bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF CRUDE PREPARATIONS OF VACCINIA ON MITOSIS AND DNA SYNTHESIS OF KB CELLS
Authors: Koziorowska Jadwiga , Włodarski Krzysztof
Published: June 2004

A morphologic study has been made on KB cells infected with various doses of vaccinia as to DNA synthesis and mitosis. Determination of mitotic indices revealed that the mitotic cell pool depended on the proportion of infected cells and the time after infection. By cytologic examination neither mitotic lesions were found nor an accumulation of mitotic cells at any one stage of mitosis was demonstrated. Radioautographs of infected cultures have shown that the frequency of cells labeled over nuclei was significantly increased as compared with control cultures.

Following the greatest dose of virus (multiplicity of 20 PFU/cell) the ratio of cells synthesizing DNA to mitotic cells increased from 45:5 at 5 hr to 50:0 at 50 hr. Concommittant with the appearance of this disparity between the DNA-synthesizing cell pool and mitotic cell pool the nuclei of cells became "lightly" labeled.

Following the lowest dose of virus (multiplicity of 0.0002 PFU/cell) the increase of the fraction of mitotic cells was proportional to the increase of the fraction of cells which were labeled over nuclei.
THE RENAL LESIONS OF ELECTROLYTE IMBALANCE
Authors: Oliver J. , MacDowell M. , Whang R. , Welt L. G.
Published: June 2004

A dietary depletion of magnesium in rats leads to the production in the thin limb of Henle's loop of the nephrons of spherical microliths composed of a matrix of PAS-positive substances and calcium phosphate (3).

These microliths grow by accretion to form intranephronic calculi.

The classical pathological syndrome of clinical nephrolithiasis is thus reproduced within the nephron; to wit, the origin of the calculus at a certain level, local traumatic damage at the site of its origin, passage with the fluid flow down the urinary passages, lodgment of the calculus at some restricting point, obstruction of fluid flow and the usual consequent localized intrarenal "hydronephrotic" alterations of regressive atrophic cellular dysplasias within the nephron. To the classical description of the two forms of urinary lithiases occurring in the bladder and in the renal pelvis must therefore be added a third form, intranephronic calculosis.

From the first origin of a microlith to its ultimate form as a calculus its organized structure is characterized by its matrix (PAS-positive materials) in which the periodic precipitation of crystalline mineral (Ca++, PO3---) occurs in a pattern simulating Liesegang rings.
DISQUISITIONS ON ORIGINAL ANTIGENIC SIN
Authors: de St.Groth S. Fazekas , Webster R. G.
Published: June 2004

Experiments in rabbits were designed to test the two unproven assumptions of the hypothesis proposed in the companion paper (1): that Original Antigenic Sin is fundamentally a restricted anamnestic response, and that there exists a trapping mechanism capable of deflecting antigen from one kind of cell and guiding it to another.

It is shown that whole-body X-irradiation, sufficient to abolish primary but not secondary production of antibodies, leaves all manifestations of the Original Antigenic Sin untouched. This proves the first assumption.

Primary immune animals challenged with very large doses of a related antigen produce an immediate response of cross-reactive antibodies, followed by a standard primary response to the challenging antigen. When boosted with an appropriate mixture of both antigens, the response is of standard secondary type to the homologous antigen, followed by a standard primary response to the crossreacting antigen. When animals are primarily vaccinated with a mixture of two related antigens, small booster doses of either will stimulate a standard secondary response only. When such animals are given very large booster doses of either antigen, the response is a compound of a homologous secondary and of an Original Antigenic Sin-type against the related antigen. Each of these findings demonstrates a corollary of the second assumption.

The results are discussed in terms of the limitations they impose on theories concerned with the production of antibodies.
THE REGULATION OF PINOCYTOSIS IN MOUSE MACROPHAGES
Authors: Cohn Zanvil A.
Published: June 2004

A method is described to study the formation of pinocytic vesicles in cultivated mouse macrophages. Vesicles which arise in the peripheral cytoplasm and are in transit to the centrosphere region are enumerated by the phase-contrast microscopy of glutaraldehyde-fixed cells. Under these conditions there is a prompt reversible response of vesicle formation to calf serum factors in the external environment. The reduction of pinosome formation by a variety of metabolic inhibitors was then studied in a medium containing 50% newborn calf serum.

