bluuebunny/crossref_metadata_2025_split huggingface dataset:
STUDIES ON THE HETEROLOGOUS IMMUNOGENICITY OF A METHANOL-INSOLUBLE FRACTION OF ATTENUATED TUBERCLE BACILLI (BCG)
Authors: Weiss David W. , Bonhag Rose S. , Leslie Patricia 
Published: June 2004

A methanol-insoluble residue (MER) of phenol-killed attenuated tubercle bacilli (BCG), which has been reported previously to be capable of evoking heightened resistance to infection with antigenically unrelated microorganisms, was found to affect as well the resistance of highly inbred mice against tumor isografts.
In most instances, the MER evoked heightened resistance against the tumor implants, but heightened susceptibility was the effect induced against two of the tumors tested, and no effect was elicited against one neoplasm. It is suggested that the heightened susceptibility occasionally produced by pretreatment with MER may also be of immunological nature, i.e. immunological enhancement.
Treatment with MER was more effective when administered some time before tumor challenge than when given simultaneously with, or after, tumor implantation. The protective effects manifested against some tumors were of a high order, a significant number of animals rejecting the neoplastic implants, and were displayed even when several months elapsed between treatment and challenge.
Living BCG and intact phenol-killed bacilli also evoked heightened resistance against some of the tumors tested, and in one experiment living BCG proved effective whereas MER did not. On the whole, however, MER was the most active (and least toxic, as shown previously) of the several tubercle bacillus preparations tested.
MER elicited heightened reactivity against first transplant generation tumors as well as against tumors maintained for considerable periods of time by repeated animal passage, and against spontaneously arising as well as against induced neoplasms. The experimental parameters necessary to demonstrate maximal effects varied somewhat from tumor to tumor. In general, however, single intraperitoneal injections of small quantities of MER, of the order of 0.25 to 1.0 mg, afforded the best protection.
GLOMERULAR PERMEABILITY
Authors: Graham Richard C. , Karnovsky Morris J. 
Published: June 2004

1. Glomerular permeability was studied by ultrastructural cytochemistry, using as protein tracers two intravenously injected peroxidases of differing molecular weight.
2. Horseradish peroxidase (molecular weight 40,000) passed rapidly through the endothelial fenestrae, across the basement membrane, and through the epithelial slits into the urinary space. Human myeloperoxidase (molecular weight 160,000 to 180,000) also passed rapidly through the endothelial fenestrae and across the basement membrane, but was impeded at the level of the epithelial slits. Both proteins were taken up in large amounts by the mesangial cells.
3. The present findings indicate that the epithelial slits are the primary filtration barrier responsible for the differential permeability to proteins of varying molecular size.
4. The observations also support the concept that an important function of the mesangial cells is the incorporation and disposal of glomerular filtration residues.
ADJUVATORS TO THE PROPAGATION OF MOUSE MAMMARY TUMOR CELLS ON EXPANSES OF SUBCUTANEOUS TISSUE
Authors: Henderson James S. 
Published: June 2004

The cells of a mouse mammary cancer were obtained with enzymes in suspensions which could be filtered to exclude all which were not single and most which were already dead.
Heavy suspensions of these individual cells were plated over the dorsal subcutaneous expanses of female weanling mice where they implanted and grew to form coalescent tumors covering the back more or less entirely.
Sparser suspensions, similarly plated (a) gave rise to fewer tumors, and (b) gave rise to tumors reaching measurable size later.
These two consequences of sparser plating left room for the testing of adjuvators to transplantation.
Adjuvator effects were obtained by splitting the subcutaneous expanses beforehand and by injecting liver along with the plated cells.
Through 28 plated generations over 4 yr the tumor maintained completely stable, morphological heterogeneity.
These findings with a complex tumor indicate strongly that its heterogeneity comes not from repeated cellular mutation late in its development, but from diverse potentiality to give rise to cells of specific and differing character, inherent in its individual cells at the time of its multicellular origin.
THE ULTRASTRUCTURE AND FUNCTION OF THE CELLS IN LYMPH FOLLOWING ANTIGENIC STIMULATION
Authors: Hall J. G. , Morris Bede , Moreno Giuliana D. , Bessis Marcel C. 
Published: June 2004

