bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-terminal amino acid sequence analyses of the alpha and beta polypeptides from four distinct subsets of sheep major histocompatibility complex class II molecules.
Authors: Puri N K , Walker I D , Brandon M R 
Published: December 2022

Abstract
Four monoclonal antibodies, SBU.II 28-1, 37-68, 38-27, and 42-20, each recognizing a distinct, non-overlapping subset of sheep class II molecules, were used to purify class II molecules from a single sheep. Four class II alpha subunits designated 28-1 alpha, 37-68 alpha, 42-20 alpha, and 38-27 alpha and five class II beta subunits designated 28-1 beta, 37-68 beta 1, 37-68 beta 2, 42-20 beta, and 38-27 beta were compared by N-terminal sequence analyses. Two distinct alpha subunits were identified; the 28-1 alpha, 37-68 alpha, and 42-20 alpha subunits all had identical N-terminal amino acids sequences, which exhibited about 75% homology with HLA-DR alpha and mouse E alpha polypeptides. In contrast, the 38-27 alpha sequence exhibited about 80% sequence homology with HLA-DQ alpha and mouse A alpha polypeptides. In general, sheep beta subunits displayed insufficient sequence homology to enable correlation with human beta-chain sequences; however, the 38-27 beta-chain sequence showed homology with the HLA-DQ beta sequence. The conserved sequence surrounding the site for N-linked glycosylation within human/mouse beta polypeptides (residues 19 to 21) was not present in sheep beta sequences and in contrast with the beta-chains of mouse and man, sheep beta polypeptides contained between 1 and 3 positionally variable cysteine residues (residues 13 to 15 inclusive). Individual sheep beta subunits exhibited extensive sequence heterogeneity and each consisted of a unique population of beta polypeptide species. At least 16 different beta polypeptide sequences were identified from a single sheep and the existence of no fewer than nine non-allelic beta genes was inferred from the sequence data. We have previously provided evidence suggesting that the sheep has multiple major histocompatibility complex class II alpha and beta genes related to those of all three HLA-D subregions. The present results suggest that a number of these genes encode HLA-DQ-like heterodimers and that a sheep DR-like alpha gene product is shared with the products of a large and heterogeneous sheep beta gene family.
Biosynthesis of C8 by hepatocytes. Differential expression and intracellular association of the alpha-gamma- and beta-subunits.
Authors: Ng S C , Sodetz J M 
Published: December 2022

Abstract
The subunit structure of C8 is unusual in that it consists of a disulfide-linked alpha-gamma-dimer and a non-covalently associated beta-chain. To gain insight into the biosynthesis and assembly of C8, we examined its production by short term cultures of rat hepatocytes. Synthesis was detected by functional assays as well as immunologically with antisera against C8, alpha-gamma or beta. Control experiments showed that all three antisera were capable of precipitating C8 from rat serum. When antiserum against C8 was used to analyze hepatocyte cell lysates, precursor as well as mature forms of alpha-gamma and beta were detected. Precursor-product relationships were confirmed by pulse-chase experiments, which also revealed a significantly faster rate of synthesis for alpha-gamma. Importantly, no single chain form of alpha-gamma was detected in the intracellular pool. Evidence that C8 is assembled before secretion was provided by analyzing cell lysates with antiserum specific for alpha-gamma or beta. Precipitation of both subunits with either antiserum confirmed they were associated. Parallel analyses of the extracellular pool revealed that alpha-gamma and beta remain associated in the media but that excess alpha-gamma is secreted as a consequence of a faster synthesis rate. These results provide evidence for differential expression of alpha-gamma and beta and are consistent with the existence of different loci for these subunits. Furthermore, they indicate that association of alpha-gamma with beta is a presecretory event in normal C8 synthesis.
Immunization with Leishmania-specific T cell not B cell lines or hybridomas can modulate the response of susceptible mice infected with viable parasites.
Authors: Gorczynski R M 
Published: December 2022