Inhibitors of both glycolysis and respiration reduced vesicle formation to low levels. This influence was most striking with cyanide, antimycin A, and anaerobiosis. This indicates an important contribution of an intact respiratory pathway in pinocytosis.

Both 2,4-dinitrophenol and oligomycin inhibited vesicle formation at low concentrations. These data suggest a central role of ATP as an energy source for vesicle formation.

Inhibitors of protein synthesis, such as puromycin and p-fluorophenylalanine, produced a prompt reduction in vesicle formation. The action of p-fluorophenylalanine was effectively reversed with L-phenylalanine.

Actinomycin D depressed pinocytosis to low levels at concentrations of 0.1 to 0.003 µg/ml. This effect was observed only after a 120 min lag phase.

A 10°C reduction in ambient temperature lowered vesicle counts to 30% of control preparations at 37°C.
HOST-PARASITE RELATIONS IN MOUSE TYPHOID
Authors: Mackaness G. B. , Blanden R. V. , Collins F. M.
Published: June 2004

The development of acquired resistance to Salmonella typhimurium has been studied in mice infected intravenously with small numbers of streptomycin-sensitive or streptomycin-resistant organisms. By the 14th day of a primary infection the mouse develops a mechanism capable of destroying completely a super infecting dose of organisms, but is unable to eliminate organisms of the primary infection. The latter are constantly returned to the circulation from necrotic foci at the sites of implantation. Passive transfer of serum from actively infected or vaccinated animals, and immunization with heat-killed organisms, increase the capacity of the host to clear organisms from the blood, but do not interfere to any significant extent with their subsequent multiplication in the tissues. It is concluded that the resistance of actively infected animals depends on a nonhumoral mechanism capable of destroying organisms from endogenous or exogenous sources.
INFECTION-IMMUNITY IN EXPERIMENTAL SALMONELLOSIS
Authors: Collins F. M. , Mackaness G. B. , Blanden R. V.
Published: June 2004

Salmonella enteritidis is highly virulent for the mouse causing an infection resembling mouse typhoid. Survivors of the infection are completely resistant to reinfection and eliminate a large challenge dose of virulent organisms within 72 hr. The antigenically related Salmonella gallinarum was almost avirulent for the mouse but animals vaccinated with this organism were equally capable of eliminating a lethal dose of virulent S. enteritidis. Living Salmonella pullorum, on the other hand, was quickly eliminated from the tissues of normal mice. Vaccination with this organism failed to evoke an effective bactericidal mechanism. Alcohol-killed vaccines of these three Salmonellae all produced an increase in blood clearance rate, but gave only marginal protection against S. enteritidis. Liver and spleen counts on these mice revealed a 1 to 2 day delay before any net increase in the total bacterial population could be observed. Immunization of mice with increasing doses of living Salmonella montevideo resulted in progressively greater killing of a challenge dose of S. enteritidis despite the absence of common somatic antigens between the two strains. The degree of protection varied with the size of the residual population of S. montevideo in the vaccinated mice. The significance of these findings in assessing the importance of various factors involved in the development of acquired resistance to Salmonella infections is discussed.
THE EFFECTS OF ANTIGENS AND OF PHYTOHEMAGGLUTININ ON RABBIT SPLEEN CELL SUSPENSIONS
Authors: Harris G. , Littleton R. J.
Published: June 2004

Phytohemagglutinin (PHA) stimulated the rate of DNA synthesis in rabbit spleen cell suspensions. Unlike antigens, previous immunization to PHA was not necessary and the specific response could not be transferred by macrophages, although lymphocytes primed by incubation in PHA were able to stimulate other spleen cells not directly exposed to PHA. When rabbits were stimulated by in vivo immunization with antigens, spleen cells proliferating in response to antigen were stimulated to divide by in vitro contact with PHA.

