bluuebunny/crossref_metadata_2025 huggingface dataset:
IMMUNOLOGIC INCOMPETENCE OF IMMUNOLOGICALLY RUNTED ANIMALS
Authors: Blaese R. Michael , Martinez Carlos , Good Robert A.
Published: June 2004

1. Adult (A x C57Bl/1)F1 hybrids regularly show runt disease when injected with adult spleen cells from A strain donors. This also occurs when A strain spleen cells are administered to adult C3H mice made tolerant of A strain tissue in the neonatal period.

2. Mice undergoing the graft versus host reaction fail to form antibodies to an intraperitoneal challenge of T2 bacteriophage. This phenomenon was observed well before any of the other overt signs of runting had occurred. Further, inhibition of antibody production to T2 phage by graft versus host reaction initiated at an interval following antigenic stimulation is demonstrated.

3. The basis for the immunologic incompetence of the host with respect to T2 phage is presumed to be the attack of immunologically competent donor cells on the lymphoid cells of the recipient.

4. The failure of the injected parent strain cells to respond to the antigen used may imply immunologic commitment of these cells.
MECHANISMS OF ENDOTOXIN TOLERANCE
Authors: Greisman Sheldon E. , Wagner Henry N. , Iio Masahiro , Hornick Richard B.
Published: June 2004

Healthy male volunteers were rendered tolerant to the pyrogenic and toxic activities of bacterial endotoxin by daily intravenous injections. Five subjects were given 0.5 µg Salmonella typhosa endotoxin for 7 days; four subjects were given Pseudomonas endotoxin, increasing over a period of 30 days from 25 to 250 µg. Reticuloendothelial system (RES) phagocytic activity was assessed by serial measurements of the clearance of I131-labeled aggregated human serum albumin. In no subject was an increase in RES phagocytic activity detectable. Such negative findings could not be attributed to decreased RES blood flow.—Additional studies on the pyrogenic responses of man to various schedules of endotoxin administration revealed: (a) Hyperreactivity of some subjects to a second injection of endotoxin administered 24 hours after the initial dose; (b) prevention of such hyperreactivity by plasma from donors tolerant to a heterologous endotoxin, but not from normal donors; (c) reduced reactivity to a second injection of endotoxin given 7 days after the initial dose; (d) reversal of induced tolerance by administration of half the dose of endotoxin followed 2 hours later by the second half; (e) reversal of induced tolerance 24 hours after administration of a heterologous endotoxin; (f) enhanced dermal reactivity to endotoxin induced inflammation during tolerance.

The observations are consistent with the hypothesis that tolerance to the pyrogenic activity of endotoxin in man is not based upon generalized enhancement of RES phagocytic activity or exhaustion of host reactivity but rather involves the participation of specific antibody which assists the RES in the clearance and inactivation of the endotoxin molecule.
THE COURSE OF EXPERIMENTAL AUTOALLERGIC THYROIDITIS IN INBRED GUINEA PIGS
Authors: Lerner Edwin M. , McMaster Philip R. B. , Exum Eurmal D.
Published: June 2004

Experimental allergic thyroiditis produced in strain 13 histocompatible guinea pigs after a single immunization with thyroid extract and Freund's adjuvant was followed for more than 2 years. The disease appeared as early as 5 days and persisted for the entire period studied, although it regressed in the later stages.

Circulating antithyroid antibody was detected at low levels as early as 7 days after immunization, and increased to a peak at the time of most severe disease. Thereafter, antibody decreased, but was still detectable in most animals as late as 2 years. There was no correlation between antibody levels and extent of disease except at the 7 week stage.

Delayed sensitivity to thyroid antigen was found as early as 5 days after immunization, and appeared to precede the development of thyroiditis in many animals. It correlated closely with thyroiditis at 5 days and 7 weeks. At 6 months, the delayed skin reaction was decreased, and a modified type of reaction appeared which persisted as long as 26 months.

The time relationship of delayed sensitivity, thyroiditis, and circulating antibody continue to confirm the role of delayed sensitivity in the pathogenesis of this disease. The accumulated data demonstrating production of thyroiditis without antibody, and the converse, tend to strengthen this view.
THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS
Authors: Johnson Richard T.
Published: June 2004

The pathogenesis of herpes simplex virus encephalitis and myelitis was studied in suckling mice using routine titration procedures and fluorescent antibody staining for the identification of infected cells. After intracerebral inoculation virus was shown to disperse rapidly in the cerebrospinal fluid (CSF), multiply in meninges and ependyma, and then invade the underlying parenchyma infecting both neurons and glia.

Following extraneural inoculation virus gained access to the central nervous system (CNS) by both hematogenous and neural pathways. After intraperitoneal and intranasal inoculation virus was found to multiply in viscera and produce viremia; foci of CNS infection then developed around small cerebral vessels.

After subcutaneous and intranasal inoculation neural spread of virus was demonstrated along corresponding peripheral and cranial nerves. This spread resulted from the centripetal infection of endoneural cells (Schwann cells and fibroblasts). Antigen was not found in axons even after infection of the corresponding ganglion cell perikaryon. Subsequent spread within the CNS was unrelated to neural tracts, and there was no evidence of axonal spread of virus in the host-virus system studied.

