bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE INTERACTION IN VITRO OF MYCOPLASMA PULMONIS WITH MOUSE PERITONEAL MACROPHAGES AND L-CELLS
Authors: Jones Thomas C. , Hirsch James G. 
Published: June 2004

Methods have been devised for establishing infection in vitro of mouse macrophages and fibroblasts with Mycoplasma pulmonis. The mycoplasmas attached to the cells and under appropriate cultural conditions grew into a lawn of microorganisms covering most of the cell surface. The mycoplasmas grew abundantly on fibroblasts cultured in minimal essential medium containing 20% fetal calf serum; supplementation of this medium with heart infusion broth was necessary to obtain similar growth on macrophages. The infection of these cells appeared to be essentially an extracellular process; only rarely were partially degraded mycoplasmas seen with phagocytic vacuoles.
The addition to heavily infected macrophage cultures of low concentrations of anti-mycoplasma antibody stimulated rapid, massive phagocytosis of the surface microorganisms. In sharp contrast, the same antiserum had no discernable effect on the mycoplasma-fibroblast relationship. The antibody effect in the macrophage system was apparently a direct opsonic one rather than an indirect result of microbial killing, since the mycoplasmas in macrophage or fibroblast cultures incorporated labelled thymidine into DNA after the addition of antiserum to the medium.
The phagocytic event and the subsequent fate of the mycoplasmas were studied in detail after the addition of antibody to the macrophage cultures. Phase-contrast cinemicrophotography revealed membrane ruffles surrounding the surface mycoplasmas and disappearance from view of the organisms; 10–30 min later translucent grapelike clusters were seen in large phagocytic vacuoles. On electronmicroscopic study the surface mycoplasmas were surrounded by pincers-like projections of the macrophage. Numerous mycoplasmas were seen in phagocytic vacuoles; in the early minutes after the addition of antibody the intracellular mycoplasmas appeared normal, but within 2 hr they appeared partially degraded with a central electron-lucent area and electron-opaque deposits at the microbial cell margin. 24 hr after the addition of antiserum, digestion of the mycoplasmas was nearly complete; the cells appeared normal except for large residual bodies composed of amorphous moderately dense material and increased lipid deposits.
Degradation of mycoplasmas within macrophages was also studied using infected cultures in which the mycoplasmas, but not the macrophages, had incorporated tritiated thymidine into DNA. The appearance of large amounts of acid-soluble radiolabel after phagocytosis stimulated by antibody confirmed the degradation of the intracellular mycoplasmas.
ANGIOTENSIN AND RENIN IN RAT AND DOG BRAIN
Authors: Fischer-Ferraro Catalina , Nahmod Victor E. , Goldstein Daniel J. , Finkielman Samuel 
Published: June 2004

An enzyme with the characteristics of classical renin was isolated from brain extracts of nephrectomized dogs. This enzyme is thermolabile, nondialyzable, and forms a vasoconstrictive material when incubated with renin plasma substrate at pH 7.
A short lasting pressor activity was also found in brain extracts of dogs and rats. This activity was due to a substance identified by chemical and pharmacological tests as angiotensin. Countercurrent distribution of brain extracts of rats showed that 38% of the pressor activity corresponded to angiotensin II and the remainder to angiotensin I. A remarkable correlation was found between angiotensin and norepinphrine concentrations in different portions of the encephalon of the dog.
HUMAN SARCOMAS IN CULTURE
Authors: Giraldo Gaetano , Beth Elke , Hirshaut Yashar , Aoki Tadao , Old Lloyd J. , Boyse Edward A. , Chopra Harish C. 
Published: June 2004