Abstract
Monoclonal antibodies (mAb), T cell lines, and T or B cell hybridomas were prepared from BALB/c, CBA, or E1 mice infected with Leishmania mexicana. Various mAb were produced which inhibited the growth and motility of parasites in vitro. T cell lines (hybridomas) were screened for their ability to release interleukin 2 on specific antigen exposure. Passive transfer of mAb or T cell lines to infected adult mice caused little perturbation of parasite growth. Recipient naive mice were immunized with purified Ig or irradiated cells from these sources and were subsequently infected with viable parasites. Only preimmunization with T cell lines (hybridomas) led to exacerbation of parasite growth, although enzyme-linked immunosorbent assays could detect the production of anti-idiotype antibodies in mAb (B cell hybridoma)-immunized mice. Either nylon wool-purified T cells or serum Ig from T cell-immunized mice could be used to immunize further naive recipients for protection against parasite growth. These data have implications for the development of anti-idiotype vaccines for Leishmania antigens.
The Optimal Dose of Antigen for the Wassermann Test
Authors: Hooker Sanford Burton , St. Clair Harriet 
Published: December 2022

Discussion and Summary
The representative protocols herewith submitted serve to illustrate several considerations which bear upon methods of choosing the proper antigenic dose. Selection of an arbitrary fraction such as one–fourth of the anticomplementary dose is obviously faulty because of the marked variations in antigenic potency among different extracts, and because with strong antigens this amount would be large enough to inhibit fixation except with strongly positive sera (table 2).
Determination of the antigenic “unit” (with its implication of constancy) and the use of a certain number of units as the dose empirically found to be optimal is a practical method leading to fairly accurate results but is faulty in principle because the positive serum used is a variable, and upon its potency depends the size of the antigenic unit. The attempt to control serum variability by using a large pool of strongly positive specimens is only a fairly practical device, which does not overcome the objection to “standardizing” one unknown by means of another. Kolmer favors 10 antigenic units while Kahn and Johnson's tables show the optimum to be 1.5 to 2 units. In table 1, above, it may readily be seen that if a serum pool had the strength represented by the 0.05 ml. amount the optimal antigenic does would contain about 2 units, whereas were it twice as strong the same optimal dose would contain at least 10 units.
Our experience indicates that the optimal dose is that quantity which gives strongest fixation with minimal amounts of reagin, that it can be closely approximated by means of appropriate titrations with any positive serum, and that it is uniform in its reactivity with serum from any stage of syphilis. In accordance with a general immunologic principle a constant may thus be determined by which serum units can more definitely be measured, thereby permitting, when desired, the establishment of a more significant and reproducible “unit” of antigen. For practical routine tests, however, with the potent types of antigen now in common use, such circuitous measurements of the antigenic unit seem unessential.
Experimental Immunization in Poliomyelitis
Authors: Aycock W. Lloyd , Kagan J. R. 
Published: December 2022

Summary
Infection results from subcutaneous injection of attenuated virus in about 25 per cent of animals. About 25 per cent of animals vaccinated with attenuated virus resisted subsequent intracerebral inoculation.
Infection results from subcutaneous injection of active virus in about 25 per cent of animals. Thus, it appears that virus subjected to “attenuation” (phenolization; glycerolization or drying) possesses little, if any, less infectivity than active virus when injected subcutaneously.
A large number of intracutaneous injections of active virus does not produce infection.
Intracutaneous injection of active virus repeated for a considerable time protects monkeys from intracerebral inoculation or prolongs the incubation period.
Of twelve monkeys receiving repeated intracutaneous injections of active virus, only one developed paralysis. Of the surviving animals, two resisted three intracerebral inoculations, two intracerebral inoculations, and two resisted one intracerebral inoculation but succumbed to a second inoculation, one of these with a prolonged incubation period, and three animals resisted a single intracerebral inoculation, but were not retested. One animal did not resist intracerebral inoculation but the incubation period was prolonged. Four of the resistant animals also received from one to five subcutaneous inoculations of active virus from which no symptoms resulted.
Blood serum of monkeys vaccinated by the intracutaneous method neutralizes the virus of poliomyelitis in vitro.
Blood sera from eight of the vaccinated animals neutralized virus in vitro 21 times, while in two other instances the virus was partially neutralized as evidenced by prolongation of the incubation period. Blood sera which only partially neutralized had on previous occasions completely neutralized the virus, in one case four times. The blood serum of one animal which did not resist intracerebral inoculation completely neutralized virus.
In respect to the epidemiology of poliomyelitis, these observations lend support to the idea that immunity may be accomplished without active symptoms, and that the neutralization of virus by serum of “normal” individuals is an indication of acquired immunity to the virus and is not a property of normal serum.
The Bacteriophage: A Method of Isolation
Authors: De Groat Albert F. 
Published: December 2022

