bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADENO-ASSOCIATED SATELLITE VIRUS INTERFERENCE WITH THE REPLICATION OF ITS HELPER ADENOVIRUS
Authors: Parks Wade P. , Casazza Anna M. , Alcott Judith , Melnick Joseph L. 
Published: June 2004

Adeno-associated satellite virus type 4 interferes with the replication of its helper adenovirus. No interferon-like soluble substance could be detected in satellite-infected cultures and other DNA- and RNA-containing viruses were not inhibited by coinfection with satellite virus under conditions which reduced adenovirus yields by more than 90% in monkey cells. Altering the concentration of adenovirus in the presence of constant amounts of satellite resulted in a constant degree of interference over a wide range of adenovirus inocula and suggested that adenovirus concentration was not a significant factor in the observed interference. The interference with adenovirus replication was abolished by pretreating satellite preparations with specific antiserum, ultraviolet light or heating at 80°C for 30 min. This suggested that infectious satellite virus mediated the interference. Satellite virus concentration was found to be a determinant of interference and studies indicated that the amount of interference with adenovirus was directly proportional to the concentration of satellite virus.
8 hr after adenovirus infection, the replication of adenovirus was no longer sensitive to satellite interference. This was true even though the satellite virus was enhanced as effectively as if the cells were infected simultaneously with both viruses.
Interference with adenovirus infectivity was accompanied by reduced yields of complement-fixing antigen and of virus particles which suggested that satellite virus interfered with the formation and not the function of adenovirus products. When cells were infected either with adenovirus alone or with adenovirus plus satellite, the same proportion of cells plated as adenovirus infectious centers. However, the number of plaque-forming units of adenovirus formed per cell in the satellite-infected cultures was reduced by approximately 90%, the same magnitude of reduction noted in whole cultures coinfected with satellite and adenovirus. This suggested that all cells infected with the two viruses were producing a reduced quantity of adenovirus.
ANTIGENS IN IMMUNITY
Authors: Nossal G. J. V. , Abbot A. , Mitchell Judith 
Published: June 2004

Details of antigen trapping and processing in the rat lymph node have been investigated by the technique of high resolution radioautography. A series of 24 adult rats was injected with 20 µg of 125I-labeled Salmonella adelaide flagella, given as either a primary or a secondary stimulus into one hind foot-pad. At intervals ranging from 3 min to 3 wk, rats were killed and the popliteal nodes were processed for electron microscopic radioautography using Kodak NTE emulsion. The present paper deals with events in the lymph node medulla, and an accompanying report describes the radically different behavior of antigen in the cortical follicles.
In the medulla, lightly labeled granulocytes were transiently encountered, but by far the greatest bulk of antigen was in macrophages. Antigen entered these cells in two ways: by direct penetration of the plasma membrane; and by pinocytosis. In either case, the antigen rapidly became surrounded by tiny vesicles which may have represented Golgi-derived "protolysosomes." Vacuolar fusion ensued and a series of progressively larger and more complex antigen-containing "phagolysosomes" was formed. Substantial amounts of antigen could be detected in such bodies for at least 3 wk.
The antigen injection, as expected, caused extensive plasma-cytopoiesis. No evidence of label in plasma cells was obtained. No special anatomic relationship between plasma cells and antigen depot sites was discovered. These results are briefly discussed in relation to current theories of immune induction.
REGULATION OF CELLULAR ANTIBODY SYNTHESIS
Authors: Möller Göran 
Published: June 2004