These findings are discussed in relation to previous and current theories of the viral "blood-brain barrier" and neural pathways of infection.
ANALYSIS OF THE EXPERIMENTAL LESION OF CONNECTIVE TISSUE PRODUCED BY A COMPLEX OF C POLYSACCHARIDE FROM GROUP A STREPTOCOCCI
Authors: Schwab John H.
Published: June 2004

Rabbits presumably sensitized to components of the streptococcal cell by natural contact with cross-reactive microbial antigens in their environment, display distinctive phases of evolving allergic response to an extract of streptococcal cells. Animals under 4 weeks of age show no gross allergic skin reaction; this is followed successively by age periods in which allergic reactions become most prominent at 4 hours, 23 hours, or 2 to 4 days after injection.

A relapsing nodular lesion, produced by cell wall components in the cell extract, occurs in neonatal rabbits which display no hypersensitivity, reaches a peak response in young animals during the period of most active growth, and decreases in severity in older rabbits while the degree of hypersensitivity is increasing. Relapses occur with greater frequency in neonatal than in older rabbits. Passive transfer of spleen cells or serum from sensitized adult rabbits has no influence on the nodular reaction in neonatal animals.
THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY
Authors: Svehag Sven-Eric
Published: June 2004

Rabbit sera were found to possess neutralizing activity (normal antibody) to polioviruses and Coxsackie B viruses. This normal antibody showed high specificity in cross-neutralization and absorption tests. It was associated with heat-stable, mercaptan-sensitive, 19S γ1-ß-macroglobulins, which formed weak complexes with the viral antigen. In rare instances, sera with normal macroglobulin antibody, also contained very low activity which was due to 7S γ2-globulins. The neutralization of poliovirus by normal 19S γ1-ß-antibody appeared to follow first order kinetics, and the thermodynamic parameters of this reaction were the same as those of serological reactions employing immune antibody.

The electrophoretic mobility, sedimentation properties, sensitivity to mercaptan, thermostability, and avidity of normal and early (up to day 3) immune antibodies to poliovirus were similar, but differed in several respects from those of late immune antibodies. Thus, the available evidence suggested, that earlier reported differences between normal and immune antibodies reflected differences between antibodies of diverse physicochemical properties rather than between normal and immune antibodies per se.

It is proposed that the normal macroglobulin antibody is associated with an immunological response to repeated stimulation with minute amounts of antigen.
IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS
Authors: Kaplan Melvin H. , Svec Kathryn H.
Published: June 2004

Sera from patients with recent streptococcal infection or non-suppurative sequelae exhibit with variable frequency a precipitin reaction in agar gel with a partially purified streptococcal antigen which has been shown previously to be immunologically related to human heart tissue. This precipitin could be absorbed from sera with normal human heart tissue homogenates but not with homogenates of other organs. Demonstration of this cross-reaction by heart absorption was found dependent both upon the serologic properties of individual sera and the nature or state of purification of the streptococcal product employed as test antigen. Evidence was obtained of a close association of heart-related and non-heart-related antigenic determinants in partially purified preparations of the streptococcal antigen by both gel diffusion and immunoelectrophoresis. On immunoelectrophoretic analysis, cross-reactive antigen exhibited a more rapid mobility toward the anode than M protein. It was destroyed by digestion with trypsin, pepsin, and chymotrypsin. Based on specific absorption tests with a Type 5 and Type 19 strain, the antigen was localized to cell walls and to a lesser extent to cell membranes of these strains.

Precipitating activity related to cross-reactive antibody was localized to the immunoglobulin zone in immunoelectrophoresis. Reactive sera showed diminution or loss of serological activity following heat inactivation at 56°C or after prolonged storage at 4°C. Sera containing cross-reactive precipitating antibody exhibited an immunofluorescent reaction with sarcolemma of cardiac myofibers, which was inhibited by streptococcal cross-reactive antigen. By this inhibition test, the immunofluorescent reaction related to cross-reactive antibody could be distinguished from that due to other heart-reactive factors.

Antibody to streptococcal cross-reactive antigen defined by precipitation-absorption tests was observed in 24 per cent of patients with recent history of uncomplicated streptococcal infection and in the majority of patients with acute rheumatic fever, rheumatic heart disease, or acute glomerulonephritis. It was observed rarely in patients with non-streptococcal related disease. These data provide evidence that induction of cross-reactive autoantibody to heart in certain individuals is associated with streptococcal infection.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Berlin Richard D. , Wood W. Barry
Published: June 2004

The metabolic reactions responsible for the release of endogenous pyrogen from rabbit granulocytes incubated in 0.15 M NaCl are specifically inhibited by the presence of K+ (and by related alkali metal ions, Rb+ and Cs+) in the medium. The inhibitory action of K+ apparently involves penetration of the cell membrane and is directly antagonized by the cardiac glycoside, ouabain. It is concluded, therefore, that the inhibition of pyrogen release by extracellular K+ is due to transport of K+ into the cell.