When a lymph node receives an antigenic stimulus the cell population in the efferent lymph changes and large basophilic cells appear. During a secondary immune response cells of this type may account for over 50% of the cells present in lymph.
When examined by electron microscopy, many of these cells were found to be primitive undifferentiated blast cells with many free ribosomes in their cytoplasm and only an occasional piece of endoplasmic reticulum. Their nuclear chromatin was sparse and the nuclei contained several nucleoli. Many other cells which were judged to be more differentiated had large numbers of ribosomes arranged in clusters which took the form of rosettes or spirals. These cells also had more ergastoplasm but this occurred usually in the form of short pieces of disorganized endoplasmic reticulum. No cells with the ultrastructure of classical plasma cells were found in efferent lymph although these cells were abundant in the stimulated lymph nodes.
It was shown that when the lymph which contained these cells was collected quantitatively no systemic immunity developed even though a vigorous immune response took place in the lymph node with the formation of many plasma cells. Failure of the systemic immune response to develop could not be explained merely in terms of the loss of antibody. It was concluded that these basophilic cells rather than antigen are responsible for propagating the immune response throughout the body and that they depend on an intact lymphatic pathway for their immediate transport. This view was supported by experiments which showed that these cells are capable of initiating immune responses in other lymph nodes of the same animal and of transferring active immunity between chimeric twins.
The most likely explanation of these results is that the basophilic lymphoid cells carry out their messenger function by developing into plasma cells at sites remote from the site at which antigen is localized. However this has yet to be proven and the possibility remains that these mobile, highly motile, RNA-rich cells may express their messenger function by transferring information to other effector cells.
THE REGULATION OF PINOCYTOSIS IN MOUSE MACROPHAGES
Authors: Cohn Zanvil A. , Parks Eileen 
Published: June 2004

A study has been conducted on the influence of nucleosides and nucleotides to induce the formation of pinocytic vesicles in cultured mouse macrophages.
Extremely high levels of cytoplasmic vesicles were found after exposure of macrophages to adenosine 5'-phosphate, ADP, and ATP. A limited vesicle response was obtained with adenosine 2'-. and 3'-phosphate, 3',5'-adenosine-phosphate, and deoxyadenosine 5'-phosphate. The di- and triphosphates of guanosine, inosine, cytidine, and uridine were stimulatory but much less active than the adenosine derivatives.
Adenosine administration resulted in high levels of pinocytic activity whereas other nucleosides, including inosine, guanosine, cytidine, and uridine, yielded little or no stimulatory effect.
Adenosine and its 5'-phosphates produced morphological effects on macrophages characterized by increased spreading, a thin, peripheral cytoplasmic veil with denser cores of oriented mitochondria and contraction of the centre-sphere region. Large numbers of pinosomes were seen in association with mitochondria-containing portions of the cytoplasm.
The stimulatory effects of adenosine and ATP were rapid and involved the majority of cells in the culture. Adenosine was unable to reverse the pinocytosis inhibition produced by 2,4-DNP, whereas ATP raised vesicle counts to high levels. Possible mechanisms for these effects are discussed.
RABBIT MACROPHAGE INTERFERONS
Authors: Smith Thomas J. , Wagner Robert R. 
Published: June 2004