Transfer of spleen cells from mice immunized against sheep red blood cells (SRBC) into irradiated (600 R) nonimmune, syngeneic mice in the presence of antigen resulted in excessive cellular 7S production 7 days later. The number of 7S plaque-forming cells usually exceeded 106 per spleen and the mean proportion varied between 1 and 70%. In occasional animals all spleen cells were producing antibodies to SRBC. Serum antibody synthesis was also excessively increased, the titers in agglutination after 2-ME treatment and in hemolysis varying between 215 and 225. The generation time of the 7S PFC was found to be 9.6 hr in the secondary hosts.
It seemed possible that the excessive production of 7S PFC and antibodies in the irradiated nonimmune recipients was caused by the absence of feedback inhibition of the immune response by antibody, a mechanism which would normally function to restrict antibody synthesis. This conclusion was strengthened by the demonstration that transfer of antigen-stimulated immune cells into actively or passively immunized irradiated recipients resulted in a marked suppression of cellular 7S synthesis. Serial transfers of antigen-stimulated immune cell populations in irradiated hosts resulted in an equally high number of 7S PFC during the first four transfer generations. However, after the fifth to seventh transfer generation the number of 7S PFC rapidly declined and disappeared within one to three passages. Serum antibodies and 7S PFC declined in parallel during the last transfer generations. Further passages of antigen-stimulated spleen cells lacking 7S PFC did not lead to reappearance of PFC. Thus, antigen-sensitive cells have a limited lifespan and/or multiplication capacity. From the hypothesis that the 7S PFC developed by division from antigen-sensitive precursors it was calculated that 38–40 divisions occurred, Thus, one antigen-sensitive precursor has the potential to give rise to 1012 7S PFC.
THE PROVOCATION OF LATENT LYMPHOCYTIC CHORIOMENINGITIS VIRUS INFECTIONS IN MICE BY TREATMENT WITH ANTILYMPHOCYTIC SERUM
Authors: Volkert Mogens , Lundstedt Claus 
Published: June 2004

The hypothesis that treatment with antilymphocytic serum (ALS) can provoke latent virus infections has been investigated.
In adult mice infections with sublethal doses of LCM virus usually result in the development of immunity to the virus and at the same time to a prolonged latent infection.
In the experiments described an intensive treatment with large doses of ALS was given to mice which had recovered from LCM virus infection. At the beginning of the treatment the mice had high titers of complement-fixing antibodies in their blood and no detectable virus. The data presented show that in spite of the immunity the ALS treatment provoked the occult virus and led to the development of viremia in all the treated mice. In some, very high virus titers were demonstrable. When the ALS treatment was discontinued the viremia disappeard again.
In most of the mice the ALS did not suppress the complement-fixing antibody titers and in some there was even a considerable increase in titer. In such cases the increases in virus titers and in antibody titers were closely related to one another. These results demonstrate once again that the complement-fixing antibodies to the LCM virus in mice probably do not influence the virus.
PAPAIN DIGESTION FRAGMENTS OF HUMAN IGM GLOBULINS
Authors: Mihaesco Constantin , Seligmann Maxime 
Published: June 2004

Papain digestion of two Waldenström IgM globulins produced a high amount of small peptides and resulted in the formation of two end products, the Fabµ and Fcµ fragments.
The Fcµ fragment is characterized by a fast electrophoretic mobility, a high content in carbohydrate, and a high molecular weight. It was demonstrated that this fragment is made of heavy chain pieces belonging to several disulfide-linked monomeric subunits, presumably representing the carboxy-terminal end of the µ-chains. Fc fragments from the two macroglobulins could not be distinguished immunologically. An appreciable proportion of IgM molecules apparently underwent degradation without the formation of a stable Fc fragment. An Fc-like fragment, analogous to the reduced Fc fragment, was obtained at early stages of papain digestion of the IgM subunits.
The Fabµ fragment, with slow and individually distinct electrophoretic mobility, bears many physicochemical and immunological similarities to the Fabγ fragment. It consists of one light chain and one Fd piece, both of which were isolated. The interaction of these two constituents was demonstrated by gel diffusion studies. Fab fragments of both IgM globulins were resolved into two subpopulations with different electric charges.
In addition to these fragments, intermediary split products were observed at early stages of the degradation process, together with a high yield of small peptides mainly derived from the papain-sensitive region of the heavy chains. Immunologic data strongly suggested that this segment of µ-chains is situated between the Fd piece and the portion included in the Fc fragment.
Several experiments indicated the importance of conformational antigenic specificity in both Fab and Fc regions of the IgM globulins.
ANTIBODY PRODUCTION IN VITRO
Authors: Harris Gilmour 
Published: June 2004

