bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF MALNUTRITION ON THE INFLAMMATORY RESPONSE
Authors: Taylor Patricia E. , Tejada Carlos , Sánchez Margarita
Published: June 2004

In the present experiments, Selye's granuloma pouch technique was applied to the study of the effect of host nutritional state on inflammation and the local tissue response. The normal response of well-nourished laboratory rats fed a diet containing 28% protein to the injection of 1% croton oil into a preformed subcutaneous air sac involved the accumulation of hemorrhagic exudate in the pouch lumen and the progressive thickening of the pouch wall, with the proliferation and maturation of fibroblasts and the eventual laying-down of collagen. In malnourished animals, fed a diet containing only 3–4% protein but adequate in all other nutrients, the above reactions were inhibited. This inhibitory effect was encountered after a relatively short period of deficiency and became more marked as the deficiency progressed. No consistent, clear-cut difference was seen in the leukocytic or neutrophilic response between the two dietary groups after the injection of 1% croton oil.

A significantly higher proportion of accidental bacterial infections was found in the pouches of malnourished animals than in those of well-nourished animals. This was considered to be a possible consequence of the depressed inflammatory response in malnourished rats.

The advantages of the granuloma pouch as an experimental procedure for the study of local reactions to different noxae, and the influence of malnutrition on these reactions have been discussed and suggestions for future studies presented.
THE IMMUNE RESPONSE TO A HYBRID PROTEIN MOLECULE
Authors: Rajewsky K. , Rottländer Elke , Peltre G. , Müller Brigitte
Published: June 2004

Upon immunization with LDH-III (subunit composition AABB) rabbits produce anti-A and anti-B antibodies in comparable amounts. These antibodies fit equally well to the hybrid enzyme and to LDH-V (AAAA) or LDH-I (BBBB) respectively, as tested by passive hemagglutination inhibition. No antibodies reacting with both LDH-I and LDH-V were detected. A minority of hybrid-specific antibodies was, however, present in the sera.

Animals primed with LDH-III respond regularly to a boosting injection of LDH-V with the production of large amounts of anti-A (but not anti-B) antibodies. A similar injection of LDH-I stimulates (if it has any effect at all) the production of anti-B antibodies only. Stimulation with one of the pure types does not impair a subsequent response to the other.

The majority of the animals primed with LDH-III responded not at all or weakly to a boosting injection of LDH-I, though antibodies to LDH-I were present in the sera at the time of stimulation. This effect can hardly be explained on the basis of serological sepcificity.

Hyporesponsiveness to LDH-III can be induced by injection of LDH-V into the newborn. Both anti-A and anti-B titers are equally depressed. Within the dose range tested, LDH-I does not exert any tolerogenic action with respect to LDH-III.

The carrier property of subunit A is evident in the induction of both immunity and tolerance to LDH-III. The early phase of the immune response to the hybrid enzyme may be carrier-specific, and receptors for the haptenic subunit B may not exist at that stage.
QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS
Authors: Wilson Darcy B. , Silvers Willys K. , Nowell Peter C.
Published: June 2004

The influence of the immunologic status of the cell donors on the proliferative behavior of rat lymphocytes in the mixed lymphocyte interaction has been studied.

Mixed cultures of cells from various parental and F1 combinations having morphologically distinguishable sex chromosomes exhibited unidirectional proliferative reactivity. The mitotic figures were predominately of parental origin.

Lymphocytes from donors made tolerant at birth to homologous transplantation isoantigens were specifically unreactive against cells bearing antigens of the tolerance inducing strain, but not to indifferent third party homologous lymphocytes.

Cells from animals that had been surgically thymectomized at birth exhibited a markedly and sometimes totally diminished reactivity against homologous lymphocytes.

Presensitization of the cell donors resulted in a curtailment of proliferative reactivity in cultures with cells bearing the immunizing antigens. This may reflect the destructive properties that lymphocytes from sensitized animals are known to possess.

The results of these experiments show that the proliferative activity of lymphocytes in the mixed lymphocyte interaction accurately reflects the immunologic status of the cell donors, and these findings provide further support for the premise that the mixed lymphocyte interaction represents a primary immunologic response by cells in culture against homologous cells bearing histocompatibility antigens.
EXPERIMENTAL STUDIES ON THE DEVELOPMENT OF THE THYMUS
Authors: Moore M. A. S. , Owen J. J. T.
Published: June 2004

Experiments utilizing chromosome marker and histological techniques in combination with parabiosis and transplanatation procedures have demonstrated an inflow of blood-home stem cells into the chick embryo thymic rudiment. There is close similarity between the histological picture in the chick and in the mouse thymic rudiment, and it is proposed that a similar developmental process takes place in both. It may be concluded that the epithelial component of the thymic rudiment, rather than producing lymphoid cells itself, furnishes an inductive environment for the proliferation and differentiation of stem cells derived extrinsically.
QUANTITATIVE ASPECTS OF THE RELEASE OF LEUKOCYTE PYROGEN FROM RABBIT BLOOD INCUBATED WITH ENDOTOXIN
Authors: Murphy P. A.
Published: June 2004

This paper describes the relations between the endotoxin concentration and leukocyte pyrogen yield when endotoxin is incubated with whole rabbit blood for 24 hr. The results provide strong evidence for the view that leukocyte pyrogen is not modified endotoxin, and also show that the simplified assay method described in the previous paper works reasonably well.
FACTORS INFLUENCING HEMATOPOIETIC SPLEEN COLONY FORMATION IN IRRADIATED MICE
Authors: Boggs Dane R. , Marsh John C. , Chervenick Paul A. , Cartwright George E. , Wintrobe Maxwell M.
Published: June 2004

Mice were irradiated repetitively at 6 wk intervals. The proliferative capacity of the hematopoietic stem cell compartment was studied after each irradiation and compared to that of age-matched controls which had been irradiated only once. Hematopoietic proliferation capacity was measured by determining the number of spleen colonies, splenic iron uptake, spleen weight, and volume of packed red cells 10 days after irradiation.

