory to depletion by anti-CD4 is sufficient to promote the full expression of murine lupus in B/W mice.
Structure and binding properties of a monoclonal anti-idiotypic autoantibody to anti-DNA with epibody activity.
Authors: Fischel R , Eilat D 
Published: December 2022

Abstract
We report the isolation and characterization of a mouse autoanti-idiotypic mAb (D7.4 IgG2a), which is directed against a major public Id (A52 IgG2b) in the murine and human autoimmune response to DNA. The natural anti-Id mAb has been produced in the course of the SLE-like disease in a female NZB/NZW F1 mouse and showed a dual specificity (epibody activity) for the public Id (A52) and for the autoantigen (DNA). The two binding activities were shown to reside in the Fab portion of the epibody and were highly specific for their respective Ag. A complete nucleotide sequence analysis of the D7.4 H and L chain V-region genes combined with computer comparisons to available Ig sequences may suggest a charge interaction between the H chain CDR3 segments of the Id and anti-Id antibodies. The D7.4 epibody may be a component of the self-binding, idiotypically connected network of natural antibodies. Alternatively, it could be elicited against the potentially pathogenic, DNA-containing immune complexes in order to facilitate their removal from the circulation of diseased individuals.
Novel deletion and a new missense mutation (Glu 217 Lys) at the catalytic site in two adenosine deaminase alleles of a patient with neonatal onset adenosine deaminase- severe combined immunodeficiency.
Authors: Hirschhorn R , Nicknam M N , Eng F , Yang D R , Borkowsky W 
Published: December 2022

Abstract
Mutations at the adenosine deaminase (ADA) locus result in a spectrum of disorders, encompassing a fulminant neonatal onset severe combined immunodeficiency (SCID) and childhood onset immunodeficiency, as well as apparently normal immune function. The extent of accumulation of the toxic metabolite, deoxyATP, correlates directly with severity of disease. We have now determined the mutations on both alleles of a child with fulminant, neonatal onset ADA- SCID and accumulation of extremely high concentrations of deoxyATP. The genotype was consistent with the severely affected phenotype. One allele carried a large deletion that arose by non-homologous recombination and included the first five exons and promoter region. The second allele carried a missense mutation (G649A) resulting in replacement of Glu217, an amino acid involved in the catalytic site, by Lys and predicting a major alteration in charge. Expression of the mutant cDNA in Cos cells confirmed that the mutation abolished enzyme activity. We have previously reported that a missense mutation at the preceding codon is similarly associated with neonatal onset ADA- SCID and accumulation of extremely high deoxyATP. These findings suggest that genotype-phenotype correlations may be apparent for ADA- SCID, despite the role that random variation in exposure to environmental pathogens may play in the initial phenotype. Such genotype-phenotype correlations may be important to consider in evaluating results of ongoing trials of "gene" and enzyme replacement therapy.
Detection of a vigorous HIV-1-specific cytotoxic T lymphocyte response in cerebrospinal fluid from infected persons with AIDS dementia complex.
Authors: Jassoy C , Johnson R P , Navia B A , Worth J , Walker B D 
Published: December 2022

Abstract
AIDS dementia complex is a common neurologic disorder in later stages of HIV-1 infection. Because virus-specific CTL have been shown to contribute to neurologic disease in certain viral illnesses, we examined the cerebrospinal fluid of HIV-1-infected persons with various stages of AIDS dementia complex for the presence of HIV-1-specific CTL. In five of six subjects studied, HIV-1-specific CTL were identified in the cerebrospinal fluid. These CTL were directed at epitopes within the gag, reverse transcriptase, envelope, and nef proteins and restricted by HLA class I Ag. In four of these subjects, virus-specific CTL were detected in higher numbers in the cerebrospinal fluid compared to the peripheral blood, suggesting a specific recruitment to or local induction within the nervous system. These studies demonstrate the presence of a vigorous and broadly directed CTL response to HIV-1 in the central nervous system of infected persons with AIDS dementia complex, and provide immunologic evidence of localized intrathecal infection. Although HIV-1-specific CTL may serve to inhibit viral replication in the central nervous system, the presence of a persistent CTL response in the central nervous system may also contribute to the neurologic disorders characteristic of HIV-1 infection.
Further Studies on the Influence of Heparin on Anaphylactic Shock in the Guinea Pig
Authors: Van de Carr F. Rene , Williams O. B. 
Published: December 2022