Although the precise molecular mechanisms which are responsible for the release of pyrogen from granulocytes incubated in K-free saline have not been elucidated, further study of the process has revealed: (a) that it is preceded by the accumulation of pyrogen within the cell, (b) that it depends upon the catalytic action of one or more sulfhydryl-containing enzymes, (c) that it does not require energy, either from glycolysis or from reactions depending on molecular oxygen, and (d) that its inhibition by K+ and by arsenite is qualitatively similar to the depression caused by these same reagents on the release of other leucocytic proteins; i.e., lysozyme and aldolase.
HOMOGRAFT IMMUNITY IN PREGNANCY
Authors: Lanman Jonathan T. , Herod Llewellyn , Fikrig Senih
Published: June 2004

The effect of homograft sensitization of a mother against her fetuses has been studied. A female rabbit was repeatedly grafted from both members of a breeding pair. Their offspring should and do become objects of homograft sensitization induced in the female by grafts from the parents. After sensitization was established, fertilized ova were transplanted from the breeding pair to the sensitized female. At the same operation, an equal number of eggs was also transplanted to the same recipient from another breeding pair against which no sensitization had been induced. In 16 such families, the survival rates for offspring born of each type of egg were found to be almost identical, indicating that homograft sensitization in the mother directed against her fetuses did not demonstrably harm them.
PROTEIN-PROTEIN INTERACTIONS AMONG L POLYPEPTIDE CHAINS OF BENCE-JONES PROTEINS AND HUMAN γ-GLOBULINS
Authors: Gally J. A. , Edelman G. M.
Published: June 2004

The L polypeptide chains of certain Bence-Jones proteins of group I have been found in three forms: monomers of molecular weight of about 20,000, dimers which monomerize in dissociating solvents, and dimers which are stable in such solvents. The L polypeptide chains of some Bence-Jones proteins of group II were found to occur naturally only as stable dimers. The L chains of normal human γ-globulin have been obtained in a reduced unalkylated form, and a fraction of these chains was found to form stable dimers under oxidizing conditions. It is suggested that a single disulfide bond is involved in stabilization of the dimer.

In experiments on the reconstitution of 7S γ-globulin, it was found that stable dimers of L polypeptide chains did not associate appreciably with Hγ chains to form a soluble product. L chains in the monomeric form, both of a reduced alkylated Bence-Jones protein and of reduced unalkylated γ-globulin, combined with Hγ chains to form a 7S product. After hydrolysis with papain, the 7S material containing the Bence-Jones L chains yielded fragments comparable to the fragments of papain-treated myeloma proteins.

As indicated by spectrofluorometric measurements, dissociable dimers and stable dimers of the L chains of a Bence-Jones protein both underwent identical thermally induced transitions in the temperature range 48–58°C. When L polypeptide chains were present in reduced alkylated γ-globulin or reduced alkylated S fragments, no transition occurred until 65°C, the coagulation temperature of γ-globulin and S fragments. Above this temperature, L chains were released into solution. These experiments suggested that free L chains and L chains bound to Hγ chains have different conformational stabilities.
THE REQUIREMENT FOR HYDROCORTISONE IN ANTIBODY-FORMING TISSUE CULTIVATED IN SERUM-FREE MEDIUM
Authors: Ambrose Charles T.
Published: June 2004

It was previously reported from this laboratory that the secondary antibody response can regularly be elicited in vitro from fragments of rabbit lymph node node cultured in Eagle's medium supplemented with normal rabbit serum. Evidence is now presented that physiological levels of hydrocortisone (0.01 to 1.0 µM) can substitute for serum in the culture medium. However, with the omission of serum, serine (0.1 mM) must be included among Eagle's "essential" amino acids for consistent optimal antibody production. In some experiments the addition of insulin (0.5 unit/ml) and vitamin B12 (0.5 µg/ml) has further enhanced the secondary response in this serum-free medium.
AROMATIC-INDUCED PREVENTION OF FATAL TOXICITY OF 7,12-DIMETHYLBENZ[a]ANTHRACENE
Authors: Huggins Charles , Ford Elizabeth , Fukunishi Ryo , Jensen E. V.
Published: June 2004

Large doses of 7,12-dimethylbenz[a]anthracene (7,12-DMBA) caused the death of rats within 1 day. A small amount of any of 5 polynuclear aromatic hydrocarbons or of an aromatic amine given before the highly toxic dose of 7,12-DMBA resulted in survival for more than 2 months and the specific atrophy of testis which follows 7,12-DMBA was largely prevented. Among the protective aromatics is 7,12-DMBA itself; a small dose of 7,12-DMBA given in advance induced protection of life against an otherwise lethal dose of 7,12-DMBA but only in a proportion of the animals, and testis was not protected from injury. The highly efficient inducers of protection were condensed aromatics composed of 4 or 5 rings.

Protection of life against toxicity of big doses of 7,12-DMBA by pretreatment with small doses of aromatics required time (ca. 5 to 8 hours) for its induction. Ethionine given a few minutes after a highly efficient inducer of protection, 3-methylcholanthrene (3-MC), abolished induction of protection; ethionine given 8 hours after 3-MC exerted no influence on its protective effect.