6 wk after the first irradiation, the hematopoietic compartment was apparently supranormal in size for, when such mice were again irradiated, their postirradiation hematopoiesis was in excess of that of the controls. Thereafter, there was a steady decline in regenerative capacity with each sequential irradiation. After the sixth irradiation, the number of spleen colonies and iron uptake were reduced to one-fifth of that of singly irradiated controls. A decline in body weight and an increase in irradiation mortality accompanied the decline in postirradiation hematopoiesis.

The degree of measured decline in hematopoietic proliferative ability was less than that observed by other investigators who studied the effect of serial transplantation of cells upon their ability to proliferate. Furthermore, even after the sixth irradiation, a marked stimulation of postirradiation hematopoiesis was induced by bleeding the animals before irradiation.
THE DETECTION OF A VIRAL INTERFERING SUBSTANCE IN THE SHOPE PAPILLOMA AND THE Vx7 AND Vx2 CARCINOMAS
Authors: Langston Deborah Pavan , Sobin Leslie H.
Published: June 2004

In vivo assay of Shope papilloma protein extract and in vitro assay of extracts from Shope papilloma, Vx7 and Vx2 carcinomas showed strong interferon-like activity in the papilloma and moderate activity in the carcinomas. The interpretation is that the presence of viral nucleic acid in all three tumors stimulated the production of this substance even though fluorescent antibody studies reveal the protein coat only in the papilloma and Vx7.
THE UPTAKE AND DIGESTION OF IODINATED HUMAN SERUM ALBUMIN BY MACROPHAGES IN VITRO
Authors: Ehrenreich Barbara A. , Cohn Zanvil A.
Published: June 2004

Mouse peritoneal macrophages take up I*-HSA from their medium during in vitro cultivation. Conditions which promote I*-HSA uptake are the same as those which stimulate formation of pinocytic vesicles. Autoradiography of cells pulsed with 125I-HSA showed that intracellular isotope is localized in perinuclear granules, or secondary lysosomes.

Following a pulse of 125I-HSA, intracellular radioactivity decreases and the amount of TCA-soluble isotope in the medium increases correspondingly. About 50% of the intracellular isotope is lost in 5 hr. The release of isotope from pulsed cells is not inhibited by parafluorophenylalanine, 2,4-dinitrophenol or by a reduction of the serum concentration of the medium. However, the processing of ingested 125I-HSA is reversibly inhibited by reduced temperature.

The TCA-soluble radioactive material excreted by pulsed macrophages was identified as monoiodotyrosine.
AN ASSAY FOR DETERMINING THE RELATIVE AFFINITY OF TRACE AMOUNTS OF LABELED ANTIBODIES
Authors: Steiner Lisa A. , Eisen Herman N.
Published: June 2004

All assay for the binding efficiency or "relative affinity" of trace amounts of radioactively labeled anti-2,4-dinitrophenyl (DNP) antibodies has been developed. The assay measures the relative ability of the labeled antibodies to combine and precipitate with antigen in the presence of a large amount of unlabeled reference antibody of the same specificity. It has been possible to correlate the relative affinity of the labeled antibodies for dinitrophenylated antigens with the association constants of the reference antibodies for simple univalent DNP ligands.
THE EXPERIMENTAL INDUCTION OF GLOMERULONEPHRITIS LIKE THAT IN MAN BY INFECTION WITH GROUP A STREPTOCOCCI
Authors: Becker Carl G. , Murphy George E.
Published: June 2004

106 rabbits received one or more courses of inoculations, spaced 1–4 months apart, with Group A streptococci, usually of strains isolated from patients with acute glomerulonephritis. 8 days to a few weeks after onset of a given infection with streptococci known to have been nephritogenic for man, marked proteinuria, often with hematuria and occasionally with azotemia, was detected in 22 of the animals. 15 of these were sacrificed a few days to a few weeks thereafter, and 10 showed renal changes like those of acute or recurrent acute glomerulonephritis in man. Such changes occurred in three other rabbits whose urine was not examined that died or were sacrificed 1–3 wk after onset of infection with streptococci of a serotype known to include a strain nephritogenic for man. The remaining seven animals in which marked proteinuria had occurred died or were sacrificed many months later, in some cases after additional infections. Two of these had become azotemic and two convulsed and died after giving birth; in these animals, there were renal changes like those that occur in man in chronic latent glomerulonephritis, toxemia of pregnancy super-imposed on chronic latent glomerulonephritis, or chronic active glomerulonephritis. Anatomical changes in the kidneys in the experimentally induced and in naturally occurring glomerulonephritis, from acute to chronic stages, are compared and illustrated. The pathogenesis of poststreptococcal glomerulonephritis is discussed.
ANTIGENS IN IMMUNITY
Authors: Nossal G. J. V. , Abbot A. , Mitchell Judith , Lummus Z.
Published: June 2004

This paper describes the trapping of antigen in lymphoid follicles of rat popliteal lymph nodes as revealed by electron microscopic radioautographs following injection of 125I-labeled Salmonella adelaide flagella and other materials.

