bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPERIMENTALLY INDUCED CHANGES IN NASAL MUCOUS SECRETORY SYSTEMS AND THEIR EFFECT ON VIRUS INFECTION IN CHICKENS
Authors: Bang Betsy G. , Bang Frederik B.
Published: June 2004

The domestic chicken was used as an experimental model in which to demonstrate morphological and functional relationships of nasal organ systems, principally of mucous systems. Mucous secretions of olfactory, respiratory, lacrimal, and accessory areas were found to have clear histochemical differences, yet were sufficiently miscible in normal circumstances to form an unbroken, synchronously moving sheet. Changes induced experimentally in host physiology did not all affect the mucous components of given areas in the same way or to the same degree. Mucosal changes were produced by the following methods:

Topically administered cocaine 20%, in a single application, temporarily paralyzed the cilia, and the consequently reduced traction apparently held mucus in the acini and effected a temporary lag in mucus excretion. Three successive applications caused acute acinar depletion and ciliary paralysis.

Hexylcaine chloride 5% immediately desquamated all intranasal epithelia, damaged the proximal portion of the acini, and induced acinar exhaustion and mucosal inflammation—effects not overcome within 5½ days.

Internal dehydration produced progressively viscous mucus, severe acinar gaping with mucus anchored in the acini, a heavy surface sheet, and deceleration or arrest of mucociliary flow.

Avitaminosis A induced reduction in the height (about 50%) of all mucosae and acini, especially the inner lining of the maxillary concha, caused an actual 50% reduction in the number of cells per acinus, and retarded the mucociliary flow rate about 50%.

Pilocarpine induced initial hypersecretion, later exhaustion, and, still later, slow production of densely staining mucus in the acinar cells; also acinar gaping.

Breeding in a germfree environment produced a greatly reduced mucosal depth throughout the nasal fossa, an extraordinary reduction in the number of cells per acinus, relative reduction in the number of acinar neck cells, and concomitant increase in ciliated cells in that region.

Exposure to a temperature of –20°C for 1 hr caused blanching of all secretory cells, acinar gaping, and temporary reduction of mucosal depth.
EXPERIMENTALLY INDUCED CHANGES IN NASAL MUCOUS SECRETORY SYSTEMS AND THEIR EFFECT ON VIRUS INFECTION IN CHICKENS
Authors: Bang Frederik B. , Foard Marie A.
Published: June 2004

Chickens 3 wk old, inoculated intranasally with a mesogenic (moderately virulent) strain of Newcastle disease virus, developed necrotic lesions of the mucous acini, predominantly of the middle turbinates. The infection subsequently spread to involve much of the rest of the mucosa, including mucous and ciliated epithelial cells, and other acini.

The early phase of adsorption of a virulent strain of the virus to the middle turbinates of chicks 5–21 days of age was studied by giving a standard inoculum intranasally to unanesthetized animals.

Variation in amounts adsorbed by individual chickens was large, but was minimized by making measurements on pools of turbinates from three chicks at intervals of 1, 3, and 5 hr after exposure of the excised turbinates to antibody, by washing, and by trypsinization. The virus released from the cells into the trypsin was designated as adherent virus, and the infectious virus in the cells after destruction of the cells by water grinding, as cell virus.

Paralysis of ciliary action by cocaine increased the number of infected cells in the turbinates about 10-fold at all three time intervals.

Pilocarpine injection before virus inoculation caused a large increase in the amount of infected cells 1 hr after virus administration, but was followed by a sharp drop in infected cells by 3 or 5 hr. Pilocarpine given after the virus decreased the number of infected cells and changed the relationship of infected cells to adherent virus.

Exposure of chicks to sustained or severe cold caused a similar but less marked effect. The drop in infected cells was restored to control values if chicks were returned to brooder temperatures.

The marked drop of infected cells produced by pilocarpine and cold in living chicks, and in cultures of chicken trachea (previous study), is consonant with the idea that virus has been adsorbed on mucus granules in the mucous cells of the turbinates and then has been reexcreted, as unincorporated virus, into the moving mucous sheet. A series of accessory data support this interpretation.
CELLS INVOLVED IN THE IMMUNE RESPONSE
Authors: Abdou Nabih I. , Richter Maxwell
Published: June 2004

Rabbits were made immunologically tolerant to either human serum albumin or bovine gamma globulin by the neonatal administration of antigen. At 10 wk of age, they were challenged with the tolerogenic antigen and found to be non-responsive. However, these tolerant rabbits could respond with humoral antibody formation directed toward the tolerogenic antigen if they were treated with normal, allogeneic bone marrow or bone marrow obtained from a rabbit made tolerant toward a different antigen. They were incapable of responding if they were given bone marrow obtained from a rabbit previously made tolerant to the tolerogenic antigen. Irradiated rabbits were unable to respond if treated with tolerant bone marrow, but could respond well if given normal bone marrow. Since it has previously been demonstrated that the antibody-forming cell, in an irradiated recipient of allogeneic bone marrow, is of recipient and not donor origin, the data presented strongly indicate that the unresponsive cell in the immunologically tolerant rabbit is the antigen-reactive cell.
THE EFFECT OF CYTOTOXIC AGENTS ON THE PASSIVE TRANSFER OF CELL-MEDIATED IMMUNITY
Authors: Tripathy S. P. , Mackaness G. B.
Published: June 2004

A system involving the passive transfer of committed lymphoid cells from Listeria-immune donors has been used to study the phases of the immune response which are sensitive to the immunosuppressive action of various cytotoxic agents. The agents investigated included cyclophosphamide, vinblastine, methotrexate, azathioprine, and X-irradiation.