The effect of high specific activity thymidme-3H on proliferation and antibody production, using the hemolytic plaque-forming technique, by spleen cell suspensions in vitro from rabbits killed after a boost of SRC's has been studied. High specific activity thymidine-3H inhibited the proliferative ay well as the antibody response to antigen, and it was conduded that this was the result of the incorporation of radioactive 3H into the nuclei of dividing cells which were synthesizing antibody in these cultures.
The stimulation of the rate of DNA synthesis by specific antigen could be correlated with the ability of antigen to maintain antibody production, as measured by the specific hemolytic plaque-forming technique, above levels found in control cultures, incubated without antigen.
Radioautographic studies of PFC's in vitro showed that the majority of the cells arose from the DNA-synthesizing population of cells in these cultures, confirming the conclusions from the results of the inhibitory effects of high specific-activity thymidine-3H on PFC's. It was found that these PFC's, labeling with thymidine-14C, formed only a small proportion of all the cells labeled in this way in these cultures. The postulation was made that antigen, in vitro, provided a stimulation for cell proliferation in the responsive population of rabbit spleen cells, but that only a small proportion of this population could be induced by antigen to synthesize antibody.
ANTIBODY PRODUCTION IN VITRO
Authors: Harris Gilmour 
Published: June 2004

The effects of actinomycin D and puromycin on spleen cell suspensions from rabbits immunized to SRC's were studied. These inhibitors, in high concentration, suppressed PFC's when added initially to recently isolated cells. When such cells were incubated for several days in the presence of both antigen and inhibitor, both actinomycin D and puromycin produced an increase in PFC's after the initial suppression. This recovery effect was best seen with cells from rabbits killed 3 days after boosting with SRC's, and was usually absent when cells were taken from rabbits killed 2 days after boosting. When actinomycin D or puromycin was added after several days in culture in the presence of SRC's, surviving PFC's were found to be not only resistant to these inhibitors, but there was also an increased number of PFC's compared to similar cultures incubated without these agents.
Radioautographic studies showed that PFC's stimulated by the presence of actinomycin D or puromycin were not incorporating precursors for RNA or protein synthesis. In view of the known mode of action of these inhibitors, it was postulated that they were stimulating antibody production by PFC's in vitro either by interfering with represser mechanisms or stimulating the completion of antibody molecules, perhaps by causing the release of preformed antibody chains from ribosomes.
Since the presence of specific antigens in vitro were necessary for these observed stimulatory effects on PFC's, and since antigens were producing an effect on antibody production on cells which were being suppressed by these inhibitors, added initially, it was further suggested that one role of antigen in the immune response was concerned with the completion of antibody synthesis on the ribosomes, perhaps by acting as an inducer as has been suggested previously (1).
THE EFFECT OF HETEROLOGOUS ANTI-LYMPHOCYTE SERUM ON MOUSE HEMOPOIETIC STEM CELLS
Authors: DeMeester Tom R. , Anderson Norman D. , Shaffer Charles F. 
Published: June 2004

The present study has demonstrated that rabbit anti-mouse lymphocyte serum (RAMLS) has the capability of destroying bone marrow cells and suppressing hemopoietic stem cell function. The in vitro incubation of bone marrow suspensions with RAMLS caused extensive cell lysis with an apparent preferential destruction of lymphoid, erythroid, and blastoid elements. Using the spleen colony assay, the number of functional hemopoietic stem cells was found to be markedly reduced in bone marrow populations exposed to RAMLS in vitro. Further, this loss of stem cell function could be produced by exposing marrow suspensions to small concentrations of antiserum which did not produce detectable cytotoxic effects on the general marrow population.
A similar effect of RAMLS upon hemopoietic stem cells was found in vivo. The intravenous injection of RAMLS into lethally irradiated mice immediately after the infusion of isogeneic marrow cells reduced the number of spleen colonies formed, indicating that the antiserum could exhibit a deleterious effect upon stem cells in the bloodstream of the intact animal. Normal animals treated with daily subcutaneous injections of RAMLS for 3 wk had a significantly reduced marrow content of functional hemopoietic stem cells, suggesting that RAMLS can affect stem cells located in situ in the bone marrow. The experiments indicate that RAMLS possesses potential marrow toxicity.
ARGININE-RICH PROTEINS OF POLYMORPHONUCLEAR LEUKOCYTE LYSOSOMES
Authors: Zeya H. I. , Spitznagel J. K. 
Published: June 2004