A lethal dose of 7,12-DMBA resulted in a considerable reduction in incorporation of tritium in DNA from tritiated thymidine while at the same time synthesis of menadione reductase was induced in liver. A small dose of 3-MC given prior to 7,12-DMBA was advantageous in partially protecting DNA synthesis.
EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Unanue Emil , Dixon Frank J.
Published: June 2004

Rats with nephrotoxic serum nephritis may show fixation of complement (C') in the glomeruli during two periods. The first period occurs immediately after the injection of the antisera and extends until the host response occurs. The second period is related to the deposit of rat gamma globulin in the glomeruli presumably occurring at the time of the immune response to the heterologous nephrotoxic serum (NTS). This second period terminates about 2 to 3 weeks after injection of NTS, presumably at the time the rat stops making antibodies to the nephrotoxic gamma globulin fixed in the glomeruli. After this period, the glomerular lesion is incapable of fixing detectable amounts of circulating C' unless the antibody response to the heterologous globulin is reactivated. The immunological events which take place in the initial 2 to 3 week period appear to produce a permanent and irreparable lesion in the glomeruli leading to chronic nephritis.

Rabbit NTS produces fixation of rat C' during both periods. Duck NTS shows no detectable fixation of rat C' until rat gamma globulin fixes in the glomeruli at the time of the host immune response to the heterologous nephrotoxic gamma globulin. Decomplementation of rats injected with rabbit NTS produces an amelioration of the initial period of nephrotoxic serum nephritis.

The fixation of C' in the glomerular lesions was studied with the use of fluorescent antibody methods. The detection of host beta-1C globulin and gamma globulin in the glomerulus pointed to an immune reaction but not necessarily an active one. The tissue C' fixation test using kidney slices and guinea pig C' proved to be a more sensitive method of detecting tissue reactants capable of fixing C', but its relationship to in vivo events is not certain.
THE PASSIVE TRANSFER OF ACQUIRED RESISTANCE TO LISTERIA MONOCYTOGENES
Authors: Miki K. , Mackaness G. B.
Published: June 2004

Five methods have been used in an effort to reveal an antibody that could account for the features of acquired resistance to Listeria monocytogenes: (a) a comparison of the growth rates of Listeria in the spleens of mice infused repeatedly with normal or immune mouse serum; (b) measurement of peritoneal clearance of Listeria in the presence of normal or immune mouse serum; (c) the survival rate of Listeria in monolayers of mouse macrophages infected in the presence of normal or immune mouse serum; (d) the effect of injecting urea extracts of spleens and peritoneal macrophages of normal or immune mice on the survival and growth of Listeria in recipient animals; (e) a comparison of survival rates in lethally infected mice following the passive transfer of cells and serum from normal or immune donors. The only evidence of passive protection was obtained when intact living cells from immune donors were used for transfer under conditions which permitted them to interact with the parasite population.
THE SUSCEPTIBILITY OF CHICK EMBRYO SKIN ORGAN CULTURES TO INFLUENZA VIRUS FOLLOWING EXCESS VITAMIN A
Authors: Huang J. S. , Bang F. B.
Published: June 2004

The conversion of chick embryonic epidermis to mucous epithelium by excess vitamin A in organ culture as reported by Fell and Mellanby (5) was shown to be accompanied by a corresponding change of susceptibility to influenza and vaccinia viruses.

Untreated epidermis of 10- to 12-day chick embryos supported the growth of influenza (PR8) virus in organ cultures and a maximum infectivity (EID50) titer was reached 2 to 3 days after infection. At the same time) the epidermis showed squamous keratinization, beginning about the 4th day of cultivation.

Addition of excess vitamin A (40 µg per ml) to the skin organ culture induced the following changes: (a) mucous metaplasia of the epidermis which was usually first evident after 4 to 5 days in the vitamin A medium, (b) increase in the daily and maximum yield of influenza virus, if the epidermis had been grown for 4 or more days in the vitamin A medium before infection took place, and (c) decrease in the production of vaccinia virus under similar conditions. The maximum yield of both viruses remained unchanged, however, if excess vitamin A was introduced to the organ culture at the time of virus inoculation.

The magnitude of increase in the yield of influenza virus in this organ culture system was found to be proportionally related to the concentration of vitamin A added 4 or more days before inoculation of this virus. Increasing doses of vitamin A however, had no effect on the short-term growth of influenza virus in tissue cultures of chorio-allantoic membrane.

Observation on the early period (2 to 12 hours) of influenza virus growth initiated in the 4-day organ cultures of chick embryonic skin showed no significant difference in virus production between the normal and the vitamin A medium groups.

The change of virus specificity apparently is not due to the presence of excess vitamin A per se, but appears to be related to the change of differentiation produced in the organ culture system.
ANTISERUM TO LEUCOCYTE LYSOSOMES
Authors: Quie Paul G. , Hirsch James G.
Published: June 2004

Antisera to rabbit polymorph granules and to rabbit erythrocytes have been prepared in guinea pigs.