Complete suppression of passive immunization was obtained by the administration of cyclophosphamide or vinblastine to recipients at the time of cell transfer or by prior X-irradiation of recipients a day before cell transfer. Methotrexate was only partially suppressive, whereas azathioprine had no effect at all. The donor cell responsible for the transfer of immunity to recipients was shown to be a resting cell which is sensitive to the action of cyclophosphamide but not to vinblastine.

The results of this investigation suggest that the donor cells undergo multiplication in the tissues of the recipient, presumably in response to specific stimulation by Listeria antigens. This in turn results in the activation of host macrophages. The immunosuppressive action of cyclophosphamide, vinblastine, and irradiation in the cell-transfer system has been discussed in relation to a direct cytotoxic action on the immune lymphoid cells of the donor and specific interference with their proliferation in the recipient, as well as impairment of macrophage production on the part of the recipient itself.
IMMUNOLOGIC STUDIES OF AUTOIMMUNE DISEASE IN NZB/NZW F1 MICE
Authors: Seegal B. C. , Accinni L. , Andres G. A. , Beiser S. M. , Christian C. L. , Erlanger B. F. , Hsu K. C.
Published: June 2004

For the past 3 years NZB and NZW mice have been maintained by sister-brother matings from English breeder stock. NZB/NZW F1 hybrids developed lupus-like nephritis during the 6th to 7th month and few survived beyond the 8th month. Renal tissues of these animals were examined with fluorescein-labeled antinucleoside sera, specific for thymine and cytosine, for the presence of denatured DNA in GCW, and with labeled antibody to mouse IgG for the presence of excess host globulin in the same areas. The following results have been obtained:

(a) All 51 hybrids, over 5 months of age, had an excess of mouse globulin in GCW. 40 animals between the ages of 5 and 12 months showed, in the same areas, antigens which bound one or both of the antinucleoside antibodies.

(b) Renal tissues of 19 NZB mice, 5–19 months old, and 27 NZW mice, 2–18 months old, were examined. Excess host globulin was seen in GCW of 13 NZB and 20 NZW animals. The tissues of only two old NZB mice, 14 months of age, bound antinucleoside antibody but none of the other animals did.

The association of rapidly fatal lupus-like nephritis in NZB/NZW F1 mice with denatured DNA and mouse globulin in GCW supports the hypothesis involving this antigen-antibody complex in the pathogenesis of the disease.
A SPECIFIC INACTIVATOR OF MAMMALIAN C'4 ISOLATED FROM NURSE SHARK (Ginglymostoma cirratum) SERUM
Authors: Jensen Joerg A.
Published: June 2004

A material which specifically inactivates mammalian C'4 was isolated from low ionic strength precipitates of nurse shark serum. The C'4 inactivator was not detected in whole serum. The conditions of its generation and its immunoelectrophoretic behavior seem to indicate that it is an enzymatically formed cleavage product of a precursor contained in whole shark serum. The inactivator was partially purified and characterized. It had an S-value of 3.3 (sucrose gradient) which was in agreement with its retardation on gel filtration, was stable between pH 5.0 and 10.0, had a half-life of 5 min at 56°C, pH 7.5, was inactivated by trypsin and was nontoxic. Its powerful anticomplementary activity in vitro and in vivo was solely due to the rapid inactivation of C'4; no other complement components were affected. No cofactor requirement was observed for the equally rapid inactivation of highly purified human and guinea pig C'4. The kinetics of C'4 inactivation and TAME hydrolysis, the greater anodic mobility of inactivated human C'4, and the influence of temperature on the rate of inactivation suggest that the inactivator is an enzyme and C'4 its substrate. This conclusion was supported by the more recent detection of a split product of C'4. Intravenous administration of the C'4 inactivator could prevent lethal Forssman shock and suppress the Arthus reaction in guinea pigs; it prolonged significantly the rejection time of renal xenografts but had no detectable effect on passive cutaneous anaphylaxis. Anaphylatoxin could be generated in C'4 depleted guinea pig serum with the cobra venom factor, but not with immune precipitates. The possible relationship between C'1 esterase and the C'4 inactivator is discussed on the basis of similarities and dissimilarities.
CELLULAR KINETICS ASSOCIATED WITH THE DEVELOPMENT OF ACQUIRED CELLULAR RESISTANCE
Authors: North Robert J.
Published: June 2004

Mice infected with either BCG or Listeria monocytogenes display the same type of cellular response pattern. In both infections there is an intense proliferation of splenic lymphoid cells, a coincident proliferation of differentiated macrophages, and a subsequent production of macrophages with increased metabolic potential. The temporal relations between these events and the onset of host resistance indicate that lymphoid cell proliferation and macrophage proliferation are essential events in the response which leads to cellular resistance against facultative intracellular parasites.
CELLULAR IMMUNITY IN VITRO
Authors: Marshall William H. , Valentine Fred T. , Lawrence H. S.
Published: June 2004

When sensitive lymphocytes are cultured with the appropriate antigen, lymphoblasts appear after 24–48 hr of incubation and the number of these increases steadily from the 2nd to the 6th or 7th day. Our problem was to discover, at a cellular level, how this increase takes place; whether it is a massive response of many cells, stepwise recruitment of cells into the lymphoblast class, or simply repeated division of a few cells to form clones.