In a study of human sarcomas maintained in culture for periods up to two years, the following observations were made.
The most prominent cell type in serially cultured osteosarcomas was fibroblastic in appearance. After 16–20 wk in culture some lines spontaneously developed foci of altered cells resembling the foci produced in monolayer cultures by oncogenic viruses. The presence of these foci in the sarcoma cultures was transient, and usually they did not reappear; but in one instance they recurred with a characteristic periodicity of several weeks. From one of the sarcoma lines, in which foci appeared after 5 months in culture, two subcultures were established from stored frozen cells and these both exhibited foci after approximately the same lapse of time. The same phenomenon has been seen with another line, suggesting that the time of appearance of foci is characteristic for particular sarcomas. Foci of similar type could sometimes be induced in monolayer cultures of human fibroblasts by filtered medium from cultured sarcomas; this bore no relation to the presence or absence of foci in the sarcoma cultures at the time the filtrate was prepared. Electron microscopy of the spontaneous and induced foci, and of the sarcoma cultures, revealed no demonstrable virus.
12 out of 15 sarcoma cultures contained an antigen (S) demonstrable by indirect immunofluorescence with human sera. It was not present in any of the original sarcoma specimens, nor in any culture lines other than sarcomas. At least 3–4 wk in culture appear to be required for its demonstration. The antigen was cytoplasmic, occurred in only a small proportion of the cells, and was unpredictably variable in its expression, even in the same culture line. It could be induced in monolayer cultures of human fibroblasts by filtrates of medium from sarcoma cultures. As with the foci, the induction of S antigen in indicator cultures was not dependent upon the expression of antigen in the sarcoma line from which the filtrates were obtained. There was no association between the presence of foci and of antigen, nor was there any apparent relation between the ability of filtrates to induce foci and their ability to induce antigen. 80% or more of the general population have S antibody, and the titer of antibody in patients with sarcoma is no higher than in normal subjects. Thus, as in the case of Burkitt's lymphoma antigen, it appears that most individuals have been exposed to S antigen. But unlike Burkitt's lymphoma, no relation has so far been established between any particular disease and a corresponding high titer or frequency of occurrence of S antibody.
The occurrence of foci of altered cells and of a common antigen, and the transmission of these two characters to indicator cells by filtrates, are all suggestive of a virus specifically associated with human sarcomas, one to which the general population is widely exposed, as indicated by the prevalence of antibody.
THE SENSITIZATION OF RATS BY ALLOGRAFTS TRANSPLANTED TO ALYMPHATIC PEDICLES OF SKIN
Authors: Tilney N. L. , Gowans J. L. 
Published: June 2004

Pedicles of skin which lacked a lymphatic drainage were raised on the backs of rats in order to study the importance of afferent lymphatics in sensitization by skin allografts. Although allografts transplanted to the alymphatic pedicles enjoyed a prolonged survival, they contracted progressively from about 3 wk after transplantation and were reduced eventually to small scars. In contrast, autografts survived unchanged in size for the life-span of the pedicles which carried them. The slow contracture of the allografts was associated with sensitization of the host because test allografts applied orthotopically were destroyed with a second-set tempo. No regeneration of lymphatics from the long-standing pedicles could be demonstrated, and it was concluded that sensitization had occurred eventually through the blood, presumably by the process of peripheral sensitization.
Allografts on skin pedicles could be destroyed rapidly by active or adoptive immunization, so it is probable that the level of sensitization to which they themselves gave rise was a low one. Although it is not disputed that afferent lymphatics are essential for the rapid destruction of skin allografts, it is clear that the absence of a lymphatic supply does not permanently exempt them from immunological attack in the rat.
RECEPTORS ON IMMUNOCOMPETENT CELLS
Authors: Davie Joseph M. , Paul William E. 
Published: June 2004

Nonimmunized guinea pigs possess rare lymphocytes which bind sufficient 2,4-dinitrophenyl-guinea pig albumin-125I (DNP-GPA) to their surface to be detected by short-term radioautography. The cells occur in the lymph nodes, spleen, peripheral blood, and bone marrow with a frequency of ∼40/100,000 lymphocytes, but are absent from the thymus. The receptors of these cells are largely specific for the haptenic group (ϵ-DNP-L-lysine) as shown by inhibition of DNP-GPA-125I binding with ϵ-DNP-L-lysine and with DNP bovine serum albumin (DNP-BSA). Furthermore, these cells specifically adsorb to agarose beads to which either DNP-GPA, DNP-BSA, or DNP-keyhole limpet hemocyanin (KLH) has been covalently linked. This hapten specific depletion of DNP-GPA-125I antigen-binding cells (ABC) correlates with a similar diminution in the capacity of adsorbed populations to transfer primary responsiveness to DNP-KLH to irradiated syngeneic recipients.
Fluoresceinated anti-immunoglobulin binds to the surface of some guinea pig lymphocytes, and all DNP-GPA-125I ABC, as shown by a double-label technique. The great majority of DNP-GPA ABC and human γ-globulin ABC possess surface Ig molecules of the γ2 heavy chain class. Preincubation of cell suspensions with anti-γ2 antibody markedly diminishes the number of DNP-GPA-125I ABC which are detected, strongly suggesting that the receptors of these cells are immunoglobulin molecules, most of which possess γ2 heavy chains.
The specificity characteristics of DNP-GPA-125I ABC are strikingly different from those of cells mediating a cellular immune response to DNP-GPA, indicating major differences in the specificity and nature of the receptors of these cell types.
THE INHERITANCE OF INDIVIDUAL ANTIGENIC SPECIFICITIES OF RABBIT ANTIBODIES TO STREPTOCOCCAL CARBOHYDRATES
Authors: Eichmann Klaus , Kindt Thomas J. 
Published: June 2004