The cationic antibacterial proteins of rabbit PMN lysosomes have been resolved into at least five subfractions. Each of these showed substantial selectivity in its antibacterial action against several pathogenic bacteria, including two smooth and two rough Escherichia coli strains, three Staphylococcus aureus strains, one S. albus, three proteus species and four different cultures of streptococcus.
Each of the subfractions possesses a different electrophoretic mobility. Amino acid analyses of the three most cationic components revealed high contents of arginine consistent with their relative electrophoretic mobilities and very high arginine to lysine ratios. Aromatic amino acids were present in very low concentrations in these proteins and their light absorption at 2800 A was correspondingly weak.
The evidence of antibacterial specificity, along with marked differences in the arginine-lysine ratios, shows that the cationic antibacterial components of rabbit PMN lysosomes are biologically and chemically heterogeneous.
HEMATOPOIETIC ORIGIN OF MACROPHAGES AS STUDIED BY CHROMOSOME MARKERS IN MICE
Authors: Virolainen Martti 
Published: June 2004

The origin of macrophages was studied in mouse radiation chimeras by chromosome marker technique. Macrophage cultures were established from peritoneal exudate, from lung washings, and from organ cultures of bone marrow, spleen, lymph node, thymus, and lung. Cultured macrophages were induced to divide by adding conditioned medium from L cell cultures.
In chimeras which were lethally irradiated and given injections of bone marrow or spleen cells, dividing macrophages were of donor type, independent of the source of the macrophages. When chimeras were established by injections of a mixture of bone marrow cells and cells from other hematopoietic tissues of two genetically different donors, the ratio of cells with different genotypes was approximately the same in bone marrow cells and in macrophage cultures. Thymus, lymph node, and peritoneal exudate cells were not found to contain precursor cells for macrophages. Precursor cells for macrophages and for bone marrow cells appeared to be equally sensitive to sublethal irradiation.
The results indicate that macrophages from different sources can all be derived from hematopoietic tissues, and suggest that only hematopoietic tissues contain precursor cells for macrophages which are capable of in vitro division. The close relationship between the source of cells in bone marrow and in macrophage cultures suggests that, at the maturation level at which the irradiated host is repopulated, the precursor or stem cells for macrophages may be identical with those for myeloid and erythroid series of cells.
THE ROLE OF AFFERENT LYMPHATICS IN THE REJECTION OF SKIN HOMOGRAFTS
Authors: Barker Clyde F. , Billingham R. E. 
Published: June 2004

Experiments have been carried out on guinea pigs of two isogenic strains to elucidate the role of afferent lymphatic vessels in the rejection of orthotopic skin homografts. Graft beds were prepared in partially isolated skin flaps with an intact sustaining vascular "umbilical cord" in which a lymphatic connection with the host could be retained or abolished at will.
In the absence of demonstrable lymphatic connections between flap and host, intra-flap homografts long outlived similar grafts transplanted to conventional sites in intact skin and, rather than being specifically rejected, died as a consequence of ischemic necrosis of the flap. When lymphatic drainage was retained, intra-flap homografts were rejected in the usual manner. Hosts of long-term intra-flap homografts did not develop sensitivity, as evidenced by the "first set" type rejection of subsequent test grafts, or by the long-term survival of a second skin graft transplanted to a new flap raised on the opposite side of the host's body.
Intra-flap skin homografts were rejected if (a) the hosts had been presensitized, (b) they were grafted concomitantly with a skin homograft placed in a conventional site, or inoculated with a suspension of donor lymphoid cells, or (c) if the lymphatic drainage was restored by reimplantation of the hitherto partially isolated flap to an appropriate vascular bed. These findings and others indicate that an intact lymphatic drainage in its bed is essential for an orthotopic skin homograft to sensitize its host.
Various experiments were carried out in which intra-flap homografts were used as "indicators" for the acquisition of specific active or adoptive immunity by their hosts.
By transplanting skin homografts to conventional beds concomitantly with intra-flap grafts and then excising the former at various intervals, it has been found that a graft must be in residence for a minimum period of 4 days to evoke the development of a detectable level of sensitivity in the host. Furthermore, by replacing either freshly prepared or long-term skin flaps bearing skin homografts in vascular beds on the trunk and determining the subsequent survival times of the homografts, evidence has been obtained suggesting that reestablishment of a functional lymphatic system in a free skin graft may take as long as 9 days.
Using intra-flap homografts as indicators of adoptive immunization of the host, we found that as few as 50 x 106 isologous peripheral blood leukocytes from a specifically sensitized animal will transfer an effective level of sensitivity. We also found that hyperimmune serum, in relatively large amount, exerts a weak but definite adverse effect upon either freshly or recently transplanted intra-flap grafts.
CELL WALL COMPOSITION AND VIRULENCE IN ESCHERICHIA COLI
Authors: Medearis Donald N. , Camitta Bruce M. , Heath Edward C. 
Published: June 2004