In these experiments lymphocytes were incubated with antigen in culture tubes for 2–4 days and then a few cells, usually less than 200, were transferred to special microchambers for further culture. In these microchambers the cells could be viewed continually with a microscope and their fate recorded over the next 3–5 days by time-lapse cinemicrography. Examination of the film produced in this way showed that lymphoblasts divided and redivided to produce clones of 64 cells or more. It was possible to measure generation times from the film for 301 cells; the majority were between 8 and 13 hr but the range was 7.5–38.0 hr. There was no clear difference between generation times of human lymphocytes stimulated with tuberculin, streptokinase-streptodrnase, extract of the American pokeweed, or in the mixed leukocyte reaction. Similar times were also found for rat cells in the mixed leukocyte reaction.

While these observations show that clonal proliferation does occur and could reasonably account for all the increase of lymphoblasts in lymphocyte cultures, the experiments, because of their design, do not exclude the possibility that other mechanisms such as recruitment may play a role as well, particularly during the first 48 hr after contact between sensitive cells and antigens.
IMMUNE RESPONSES IN VITRO
Authors: Pierce Carl W.
Published: June 2004

The effects of hyperimmune anti-sheep erythrocyte (SRBC) antibody on the plaque-forming cell (PFC) response to SRBC by mouse spleen cells in vitro were studied. Anti-SRBC antibody specifically suppressed the PFC response against SRBC. The degree of suppression was directly related to the amount of antibody added and was overcome by large amounts of antigen. Suppressive activity was absorbed from the sera by SRBC and could be partially eluted from the antigen by heat. The PFC response in cultures stimulated with antigen-antibody complexes prepared with high concentrations of antibody were suppressed; however, some complexes prepared at lower antibody concentrations stimulated greater responses than SRBC alone.

Antibodies collected after four immunizations had greater suppressive ability than those collected after two immunizations. The degree of suppression was as great whether antibody was added at the initiation of the cultures or 24 hr later, suggesting that during the first 24 hr the culture system was antigen-dependent.

Incubation of separated lymphoid cells with antibody did not impair their ability to develop a PFC response in vitro. However, if macrophages were incubated with antibody either before or after incubation with SRBC, the subsequent PFC response by lymphoid cells was suppressed.

The data are consistent with the conclusion that antibody suppresses the PFC response in vitro by neutralizing the antigenic stimulus at the macrophage-dependent phase of the response.
GLOMERULAR PERMEABILITY
Authors: Venkatachalam M. A. , Karnovsky Morris J. , Cotran Ramzi S.
Published: June 2004

Wistar/Furth rats were made nephrotic by daily administration of amino-nucleoside of puromycin, and the ultrastructural localization of horseradish peroxidase (mol wt 40,000) in the renal glomerulus was studied from 1 min to 20 hr after intravenous injection of the tracer. In control rats, peroxidase permeated the endothelial fenestrae, the basement membrane, and the epithelial slits, and was present in tubular lumina. Nephrotic glomeruli showed relatively normal basement membranes, extensive fusion of foot processes with formation of "close" intercellular junctions, and large vacuoles and pockets in epithelial cells. On serial sections some of the epithelial vacuoles communicated on one side with the extracellular space overlying basement membrane, and on the other side with the urinary space. In nephrotic animals, peroxidase permeated the basement membrane and the close junctions, and was present in many of the vacuoles and pockets as early as 1 min after injection. Only small numbers of peroxidase-positive vacuoles remained in. epithelial cells 1 hr or more after injection of the tracer. It is suggested that the epithelial pockets and vacuoles form pathways across which leaking proteins can be transferred across the epithelium into the urinary space. Epithelial vacuoles may also be absorption droplets designed to "conserve" leaking proteins, but this function was not prominent in our experiments with peroxidase.
IDIOTYPY OF RABBIT ANTIBODIES
Authors: Oudin Jacques , Michel Mauricette
Published: June 2004

Sera of rabbits immunized against Salmonella typhi have been studied for the idiotypy of certain of their components, i.e., the property of these components to possess an antigenic specificity which is different in individual rabbits, and which varies with the antigens against which these rabbits have been immunized. The reagent used (precipitating anti-idiotypic sera) have been prepared by injecting rabbits with bacteria agglutinated by anti-S. typhi sera (immunizing sera) as was done in the first observations by the authors of the phenomenon in the rabbit. These first observations have been confirmed and extended.

In contrast to allotypy, the anti-idiotypic sera precipitate the corresponding immunizing sera, but not the sera taken in the immunizing rabbits prior to their immunization against S. typhi, nor the immunizing sera absorbed with the somatic antigen of S. typhi, demonstrating that idiotypes are antibodies.

The idiotypic specificities of the antibodies of one rabbit against S. typhi are not detected in the antibodies of the same rabbit against another noncross-reacting Salmonella (S. tranoroa) and vice versa; nor are they detected in the anti-pneumococcal antibodies of the same rabbit.

Each anti-idiotypic serum fails to precipitate anti-S. typhi sera of rabbits other than the immunizing one except for certain extremely faint reactions, the significance of which has not been established. The idiotypic specificities of anti-S. typhi antibodies of three rabbits were not found in anti-S. typhi antibodies of their parents. This lack of a sign of hereditary transmission of idiotypic specificities contrasts with allotypy. The apparent role of random chance in the determinism of the idiotypic patterns or of the idiotypic determinants has been discussed.