Using the technique of specific hemolytic plaque formation by individual cells synthesizing γM-antibody to sheep red cells (plaque-forming cells), no evidence was obtained that stimulation of cell division by PHA resulted in specific antibody formation, although the presence of antigen resulted both in stimulation of cell proliferation and the production of plaque-forming cells. The presence of both sheep red cells and PHA in the medium of the same cell suspensions did not enhance the production of plaque-forming cells although there was a summative effect on DNA synthesis.
THE EOSINOPHILIC LEUKOCYTE
Authors: Ross Russell , Klebanoff Seymour J.
Published: June 2004

This study has presented the fine structure changes in the eosinophilic leukocyte in the rat uterus during the estrous cycle. Eosinophils were seen to emigrate into the uterine connective tissues from the blood stream. Just prior to, during estrus, and 1 day postestrus, eosinophilic leukocytes underwent lysis releasing their contents into the extracellular spaces and both whole eosinophils and individual granules from lysed cells were ingested by resident macrophages. No phagocytic activity by eosinophils was observed.

The possible relationship of the turnover of eosinophils to the profound morphologic and chemical changes in the uterus during the estrous cycle was discussed.
ANTIBODY FORMATION BY SINGLE CELLS FROM LYMPH NODES AND EFFERENT LYMPH OF SHEEP
Authors: Cunningham A. J. , Smith J. B. , Mercer E. H.
Published: June 2004

The antibody-forming cells which appear in the popliteal lymph node and efferent lymph of the sheep following immunization with boiled Salmonella have been studied by light and electron microscopy. Cells were incubated in monolayers with target erythrocytes sensitized with bacterial lipopolysaccharide. Three types of interaction between a proportion of the lymph cells and the erythrocytes surrounding them have been shown to indicate antibody formation: plaque-formation, immuno-cyto-adherence, and localized agglutination.

At the peak of the response, 4 days after antigenic stimulation approximately 1 cell in every 200 from lymph node suspensions produces detectable specific antibody, while up to 1 cell in 20 in the lymph is active.

For light microscope examination, individual antibody-forming cells were smeared in serum and stained with Leishman's stain. For electron microscopy, a number of active cells were clumped with antiserum to form a specimen of convenient size, then sectioned. Most of the active cells from efferent lymph are large and basophilic, while a small proportion are blastlike. These cells contain abundant free ribosomes and very little endoplasmic reticulum. In the node only, an additional class of antibody-forming plasma cells is found which have considerable amounts of endoplasmic reticulum in their cytoplasm.
OCCURRENCE AND PROPERTIES OF A MACROGLOBULIN DIMER IN SOME HYPERGLOBULINEMIC SERA
Authors: Suzuki T. , Deutsch H. F.
Published: June 2004

A 22S human γM-globulin component has been subjected to various study. It appears to be a dimer of 19S proteins and can undergo reversible molecular transitions which are both pH and temperature dependent. The 22S material regenerated from its 8S subunits no longer undergo similar transformations. Efforts to demonstrate that the 22S material was an antigen-antibody complex of 19S molecules were unsuccessful. Complex precipitin reactions in gels are given by macroglobulins containing this component with antibody to L chains.
MEDIATORS OF INFLAMMATION IN LEUKOCYTE LYSOSOMES
Authors: Seegers Winnifred , Janoff Aaron
Published: June 2004

The mast cell-rupturing component present in the lysosomes of rabbit exudate PMN neutrophil leukocytes has been identified and some of its physical and chemical properties have been described.

The active agent is a low molecular weight (1200 to 2400) polypeptide containing a relatively large proportion of the basic amino acid, arginine. It is thermostable and dialyzable, and does not cause contraction of the isolated guinea pig ileum. The mast cell-rupturing activity of the agent is destroyed by trypsin.

A second permeability factor with a larger molecular weight is present in crude extracts of PMN granules. Although this substance does not lyse mast cells, it is capable of evoking delayed permeability responses in rabbit skin.
PHYLOGENETIC ORIGINS OF ANTIBODY STRUCTURE
Authors: Marchalonis J. , Edelman G. M.
Published: June 2004

The anuran amphibian, Rana catesbiana, has been found to possess at least two kinds of immunoglobulins corresponding to γG- and γM-classes. These classes have the same chain structures as those of their counterparts in higher animal species. Light chains of both immunoglobulins had molecular weights of 20,000. Heavy chains of the γM-class had molecular weights of 72,100; those of the γG-class had molecular weights of 53,600. The carbohydrate content of the γG-immunoglobulin was 2.1%, and that of the γM-protein was 10.8%. The amino acid compositions of the immunoglobulins were generally similar to those of mammalian immunoglobulins.