The inheritance of individual antigenic specificities (IAS) of rabbit antibodies to the Group C streptococcal carbohydrate was demonstrated in a selectively bred rabbit family. The IAS of the antibodies from 3 proband rabbits were also observed in the Group C antibodies in as many as 7 out of 42 related rabbits, but in none of the Group C antibodies from 48 unrelated rabbits, Immunodiffusion analyses and quantitative radioprecipitin experiments revealed that this cross-specificity may be either partial or complete.
Quantitative inhibition of the precipitin reaction between the proband antibody and its antiserum by preimmune IgG revealed 30-fold differences in the proportion of molecules with cross-specificity for the proband antibody. This proportion is higher in the preimmune IgG of the proband rabbit and of those relatives which produced cross-precipitating antibodies than it is in the IgG of rabbits which had the same group a allotype, but did not produce cross-precipitating antibodies. The proportion is much lower in the IgG of rabbits with a group a allotype different from that of the proband antibody. These data suggest that serologically detected individual antigenic specificities are inherited markers of immunoglobulins.
REGULATION OF THE IMMUNE RESPONSE
Authors: Kappler John W. , Hoffmann Michael , Dutton Richard W. 
Published: June 2004

The effect of passively transfered antiserum against sheep erythrocytes (SRBC) on the antigen stimulated increase of SRBC-specific plaque-forming cells (anti-SRBC-PFC) and SRBC-specific thymus-derived lymphocytes (SRBC-specific T-cells) in the mouse spleen was examined. A dose of antiserum which severely suppressed the development of anti-SRBC-PFC did not prevent the increase in SRBC-specific T-cells, as measured by their ability to cooperate in the in vitro response to trinitrophenylated (TNP) SRBC. It was shown that the insensitivity of these T-cells to antiserum could not be explained by their low antigen requirement as compared to that of PFC.
In the in vivo response of mice to TNP-SRBC, antibody specific for TNP suppressed the appearance of both anti-TNP- and anti-SRBC-PFC. The presence of free SRBC specifically prevented the suppression of the anti-SRBC-PFC. These observations are consistent with opsonization by phagocytic cells as the primary means of the observed suppression of PFC development by antibody.
MACROPHAGE-MELANOMA CELL HETEROKARYONS
Authors: Gordon Saimon , Cohn Zanvil 
Published: June 2004

Dormant macrophage nuclei initiate DNA synthesis 2–3 hr after fusion of macrophages with exponentially growing melanoma cells. Cycloheximide treatment (1–5 µg/ml) of heterokaryons during the preceding lag period inhibits the initiation of macrophage DNA synthesis, in a reversible fashion. Each type of cell was also treated with streptovitacin A, an irreversible inhibitor of protein synthesis. Pretreatment of the melanoma cells (0.5–2 µg/ml), 1 hr before fusion, inhibited the induction of macrophage DNA synthesis in heterokaryons, whereas pretreatment of macrophages (1–20 µg/ml) had no effect. Melanoma cell pretreatment reduced the incorporation of leucine-3H into the cytoplasm and nuclei of heterokaryons, whereas macrophage pretreatment had no effect. These experiments suggested that melanoma proteins played an important role in the initiation of macrophage DNA synthesis.
The relationship between the melanoma cell cycle and macrophage DNA synthesis was studied with synchronous melanoma cells. If the melanoma cells were in S phase at the time of fusion, macrophage DNA synthesis occurred 2 hr later. However, the fusion of melanoma cells in G1 delayed macrophage DNA synthesis until the melanoma nuclei had entered S. Experiments with actinomycin and cycloheximide showed that RNA and protein, essential to achieve DNA synthesis in the macrophage nucleus, were made during late G1 as well as S.
Melanoma cells and macrophages differ in their radiolabeled acid-soluble products after incubation in thymidine-3H. Thymidine taken up by the macrophage remained unphosphorylated, whereas it was recovered mainly as thymidine triphosphate from melanoma cells.
These findings, as well as those reported previously, suggest that the melanoma cell provides the RNA, protein, and precursors which initiate macrophage DNA synthesis. In the absence of a requirement for new macrophage RNA and protein synthesis, other changes must be responsible for the 2 hr delay in DNA synthesis. These may involve physical changes in DNA, associated with swelling, as well as the transport of melanoma products into the macrophage nucleus.
HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS
Authors: Dausset Jean , Rapaport Felix T. , Cannon Frances D. , Ferrebee Joseph W. 
Published: June 2004