Unless it were admitted that antibodies with similar functions do not exist in different individuals, idiotypy apparently adds an order of magnitude to the antibody variability which had been previously envisaged. In one given individual, the heterogeneity of the idiotypic specificities seems to be less extended than that of the antibody functions. The possible relationships between these two levels of molecular variability and between the corresponding levels of cellular variability have been discussed.
ANTIBODIES OF THE IgA TYPE IN INTESTINAL PLASMA CELLS OF GERMFREE MICE AFTER ORAL OR PARENTERAL IMMUNIZATION WITH FERRITIN
Authors: Crabbé P. A. , Nash D. R. , Bazin H. , Eyssen H. , Heremans J. F.
Published: June 2004

In adult germfree C3H mice immunized with horse spleen ferritin, either subcutaneously or intraperitoneally, plasma cells containing specific antibodies were found in lymph nodes and spleen and, in smaller numbers, also in the lamina propria of the intestine. In extraintestinal sites, these antiferritin-containing plasma cells were mainly of the IgM class after a single stimulation, and of the IgG1 class after repeated stimulation. In the intestine, all the anti-ferritin-containing cells appeared to be of the IgA class. Circulating antibodies, after repeated stimulation, were for the major part IgG1 and IgG2.

In germfree mice given ferritin in their drinking water, antiferritin-containing cells were abundant in the intestinal mucosa, much less numerous in the mesenteric lymph nodes, and extremely scarce in other lymphoid tissues. All these cells, whatever their location, appeared to belong exclusively to the IgA class. Similarly, all the circulating antibody in these animals was found to be IgA.

These findings illustrate the role of the gut as a site of antibody synthesis, as well as its selective commitment to the production of antibodies of the IgA class.
INITIATION OF ANTIBODY RESPONSES BY DIFFERENT CLASSES OF LYMPHOCYTES
Authors: Strober Samuel
Published: June 2004

Thoracic duct cells and spleen cells were tested for their ability to restore the primary antibody response of X-irradiated rats to bovine serum albumin (BSA), sheep red blood cells (SRBC), horse spleen femtin (HSF), and Salmonella typhi flagella. Spleen cells were at least as efficient as thoracic duct cells in restoring the response to BSA, HSF, and Salmonella typhi flagella.

In further experiments thoracic duct cells lacking large dividing lymphocytes were tested for their ability to restore the primary response. Large lymphocytes were eliminated by the in vitro incubation of thoracic duct cells for 24 hr at 37°C or by treatment of thoracic duct cell donors with the mitotic inhibitor vinblastine sulfate 24 hr prior to cannulation of the thoracic duct.

Experiments with SRBC show that incubated cells and cells from vinblastine-treated donors are as efficient as normal cells in restoring the primary antibody response. On the other hand, experiments with HSF and Salmonella typhi flagella show that incubated cells and cells from vinblastine-treated donors are about five times less efficient than normal cells in restoring the response. Normal thoracic duct cells were more efficient than incubated cells but less efficient than cells from vinblastine-treated donors in restoring the early response to BSA.

The experimental findings indicate that the classes of thoracic duct lymphocytes which initiate the primary antibody response to SRBC differ from the classes which initiate the response to HSF and Salmonella typhi flagella, or BSA.
COMPARISON OF THE IMMUNE RESPONSIVENESS OF NZB AND NZB x NZW F1 HYBRID MICE WITH THAT OF OTHER STRAINS OF MICE
Authors: Cerottini Jean-Charles , Lambert Paul-Henri , Dixon Frank J.
Published: June 2004

The immune responsiveness of (NZB x NZW) F1 hybrid mice (NZB/W) has been compared with that of three other strains of mice, A/J, BALB/c, and CBA/J. The antigens used included sheep red blood cells (SRBC), keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA), and human γ-globulin (HGG). It was found that important strain differences existed in the amount of antibody produced, but the relative immune responsiveness depended very much upon the nature of antigen. By comparison with the other strains tested, NZB/W mice had a higher antibody production to some antigens (SRBC and BSA) but were low responders to others (KLH).

Induction of unresponsiveness to HGG by treatment with ultracentrifuged HGG was studied in the strains cited above. NZB/W mice became tolerant after injection of HGG ultracentrifuged at 100,000 g for 2 hr. Similar experiments carried out with another preparation of HGG (centrifuged at 20,000 g for 30 min) failed to reveal any abnormal behavior of NZB/W mice as compared to BALB/c or A/J mice.

These results do not support the concept that NZB/W mice possess a general immune hyperreactivity or a relative inability to be made tolerant to protein antigens. However, they do not rule out the possibility that these mice have a genetically determined hyperresponsiveness to some antigens, in particular to nuclear antigens.
TRANSFER OF RESPONSIVENESS TO HAPTEN CONJUGATES OF POLY-L-LYSINE AND OF A COPOLYMER OF L-GLUTAMIC ACID AND L-LYSINE TO LETHALLY IRRADIATED NON-RESPONDER GUINEA PIGS BY BONE MARROW OR LYMPH NODE AND SPLEEN CELLS FROM RESPONDER GUINEA PIGS
Authors: Foerster John , Green Ira , Lamelin Jean-Pierre , Benacerraf Baruj
Published: June 2004

Hartley guinea pigs genetically unresponsive to hapten-PLL (poly-L-lysine) conjugates were lethally irradiated and given allogeneic bone marrow from Hartley responder animals. Many of the animals died of graft versus host disease before their response to 2,4-dinitrophenyl-PLL (DNP-PLL) could be measured. The immune response of the surviving recipient animals was evaluated by anti-DNP antibody production, development of delayed hypersensitivity to DNP-poly-L-lysine, as well as by lymph node cell stimulation in vitro by this antigen. 12 of 14 recipient animals thus treated made an immune response as measured by 2 of the 3 parameters.