The antigen was taken up vigorously, and to an approximately equal extent, by both primary and secondary follicles. The rate of uptake was faster in preimmunized than in virgin adult rats. The bulk of the antigen in follicles was extracellular, and persisted in this location for at least 3 wk. Label was most frequently found at or near the surface of fine cell processes. Many of these were branches of dendritic follicular reticular cells. Such processes interdigitated with equally fine processes of lymphocytes, creating an elaborate meshwork. In some cases, antigen was found between lymphocytes which appeared to be in close apposition. Occasionally, a few grains appeared over lymphocyte nuclei and study of serial sections suggested that this probably represented true entry of small amounts of antigen into lymphocytes.

The characteristic "tingible body" macrophages (TBM) of germinal centers appeared to play only a secondary role in follicular antigen retention. They showed degrees of labeling over their phagocytic inclusions varying from negligible to moderately heavy. Moreover, follicles lacking or poor in TBM retained antigen just as effectively as those containing numerous TBM. The hypothesis is advanced that TBM may be derived from monocytes that migrate down from the circular sinus.

Follicular localization of three other materials was also studied, though not in such detail. These were 125I-HSA complexed to anti-HSA: 125I-labeled autologous IgG; and 125I-monomeric flagellin. All of these showed the basic features of intercellular, membrane-associated deposition noted with 125I-flagella.

The role of follicular antigen depots in immune induction is discussed. The tentative conclusion is reached that follicular antigen in a primary follicle encounters natural antibody on the surface of certain antigen-reactive lymphocytes. The resultant reaction causes blast cell transformation and eventually the genesis of a germinal center.
THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION
Authors: Byers Vera S. , Sercarz Eli E.
Published: June 2004

A set of conditions has been described under which primed rabbit lymph nodes produce a secondary antibody response upon in vivo stimulation with a large dose of antigen, but are subsequently "exhausted;" that is, lymph node cultures prepared at intervals following the booster injection cannot be re-stimulated to display tertiary responses. Rabbits given 100-fold less antigen in the booster inoculum were able to give a tertiary response upon in vitro challenge. The system used permits neither induction nor continuation of a primary response to BSA in vitro. Since it could be demonstrated that no memory cells were generated by the booster injection within the intervals between in vivo injection and culture, the tertiary response in nonexhausted nodes must have been due to residual memory cells which remained untriggered by the in vivo booster injection.

The unresponsive state was not caused by antibody feedback.

These results are interpreted to mean that a population of memory cells can be exhausted by a supraoptimal dose of antigen, rendering the node temporarily incapable of further response. This implies that long-lived memory is not due to asymmetric division of memory cells. The source and fate of memory cells is discussed with regard to this evidence.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Kozak Marilyn Sue , Hahn Helmut H. , Lennarz William J. , Wood W. Barry
Published: June 2004

Small quantities of highly purified granulocytic pyrogen have been separated from contaminating proteins by disc electrophoresis in polyacrylamide gel. The biologically active material thus isolated was shown to be electrophoretically homogeneous at pH 9 and pH 3.8.

Earlier work on the chemical properties of the pyrogen molecule has been extended to include: (a) estimation of its molecular weight by gel filtration; (b) demonstration of free sulfhydryl groups essential for its biological activity; and (c) evidence that it is not inactivated by exhaustive extraction with ethanolether or n-heptane.
AN INTESTINAL THREADWORM AS A RESERVOIR AND INTERMEDIATE HOST FOR SWINE INFLUENZA VIRUS
Authors: Shotts Emmett B. , Foster John W. , Brugh Max , Jordan Helen E. , McQueen James L.
Published: June 2004

A laboratory model exemplifying Shope's concept of virus carriage by helminths was developed using Strongyloides ratti (Sandground, 1925), swine influenza virus, and caesarean-originated, barrier-sustained (COBS) mice and rats.

It was shown that S. ratti can act as a carrier of swine influenza virus and infect mice, despite the fact that the nematode has undergone a complete life cycle after exposure to virus in infected rats.

COBS rats were inoculated with the virus via the intranasal route and subsequently infected with S. ratti. The larvae and eggs found in the feces collected from these rats were allowed to develop in vitro. These second generation filariform larvae were then inoculated subcutaneously into COBS mice. At necropsy, 5–8 days postinoculation, swine influenza virus was isolated from 15% of the mouse lungs. In control studies, swine influenza virus was not isolated from the feces of the COBS rats which served as a source of both unexposed and exposed S. ratti. Swine influenza virus was recovered in vitro from S. ratti homogenates. It is suggested that this laboratory model be used to study more closely the various aspects of the ecology of virus-helminth relationships in vertebrate hosts.
THE DERIVATION OF TWO DISTINCT ANAPHYLATOXIN ACTIVITIES FROM THE THIRD AND FIFTH COMPONENTS OF HUMAN COMPLEMENT
Authors: Cochrane C. G. , Müller-Eberhard H. J.
Published: June 2004

Anaphylatoxin activity was derived from both human C'5 and C'3 molecules. This was achieved in the case of C'5 by interaction with trypsin or with EAC'4, oxy2a, 3. The smooth muscle-contracting material obtained from the treated C'5 was found to be a fragment of approximately 9,000–11,000 molecular weight. Its action was inhibited with antihistamine. The trypsinized C'5 also increased vascular permeability in guinea pig skin.

When human C'3 was incubated with C'3 inactivator complex, which consists of a cobra venom protein and a ß-globulin of human serum, anaphylatoxin activity was observed. The activity was associated with a fragment cleaved from the C'3 molecule, having a molecular weight of between 6,000 and 15,000 as determined by gel filtration techniques. Similar activity was derived from C'3 by the C'3-converting enzyme in free or in cell-bound form.