Abstract
In an earlier paper (1) we confirmed the observations of Kyes and Strauser (2) with regard to the inhibitory effect of heparin on the anaphylactic syndrome. In our studies guinea pigs hypersensitive to horse serum, instead of pigeons hypersensitive to sheep serum, as used by Kyes and Strauser, were employed. In view of the failure of Hanzlik, Butt and Stockton (3), of Hyde (4), and of Reed and Lamson (5) to support our findings, we present additional data which substantiate our previous findings, using as a criterion of shock the classical symptoms of anaphylaxis. We have checked the reaction by the Dale and by the bronchospasm method of Koessler and Lewis (6). In a limited number of animals we controlled the coagulation time of the blood by means of the capillary tube method prior to the injection of the shocking dose of the antigen and also at the height of shock.
The Effect of Bacteriophage upon the Phenomena of Leukocytosis and Phagocytosis
Authors: Nelson A. R. 
Published: December 2022

Summary and Conclusions
The intravenous injection of anti-staphylococcus bacteriophage exerts a marked influence on the type of leukocytic response elicited by susceptible staphylococci, but has only a slight effect upon the type of response due to resistant organisms. This influence is characterized by the fact that a single injection of the bacteriophage together with susceptible organisms causes a decrease in the degree and time of appearance of the leukocytosis as compared with that due to susceptible organisms alone. Repeated injections of the bacteriophage increase the period of leukopenia and decrease the degree of leukocytosis as compared with that due to susceptible organisms alone. The bacteriophage does not alter the type of response due to resistant organisms in any way comparable to the effect of the bacteriophage on the type of leukocytic response due to susceptible organisms. When leukocytes and organisms are brought into contact with the anti-staphylococcus bacteriophage in vitro, either in the presence or absence of serum, the degree of phagocytosis in the case of susceptible organisms is markedly increased, whereas in the case of resistant staphylococci the degree of phagocytosis is practically unaffected. When anti-staphylococcus bacteriophage is injected intravenously there is an almost immediate increase in the phagocytic power of the leukocytes for susceptible organisms, whereas for resistant organisms the phagocytic power remains practically unaltered. The opsonic power is not altered appreciably in either case.
Anaphylaxis
Authors: Sherwood Noble P. 
Published: December 2022

Abstract
Since the work of Gay and Southard (1) in 1907 a number of papers have appeared describing histological and physiological changes in intact and isolated hearts of the guinea pig, dog, cat, rabbit and frog. Since the completion of this work Gahringer (2) reported on clinical anaphylaxis in pigeons and more recently Hanzlik (3) has reported on the “crop reaction” in pigeons. So far as I know there has been no work reported on sensitization phenomena in the embryonic chick. This would seem desirable because it would afford an opportunity to study sensitization phenomena in an intact living organism before the heart had connections with the central nervous system and before even the anlage of the liver and other organs were in evidence, providing sensitization could be established. It would also permit of the study of such phenomena in an exceedingly simple isolated heart whose functional disturbances as recently pointed out by Lewis (4) are quite comparable to those of the adult mammalian heart.
Further Observations Concerning the Sensitization of Tuberculous Guinea Pigs
Authors: Dienes L. 
Published: December 2022