The segregation of the canine DL-A leukocyte group antigen(s) b, c, d, e, f, g, h, k, l, and m has been traced in 141 consecutive matings in the Cooperstown Colony of beagles. All of the leukocyte antigen(s) were regularly transmitted en bloc from parent to offspring, with no instance of independent segregation. A total of 23 haplotypes, including six different DL-A antigen patterns (gl, bkhfm, bkcd, e, be, fgl) was observed. 31 different DL-A phenotypes were observed in a population of 100 mongrel dogs. A number of statistically significant positive and negative associations between individual DL-A antigenic components occurred in this population. The results support the concept of the DL-A system as a complex immunogenetic system governed by a single region (or locus) of an autosomal pair of chromosomes.
Studies of skin, kidney, heart, and liver allografts in the Cooperstown Colony indicated that the longest allograft survivals occur under genetically and serologically defined conditions of donor-recipient DL-A compatibility. Skin and renal allografts generally behaved in parallel fashion, while cardiac allografts survived for longer periods of time (MST = 47.1 days) than kidneys (MST = 28.1 days) or skin (MST = 25.1 days) under conditions of DL-A identity. Heart transplants were rejected at a more rapid rate than kidney, however, in DL-A-incompatible donor-recipient combinations. Liver transplants were accorded the longest survival time (MST = 76.2 days) under conditions of DL-A identity, but were rejected at a rapid rate (MST = 5 days) in DL-A-incompatible nonlittermate donor-recipient pairs.
The results provide further evidence that the DL-A system is the principal system of histocompatibility in the canine species. The differences in survival of different organs under similar conditions of donor-recipient DL-A compatibility suggest, however, the existence of a number of unknown variables which may also be capable of significantly affecting allograft behavior.
LEUKEMIA EVOKED WITH 7, 8, 12-TRIMETHYLBENZ(A)ANTHRACENE IN RAT
Authors: Bird Colin , Huggins Charles 
Published: June 2004

An early sign of erythroblastic leukemia in rat was nodule formation in the spleen. Hyperplastic foci of stem cells, indistinguishable histologically from leukemic stem cells, were found in the red pulp whereas the malpighian corpuscles were uninvolved.
Anemia is a normal phenomenon in immature rats and the spleen of the prepubertal rat possesses considerable hemopoietic potential. Pulse-doses of 7, 8, 12-trimethylbenz(a)anthracene prevented the physiologic hematological development of maturing rats and was associated with subsequent development of leukemic stem cells in the red pulp of the spleen.
Significant enzyme changes were observed in leukemic spleens. Compared with the spleens of normal littermates, the concentration of lactate dehydrogenase rose while that of malate dehydrogenase fell; the content of alkaline phosphatase rose whereas acid phosphatase fell. Increased alkaline phosphatase activity in leukemic spleen was attributed to nonleukemic foci of myelopoiesis.
SPECIFIC IMMUNE RESPONSE GENES OF THE GUINEA PIG
Authors: Bluestein Harry G. , Ellman Leonard , Green Ira , Benacerraf Baruj 
Published: June 2004

The ability of guinea pigs to form immune responses specific for each of the random copolymers, L-glutamic acid and L-alanine (GA) and L-glutamic acid and L-tyrosine (GT), is under the control of distinct autosomal dominant genes. By testing for the ability to respond to these copolymers among the progeny from the reciprocal backcross mating of responder (2 x 13)F1 animals with the appropriate nonresponder parental strain, we have demonstrated that different unigenic autosomal dominant traits control the ability to respond to GA and GT respectively. The data further shows that the GA gene is linked to the poly-L-lysine (PLL) gene and to the locus determining the major strain 2 histocompatibility specificities and that the GT gene is linked to the locus controlling the expression of major strain 13 histocompatibility specificities.
Analysis of the inheritance of the GT and PLL genes among the offspring from a mating of responder (2 x 13)F1 guinea pigs with random-bred guinea pigs unable to respond to GT or PLL demonstrate that these genes segregate away from each other. Thus, the PLL gene and the genes to which it is linked, the GA gene and the major strain 2 histocompatibility locus, behave as alleles or pseudoalleles to the GT gene and the major strain 13 histocompatibility locus.
CHOLESTEROL METABOLISM IN THE MACROPHAGE
Authors: Werb Zena , Cohn Zanvil A. 
Published: June 2004