The C'5 anaphylatoxin failed to cross-desensitize guinea pig ileum to the contracting capacities of C'3 and guinea pig anaphylatoxin and vice versa. Anaphylatoxin prepared from C'3 by all methods mentioned above caused cross-desensitization to the other C'3 derivatives, but failed to desensitize to guinea pig anaphylatoxin.
CYTOLOGICAL EVIDENCE FOR A RELATIONSHIP BETWEEN NORMAL HEMATOPOIETIC COLONY-FORMING CELLS AND CELLS OF THE LYMPHOID SYSTEM
Authors: Wu A. M. , Till J. E. , Siminovitch L. , McCulloch E. A.
Published: June 2004

The relationship between hematopoietic colony-forming stem cells and cells in the thymus and lymph nodes of unirradiated mice has been investigated using a chromosome-marker technique. It was found that a high proportion of cells in the thymus may belong to the same clone as normal hematopoietic colony-forming cells. It was also found that cells belonging to the same clone as colony-forming cells may reach the lymph nodes, and that nodes containing such cells can participate in an immunological response against sheep red cells. Either the precursors of cells in thymus and lymph node are identical with hematopoietic colony-forming cells, or they are both descendants of a common precursor which has not yet been identified. The results are compatible with the view that cells of the hematopoietic system and the immune system may be derived from the same stem cell.
ANTIGENIC MODULATION
Authors: Old Lloyd J. , Stockert Elisabeth , Boyse Edward A. , Kim Jae Ho
Published: June 2004

Antigenic modulation (the loss of TL antigens from TL+ cells exposed to TL antibody in the absence of lytic complement) has been demonstrated in vitro. An ascites leukemia, phenotype TL.1,2,3, which modulates rapidly and completely when incubated with TL antiserum in vitro, was selected for further study of the phenomenon. Over a wide range of TL antibody concentrations modulation at 37°C was detectable within 10 min and was complete within approximately 1 hr. The cells were initially sensitized to C' by their contact with antibody, thereafter losing this sensitivity to C' lysis together with their sensitivity to TL antibody and C' in the cytotoxic test. The capacity of the cells to undergo modulation was abolished by actinomycin D and by iodoacetamide, and by reducing the temperature of incubation to 0°C. Thus modulation apparently is an active cellular process. Antigens TL. 1,2, and 3 are all modulated by anti-TL.1,3 serum and by anti-TL.3 serum. This modulation affects all three TL components together, even when antibody to one or two of them is lacking. aAnti-TL.2 serum does not induce modulation and in fact impairs modulation by the other TL antibodies. The influence of the TL phenotype of cells upon the demonstrable content of H-2 (D region) isoantigen, first shown in cells modulated in vivo, has been observed with cells modulated in vitro. Cells undergoing modulation show a progressive increase in H-2 (D region) antigen over a period of 4 hr, with no change in H-2 antigens of the K region. Restoration of the TL+ phenotype of modulated cells after removal of antibody is less rapid than TL+ → TL- modulation and may require several cell divisions.
AUTOLOGOUS IMMUNE COMPLEX NEPHRITIS INDUCED WITH RENAL TUBULAR ANTIGEN
Authors: Glassock Richard J. , Edgington Thomas S. , Watson J. Ian , Dixon Frank J.
Published: June 2004

The pathogenetic mechanism involved in a form of experimental allergic glomerulonephritis induced by immunization of rats with renal tubular antigen has been investigated. A single immunization with less than a milligram of a crude renal tubular preparation, probably containing less than 25 µg of the specific nephritogenic antigen, is effective in the induction of this form of chronic membranous glomerulonephritis. In the nephritic kidney autologous nephritogenic tubular antigen is found in the glomerular deposits along with γ-globulin and complement. When large amounts of antigen are injected during induction of the disease the exogenous immunizing antigen can also be detected in the glomerular deposits. It appears that this disease results from the formation of circulating antibodies capable of reacting with autologous renal tubular antigen(s) and the deposition of these antibodies and antigen(s) plus complement apparently as immune complexes in the glomeruli. This pathogenetic system has been termed an autologous immune complex disease and the resultant glomerulonephritis has been similarly designated.
STUDIES ON HUMAN ANTIBODIES
Authors: Yount William J. , Dorner Marianne M. , Kunkel Henry G. , Kabat Elvin A.
Published: June 2004

The composition of various isolated antibodies was determined by quantitative analyses for heavy chain subgroups and light chain types. Certain antibodies such as anti-tetanus toxoid and anti-A isoagglutinins were predominantly of the major γG1-type. However, a high preponderance of molecules of the minor γG2-subgroup was found for antibodies to dextran, levan, and teichoic acid. These findings explain some unusual features previously noted for anti-dextrans such as weak PCA reactions and lack of Gm antigens.

Studies of several isolated antibodies from single heterozygous individuals showed a selective absence of genetic markers in certain antibodies and their presence in others. The "allelic exclusion" principle was clearly evident in the isolated antibodies of two different individuals.

Large differences in the ratio of kappa to lambda light chains were observed for the same type of antibody from different individuals. Subfractionation of dextran antibodies by affinity for specific glycosidic linkage or combining site size produced marked changes in the ratios. The isomaltohexaose eluates of the dextran antibodies from two subjects were primarily kappa and the isomaltotriose eluates were predominantly lambda.