Abstract
In a former paper (1) we stated that in the study of sensitization of tuberculous guinea pigs we met with the difficulty that the procedure which in the majority of animals gave strong sensitization from August until November 1926, in the following months only rarely gave positive results. With the timothy pollen we were unable to reproduce the strong sensitization which we observed in one guinea pig in November. For awhile we concentrated our efforts on the timothy pollen. After unsuccessful trials with small and large doses injected subcutaneously over long periods we have been led to try to inject the pollen and the tubercle bacillus together, and then to inject the pollen in the tuberculous lesions. One out of three guinea pigs treated in the last mentioned way developed strong sensitiveness.
Studies on the Antigenic Properties of the Ultraviruses
Authors: Schultz E. W. , Bullock L. T. , Lawrence F. 
Published: December 2022

Summary
No evidence of specific complement fixation could be demonstrated when immune sera, produced in rabbits with pure vaccinia brain-virus, were tested against antigens prepared from the lesions of cutaneous vaccinia or against brain-virus antigens. No specific complement fixation occurred when immune sera, produced with cutaneous vaccinia virus, were tested against antigens prepared from brain-virus. Although the latter sera fixed complement in the presence of antigens prepared from cutaneous vaccinia pulp, an almost equivalent degree of complement fixation was observed in the presence of antigens prepared from bacteria cultured from this pulp. Antisera produced against bacteria, harvested from the pulp of cutaneous vaccinia lesions, fixed complement, in the presence of antigens prepared from cutaneous vaccinia lesions. No evidence for the presence of specific precipitins in the two kinds of vaccinia immune sera could be elicited. Precipitates, which did occur in certain cases, were shown to be due to unspecific reactions. Virulicidal antibodies were easily demonstrable in all the immune sera examined for this property.
Susceptibility of Eskimos to the Common Cold and a Study of Their Natural Immunity to Diphtheria, Scarlet Fever and Bacterial Filtrates
Authors: Heinbecker Peter , Irvine-Jones Edith I. M. 
Published: December 2022

Summary
Eskimos are very susceptible to upper respiratory infections on contact with the outside world. Ordinary bacterial infections rarely occur. Diphtheria and scarlet fever are unknown clinically and in a group of about fifty subjects all were negative to the Dick test and all the adults were also Schick negative. Children up to the age of twelve years were invariably Schick positive.
Three serums were found to contain antitoxin both for diphtheria and scarlet fever. It is therefore concluded that the immunity to the disease and the negative skin tests depend on the presence of antitoxin. This is interpreted as being due to a natural hereditary immunity dependent upon some non-specific antitoxic mechanism. Skin reactions with filtrates of streptococci isolated from cases of rheumatic fever were mildly positive in a small percentage of cases. Neutralizing antitoxin was demonstrated in all three sera but it was not invariably present for all three toxins. The Eskimos showed a high percentage of positive reactions when tested with a staphylococcus aureus filtrate.
Studies on the Antigenic Properties of the Ultraviruses
Authors: Schultz E. W. , Hoyt J. 
Published: December 2022

Summary
No evidence of specific complement fixing antibodies against the virus of herpes was found in the serum of rabbits which had been immunized by different routes with virus-brain suspensions. These immune sera also failed to present any evidence of specific precipitating antibodies. Virulicidal antibodies were demonstrable in all of the immune sera tested for this property.
Methods of Obtaining and Preserving Antibodies
Authors: Darányi J. 
Published: December 2022

Abstract
Whereas in the treatment of animals with bacteria or toxin-antigens a certain poisoning results from the first injection, the danger of the treatment with protein-antigens (e.g., blood corpuscles and heterologous sera) lies in the anaphylactic shock, which usually occurs after the second or third injection. It is well known how difficult it is to produce efficient antibodies against protein-antigens on account of the hypersensitiveness. The danger of anaphylaxis increases especially when we endeavor to immunize to a high degree and in this way collect antibodies in the animal blood. The best method of antibody production is the intravenous application of the antigens; however, this form of immunizing causes the greatest number of anaphylactic deaths. Subcutaneous or intraperitoneal injections do not give sufficient stimulation for antibody formation. The acknowledged best antibody producers are rabbits, in the serum of which we can collect hemolysins, agglutinins, precipitins, etc., much better than in the larger animals.
Quantitative Studies on the Action of Compound Hemolysins
Authors: Gahl Rudolf 
Published: December 2022