After a single injection of phage antigen (f2), the order of appearance of phage-neutralizing activity in the frog immunoglobulin classes was (a) γM-antibodies, and (b) γG-antibodies.

The results of this and previous studies suggest that the γG-immunoglobulins emerged at some point in evolution between the elasmobranchs and the anuran amphibians.
EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS
Authors: Des Prez Roger M. , Bryant Richard E.
Published: June 2004

The divalent ion requirements of rabbit platelet injury by endotoxin have been defined by the use of various anticoagulant solutions and have been compared to the divalent ion requirements of platelet injury produced by addition of antigen to immune platelet-rich plasma. The endotoxin-platelet interaction takes place in citrated blood. Platelet damage by antigen is inhibited by citrate, but preincubation of antigen and immune platelet-poor plasma in the absence of citrate results in a substance, presumably antigen-antibody complement complex, which then does injure platelets in the presence of citrate. Neither endotoxin nor preincubated antigen injures platelets in the presence of sodium EDTA in concentrations sufficient to interact with all divalent cations present in plasma.

These observations have been interpreted by viewing the platelet-endotoxin interaction as a consequence of platelet phagocytosis of endotoxin, a reaction not requiring complement but requiring definite small concentrations of divalent cations. The interaction of antigen and platelets is regarded as a two phase reaction, the first requiring the participation of complement and concentrations of divalent cation larger than those provided in citrated plasma, the second requiring smaller concentrations of divalent cation, no further participation of complement, and active in citrated plasma. This second phase is regarded as representing platelet phagocytosis of immune complexes.
MECHANISMS OF ENDOTOXIN TOLERANCE
Authors: Greisman Sheldon E. , Young Edward J. , Woodward William E.
Published: June 2004

The mechanisms underlying the pyrogenic refractory state which develops rapidly during a continuous intravenous infusion of bacterial endotoxin have been further explored. The findings demonstrate that: (a) rabbits rendered refractory to a continuous intravenous infusion of E. coli endotoxin at a standard rate (18 x 10–4 µg/min) become highly refractory to a single intravenous test bolus of endotoxin, but remain fully responsive to preformed endogenous pyrogen and to substances known to release endogenous pyrogen, i.e. influenza virus, old tuberculin in specifically sensitized rabbits, and staphylococcal enterotoxin; (b) administration of fresh whole blood from normal donors containing an average of 1.6 – 108 granulocytes fails to restore febrile responsiveness to the continuing E. coli endotoxin infusion; (c) refractory phase plasma and liver homogenates exhibit no enhanced capacity to inactivate E. coli endotoxin pyrogenicity; (d) splenectomized animals readily develop the pyrogenic refractory state during E. coli endotoxin infusions and exhibit diminished, rather than the increased inflammatory responses to intradermal endotoxin seen in sham-operated controls; (e) continuous intravenous infusions of gelatin-stabilized, heat-killed pneumococci produce sustained fevers; and (f) continuous intravenous infusions of old tuberculin into specifically sensitized animals rapidly elicit a pyrogenic refractory state.

The present observations, considered together with those of other investigators, support the hypothesis that pyrogenic unresponsiveness to endotoxin involves two distinct immunologic mechanisms. In terms of this hypothesis, the rapid reduction in febrile responsiveness to endotoxin is mediated by desensitization at the cellular level. With small doses of endotoxin, such as those employed in the present studies, this desensitization is primarily specific; with larger doses, nonspecific mechanisms are superimposed. So long as the subsequent doses of endotoxin are closely spaced or continuously infused, optimal conditions are provided for cellular desensitization and pyrogenic unresponsiveness to a given quantity of endotoxin can be induced rapidly and maintained without the requirement for antibody. However, as the interval between endotoxin challenge is lengthened, cellular desensitization wanes and tolerance becomes increasingly dependent upon those antibodies directed against the common toxophore groupings responsible for endotoxin pyrogenicity which assist the reticuloendothelial system in the clearance and destruction of this molecule.
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.
STUDIES OF PPLO INFECTION
Authors: Aleu Fernando , Thomas Lewis
Published: June 2004