Strain 13 guinea pigs, genetically unable to respond immunologically to DNP-PLL and to DNP-GL (2,4-dinitrophenyl-L-glutamic acid L-lysine copolymer) were lethally irradiated and given bone marrow from (2 x 13) F1 responder animals or strain 13 bone marrow and (2 x 13) F1 lymph node and spleen cells. A high proportion of the animals survived this procedure; no evidence of graft versus host disease was observed. Three of three strain 13 animals irradiated and, given strain 13 bone marrow and (2 x 13) F1 lymph node and spleen, and then immunized with DNP-PL, made a specific immune response. 7 of 10 irradiated strain 13 animals given strain 13 bone marrow and (2 x 13) F1 lymph node and spleen made an immune response to DNP-GL. However, only one of six irradiated strain 13 animals made a vigorous immune response to DNP-GL after reconstitution with (2 x 13) F1 bone marrow alone.

The ability to transfer the immune response to PLL antigens from responder to nonresponder animals demonstrates unequivocally that the defect in the non-responder animals is immunological rather than due to some other type of non-immunological mechanism. The bone marrow contains all the immunological cells necessary for the expression of the PLL gene. However, the finding that (2 x 13) F1 lymph node and spleen cells were more effective than (2 x 13)F1 bone marrow cell populations (known to be a rich source of monocyte precursors) suggests that the cells in which the PLL gene function is expressed may be lymphocytes rather than monocytes and macrophages.
CELLS INVOLVED IN THE IMMUNE RESPONSE
Authors: Daguillard Fritz , Richter Maxwell
Published: June 2004

Cells of the different lymphoid organs in the normal adult rabbit were investigated for their capacity to respond in vitro to a number of stimuli, such as phytohemagglutinin (PHA), anti-rabbit immunoglobulin antiserum (GARIG) and allogeneic and xenogeneic lymphoid cells, and for their capacity to adsorb radioactively-labeled anti-immunoglobulin antiserum. The bone marrow cells responded minimally to PHA, GARIG, and the allogeneic and xenogeneic stimuli. The thymus cells were unable to respond to stimulation with GARIG although they responded to the other stimuli. The cells of the other lymphoid organs tested responded to all the mitogenic agents, to varying degrees.

On the basis of the results presented and the findings of other investigators, it is concluded that:

1. The response of the cells to GARIG indicates a potential capacity to mediate humoral immunity and requires the presence of immunoglobulin or immunoglobulin-like recognition sites on the cell surface.

2. The response of the cells to PHA and allogeneic and xenogeneic cells indicates a potential capacity to mediate cellular immunity and does not necessitate the presence of immunoglobulin-recognition sites on the cell surface.

3. The thymus in the normal adult rabbit consists of cells capable of mediating cellular immunity only.

4. The other lymphoid organs appear to possess cells capable of mediating humoral and cellular immunity.
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Dubos Rene , Lee Chi-Jen , Costello Richard
Published: June 2004

The effects of neonatal influences on the growth and longevity of mice were studied by using animals derived from a highly inbred germfree colony that had been reassociated with a microbial flora free of known pathogens.

The size of the animals at weaning time could be conditioned predictably by manipulating the diet of their mothers during gestation and lactation or by shortening or lengthening the period of lactation.

A deficient diet during gestation or during lactation decreased the metabolic efficiency of the adult animal, even if it was fed an optimum diet after weaning. The effect was greatest when malnutrition occurred during both pregnancy and lactation. In contrast, an optimum diet during gestation and lactation rendered the animal less susceptible to the depressing effects of nutritional deficiency during adult life.

A marked and lasting growth depression could be reproducibly achieved by contaminating newborn mice orally with an unidentified enterovirus. But neonatal infection with enterobacteria or mycobacteria even though severe, did not significantly alter the growth rate.

Regardless of its initial cause, the depression of the growth rate during the preweaning period persisted throughout the whole life span of the animals, even when they were placed under optimum sanitary and nutritional conditions after weaning.

Agencies (nutritional or infectious) which brought about a depression of whole body weight also affected the absolute and relative sizes of the various organs, especially of the brain.

By manipulating neonatal influences, it was possible to produce at will in a given colony of highly inbred mice a family of strikingly different growth curves. This could be done without causing the death of any animal or affecting longevity.
QUANTITATIVE STUDIES ON ANTIGENIC RECOGNITION
Authors: Ramseier Hansruedy
Published: June 2004

Lymphoid cells from normal animals from two genetically alien but isogenic strains of mice or rats elaborated a factor into the medium during in vitro cultivation. Similarly, lymphoid cells from specifically presensitized animals mixed and cultivated with donor-type lymphoid cells, as well as normal or specifically immunized mouse spleen cells exposed to heterologous red blood cell antigens, formed this factor. Culture supernatants of genetically identical lymphoid cells lacked activity.

This factor was measured by its ability to induce accumulations of polymorphonuclear cells following injection into the skin of normal hamster hosts. Gentle trypsinization of excised 24 hr cutaneous reactions permitted quantitative estimation of the number of polymorphonuclear cells accumulated and, therefore, of the activity of the factor.