Both antigranule and antierythrocyte sera are hemolytic and both exhibit striking cytotoxicity on leucocytes. The sequence of toxic events, as observed by phase contrast cinemicrophotography and electron microscopy, consists of explosive granule lysis, cell swelling, cytoplasmic liquifaction, and nuclear fusion. Other rabbit cells are also susceptible to these cytotoxic effects, but cells, including polymorphs, of other mammals are not.

Cytotoxic action of the antisera requires, in addition to the antibody, heat-labile serum factors and divalent cations, suggesting that the action is a combined one of antibody and complement.

The morphologic observations have been supported by biochemical studies demonstrating release into the medium of granule-bound hydrolases following exposure of polymorphs or of isolated granules to the antigranule or antierythrocyte sera.

Granulolytic activity of the antisera can be reduced or removed by absorption with either rabbit leucocyte granules or with erythrocytes, indicating that leucocyte granules and erythrocytes have an identical or similar membrane constituent.

The observations lend support to the notion that lysosomal hydrolases may exert autolytic effects in some situations.
H CHAIN SUBGROUPS OF MYELOMA PROTEINS AND NORMAL 7S γ-GLOBULIN
Authors: Grey Howard M. , Kunkel Henry G.
Published: June 2004

Through the use of a variety of antisera to isolated myeloma proteins, four subgroups of 7S γ-globulin type proteins were readily distinguished. The first, the Vi subgroup, consisted of ten of 64 myeloma proteins studied. The second, the We group, contained the majority of myeloma proteins. The third, the Ge subgroup, included three of 50 myeloma proteins. The fourth remains ill-defined and appears heterogeneous.

Counterparts for both the Vi and the Ge subgroup, were found in the Fr II γ-globulin and in the normal γ-globulin of all of a large number of individual sera studied.

The unique antigenic character of both groups was localized to the H chains, although different determinants were involved for different antisera. An essential role of intact disulfide bonds was apparent with certain rabbit antisera.

In addition to the special antigenic characteristics, the Ge subgroup showed in each instance a fast mobility for the F fragments produced by papain which was not found for other myeloma proteins.
EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS
Authors: Des Prez Roger M.
Published: June 2004

The platelet injury produced by bacterial endotoxin and thrombin have been compared in studies utilizing citrated rabbit platelet-rich plasma. Endotoxin-induced platelet injury is characterized by a lag period, is progressive, and does not produce gross clot formation. Thrombin-induced platelet injury is immediate, non-progressive, and is associated with clot formation. The quantity of thrombin required to produce clot formation in this citrated system is less than that required to produce release of platelet 5-hydroxytryptamine. The endotoxin-induced platelet injury required extremely large quantities of heparin for inhibition. The platelet injury induced by thrombin can be inhibited by small quantities of heparin. It is concluded that the injurious effects of endotoxin on platelets is mediated through some mechanism other than thrombin formation.
ELECTROPHORETIC SEPARATION AND PROPERTIES OF MOUSE ANTIHAPTEN ANTIBODIES INVOLVED IN PASSIVE CUTANEOUS ANAPHYLAXIS AND PASSIVE HEMOLYSIS
Authors: Nussenzweig Ruth Sonntag , Merryman Carmen , Benacerraf Baruj
Published: June 2004

Some properties of mouse antibodies produced by hyperimmunization with conjugated haptens, emulsified in complete adjuvant, have been investigated. Under these conditions two antigenically different types of precipitating antibody, with small differences in their electrophoretic mobilities, both migrating in the γ-region, are produced. Both antibody types were shown to be different from the ß2A-globulins) as revealed by the absence of reaction with specific rabbit antisera against mouse ß2A-myeloma globulins.

γ2 or the slower migrating antibodies, similarly to what has been described for the guinea pig, were able to provoke lysis of antigen-coated tanned sheep erythrocytes, in the presence of complement. This activity could not be detected in the faster migrating antibody type. The slower migrating fractions of the γ2-antibodies were able to transfer passive cutaneous anaphylaxis (PCA) in the guinea pig, but not in their own species.

γ1-Antibodies were found to be capable of sensitizing the mouse for cutaneous anaphylaxis.

The sensitivity of these antibodies to reduction and alkylation was different, the lytic activity being practically abolished, the PCA titers in mice much reduced, and the PCA activity in guinea pigs only partially inactivated.
PROLIFERATIVE ACTIVITY OF THE LYMPHATIC TISSUES OF RATS AS STUDIED WITH TRITIUM-LABELED THYMIDINE
Authors: Craddock Charles G. , Nakai George S. , Fukuta Hajime , Vanslager Louise M.
Published: June 2004

Cytokinetic data are presented, employing quantitation of H3DNA in the lymphatic tissues of normal rats serially sacrificed after H3Tdr administration. A marked difference in the patterns of initial labeling and label loss was observed between the thymus and peripheral lymphatic tissue.