The one anti-levan antibody studied was uniquely homogeneous, consisting exclusively of γG2-heavy chains and kappa light chains. By these criteria as well as others, it closely resembled myeloma proteins.
PREVENTION OF WASTING DISEASE BY PREGNANCY ASSOCIATED WITH HYPERTROPHY OF THE FETAL THYMUS
Authors: Elders M. J. , Parham B. A. , Hughes E. R.
Published: June 2004

Neonatally thymectomized female mice were studied and compared to appropriate controls. Neonatal thymectomy appears to decrease fertility significantly in the female C3H/HeJ mouse. However, if a thymectomized female mouse becomes pregnant, pregnancy offers significant protection against wasting disease and death. The maternal thymus appears to play no significant role in the development of the fetus as measured by gross examination and organ weights. Offspring of thymectomized females had comparable body and organ weights when compared to offspring from sham-operated females, except for the thymus gland and gastrointestinal tract. The absence of the maternal thymus gland did stimulate a significant increase in the gland weight of her offspring compared to sham-operated control female offspring. Parity, per se, in intact females also causes a significant increase in the weights of the thymus of newborn offspring.
INTRAPHAGOCYTIC ß-N-ACETYLGLUCOSAMINIDASE
Authors: Ayoub Elia M. , McCarty Maclyn
Published: June 2004

The ß-N-acetylglucosaminidases of rabbit and human polymorphonuclear leukocytes and of rabbit alveolar macrophages have been studied in comparison with the ß-N-acetylglucosaminidase derived from a soil bacillus which had previously been shown to hydrolyze the group-specific polysaccharide of Group A streptococci. The phagocytic enzymes are lysosome associated and have an acid pH optimum. In contrast, the soil bacillus enzyme is an extracellular product, has a higher pH optimum, and is probaby of smaller molecular size.

When tested on p-nitrophenyl-ßN-acetylglucosaminide as substrate, the Km of the phagocytic enzymes is slightly higher than that of the soil bacillus. However, there were extreme differences in their effect on the Group A streptococcal polysaccharide. Thus, 5 x 106 units of the alveolar macrophage enzyme were required to hydrolyze the available N-acetylglucosamine of 1 mg of polysaccharide in 18 hr, while 100 units of the soil bacillus enzyme were sufficient to achieve this hydrolysis. In both cases, the serological reactivity of the polysaccharide is altered with loss of Group A specificity and acquisition of a new specificity characteristic of A-variant streptococci. Possible explanations for differences in the activity of the enzymes are considered, and the role of the phagocytic enzymes in intracellular degradation of Group A streptococci is discussed.
INDUCTION OF BONE MARROW COLONY-STIMULATING ACTIVITY BY A FILTERABLE AGENT IN LEUKEMIC AND NORMAL MOUSE SERUM
Authors: Foster Roger , Metcalf Donald , Kirchmyer Rosemary
Published: June 2004

1. Leukemic Swiss mice of ICR/Ha strain which had been injected at birth with a lymphoid-leukemia-inducing virus preparation yielded sera which produced elevations of serum colony-stimulating activity within 16 hr and significant plasma-LDH-enzyme elevation at 4 days when injected intraperitoneally into normal ICR/Ha Swiss mice. Colony-stimulating activity was assayed in vitro by the stimulation of hemopoietic colony formation by DBA/1 bone marrow cells.

2. The inducing agent in leukemic serum was passageable, filterable, sedimentable, and heat-, ether-, and UV-labile.

3. A similar agent was recovered from normal Swiss serum after blind serial passages through normal mice.

4. LDH elevating virus induced a similar elevation of serum colony-stimulating activity when injected at high titers, and cross-resistance was demonstrated between LDH virus and the passaged leukemic serum agent.
THE PRIMARY IMMUNE RESPONSE IN MICE
Authors: Franzl Robert E. , McMaster Philip D.
Published: June 2004

The manner in which a single injection of S. typhosa endotoxin effects the primary hemolysin response to sheep erythrocytes in the mouse has been shown to depend on the dosage, route, and time of administration of the endotoxin, as well as on the route employed for the injection of antigen. The normal production of antibody, following an intravenous or an intraperitoneal injection of red blood cells, is suppressed if the bacterial lipopolysaccharide is given before and by the same route as the antigen. The response to an intraperitoneal injection of sheep red cells is also inhibited if preceded by an intravenous injection of endotoxin. By contrast, hemolysin formation to intravenous antigen is enhanced considerably by a previous intraperitoneal injection of endotoxin, and the response both to intravenous and to intraperitoneal injections of the antigen increases if the endotoxin is given by the same route either simultaneously or shortly after the foreign red cells. These findings are discussed in regard to the physiological action of bacterial endotoxins and the early events in antibody formation.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Sell Stewart
Published: June 2004

Rabbit antisera to immunoglobulin allotype Ab4 will stimulate a maximum of 77% (mean ± SEM = 39.78 ± 4.8) blast transformation of Ab4Ab4 homozygous lymphocytes in vitro and a maximum of 39% (mean ± SEM = 19.77 ± 1.6) blast transformation of heterozygous Ab4Ab5 lymphocytes. Similarly anti-Ab5 sera will induce a maximum of 82% (mean ± SEM = 50.83 ± 7.0) blast transformation of Ab5Ab5 homozygous lymphocytes in vitro and a, maximum of 42% (mean ± SEM = 16.1 ± 1.6) blast transformation of heterozygous Ab4Ab5 lymphocytes. Thus, the lymphocytes of an allotypically heterozygous rabbit appear to be selected to produce or express only one of the two genetically supplied allotypic determinants controlled by the "b" locus. A similar conclusion has been made in regard to allotypic expression by immunoglobulin-producing plasma cells.