The factor present in culture fluids could be defined as a product of antigenic recognition (PAR). PAR was formed only when immunologically competent cells were exposed to cells carrying histocompatibility antigens of recognizable foreignness. This view was based chiefly on the observation that, whereas lymphoid cells from specifically tolerant mice failed to recognize the paralytogen, they did recognize antigens of an unrelated mouse strain. In addition, immunocompetence was of paramount importance, since cocultivation of immunologically incompetent, yet strongly incompatible, rat thymocytes did not result in the formation of PAR.

Formation of PAR was observed in very simple media. A source of energy and a suitable culture vessel were found to be the only essential nonimmunological factors for PAR to be elaborated. The presence of inhibitors of glycolysis in the medium during cultivation of mixtures of immunocompetent cells of disparate origin severely inhibited the recognition process. With cell mixtures of the immunological one-way variety, treatment of aggressor cells with inhibitors of glycolysis or of protein synthesis interfered with antigenic recognition, whereas similar treatments of the target cells were without effect.

The findings presented sustain the thesis that the elaboration of PAR is a very early event in the immune process.
THE DISTRIBUTION OF LARGE DIVIDING LYMPH NODE CELLS IN SYNGENEIC RECIPIENT RATS AFTER INTRAVENOUS INJECTION
Authors: Griscelli Claude , Vassalli Pierre , McCluskey Robert T.
Published: June 2004

The distribution of large dividing lymph node or thoracic duct lymph cells, labeled in vitro with 3H-thymidine, was studied in syngeneic recipient rats after intravenous injection. In most experiments the donor rats had been immunized with Bacillus pertussis 4 days earlier, but in some instances cells from nonimmunized donors were used. In smears, the labeled donor cells had the appearance of large lymphocytes or large pyroninophilic cells. By electronmicroscopy, the majority of labeled donor cells were seen to have only scanty endoplasmic reticulum.

It was found that the labeled cells rapidly "homed" to lymphoid tissue and recirculated in the recipient, in a fashion resembling that of small lymphocytes. However, the distribution of labeled cells was found to depend upon the source of the donor cells. Cells from mesenteric lymph nodes or thoracic duct lymph showed a marked preferential accumulation in lymphoid tissue within or adjacent to the intestine, whereas cells from peripheral nodes accumulated preferentially in peripheral lymph nodes. Cells from any of these sources showed an equal tendency to accumulate in the white pulp of the spleen.

Suspensions of small lymphocytes, labeled in vitro with 3H-uridine, did not display a similar tendency to localize preferentially in lymphoid tissue in certain regions.

It was also found that large dividing lymph node cells from donors immunized with an antigen (2,4-dinitrophenyl-bovine gamma globulin (DNP-BGG) or B. pertussis) showed a greater tendency to accumulate in a recipient lymph node containing that antigen than in the contralateral node.

It was not determined whether the selective accumulation of large dividing lymphoid cells from different sources in lymphoid tissue of different regions in recipients was due to an antigen recognition mechansim or was the result of two different populations of cells with different "homing" mechanisms.
PATHOGENESIS OF CHRONIC DISEASE ASSOCIATED WITH PERSISTENT LYMPHOCYTIC CHORIOMENINGITIS VIRAL INFECTION
Authors: Oldstone Michael B. A. , Dixon Frank J.
Published: June 2004

Tissue injury (chronic disease) associated with persistent LCM infection is apparently caused by the host immune response to the virus. Employing parabiosis or cell transfer from hyperimmune donors to isologous virus carriers, the tissue injury of chronic disease could be initiated and/or intensified. Furthermore, the transfer of anti-LCM antibody to SWR/J carrier mice results in acute necrotizing inflammatory lesions in regions of viral persistence, followed by chronic mononuclear infiltrates quite similar to those seen after the transfer of immune cells.

The pathogenesis of the nonglomerular tissue injury of chronic LCM disease is apparently at least in part related to the interaction of circulating anti-LCM antibody with viral antigen at the tissue site. Trapping of circulating virus-antibody complexes in the glomerular filter is apparently the major cause of the glomerulonephritis.
IN VITRO AND IN VIVO STUDIES OF THE IMMUNE RESPONSE TO SHEEP ERYTHROCYTES USING PARTIALLY PURIFIED CELL PREPARATIONS
Authors: Haskill J. S. , Byrt Pauline , Marbrook J.
Published: June 2004

The BSA density-gradient technique for separating mouse spleen cells into partially purified populations has been used to compare the responsiveness of such populations to SRBC using in vivo and in vitro techniques. Two major populations were distinguished, one of which responded very well in vivo with an exponential dose response and poorly in vitro (fraction 3), and another which responded in vivo and in vitro with a linear dose response (fraction 2). A light density, radiation-resistant component was identified which markedly stimulated the response of fraction 3 in vitro, and a density gradient profile was obtained for this cell which did not correspond with a macrophage profile. A high density, radiation-sensitive cell was identified which stimulated the response of PFC precursors in lighter regions of the gradient. The activity of this cell could be replaced using thymus cells. A density profile for the PFC precursor cell was obtained by assaying small numbers of spleen cell fractions in the presence of an excess of the two auxiliary cell types.
IN VITRO INDUCTION OF A PRIMARY RESPONSE TO THE DINITROPHENYL DETERMINANT
Authors: Segal Shraga , Globerson Amiela , Feldman Michael , Haimovich Joseph , Sela Michael
Published: June 2004