Uridine diphosphate galactose 4-epimerase and phosphomannose isomerase-deficient mutants of Escherichia coli O111:B4 were studied to test the hypothesis that in E. coli a specific relationship exists between O antigenicity, virulence, and capacity to resist phagocytosis. The first mutant, designated J-5, produces a cell wall lipopolysaccharide, the side chains of which do not contain galactose, glucose, N-acetylglucosamine, or colitose. The second mutant produces a cell wall lipopolysaccharide which lacks only colitose. The capacity of these various organisms to kill mice was strikingly different. E. coli O111 was 1000 times as virulent as J-5, and 100 times as virulent as L-2.
The capacity of the organisms to kill mice was correlated with their ability to resist phagocytosis and to persist in the peritoneal cavity. The parent strain of O111 resisted phagocytosis by macrophages in vivo and polymorphonuclear leukocytes in vitro. The mutants did not, and the organism most deficient in the saccharide component of its LPS was most susceptible to phagocytosis and least virulent. These results were corroborated by growing the mutants in appropriately supplemented media which permitted the synthesis of complete LPS, reversed the susceptibility to phagocytosis, and restored virulence. Finally, serological reactivity was consistent with previous observations which had demonstrated that the O antigenicity of E. coli is determined by the saccharide composition of its cell wall lipopolysaccharide. Despite the difference in the capacity of the various log-phase organisms to kill mice when injected intraperitoneally, purified lipopolysaccharides extracted from them did not differ significantly in their capacity to kill or produce fever. Thus virulence was shown to be independent of endotoxin activity which in turn seemed to be unrelated to the saccharide composition of the cell wall LPS.
Collectively, these data provide at least a partial molecular definition of virulence in E. coli by demonstrating that the presence or absence of specific sugars in its cell wall lipopolysaccharide is a determinant of its antiphagocytic capacity and its virulence.
THE ORIGIN AND KINETICS OF MONONUCLEAR PHAGOCYTES
Authors: van Furth Ralph , Cohn Zanvil A. 
Published: June 2004

The origin and turnover of efferent populations of mouse mononuclear phagocytes has been described. Mononuclear phagocytes were defined as mononuclear cells which are able to adhere to glass and phagocytize.
In vitro labeling studies with thymidine-3H showed that monocytes in the peripheral blood and peritoneal macrophages do not multiply and can be considered end cells in a normal, steady state situation. However, the mononuclear phagocytes of the bone marrow appear to be rapidly dividing cells.
This conclusion was supported by in vivo labeling experiments. A peak of labeled mononuclear phagocytes of the bone marrow was found 24 hr after a pulse of thymidine-3H. This was followed, 24 hr later, by a peak of labeled monocytes in the peripheral blood. From these experiments it was concluded that the rapidly dividing mononuclear phagocytes of the bone marrow, called promonocytes, are the progenitor cells of the monocytes. Labeling studies after splenectomy and after X-irradiation excluded other organs as a major source of the monocytes.
Peak labeling of both the blood monocyte and peritoneal macrophages occurred at the same time. A rapid entry of monocytes from the blood into the peritoneal cavity was observed, after a sterile inflammation was evoked by an injection of newborn calf serum. These data have led to the conclusion that monocytes give rise to peritoneal macrophages.
No indications have been obtained that mononuclear phagocytes originate from lymphocytes.
In the normal steady state the monocytes leave the circulation by a random process, with a half-time of 22 hr. The average blood transit time of the monocytes has been calculated to be 32 hr. The turnover rate of peritoneal macrophages was low and estimated at about 0.1% per hour.
On the basis of these studies the life history of mouse mononuclear phagocytes was formulated to be: promonocytes in the bone marrow, → monocytes in the peripheral blood, → macrophages in the tissue.