Interferon is produced in cultures of rabbit leukocytes in response to infection with Newcastle disease virus or in the absence of known viral infection. The macrophage appears to be the responsible producing cell. Cultures prepared from sterile peritoneal exudates, which contained about 90% macrophages, are at least as efficient as cultures of rabbit kidney (RK) cells in their capacity to synthesize NDV-induced interferon. Interferon can be detected in the medium by 2 hr after viral infection and the titers usually reach a peak of 10,000 PDD50/ml by 4–6 hr. Exposure to actinomycin prior to or shortly after viral induction effectively blocks interferon synthesis by cells of both types. However, macrophages become refractory to actinomycin by 30–60 min compared with 607–120 min for RK cells, a finding which suggests earlier and more rapid transcription of interferon-specific messenger RNA in macrophages. Macrophages harvested from the peritioneal cavity of rabbits injected intravenously with NDV 48 hr previously also exhibit slightly reduced capacity to synthesize interferon, but this tolerant state is less marked than is tolerance to production of circulating interferon in intact rabbits.
Interferon is also synthesized by rabbit macrophages not infected with virus but simply incubated at 37°C in medium with or without added bacterial endotoxin. Uninfected polymorphonuclear leukocytes, rabbit kidney and spleen cells produced no detectable interferon under similar conditions of cultivation. No interferon was released by intact macrophages incubated at 4°C or by ultrasonically disrupted macrophages incubated at 37°C. Although interferon titers were found to be higher when uninfected cultures were exposed to 10–100 µg/ml of E. coli lipopolysaccharide, unavailability of suitable pyrogen-free maintenance media precluded answering the question whether macrophages can continually synthesize and release interferon spontaneously. Interferon yields from uninfected macrophages were only 1% or less of the yields from NDV-infected macrophages, but the rates of synthesis were similar under both conditions. Studies with actinomycin and puromycin revealed that sequential transcriptive and translational events are required for de novo interferon synthesis by uninfected cells in a manner similar to virus-induced interferon synthesis.
The physical properties and molecular weights of these rabbit interferons are discussed in the following report (12).
DEMONSTRATION BY IMMUNOFLUORESCENCE OF THE FIXATION OF PERFUSED ANTIBODY TO HUMAN COLLAGEN IN HUMAN KIDNEY
Authors: Rothbard Sidney , Watson Robert F. 
Published: June 2004

Rabbit serum containing antibody to human collagen, perfused through human infant kidneys obtained at autopsy, gives an immunofluorescent reaction with an antigen in the basement membranes of the glomeruli and the tubules. This reaction was shown to be specific by the absence of reaction with normal rabbit serum, antibody to carp collagen, or anti-human collagen serum absorbed with human collagen. Slight cross-reactions were found in the human kidneys with antibody to chicken or rat collagen.
There was no evidence that a collagen-like protein in human serum or an antigen common to human erythrocytes and renal glomeruli enters into this immunofluorescent reaction.
Perfusion of the kidneys with purified collagenase before the introduction of the antibody to human collagen altered the antigen so that antibody could not be demonstrated in the basement membranes by immunofluorescence. Testicular hyaluronidase used in the same way did not affect the immunofluorescent reaction.
This method of perfusion provides another means for studying antigens in human organs by immunofluorescence.
These observations in human kidneys extend our earlier findings in laboratory animals and indicate that an antigen, collagen, is also present in human renal glomerular and tubular basement membranes.
SPECIFIC TRANSPLANTATION ANTIGENS OF MOUSE SARCOMAS INDUCED BY ADENOVIRUS TYPE 12
Authors: Sjögren H. O. , Minowada J. , Ankerst J. 
Published: June 2004

A specific isograft resistance against three different mouse adeno 12 sarcomas was demonstrated in mice treated with four to eight doses of viable or X-ray-killed adeno 12 mouse tumors. Whole-body X-ray irradiation with 350 R 24 hr previous to the test challenge did not abolish the resistance, indicating that it was due to a true anamnestic immune reaction. This was further proven by the finding that similar treatment with tumors of other origin did not induce any immunity, nor did the treatment with adeno 12 tumor material induce any immunity against two neoplasms of Schmidt-Ruppin-Rous viral origin.
The previous report by Trentin et al. (17) that adeno 12 infection leads to a specific transplantation immunity was fully confirmed. When the specificity of this virus-induced immunity was studied it was discovered that besides adeno virus type 12, type 7 and probably type 18 also gave the same type of resistance while adenovirus type 5 did not. A contamination of the adeno 7-infected mice with adeno type 12 was excluded by testing pooled sera from these animals for anti-adeno 12 CF or HI antibodies.
CYTOTOXIC POTENTIAL OF STIMULATED HUMAN LYMPHOCYTES
Authors: Holm Göran , Perlmann Peter 
Published: June 2004