Previous data indicate that each lymphocyte carries or expresses more than one immunoglobulin group specificity (IgG, IgA, IgM) while each plasma cell carries only one. One possible interpretation of these data is that, while the production of immunoglobulin groups and allotypic specificities are under similar control in both the lymphocyte and the plasma cell, the lymphocyte produces immunoglobulin that remains in or attached to itself and the plasma cell produces immunoglobulins that are secreted rapidly.
THE EFFECT OF HETEROLOGOUS ANTI-LYMPHOCYTIC SERUM ON THE SMALL LYMPHOCYTE POPULATION OF RATS
Authors: Agnew Hewes D.
Published: June 2004

Treatment of Lewis strain rats with a single subcutaneous dose of rabbit anti-rat thymocyte serum (RARTS) resulted in a marked depletion of small lymphocytes in the blood and thoracic duct lymph for approximately 10 days. While the thoracic duct lymphocytes were declining in numbers, rabbit antibody could be detected on the surfaces of a high percentage of the lymph cells. Furthermore, the thoracic duct lymphocytes were unable to initiate graft vs. host reactions during the period of depletion, even when injected in extremely large doses. Approximately 2 wk after treatment, the numbers and immune competence of the small lymphocytes returned to normal.
PREDICTED AND UNPREDICTED CROSS-REACTIONS OF AN ACETYLPHOSPHOGALACTAN OF SPOROBOLOMYCES YEAST
Authors: Heidelberger Michael , Slodki Morey E.
Published: June 2004

The teichoic acid of streptococcal Group N, with end groups of galactose phosphate, had been shown to cross-react with antipneumococcal sera of types VI, XIV, XVI, and XXVII. End groups of D-galactose-1-phosphate in the phosphogalactans of Sporobolomyces yeasts made it predictable that these galactans would precipitate the same antipneumococcal sera and also antisera to streptococcal Group N. The predictions were verified, and other unpredicted reactions were found. Precipitation of much of the antibody in an antipneumoccal type XVIII horse serum was shown to be due to O-acetyl-D-galactose residues in the phosphogalactan, in accord with earlier information that an O-acetyl sugar was a principal determinant of S XVIII. The new results identify this sugar as D-galactose. Since it is linked 1,3- in S XVIII, the O-acetyl group in the Sporobolomyces galactan is probably also on a 1,3-linked residue. Another major cross-reaction in anti-S. paratyphi A serum characterizes the galactose residues in the "O" polysaccharide of the bacillus as members of the D-series probably linked in tandem 1,6-, 1,6-; 1,6-, 1,3-; 1,3-, 1,6-; or 1,3-, 1,3-. Reactions of periodate-oxidized-reduced products confirm the conclusions stated above. Quantitative data are given.
THE THYMUS AND RECOVERY FROM CYCLOPHOSPHAMIDE-INDUCED TOLERANCE TO SHEEP ERYTHROCYTES
Authors: Aisenberg Alan C. , Davis Caroline
Published: June 2004

Recovery from specific immunological tolerance to sheep erythrocytes induced with the drug cyclophosphamide was studied with the hemolytic plaque technique of Jerne. The base line plaque (19S antibody-forming cell of the unstimulated spleen) and the proliferative response to antigen, both of which had disappeared during tolerance induction, returned with the recovery of specific immunological reactivity.

When cyclophosphamide is injected without sheep cells there is temporary immunological unreactivity and lymphoid depletion of the spleen, but specific tolerance is not induced. Recovery is largely complete at the end of 2 wk and does not require the participation of the thymus.

When cyclophosphamide is injected together with sheep cells, 18 days after drug injection, tolerance is still complete. In nonthymectomized mice there is rapid recovery during the next 10 wk, followed by much slower restoration over the remaining 20–30 wk of observation. The entire recovery process evidently takes 40–50 wk. In thymectomized CBA mice only minimal recovery takes place in the first 10 wk and no further restoration occurs thereafter. Thymectomy performed 18 days after tolerance is induced, when tolerance is complete, is equally effective in preventing this recovery.
ANTIBODIES TO INTESTINAL MICROVILLOUS MEMBRANES
Authors: Kopp William L. , Trier Jerry S. , Mackenzie Iain L. , Donaldson Robert M.
Published: June 2004

Antibodies (AbMVM) were produced in rabbits to microvillous membranes isolated from hamster small bowel. Incubation of frozen sections of hamster small bowel with fluorescein-labeled AbMVM showed specific reaction with brush borders, but not with other intestinal cellular components. Electron microscopy with ferritin-conjugated AbMVM localized the antigens more precisely to the surface mucopolysaccharide coat of the brush borders. AbMVM also reacted with the brush border of colon and of proximal renal tubules of hamsters but not with those of hamster stomach or gall bladder. It also reacted with the brush borders of some rat and human tissues, but not with those of rabbits. In addition, fluorescent-labeled AbMVM combined specifically with cell walls of some yeasts, but not of several bacteria. AbMVM also contained a weak precipitin to a component of hamster serum, which migrated like prealbumin in immunoelectrophoresis.
PHAGOCYTOSIS IN SUBACUTE BACTERIAL ENDOCARDITIS
Authors: Quie Paul G. , Messner Ronald P. , Williams Ralph C.
Published: June 2004

The opsonic properties of immune γG-globulins isolated from patients with chronic septicemic conditions, principally subacute bacterial endocarditis were studied. Opsonic capacity as well as complement-fixing properties of γ-globulins appeared to be closely associated with integrity of Fc structures. Progressive pepsin digestion of immune γG-globulins, as monitored by successive loss of Gm(a) and Gm(b) antigens, abolished opsonic activity. Colostral γA, containing agglutinating antibacterial antibodies but no demonstrable complement-fixing activity, was devoid of opsonic capacity. Reduction of γ-globulin opsonins with 0.01 or 0.1 M mercaptoethanol progressively abolished opsonic activity in parallel with loss of ability of treated γ-globulins to fix complement with bacteria. Treatment of γ-globulin opsonins with 0.01 M sodium metaperiodate also produced complete loss of opsonic capacity in parallel with loss of Gm(b) Fc antigens. These findings, together with antiopsonic effects demonstrable with anti-γ-globulin factors showing primary reactivity with Fc structures, indicate that the opsonic property of immune γ-globulins requires the participation of structures integral to the Fc region of γ-globulin.
PHENOTYPIC EXPRESSIONS OF THE MAJOR HISTOCOMPATIBILITY LOCUS IN MAN (HL-A): LEUKOCYTE ANTIGENS AND MIXED LEUKOCYTE CULTURE REACTIVITY
Authors: Amos D. Bernard , Bach Fritz H.
Published: June 2004