The ultrastructure of the experimental encephalopathy caused by Mycoplasma neurolyticum toxin has been studied. The primary changes are (a) massive distention of astrocytes by fluid, associated with degenerative changes in these cells, (b) mechanical displacement and compression of myelinated axons by swollen astrocytic processes, (c) the appearance of free, extracellular fluid in the white matter, and (d) early primary myelin degeneration without damage to axons.
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.
HEAVY CHAIN SUBCLASSES OF HUMAN γG-GLOBULIN
Authors: Bernier G. M. , Ballieux R. E. , Tominaga K. T. , Putnam F. W.
Published: June 2004

Two antigenic types of naturally occurring proteins related to the papain produced Fc fragment of γG-globulin have been studied. Most normal and myeloma γG-globulins are related to one or the other of these proteins, based on antigenic and structural characteristics of their heavy chain. Molecules bearing the determinant "Cr" are approximately 10 times as abundant as those bearing the determinant termed "Zu" in pools of normal γG-globulin and among a large group of γG-myeloma globulins. Both populations have properties of typical γG-globulin antibodies. Splenic cells, stained for these two populations with specific fluorescent antibody preparations, are found to contain one or the other of the two populations of γG-globulin, but not both. Approximately 10 times as many cells contain the Cr determinant as contain the Zu determinant.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Sell Stewart
Published: June 2004

Sheep antisera specific for the three major immunoglobulin groups of the rabbit, i.e. IgG (γ-chain), IgA (α-chain), and IgM (µ-chain), are each able to induce blast transformation of the peripheral lymphocytes of the rabbit when added to in vitro cultures. The per cent of lymphocytes transformed with each antiserum indicate that one-fourth of the peripheral lymphocytes carry or have the capacity to synthesize molecules of all three of the major immunoglobulin groups, and that the remaining three-fourths carry or have the capacity to synthesize only two (IgG and IgM). The data do not permit direct conclusions concerning the ability of a single cell to produce molecules belonging to more than one immunoglobulin group at the same time, or the ability of a given cell to make a transition from the synthesis of molecules of one immunoglobulin group to those of another group.
STUDIES ON THE LEUKOCYTOSIS AND LYMPHOCYTOSIS INDUCED BY BORDETELLA PERTUSSIS
Authors: Morse Stephen I. , Riester Sallie K.
Published: June 2004

By the use of radioautographic techniques it was shown that the lymphocytosis induced by Bordetella pertussis in mice was not caused by an increased production of lymphocytes but was primarily due to the entry into the circulation of mature cells from tissue pools. The accompanying polymorphonuclear leukocytosis was due to both proliferation of myeloid elements and entry of mature cells from tissue reserves, with the former the predominant mechanism.
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.
EXPERIMENTAL TRANSMISSION OF INFLUENZA VIRUS INFECTION IN MICE
Authors: Schulman Jerome L.
Published: June 2004

Immunization of mice by infection or intraperitoneal injection with homotypic A2, heterotypic A0, or recombinant A0A2 virus have differing effects on transmission of influenza A2 virus infection. Immunization by infection with A2 virus resulted in refractoriness to reinfection either by artificial aerosols or by exposure to infected cage-mates. Immunization by inoculation with inactivated A2 virus vaccine resulted in a decreased susceptibility to transmitted infection in immunized contacts, but following A2 virus challenge, transmission of infection by immunized infectors was not altered. Immunization by infection with influenza A0 virus or recombinant A0A2 virus resulted in a decreased susceptibility to transmitted A2 virus infection in immunized contacts, and to decreased transmission after A2 virus infection in immunized infector mice. These differing effects on transmission of infection are attributed to differences in specific local immunologic responses following the various immunization procedures.
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 (<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.
STUDIES ON HUMAN ANTIBODIES
Authors: Dorner Marianne M. , Bassett Emmett W. , Beiser Sam M. , Kabat Elvin A. , Tanenbaum Stuart W.
Published: June 2004

Human dextran-antidextran-specific precipitates from individuals immunized with dextrans containing either one or two antigenic determinants, were analyzed for their content of various amino acids. Large differences in certain amino acids were found among α-(1 → 6)-specific antidextrans. Wide variations were also observed in antidextran fractions from a given individual specific for α-(1 → 6)- and α-(1 → 2)-linked glucose residues.
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.