The data are compatible with other indications of rapid cell renewal in the thymus. There is suppression of initial uptake of H3Tdr into the DNA of each large lymphocytic progenitor cell in the thymus, apparently because of a feedback of thymidine containing material from small lymphocytes in the thymus. Depletion of the thymus of small cells, as by operative stress or whole body x-ray, leads to a marked increase in the uptake of H3Tdr into the DNA of large thymocytes. This finding, which is in agreement with the previous findings of Sugino et al. (33, 34) suggesting transfer of thymine nucleotides from small thymus lymphocytes to precursor cells, may or may not be related to the apparent transfer of DNA label between thymic cells. The evidence for the latter consists of the curvilinear dilution of the DNA label in the thymus proliferating cell population and the relationship between the rate of DNA label dilution in large cells and the H3DNA in the small cells in the thymus.

After the DNA label in progenitor cells in the thymus and lymph nodes has entered the small cell population, the subsequent dilution of grains in these dividing cells follows the same slope as the loss of radioactivity from the entire lymph node. There is a long retention of some H3DNA label in the dividing lymph node cell population. This suggests that the loss of radioactivity from the dividing cells and from the small cell population as a whole occurs equally. This pattern prevails regardless of whether the percentage of large and small cells is altered experimentally. These findings can be explained by an interchange of the DNA nuclear label between small lymphocytes and large lymphocytes. This could occur by some process such as phagocytosis or pinocytosis, or by transformation of the small lymphocyte into a large, dividing cell. The data fit best with the latter possibility. All or any of these mechanisms would lead to an equilibration of the DNA label between large and small cells. This finding prevents the assignment of a finite life span to lymphocytes on the basis of DNA labeling kinetics. Nevertheless, there appear to be at least two different types of lymphocytes. One, the "thymus-type" lymphocyte, is found in the thymus cortex, bone marrow and germinal centers of lymphoid follicles. The other type, found abundantly in the widespread peripheral lymphatic tissue, shows a very prolonged retention of DNA label and is believed to be the recirculating, "immunologically committed" cells described by others. These cells do not appear to enter the thymus cortex.
A COMPARISON OF THE SPECIFICITY OF INHIBITION BY PHOSPHONATE ESTERS OF THE FIRST COMPONENT OF COMPLEMENT AND THE ANTIGEN-INDUCED RELEASE OF HISTAMINE FROM GUINEA PIG LUNG
Authors: Becker Elmer L. , Austen K. Frank
Published: June 2004

The ability of a number p-nitrophenylethyl alkyl, phenyl alkyl, chloroalkyl, and aminoalkyl phosphonates to inhibit the activated first component (C'1a) of guinea pig complement, and the antigen-induced release of histamine from sliced, perfused guinea pig lung has been compared. C'1a in its reactivity with these phosphonates is distinctly more similar to trypsin than to any of the other enzymes studied previously. It is suggested that both trypsin and C'1a possess an anionic group in the active center of the respective enzyme, but the distance between the anionic and esteratic site in C'1a might be less than in trypsin.

The pattern of inhibition of histamine relase by the alkyl, phenyl alkyl, and chloroalkyl phosphonates is similar to the inhibition of C'1a by these compounds, although distinct differences are apparent. The aminoalkyl phosphonates are distinctly less active inhibitors of histamine release than the corresponding alkyl phosphonates, whereas the reverse is true of the inhibition of C'1a. On the basis of these differences, it is tentatively concluded that the organophosphorus-inhibitable enzymes in the guinea pig systems studied here are similar but not identical.
IMMUNOFLUORESCENT STUDIES OF ADENOVIRUS 12 TUMORS AND OF CELLS TRANSFORMED OR INFECTED BY ADENOVIRUSES
Authors: Pope John H. , Rowe Wallace P.
Published: June 2004

Complement-fixing (CF) antibody-positive sera from hamsters bearing adenovirus type 12 (Ad. 12)-induced tumors revealed specific immunofluorescent stainable antigens in essentially all Ad. 12 hamster tumor cells. The antigens were primarily in the form of cytoplasmic flecks; less frequent staining was seen as nuclear flecks or homogeneous staining of nucleus and cytoplasm of a small proportion of cells. Tumor cells did not stain with rabbit antisera to crude Ad. 12 virus or A and C antigens. The hamster serum also stained cytoplasmic flecks in an Ad. 12-induced BALB/c mouse tumor and Ad. 12-"transformed" hamster embryo tissue culture cells.

The hamster serum also stained fleck-shaped antigens in hamster and human cell cultures inoculated with homologous and heterologous adenovirus types, although the hamster cells did not react with the rabbit Ad. 12 antiserum.

Attempts to identify the fluorescent-stainable fleck-shaped antigens indicated that they are not previously recognized viral antigens and that the cytoplasmic antigens formed in hamster cell cultures inoculated with Ad. 12 are different from those in tumors and in acutely infected human cell cultures.
RUNT DISEASE INDUCED IN NEONATAL MICE BY STERILE BACTERIAL VACCINES
Authors: Ekstedt Richard D. , Nishimura Edwin T.
Published: June 2004

A form of runt disease has been produced in neonatal CF-1 and ICR mice by the repeated injection of 109 washed, autoclaved, saline-suspended staphylococci or streptococci. The most severely affected animals showed a marked decrease in lymphoid tissues and resembled grossly and microscopically animals suffering from the classical runt or wasting disease described by others. The timing of the initial antigenic stimulation was of importance, and animals started on their course of injections at an age of 48 hours or older showed no effect. There was a considerable variation in the severity of the disease within litters and from one litter to another. This variation could not be ascribed to a difference in susceptibility between sexes, since both male and female mice were observed to runt under appropriate conditions. Germ-free ICR mice were much more resistant to the runting phenomenon than conventional animals of the same strain, but could be induced to runt by injection of the staphylococcal vaccine suspended in homologous antiserum.