Summary
A method of plotting hemolytic data was developed and it was shown that curves representing the same percentage of hemolysis are parallel, as long as the concentration of blood cells in the mixture is not changed, and can be made to coincide by a shift of one or both coördinate axes. The shape of the curves is, therefore, independent of the concentration or titer of amboceptor and complement serum. This conclusion was derived under certain assumptions, the principal one being that the components are individual substances and not mixtures of two or three. A comparison of the shape of such “characteristics” should, therefore, permit conclusions as to the purity of the components used for the tests.
Cell Antigens and Individual Specificity
Authors: Landsteiner Karl 
Published: December 2022

Abstract
The general aspects of immunological specificity have been discussed before this society in a masterly manner by authorities like Hektoen and Wells, on former similar occasions. If the following review concerns itself again with related matters, this may be justified by the broadening of the subject of serological specificity which has branched off from medical immunology as a somewhat independent line of research.
The interest in the particular topic of blood antigens has been revived of late by investigations centering round several distinct issues, such as the principles of species specificity, the chemical nature of cell antigens and the human blood groups. Beginning with the blood groups, one of the questions which has arisen is whether the differences of human blood are limited to the four groups or whether there are other variations.
Cytokine synthesis by intestinal intraepithelial lymphocytes. Both gamma/delta T cell receptor-positive and alpha/beta T cell receptor-positive T cells in the G1 phase of cell cycle produce IFN-gamma and IL-5.
Authors: Yamamoto M , Fujihashi K , Beagley K W , McGhee J R , Kiyono H 
Published: December 2022

Abstract
Murine intestinal intraepithelial lymphocytes (IEL) have been shown to contain subsets of alpha/beta TCR+ and gamma/delta TCR+ T cells that spontaneously produce cytokines such as IFN-gamma and IL-5. We have now determined the nature and cell cycle stage of these cytokine-producing T lymphocytes in EIL by using IFN-gamma- and IL-5-specific ELISPOT assay, cytokine-specific mRNA-cDNA dot-blot hybridization and polymerase chain reaction, and flow cytometry (FACS) for DNA analysis. When CD3+ T cells from IEL of normal C3H/HeN mice were separated into low and high density fractions by discontinuous Percoll gradients, IFN-gamma and IL-5 spot-forming cells were only found in the former population. Analysis of mRNA for these cytokines by both IFN-gamma- and IL-5-specific dot-blot hybridization and polymerase chain reaction revealed that higher levels of message for IFN-gamma and IL-5 were also seen in the low density fraction. However, cell cycle analysis of these two fractions by FACS using propidium iodide showed a similar pattern of cell cycle stages in both low and high density populations (G0 + G1 approximately 96 to 98% and S/G2 + M approximately 2 to 4%). Finally, mRNA from gamma/delta TCR+ and alpha/beta TCR+ T cells in both low and high density fractions of IEL were analyzed for IFN-gamma and IL-5 message by polymerase chain reaction. After 35 cycles of amplification, both gamma/delta TCR+ and alpha/beta TCR+ T cells in the low density fraction expressed higher levels of message for these two cytokines when compared with the high density population. These results have now shown that both gamma/delta and alpha/beta TCR+ IEL can be separated into low and high density subsets and both fractions possess a similar stage of cell cycle. However, only the low density cells (in G1 phase) of both gamma/delta and alpha/beta TCR types possess increased cytokine-specific mRNA and produce the cytokines IFN-gamma and IL-5. Our results suggest that alpha/beta TCR+ and gamma/delta TCR+ IEL can produce cytokines without cell proliferation.