Viable and immunologically competent lymphocytes from unsensitized donors damage allogeneic tissue culture cells in the presence of phytohemagglutinin (PHA). This cytotoxicity is specific since syngeneic tissue culture cells are not at all or only slightly damaged under similar experimental conditions. In this investigation, the relation between the stimulation of human lymphocytes and their cytotoxicity was studied. Chang cells (human liver) served as target cells in all experiments. Cell damage was quantitated by measuring the release of isotope from target cells labeled with chromate-51Cr.
The cytotoxicity of the lymphocytes was dependent on the concentration of PHA in the incubation medium. Cell damage was maximal at concentrations of 4–8 µl PHA/ml. Higher concentrations were inhibitory although aggregation was increased and no injury of the lymphocytes was noted. Stimulation of DNA and RNA synthesis in PHA-treated lymphocytes each followed dose response curves which were similar to that of cytotoxicity.
In order to establish whether stimulation without mixed aggregation of lymphocytes and target cells would suffice for cytotoxicity, a series of nonagglutinating stimulants were investigated. Lymphocytes pretreated with a crude filtrate of Staphylococcus aureus for periods of 0.5–72 hr damaged Chang cells even in the absence of PHA. Lymphocytes from a tuberculin-positive donor were strongly cytotoxic after prestimulation with PPD while those from a negative donor were inactive. Moreover, strong cytotoxic effects were also obtained with lymphocytes which had been stimulated by preincubation with allogeneic lymphocytes in mixed culture. When two stimulants were applied at the same time, additive cytotoxic effects were seen. Addition of PHA to the lymphocyte/Chang cell mixtures potentiated the cytotoxicity of prestimulated lymphocytes. The cytotoxic potential of the lymphocytes was in all cases correlated to the degree of stimulation recorded as transformation into blast cells, and was independent both of the degree of aggregation and of the stimulating factor.
These findings are compatible with the assumption that injury of the Chang cells reflected an immunologically nonspecific activity of lymphocytes enhanced by stimulation. The possible importance of this activity for a number of tissue-damaging immune reactions in vivo is pointed out.
STUDIES OF THE CELLS IN THE AFFERENT AND EFFERENT LYMPH OF LYMPH NODES DRAINING THE SITE OF SKIN HOMOGRAFTS
Authors: Hall J. G. 
Published: June 2004

Intermediate lymph (efferent from the prefemoral lymph node) was collected for 600 hr from both flanks of each of four sheep that had an autograft of skin on the left flank and a homograft of skin on the right flank.
8 days after the grafts had been applied considerable numbers of large basophilic cells, apparently identical with those that appear during immune responses to conventional antigens, appeared in the lymph draining from the homografts. No such cells appeared in the lymph draining from the autografts. At this time the homografts were already showing signs of rejection and were apparently dead well before the cellular response in the lymph reached a peak, about 350 hr (14–15 days) after the homografts had been applied. During the peak of the response up to 40% of the cells in the lymph were basophilic cells and in one experiment such cells were leaving the lymph node at a rate of 200 million per hr.
Peripheral lymph (afferent to the popliteal lymph node) draining from the sites of homografts of skin was collected from five sheep. This lymph contained few white cells (&lt;1000 per mm3) and showed only an insignificant lymphoid cell reaction. Although the percentage of macrophage-like cells was increased significantly there were few signs of a lymphoid cell reaction; the lymph also contained much amorphous debris.
Experiments in which the basophilic cells from the efferent lymph were labeled in vitro with thymidine-3H and returned to the sheep by intravenous injections were carried out in six sheep. The presence of the labeled cells in the grafts, blood, and other tissue was detected by liquid scintillation counting of nucleic acid extracts of biopsy and postmortem material and by radioautography. 2–3 labeled cells out of every 1000 injected entered the homografts but hardly any entered the autografts. However, labeled basophilic cells that had originated in response to bacterial antigens entered the homografts with equal facility. It is thus hard to believe that the immunological specificity of a lymphoid cell endows it with a specific "homing" capability. Furthermore, in all the experiments the specific radioactivities of the nucleic acids extracted from the blood mononuclear cells were approximately of the same order as those of the nucleic acids extracted from the homografts. It was concluded that most of the mononuclear cells that infiltrate homografts represent a random selection from the mononuclear cell population of the blood.
THE GENETIC CONTROL OF γ-GLOBULIN HEAVY CHAINS
Authors: Litwin Stephen D. , Kunkel Henry G. 
Published: June 2004