Phagocytosis of cholesterol-containing particles resulted in the formation of an intralysosomal cholesterol compartment. Cholesterol was excreted out of the macrophage with a single exponential rate which depended on the concentration of acceptor lipoproteins in the medium. Exchange kinetics performed on cells which had ingested particulate cholesterol suggested that excretion occurred by the same mechanism as exchange.
Cholesterol esters as particulate albumin coacervates were taken up by macrophages and hydrolyzed by a lysosomal cholesterol esterase with optimal activity at pH 4.0. Cholesteryl linoleate was hydrolyzed much more readily than cholesteryl palmitate. The amount of cholesterol esterase and its specific activity increased during the in vitro cultivation of macrophages. Intralysosomally, cholesteryl linoleate and palmitate were hydrolyzed to free cholesterol which was excreted from the macrophage and recovered in the medium. Since cholesteryl linoleate was hydrolyzed more rapidly than free cholesterol was excreted into the medium, free cholesterol accumulated intralysosomally. Cholesteryl palmitate was hydrolyzed more slowly, and the rate of hydrolysis was limiting for excretion of the free cholesterol from within the lysosome.
GENETIC POLYMORPHISM IN HUMAN GLYCINE-RICH BETA-GLYCOPROTEIN
Authors: Alper Chester A. , Boenisch Thomas , Watson Lillian 
Published: June 2004

Extensive polymorphism of glycine-rich ß-glycoprotein (GBG) was found in human sera. In all instances, GBG consisted of at least five components on electrophoresis. Patterns were such that they provided evidence for four alleles (at a locus designated Gb) which were expressed as autosomal codominant traits. GbS and GbF were found in all populations but with different frequencies, GbF1 was found in Negroes, and GbS1 was found in Caucasians.
From electrophoretic studies of GBG, evidence was obtained that suggested that the GBG molecule was a tetramer consisting of A and B subunits in a proportion of about 1.6:1. The genetically controlled differences in GBG embodied in the Gb system indicated the presence of a third moiety of the molecule (C), possibly a polypeptide subunit. Electrophoretic studies of fragments from defined types of GBG suggested that GBG cleavage induced by complement or properdin activation in serum occurred through this C moiety, since two variants were detectable in one fragment and two were found in the other fragment.
On comparison of fetal-maternal Gb types, approximately one-half the pairs showed differences. This indicated that GBG did not cross the placental barrier.
BASOPHILIC LEUKOCYTES IN ALLERGIC CONTACT DERMATITIS
Authors: Dvorak Harold F. , Mihm Martin C. 
Published: June 2004

A variety of cell-mediated hypersensitivity reactions in experimental animals include a prominent infiltrate of basophilic leukocytes. This form of reactivity has been designated cutaneous basophil hypersensitivity and is favored when sensitization to several types of antigen is accomplished without the use of complete Freund's adjuvant.
A similar type of hypersensitivity response was sought in man using morphologic techniques which permit identification of basophilic leukocytes. Eight individuals with allergic contact dermatitis to a variety of allergens were studied and six of these developed typical contact reactions with erythema, edema, and epidermal vesicles. The microscopic findings in 3-day biopsies from these individuals differed significantly from classic descriptions of tuberculin hypersensitivity and showed, in addition to mononuclear cells and the characteristic epidermal changes, a substantial infiltrate of basophilic leukocytes and evidence of altered vascular permeability with vascular compaction, dermal edema, and fibrin deposition. Serial biopsies from one individual permitted analysis of the microscopic pathology as it unfolded at successive intervals after patch test. The initial lesion consisted of perivascular accumulations of lymphocytes; this was followed by an influx of basophils and, subsequently, of eosinophils.
These findings associate contact allergy in man with the parallel reactions of cutaneous basophil hypersensitivity in animals and provide further evidence for the heterogeneity of the cellular immune response. The data are consistent with the hypothesis that interaction between sensitized lymphocytes and antigen, at a local test site, is responsible for the attraction of basophils. They also directly implicate the clotting system in delayed-type reactions and suggest the possibility of a synergistic relationship between cellular immunity and reactions mediated by basophil-bound, homocytotrophic antibody.