Abstract
Efforts to determine the intimate nature of the bacteriophage have been complicated by the problem of freeing it from substances, known and unknown, which are necessarily present in the filtrates. Being in a colloidal state, or at least being closely associated with the proteins of the culture medium or of the products of bacterial lysis, the bacteriophage is most certainly influenced in its reactions by these accompanying colloids and objection may be made to the results of any studies which fail to take this source of error into account.
Two methods have been developed to purify the bacteriophage, removal of the proteins of the filtrate by passing it through membranes of gradually decreasing permeability (1), and fractional precipitation by certain general precipitating agents (2). By either of these methods bacteriophage solutions are obtained which are of sufficient purity for therapeutic purposes as they do not cause allergic reactions.
A Study of the Reaction in Sensitized Smooth Muscle to Mixture of Antigen and Sensitized Tissue
Authors: Ramsdell Susan Griffith 
Published: December 2022

Abstract
In a study of the nature of the stimulus to smooth muscle, using the isolated uterus of the sensitized guinea pig, Alexander, Becke and Holmes (1) used mixtures of various tissues of sensitized animals and the homologous antigen as the stimulating substance. They found that when mixtures of lung or liver or uterine tissue from an egg-white sensitized guinea pig were ground with egg-white and added to a Dale bath, the reaction was more prolonged than that in the control bath to which egg-white only had been added.
This result suggests certain conclusions: (1) That there is a reaction between the cell-contents set free by the grinding and the antigen, the product of which acts as a secondary stimulating substance to the muscle.
The Rapid Production of Immunity to Ricin
Authors: Isaacs M. L. , Grant Agnes H. 
Published: December 2022

Summary and Conclusions
Our results indicate, therefore, that guinea pigs receiving a fatal intraperitoneal injection of ricin may be saved if, at the same time, they receive one to three subcutaneous injections of a weaker ricin solution. The animals which survive develop ulcers at one or more of the sites of subcutaneous inoculation. These ulcers appear at the end of four to six days and disappear within another seven.
Some Experiments on the Antigenic Properties, Filterability, and Microscopy of Vaccine Virus
Authors: Hunt L. W. , Falk I. S. 
Published: December 2022

Summary
Rabbits were rendered immune to subsequent vaccination by scarification when they had been given three injections of vaccine virus inactivated by any of the following methods: Heated at 60°C. for one hour. Treated with 0.1 per cent formaldehyde for twelve hours. Treated with immune serum for twelve hours, and then heated for one hour at 60°C. Heated at 60°C. for one hour, the solution centrifugated and the supernatant liquid used for injection. Intravenous, intradermal, intraperitoneal and subcutaneous injections were equally effective. Rabbits were passively immunized by the intravenous injection of serum from an animal immunized by the intravenous injection of living virus, and by the intravenous injection of serum from an animal immunized by scarification. Successful passive immunization appears to depend upon the amount of serum injected. This immunization does not appear to be due to the presence of living virus in the immune serum. The “immediate reaction” was shown by these animals as further evidence that immunity to vaccinia had been established. Normal rabbits as well as immune rabbits can tolerate the intraperitoneal injection of large doses of potent vaccine virus. No evidence was obtained that the virus existed in the filtrates from a Berkefeld (N) filter or a plaster of Paris filter. The vaccine virus was not made visible by treatment with various concentrations of acids, bases and salts or by immune serum.
Characterization of L-glutamic acid60-L-alanine30-L-tyrosine10-specific suppressor T cells in responder mice restricted by Igh-C-linked genes.
Authors: Lake J P , Kapp J A , Pierce C W 
Published: December 2022