The evidence is reviewed that a single genetic system, the major histocompatibility locus in man, HL-A, determines most of the antigens measured by presently available leukocyte isoantisera, and also controls reactivity in one-way mixed leucocyte culture tests. Studies in 12 families are presented to support this conclusion. Some interesting exceptions to the general typing—MLC tests correlation are presented and discussed.
CHEMICAL CHARACTERIZATION OF GLYCOPEPTIDES FROM HUMAN γM-GLOBULINS
Authors: Davie Joseph M. , Osterland C. Kirk
Published: June 2004

A survey of human pathological macroglobulins revealed that γM can be divided into at least two groups on the basis of carbohydrate composition. Differences between the two groups exist in the total percentage of carbohydrate (10.69 ± 1.49% for group 1, 7.71 ± 0.65% for group II) which is attributable to variation in hexose content. Glycopeptides from macroglobulins of each group were purified from pronase digests and characterized chemically. Macroglobulins from each group contain three types of oligosaccharides. Glycopeptide I for each group consisted of mannose, galactose, and NAG with a ratio of 3:2:1 for group I and a ratio of 2:1:2 for group II. Glycopeptide II consisted of mannose, galactose, and NAG (9:1:2) for group I, and mannose, fucose, galactose, and NAG (2:1:3:2) for group II. Glycopeptide III in both groups consisted of mannose, fucose, galactose, NAG, and sialic acid with a ratio of 6:2.5:2.5:5.5:2 for group I and a ratio of 5:1:1:6:1 for group II. Molecular weight estimations by gel filtration indicates that there are 10 glycopeptides I and II and 20 units of glycopeptide III per molecule of γM.
ISOZYMES OF ACID PHOSPHATASE IN NORMAL AND CALMETTE-GUÉRIN BACILLUS-INDUCED RABBIT ALVEOLAR MACROPHAGES
Authors: Axline S. G.
Published: June 2004

The acid phosphatase activity of normal alveolar and BCG-induced alveolar macrophages has been examined. Five electrophoretically distinct forms of acid phosphatase have been identified in both normal and BCG-induced macrophages. The acid phosphatases can be divided into two major categories. One category, containing four distinct forms, is readily solubilized after repeated freezing and thawing or mechanical disruption The second category, containing one form, is firmly bound to the lysosomal membrane and can be solubilized by treatment of the lysosomal fraction with Triton X-100.

The Triton-extractable acid phosphatase and the predominant aqueous soluble acid phosphatase have been shown to differ in the degree of membrane binding, in solubility, in net charge, and in molecular weight. The two pre-dominant phosphatases possess identical pH optimum and do not differ in response to enzyme inhibitors.

BCG stimulation has been shown to result in a nearly twofold increase in acid phosphatase activity. A nearly proportionate increase in the major acid phosphatase forms has been observed.
INCORPORATION OF SULFATE BY THE MOUSE THYMUS: ITS RELATION TO SECRETION BY MEDULLARY EPITHELIAL CELLS AND TO THYMIC LYMPHOPOIESIS
Authors: Clark Sam L.
Published: June 2004

The thymus was examined in suckling mice during normal development and the involution and regeneration produced by injection of cortisol, in experiments designed to test the hypothesis that medullary epithelial cells secrete a ymphopoietic hormone responsible for controlling the magnitude of thymic lymphopoiesis. Cellular events were observed by light and electron microscopy. Lymphopoiesis was assessed, after injection of thymidine-3H, by counting the proportion of lymphocytes labeled in radioautographs of thymus. Cortical lymphopoiesis was distributed heterogeneously, being concentrated in the subcapsular region, but medullary lymphopoiesis was statistically homogeneous in distribution and similar in magnitude to the average level of cortical lymphopoiesis in suckling mice. Therefore counts of the labeling index in the medulla were used to estimate the size of the proliferating population of lymphocytes. Epithelial secretory activity was estimated by measuring the incorporation of 36sulfate by the thymus, using gel filtration chromatography to isolate soluble macromolecular 35sulfate—presumed on radioautographic evidence to represent the mucoid epithelial secretory product.

Incorporated 35sulfate accumulated rapidly for 4 hr, reached a peak at 12 hr, and had fallen to half that level by 24 hr after a single injection—as would be expected of a secretory product. During normal postnatal development the size of the proliferating population of lymphocytes and the magnitude of 35sulfate incorporation increased in parallel. During acute involution induced by cortisol both parameters diminished greatly but rose to high levels during subsequent regeneration. Accordingly, lymphopoiesis and sulfate incorporation —as defined and measured in these experiments—correlated linearly over a wide range of variation, providing circumstantial evidence to support the hypothesis that medullary epithelial cells secrete a sulfated mucoid lymphopoietic hormone. This conclusion is discussed in terms of the roles of thymus and adrenal cortex in development of the lymphoid system and maturation of immunological competence.
CYTOTOXICITY MEDIATED BY SOLUBLE ANTIGEN AND LYMPHOCYTES IN DELAYED HYPERSENSITIVITY
Authors: Ruddle Nancy H. , Waksman Byron H.
Published: June 2004