The relationship of the runting phenomenon described here and classical runt disease or runting by adrenal hormones is discussed.
IMMUNOFLUORESCENT STUDIES OF THE HISTOPATHOGENESIS OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS INFECTION
Authors: Wilsnack Roger E. , Rowe Wallace P.
Published: June 2004

LCM virus antigen was visualized in infected tissue cultures and mouse tissues by the direct immunofluorescent procedure. In all instances, antigen was localized to the cytoplasm.

In intracerebrally infected mice, antigen was almost completely restricted to meninges, choroid plexus, and ependyma; at no time were neurons involved. Mice infected by intraperitoneal inoculation of a viscerotropic strain demonstrated antigen chiefly in liver parenchyma, splenic reticulum, bronchi, and alveolar cells.

Congenitally infected mice showed antigen in almost all cell types observed, but generally in only a minority of cells; infection was often focal in distribution. Liver, kidney, pregnant uterus, and trophoblast were most extensively involved. No antigen was observable in ova of a pregnant mouse.
THE FATE OF BACTERIA WITHIN PHAGOCYTIC CELLS
Authors: Cohn Zanvil A.
Published: June 2004

The fate of a heat-stable Escherichia coli agglutinogen within three types of rabbit phagocytic cells was examined. A system is described whereby quantitative ingestion of viable E. coli by suspensions of PMN leucocytes, BCG-induced alveolar macrophages, and oil-induced peritoneal macrophages took place in vitro. After various periods of intracellular residence aliquots were injected intraperitoneally into NCS mice and the resulting agglutinins assayed. The loss of immunogenicity within phagocytes was estimated by comparison with a dose-response titration prepared with bacteria alone. Under these conditions no increase in immunogenic mass occurred in vivo or in vitro when viable organisms were employed.

PMN leucocytes and alveolar macrophages destroyed the majority of the immunogen within 2 hours of intracellular residence. In contrast, the immunogenicity of E. coli was maintained within peritoneal macrophages for periods up to 5 hours. The use of heat-killed bacilli or specific immune serum did not significantly influence the intracellular fate of the immunogen. Residual immunogenicity was associated with a particle having the same centrifugal properties as the intact organism and essentially none was released in a soluble form. Intracellular residence within phagocytic cells did not influence the resulting temporal sequence of antibody formation nor the proportions of mercaptoethanol-sensitive and resistant immune globulins.
ELECTRON MICROSCOPY OF IN VITRO ENDOCYTOSIS OF T2 PHAGE BY CELLS FROM RABBIT PERITONEAL EXUDATE
Authors: Aronow Rita , Danon David , Shahar Avraham , Aronson Moshe
Published: June 2004

Macrophages from rabbit peritoneal exudate cells incubated in vitro with T2 bacteriophage from 10 up to 120 minutes show phage particles adsorbed to cell membranes, in the process of being engulfed by means of rhopheocytosis, micropinocytosis, and phagocytosis, and localized within dense vacuoles, semi-dense vacuoles, and clear vacuoles of the cytoplasm.

The electronmicrographs suggest that newly formed endocytic vacuoles containing phage particles fuse with one another and also fuse with dense bodies of the cytoplasm as they migrate towards the cell interior, thus yielding larger vacuoles of varying densities containing higher concentrations of phage.

The polymorphonuclear cells present in a small proportion in the peritoneal exudate cells also endocytosed phage particles. The T2 particles are found in large cytoplasmic vacuoles surrounded by an electron-opaque material presumably derived from cytoplasmic granules.

No disintegration of T2 phage within the macrophage following incubations up to 120 minutes could be demonstrated; however, disrupted phage particles were noted within cytoplasmic vacuoles of polymorphonuclear leucocytes after 15 minutes' incubation.
FURTHER OBSERVATIONS ON THE RELEVANCE OF SEROLOGIC RECAPITULATIONS OF HUMAN INFECTION WITH INFLUENZA VIRUSES
Authors: Davenport F. M. , Hennessy A. V. , Drescher J. , Mulder J. , Francis T.
Published: June 2004

By use of a photometric method which objectively distinguishes between homologous and heterologous antibody reactions, the age distribution of specifically reacting swine and Asian antibodies present in sera of persons not recently exposed to either virus was established. The findings support the thesis that the unique distribution by age of swine and Asian antibodies recognizes two past periods of prevalence of swine and Asian-like viruses, respectively. The findings apparently refute the conclusion that the existence of age-specific Asian and swine antibody patterns is primarily attributable to the undirected or passive accumulation of experience with Asian or swine antigens present as minor antigenic components in most strains of influenza A.
THE EVOLUTION OF THE IMMUNE RESPONSE
Authors: Finstad Joanne , Good Robert A.
Published: June 2004

1. Studies of the immune response have been carried out in more than 1700 lampreys representing three stages in the life cycle of these animals.