Abstract
A Ts cell subset has been identified in the spleens of responder mice 3 to 6 wk after immunization with an optimally immunogenic dose of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). These Ts were positively selected by panning procedures by using a mAb (1248 A4.10) produced by immunization of rats with semipurified mouse GAT-specific, single polypeptide chain suppressor factor. These Ts cells inhibited the activity of virgin Th cells but not memory Th cells and this activity was genetically restricted by genes which are linked to the Ig H chain (Igh) locus on chromosome 12. Use of the Igh recombination strain, BAB.14, which has a crossover near the VHCH region junction, demonstrated that the genes regulating the Igh restriction map telomeric to the VH genes. The Igh-linked restriction regulated the interaction of A4.10+ Ts cells with virgin T cells and not B cells. However, A4.10+ Ts did not act directly on Lyt-2-Th cells, but required the presence of Lyt-2+ cells for suppression. Suppression by GAT-primed A4.10+-Ts cells also required syngenicity at Igh-linked genes by both Lyt-2- and Lyt-2+ T cells. These results indicated that A4.10+-Ts cells were inducer Ts cells which activated Lyt-2+ effector Ts cells which prevented primary GAT specific Th cell activity. The interaction between A4.10+-Ts inducer and effector Ts cells and/or the interaction of the effector Ts and its target cell were restricted by genes linked to the Igh constant region.
Time dependence of B cell processing and presentation of peptide and native protein antigens.
Authors: Lakey E K , Casten L A , Niebling W L , Margoliash E , Pierce S K 
Published: December 2022

Abstract
Th cell recognition of globular proteins requires the uptake and intracellular processing of the native Ag by an APC to produce a peptide fragment containing the T cell antigenic determinant, which is recognized in conjunction with Ia. This report describes the time course of the processing and presentation of a soluble globular protein Ag, pigeon cytochrome c (Pc), and of the presentation of a C-terminal peptide fragment of Pc, residues 81 to 104 (Pc 81-104), which does not require processing. Splenic B cells, acting as APC, require 6 to 8 h incubation with native Pc to process and present it to an I-Ek-restricted Pc-specific T cell hybrid, resulting in the secretion of IL-2. Moreover, the time required for B cells to process Pc is the same whether the Ag is taken up by nonspecific fluid phase pinocytosis or by binding to surface Ig. Once processed, Ag is lost from the B cell surface by 8 to 12 h, although when provided with fresh Pc, the same B cells are still capable of processing and presenting. In contrast to native Pc, only 1 to 2 h are required for the peptide fragment Pc 81-104 to become associated with B cells in a stimulatory fashion, and this time is similar for live and paraformaldehyde-fixed B cells, which cannot internalize or process the peptide. Washed free of excess peptide after 2 h, B cells lose their ability to stimulate T cells by 8 to 12 h, with a time course indistinguishable from that for the loss of processed native Pc. Prolonged incubation of B cells with the peptide for 18 to 24 h results in a dramatic loss of the ability to present Pc 81-104. Even when provided with fresh Pc or Pc 81-104, these cells have diminished ability to present these Ag. This loss is selective, inasmuch as these B cells remain equivalent to untreated B cells in the presentation of an unrelated Ag, OVA, to an I-Ak-restricted specific T cell. However, the ability to present another I-Ek-restricted antigenic peptide of the D glycoprotein of HSV to its specific T cell is also diminished. Loss of activity is observed after incubation only with the peptide and not with the native protein and is not due to a depletion of the antigenic peptide from the incubation medium.(ABSTRACT TRUNCATED AT 400 WORDS)
Functional abolition of monocyte HLA-DR by aldehyde treatment. A novel approach to studies of class II restriction elements in antigen presentation.
Authors: Rhodes J , Tite J 
Published: December 2022