The cytopathic effect of lymph node cells from tuberculin-sensitized rats on rat embryo fibroblasts in the presence of PPD was not enhanced by admixture of normal (nonsensitized) lymph node cells. Preincubation studies showed that this in vitro response is initiated by the reaction of lymphocytes with specific antigen, beginning within 30 min, rather than uptake of antigen by the fibroblasts. The supernatant fluids from suspensions of sensitized cells incubated with PPD for 17 hr or more possessed cytotoxic activity. The target fibroblasts showed a marked increase in acid phosphatase content within 48 hr after the addition of sensitized lymph node cells and antigen.
THE UPTAKE, STORAGE, AND INTRACELLULAR HYDROLYSIS OF CARBOHYDRATES BY MACROPHAGES
Authors: Cohn Zanvil A. , Ehrenreich Barbara A.
Published: June 2004

The exposure of cultivated mouse macrophages to sucrose (0.009–0.03 M) leads to the formation of large phase- and electron-lucent, acid phosphatase-positive vacuoles in the perinuclear region. The vacuolization process and the uptake of sucrose-14C is blocked by inhibitors of pinocytosis and stimulated by calf serum in the medium. These results suggest the uptake of sucrose by pinocytosis and its subsequent segregation and storage in secondary lysosomes. The addition of sucrose also increases the total content of three macrophage lysosomal hydrolases.

The addition of invertase to the environment of sucrose-laden macrophages leads to the prompt shrinkage of the sucrose-containing lysosomes. This is accompanied by the intracellular hydrolysis of sucrose to fructose and glucose residues which are promptly excreted into the medium. The uptake of invertase, as indicated by the shrinkage of sucrose-containing vacuoles, is blocked by inhibitors of pinocytosis. No effect was noted when invertase was added to macrophages laden with Ficoll, a polysucrose which is not hydrolyzed by the enzyme.

The influence of other carbohydrates was then investigated. Monosaccharides with molecular weights up to 220 did not produce vacuolization. However, a certain number of di-, tri-, and tetrasaccharides produced vacuolization identical with that of sucrose. Each of the disaccharides which produced vacuolization was resistant to the complement of macrophage hexosidases, whereas those that were ineffective were degraded by either macrophage or serum enzymes. The addition of ß-glucosidase to cellobiose-laden macrophages resulted in the shrinkage of vacuoles but did not alter the vacuoles of sucrose containing cells.

The ability of small, neutral carbohydrates to produce lysosomal swelling is dependent upon both molecular weight and their resistance to lysosomal hydrolases.
THE FATE OF PEPTIDES PINOCYTOSED BY MACROPHAGES IN VITRO
Authors: Ehrenreich Barbara A. , Cohn Zanvil A.
Published: June 2004

A series of small peptides, such as might arise in the course of intralysosomal protein digestion, were screened for the ability to escape, intact, from mouse peritoneal macrophage lysosomes. Inability to penetrate lysosomal membranes was inferred from a peptide's induction of lysosomal swelling, or vacuolization, in cultured macrophages.

Two of the peptides tested, (D-Glu)2 and (D-Ala)3, induced vacuolization. Neither peptide was susceptible to hydrolysis by enzymes in macrophages or in the serum-containing culture medium. Their morphological effect was inhibited by parafluorophenylalanine, an inhibitor of pinocytosis. Once formed by either peptide, the vacuoles persisted for several hours in peptide-free medium. Quantitative studies of radioactively labeled (D-Glu)2 confirmed the morphological evidence that (D-Glu)2 is taken up by pinocytosis and stored, intact, in macrophage lysosomes.

The majority of the peptides which failed to induce vacuolization—(L-Ala)2, L-Ser·L-Ala, L-Val·L-Ala, L-Ala·L-Thr, Gly·D, L-Phe, L-Ala·D-His, (L-Ala)3, (L-Glu)2, and D-Leu·L-Tyr—were found to be susceptible to hydrolysis by cellular or serum peptidases. Their failure to induce vacuolization was attributed to their hydrolysis to subunits capable of penetrating lysosomal membranes.

Some of the peptides which had failed to induce vacuolization—(D-Ala)2, D-Ser·D-Ala, D-Val·D-Ala, Gly-D-Asn, D-Ala·D-Thr, and D-Arg·D-Val—were found to be indigestible. Except for the cytotoxic peptide D-Arg·D-Val, peptides in this category all had lower molecular weights and volumes than (Glu)2 or (Ala)3. It is inferred that these peptides are small enough to escape from macrophage lysosomes, while (Glu)2 and (Ala)3 are too large to escape intact. The implications of this inference for the mechanism of intracellular digestion of pinocytosed proteins are discussed.
RELATION OF RHEUMATIC-LIKE CARDIAC LESIONS OF THE MOUSE TO LOCALIZATION OF GROUP A STREPTOCOCCAL CELL WALLS
Authors: Ohanian S. H. , Schwab J. H. , Cromartie W. J.
Published: June 2004

Mice injected intraperitoneally with isolated cell wall fragments of Group A streptococci develop a carditis similar to that previously observed in mice injected with crude extracts of this organism. Neither the soluble cytoplasmic components of Group A streptococcal cells nor the nonfragmented cell walls produced carditis in this experimental model. Fluorescein and 125I-labeled antibodies specific for Group A streptococcal cell wall antigens were used to demonstrate that, for 5 wk after injection, cell wall material is localized around the sites of active lesions in the heart. In addition, the cell wall antigen accumulates in the liver, spleen, mediastinal lymph nodes, and the adjacent loose connective tissue, where it persists for at least 10 wk.