The genetic control of γG1-heavy chains was investigated by taking advantage of two recently described genetic antigens, Gm(z) and Gm(y), both produced by heteroimmunization of rabbits with myeloma proteins. These were studied in conjunction with known genetic markers, Gm(a) and Gm(f). The results indicated that among Caucasians there are two major allelic genes, Gmza and Gmfy, coding for distinct varieties of γG1-heavy chains. Each of these contains a pair of genetic antigens which are located on different fragments of the chain and can be separated by enzymatic splitting with papain. The different areas of the heavy chains appear to be under the control of the same gene. In Mongoloid populations a grouping of three genetic antigens, Gm(f), (y), and (a), was found on isolated myeloma proteins and normal γ-globulins indicating the presence of a Gmfya gene. The possible genetic events leading to the contrasting Caucasian and Mongoloid genes are discussed. In the γ-globulin system the occurrence of multiple genetic antigens in different positions of the same heavy chains is the general rule.
A better understanding of the relationships between the genes for the γG1-subgroup to those for the γG2- and γG3-subgroup has been obtained through the use of the multiple genetic markers. Strong evidence was obtained for intergenic crossover mechanisms to explain racial differences in the relationships of these genes as well as certain unusual gene complexes found through family studies. Further evidence was obtained for mapping the closely linked genes for the three subgroups in a specific order.
POSTTHYMECTOMY WASTING ASSOCIATED WITH AUTOIMMUNE PHENOMENA
Authors: Yunis Edmond J. , Hong Richard , Grewe Mary Alice , Martinez Carlos , Cornelius Eugene , Good Robert A. 
Published: June 2004

1. Mice of A and C57BL/6 Ks strains, thymectomized at birth acquire wasting disease in 84.1% (A) and 77.1% (C57BL/6 Ks) of the cases. There is no sex predelection.
2. Anemia in these animals is characterized by shortened red cell survival and increased fragility to hypotonic salt solutions. Among thymectomized A mice reticulocytosis is absent and extramedullary hematopoiesis is found in the spleen in the presence of bone marrow hypoplasia for the erythroid and lymphocyte series.
3. Positive antiglobulin tests of the red cells were observed in all the thymectomized C57BL/6 Ks (7/7) and 71.2% of the A strains (62/87). Normal mice do not show positive Coombs' tests.
4. The globulin coat on the A strain consists of IgM, whereas ß1C and IgG are not detectable. By contrast, red cell coats of NZB mice developing spontaneous autoimmune hemolytic anemia show IgM and ß1C, but these erythrocytes do not react with anti-gamma chain antibodies. Another difference in the globulin coats of the two types of erythrocytes is that the IgM on NZB red cells has available light chain determinants but these are apparently hidden or absent in the case of sensitized erythrocytes. The difference in antibody coating, association with a component of complement in one but not the other, suggests a different mechanism for the immune surface phenomenon in each instance.
5. Anemia in NZB mice is associated with reticulocytosis while that in thymectomized A mice is not.
6. Thymectomy appears to initiate a chain of events leading to a series of autoimmune phenomena which may be due to alteration in host response consequent to loss of thymic tissue and thymic dependent functions or alternatively to infection to which increased susceptibility exists as a result of thymic extirpation.
SEQUENTIAL CHANGES IN CLASSES OF RNA DURING COMPENSATORY GROWTH OF THE KIDNEY
Authors: Malt Ronald A. , Miller Walter L. 
Published: June 2004

The synthesis of nuclear precursors of rRNA and of cytoplasmic mRNA has been estimated in mouse kidneys following contralateral nephrectomy.
1. The production of nuclear rRNA parallels mitotic activity in the proximal tubule cells. Its peak is 2 days after nephrectomy; there may be a second peak at 8 days.
2. The production of mRNA is almost the reciprocal of rRNA production. It is least at 2 days and most at 4 days after nephrectomy. It may also decrease immediately after nephrectomy.
3. Growing kidney cells may build a store of ribosomes before they elaborate mRNA. The sequential relation between rRNA and mRNA synthesis raises the possibility that production of rRNA could regulate the production of mRNA and that the stimulus to compensatory hypertrophy might need to act only long enough to set into motion the machinery for making rRNA, either directly or as a consequence of exhausting mRNA.