Primary antibody response against the dinitrophenyl group has been elicited in vitro after the stimulation of normal mouse spleen explants with 2,4-dinitrophenyl (DNP)-hemocyanin or α-DNP-poly-L-lysine (PLL). Antibodies were detected in the culture medium by the inactivation of DNP-T4 phage. The specificity of the reaction was manifested by the lack of the capacity of the medium to inactivate the unmodified bacteriophage and by the inhibition of the inactivation of DNP-T4 with DNP-lysine.
ANTIBODY-MEDIATED SUPPRESSION OF THE IMMUNE RESPONSE IN VITRO
Authors: Feldmann Marc , Diener Erwin
Published: June 2004

Antibody-mediated suppression of the in vitro immune response to polymerized flagellin of Salmonella adelaide and to sheep erythrocytes was studied at the cellular level. Normal mouse spleen cells, preincubated in vitro with mixtures of antigen and antibody for short periods of time before being washed, did not respond to an optimal antigenic challenge in vitro, whereas similar cells treated with antibody alone gave a normal response. The degree of immune suppression was found to depend on the time of preincubation. Significant immune suppression could be induced in as short a time as 15 min, whereas profound suppression (90%) required the incubation of cells with mixtures of antigen and antibody for 4–6 hr. Mouse spleen cells treated similarly were also unable to respond subsequently to the antigen upon transfer to lethally irradiated hosts, as measured at both the level of the antigen-reactive cell and that of serum antibody production. These results were taken as evidence that in vitro an effect of antibody-mediated suppression occurred at the level of the immunocompetent cell.

Similarities between immune tolerance and antibody-mediated suppression in vitro were described, and the significance of the findings discussed in the light of current concepts of the mechanism of antibody-mediated suppression.
ALLOGENEIC THYMUS GRAFTS AND THE RESTORATION OF IMMUNE FUNCTION IN IRRADIATED THYMECTOMIZED MICE
Authors: Aisenberg Alan C.
Published: June 2004

Irradiated and thymectomized CBA mice are markedly depressed in several immunological parameters (skin homograft rejection, graft-vs.-host activity and hemolytic plaque-forming cells of the spleen, hemolysin and hemagglutinin formation, and peripheral lymphocyte counts). In the present experiments the ability of homografts of neonatal thymus placed beneath the kidney capsule to restore immunological capacity of such animals was studied.

Thymus homografts which share the same H-2 locus with the CBA mouse were permanently tolerated and immunological restoration was complete. Skin from the thymus donor was specifically retained, but third party skin with even minor (non-H-2) incompatibility was normally rejected and hemolytic plaque-forming cells of the spleen were restored.

Thymus homografts which differ at the H-2 locus were promptly rejected and led to accelerated rejection of skin subsequently grafted from the thymus donor. With such H-2 incompatible thymus grafts, third party skin with minor histo-incompatibility was retained while there was slight to moderate restoration of rejection of skin with major (H-2) incompatibility. Graft-vs.-host activity was restored, but there was no return of plaque-forming spleen cells, hemolysins, hemagglutinins, or peripheral lymphocyte counts.

In view of the cross-reactivity at the H-2 locus in CBA mice between thymus and third party skin donors, it was felt that restoration of skin rejection and graft-vs.-host activity could be adequately explained on the basis of immunization by the thymus graft and did not require the postulation of true immune restoration or a thymus hormone.
CYTOGENETIC STUDIES OF LEUKEMIA INDUCED BY 6,8,12- AND 7,8,12-TRIMETHYLBENZ(A)ANTHRACENE
Authors: Sugiyama Taketoshi , Brillantes Filomena P.
Published: June 2004

Cytogenetic studies on 64 rat leukemias induced with 7,8,12- and 6,8,12-trimethylbenz(a)anthracene were performed. Highly distinctive changes were found repeatedly in one special pair of chromosomes. 10 leukemias (15.6%) showed the presence of stemline(s) with trisomy of the largest telocentric chromosome (C-1 trisomy). Another chromosome abnormality, elongation of one of the pairs of the same chromosome (long C-1), was found in 5 leukemias (7.8%) as the predominant stemline and in 7 other cases as a small cell population. This chromosome abnormality, despite slight differences in their elongation rate, was defined as a new specific chromosome abnormality. Other chromosome abnormalities not related with C-1 chromosome were found in 8 cases (12.5%). The remaining 41 leukemias (64.1%) had the predominant stemline with normal karyotype. From this study it appears that three structurally different hydrocarbon carcinogens, 7,12-dimethylbenz(a)anthracene and 7,8,12- and 6,8,12-trimethylbenz(a)anthracene act on blood-forming cells by a common specific mechanism.
ALLOTYPE EXCLUSION IN UNIFORM RABBIT ANTIBODY TO STREPTOCOCCAL CARBOHYDRATE
Authors: Kindt Thomas J. , Todd Charles W. , Eichmann Klaus , Krause Richard M.
Published: June 2004

Rabbit antibodies to streptococcal polysaccharide are described which show selectivity of expression of the allotypic specificities on both the heavy (H) and light (L) chains. One of these antibodies binds weakly to Sephadex. A purification method based on this binding has yielded antibody completely lacking any group a allotypic marker on its H chains.
RAPID LYMPHOCYTE RECOGNITION OF HISTOINCOMPATIBILITY
Authors: Andersson J. , Killander D. , Möller E. , Möller G.
Published: June 2004

The mechanism of growth stimulation in allogeneic lymphocytes mixed in vitro was studied at the cell level by means of cytophotometric techniques. A pronounced increase in fluorescence intensity of fixed and acridine orange (AO) stained lymphocytes was observed as soon as after 1–3 hr in mixed culture. No increase in the amount of DNA took place during this time. The higher fluorescence intensity was due to an increased accessibility of AO binding sites in the deoxyribonucleoprotein (DNP) complex, most probably as a result of weakened bonds between the DNA and the protein moiety in the DNP complex. Similar DNP changes have been found in other systems of growth stimulation and may be one prerequisite for later induction of cellular synthetic processes.