Abstract
The effect of low concentration aldehyde treatment (0.0012 to 0.005%) on the expression of HLA-DR Ag by human monocytes was investigated. This treatment was shown to selectively abolish the expression of HLA-DR determinants defined by a monomorphic mAb (YE2.36) in a rosette assay. The expression of class I MHC Ag and Fc gamma R remained unaffected. As a result, the presentation of the recall Ag tetanus toxoid and streptokinase-streptodornase (SK-SD) to freshly isolated autologous T cells and T cell clones was completely inhibited. Increasing the concentration of aldehyde to 0.05% consistently produced partial restoration of Ag-presenting capacity. Low dose aldehyde treatment did not affect monocyte viability or membrane turnover. Thus, aldehyde-treated monocytes produced a second generation of HLA-DR and expression was almost completely restored to normal after 24 h of culture. The presentation of monocyte class II Ag as alloantigens was also inhibited by low dose aldehyde treatment but inhibition was much less marked when monocytes were aldehyde treated at 2 h rather than at 24 h of culture. This is consistent with the reexpression of HLA-DR which occurred readily in the first 24 h of culture and much less readily thereafter. Low dose aldehyde treatment did not affect Ag uptake and processing. However, monocytes which had been pulsed with Ag, aldehyde-treated to abolish HLA-DR, and then cultured to allow regeneration of HLA-DR could present Ag only when given a second Ag pulse, suggesting that once the association between microbial Ag and HLA-DR had formed the Ag was not then free to reassociate with novel HLA-DR. Low dose aldehyde treatment did not affect monocyte IL-1 production, neither did it inhibit the detection of HLA-DR by soluble mAb in FACS analysis. These results are consistent with the view that low dose aldehyde treatment disrupts the tertiary structure of human Ia molecules such that allostimulatory determinants and restriction elements for exogenous Ag are rendered inaccessible to T lymphocyte receptors and to cell-bound anti-DR mAb in the rosette assay, although DR determinants may remain accessible to soluble mAb.
Regulation of tumor necrosis factor/cachectin and IL-1 secretion in human mononuclear phagocytes.
Authors: Burchett S K , Weaver W M , Westall J A , Larsen A , Kronheim S , Wilson C B 
Published: December 2022

Abstract
To determine whether the production and secretion of TNF and IL-1 by human mononuclear phagocytes could be independently modulated, we examined secretion of TNF and IL-1 by fresh monocytes and monocytes pretreated with IFN-gamma or granulocyte macrophage CSF before LPS stimulation. TNF and IL-1 secretion were in part differentially modulated. Fresh monocytes secreted large amounts of TNF and IL-1 after LPS stimulation and less than 6% as much without LPS. The capacity to secrete TNF in response to LPS decreased slightly in cultured monocytes but was markedly augmented by IFN-gamma (approximately five-fold more than fresh monocytes). In contrast, cultured monocytes secreted less than 5% as much IL-1 as fresh monocytes and, although augmented by IFN-gamma, IL-1 secretion remained much less than by fresh monocytes. These differences in modulation were reflected by differences in the molecular mechanisms regulating TNF and IL-1 secretion. TNF secretion was regulated primarily by changes in the duration of increased transcription and by an apparent increase in translation or protein stability in response to LPS; greater than 95% TNF produced was secreted under all conditions. In contrast, the changes in IL-1 secretion reflected primarily post-transcriptional regulation of IL1-alpha mRNA, transcriptional and post-transcriptional regulation of IL-1 beta mRNA and a decrease in the fraction of IL-1 secreted by cultured compared with fresh monocytes (10 and 60%, respectively). Changes in translational efficiency or protein processing or stability appeared not to be important mechanisms regulating IL-1 secretion. Additional evidence that TNF and IL-1 can be differentially modulated was the selective decrease in TNF secretion and the failure of IFN-gamma to enhance TNF secretion by cultured monocytes from neonates, whereas results for IL-1 were similar with adult and neonatal monocytes. Results with tissue macrophages were similar to those with cultured monocytes. These results indicate that TNF and IL-1 production and secretion by mononuclear phagocytes can be differentially modulated, reflecting in part different mechanisms of regulation; this may allow them to play partially independent roles in the host immune response.