Increased AO binding only occurred when the lymphocyte donors were incompatible at the major histocompatibility locus (HL-A); there was no change in AO binding in cases of HL-A identity. The AO binding reaction probably reflects a specific recognition of HL-A antigens, whereas other antigenic discrepancies between the individuals do not seem to cause an analogous response.
RUBELLA INFECTION OF SYNOVIAL CELLS AND THE RESISTANCE OF CELLS DERIVED FROM PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Grayzel Arthur I. , Beck Carolyn
Published: June 2004

The mechanism of growth stimulation in allogeneic lymphocytes mixed in vitro was studied at the cell level by means of cytophotometric techniques. A pronounced increase in fluorescence intensity of fixed and acridine orange (AO) stained lymphocytes was observed as soon as after 1–3 hr in mixed culture. No increase in the amount of DNA took place during this time. The higher fluorescence intensity was due to an increased accessibility of AO binding sites in the deoxyribonucleoprotein (DNP) complex, most probably as a result of weakened bonds between the DNA and the protein moiety in the DNP complex. Similar DNP changes have been found in other systems of growth stimulation and may be one prerequisite for later induction of cellular synthetic processes.

Increased AO binding only occurred when the lymphocyte donors were incompatible at the major histocompatibility locus (HL-A); there was no change in AO binding in cases of HL-A identity. The AO binding reaction probably reflects a specific recognition of HL-A antigens, whereas other antigenic discrepancies between the individuals do not seem to cause an analogous response.
QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS
Authors: Wilson Darcy B. , Nowell Peter C.
Published: June 2004

Studies were designed to provide some explanation for the unexpectedly large proportion (2%) of parental rat strain peripheral blood lymphocytes that are reactive in the mixed lymphocyte interaction (MLI) to a strong homologous transplantation isoantigen(s) present on cells from an F1 donor. The possibilities considered involve nonspecific activation and multispecific reactivity on the part of the responding cells.

The essential findings of this study were:

(a) In 3-way mixed cultures, lymphocytes obtained from tolerant animals were not "recruited" to proliferate in the presence of cells from normal, isologous donors which were in the process of responding to F1 cells bearing the tolerance-inducing antigens. With the use of chromosome markers and normal and tolerant parental strain donors of different sexes, the responsive cells were identified and proved to be derived from the normal and not the tolerant donor.

(b) The magnitude of the proliferative response is increased additively when potentially reactive cells are exposed to two antigen systems simultaneously. On the other hand, doubling the "gene-dosage" of the genetic determinants of the H isoantigens employed had no effect on the responding cells.

(c) A state of induced immunologic tolerance to one H isoantigen system did not alter the response capacity of cells from such a donor to an alternative antigen system.

(d) Mixed cultures of heterologous cells from human and rat donors displayed a proliferative response which was less than that of homologous mixed cultures from human or rat donors. Prior sensitization of rat donors with human cells, however, greatly increased the mitotic activity of rat lymphocytes stimulated with human cells.

These results suggest that the large number of responsive cells in the MLI do not include a significant number recruited or activated in some nonspecific manner. Rather, they appear to be fully specific in their response capacities so that a given lymphocyte does not react to a multiplicity of different antigens. The degree of proliferation depends on the number of different antigen systems presented to the responding population and not on the number of genetic determinants or "gene dosage" of a given isoantigen system. Finally, on a cell-for-cell basis, the peripheral blood lymphocyte population contains more cells reactive to histocompatibility isoantigens within the species than to heterologous antigens of a different species.
EVALUATION OF THE RENAL TOXICITY OF HEME PROTEINS AND THEIR DERIVATIVES: A ROLE IN THE GENESIS OF ACUTE TUBULE NECROSIS
Authors: Braun Sheldon R. , Weiss Frederick R. , Keller Allen I. , Ciccone J. Richard , Preuss Harry G.
Published: June 2004

This investigation studies the toxicity of heme proteins and/or their break-down products on renal function. Heme proteinemia precedes acute tubule necrosis at a frequency great enough to suggest a causal relationship between the two events. Physiological and metabolic functions of kidney slices are investigated in several models of acute tubule necrosis. Organic acid and organic base transport is depressed earliest. These alterations in tubule function cannot be explained by ischemia or obstruction alone. Heme proteinemia in rats or incubation of renal slices in medium containing heme proteins yields several interesting observations. Neither in vivo or in vitro do hemoglobin and methemoglobin alone produce a depressive effect on the transport systems studied. However, parallel to many clinical situations, when such secondary insults as hypoxia and elevated ammonia concentrations are included in the experimental design, transport functions are depressed. Ferrihemate, a molecule smaller than hemoglobin or methemoglobin, depresses transport function without secondary insults. From these studies it is concluded that heme proteins play a role in tubule dysfunction seen in acute tubule necrosis. A model is presented that collates these data with other factors known to play a part in the pathogenesis of this renal syndrome.