2. Lampreys used in this study were unable to clear certain soluble protein antigens and bacteriophage and were unable to make antibodies to these antigens. Hemocyanin was cleared from the circulation.

3. The immune responses demonstrated in lampreys include the production of specific antibody to killed Brucella cells, the rejection of skin homografts, and the development of a delayed allergic response to old tuberculin.

4. A responsive proliferation of lymphoid cells occurred in the protovertebral arch following antigen-adjuvant stimulation.

5. Electrophoretic and immunoelectrophoretic analysis of lamprey serum revealed gamma globulin. Ultracentrifugal analysis of serum revealed proteins with sedimentation coefficients of 17S, 8S, 7S, and 3S.

6. The antibodies thus far observed in the lamprey are of relatively high molecular weight and destroyed by 2-mercaptoethanol.

7. In the lamprey it would appear that there is reflected the coordinate evolution of a primitive thymus, primitive spleen containing lymphoid foci, a family of lymphocytes in the peripheral blood and capacity for gamma globulin synthesis and expression of adaptive immunity.
THE IDENTIFICATION AND ISOLATION OF TWO MOUSE-TOXIC PROTEIN COMPONENTS IN EXTRACTS FROM PASTEURELLA PESTIS
Authors: Montie Thomas C. , Montie Diane B. , Ajl Samuel J.
Published: June 2004

The toxin activity of Pasteurella pestis cells, strain "Tjiwidej," was found to be associated with two proteins. Using a disc electrophoresis technique in conjunction with mouse lethality, two toxic proteins were isolated exhibiting intraperitoneal LD50's of less than 1.0 to 1.5 µg protein. Each produced a single characteristic precipitin band on agar gel diffusion plates. The slower migrating toxin in gel diffusion or disc electrophoresis was designated as toxin A. It was shown to be sensitive to deoxycholate and digitonin, did not accumulate in 5-fluorotryptophan treated cells, and was associated with the membrane fraction of the cell. The faster migrating toxin B, apparently is resistant to surface-active agents, and is not affected by treatment of cells with 5-fluorotryptophan. Toxin B is associated with the soluble or cytoplasmic fraction of the cell. This evidence suggested that each toxin represented a distinctly different molecular species. The possibility is discussed that toxin B is synonymous with the murine toxin previously isolated by paper curtain electrophoresis which revealed only one antigen band in the Oudin precipitin reaction.
IN VITRO STUDIES OF CELLULAR HYPERSENSITIVITY
Authors: Carpenter Robert R. , Brandriss Michael W.
Published: June 2004

Some characteristics of inhibition of cell migration induced in tissue culture by the addition of specific antigen were studied. The following characteristics were found to be shared by this type of cellular hypersensitivity and delayed cutaneous sensitivity:

1. Specificity for the carrier moiety of haptene protein conjugates. The picryl protein conjugate used to sensitize guinea pigs inhibited migration of monocytic cells from these animals. Other picrylated proteins produced little inhibition.

2. Enhancement by mycobacterial adjuvants. Incorporation of tubercle bacilli with picrylated proteins in adjuvant-antigen emulsions stimulated the development of this cellular hypersensitivity to antigen.

3. Independence of circulating antibody. In contrast to cellular hypersensitivity, serum antibody (a) reacted with any of a number of picrylated proteins, (b) developed well in the absence of mycobacterial adjuvant, and (c) persisted in unchanged titer for 5 weeks in animals sensitized with saline solutions of antigen. During this time cellular hypersensitivity decreased remarkably.

The in vitro system described provides a direct method to measure cell-antigen interaction and permits study of an aspect of the immune response not mediated by humoral antibody.

The relation of cellular hypersensitivity to antibody formation and delayed hypersensitivity is discussed.
STRUCTURAL ASPECTS OF HUMAN ERYTHROCYTE AUTOANTIBODIES
Authors: Leddy John P. , Bakemeier Richard F.
Published: June 2004

The 7S γ-globulins causing erythrocyte autosensitization in 20 patients were isolated by elution and examined for homogeneity or heterogeneity of their L chain types and electrophoretic dispersion. The isolated erythrocyte autoantibodies from 12 patients contained only 1 detectable L chain type. Two of these "monotypic" populations showed appreciable restriction of electrophoretic dispersion, while 2 others more nearly resembled the electrophoretic heterogeneity of normal γ-globulins. The autoantibodies from the other 8 patients exhibited L chains of both types. The single "bitypic" population so tested was relatively polydisperse electrophoretically. As a comparison, anti-Rho isoantibodies from 5 of 6 donors without known hematologic disease showed bitypic reactions, and 2 of these isoantibody populations were relatively polydisperse electrophoretically. One Rh isoantibody is described which contained only 1 demonstrable L chain type.

The structural similarities to "paraproteins" observed in a significant proportion of these erythrocyte autoantibodies raise the possibility of their origin from a restricted population of antibody forming cells, and may have implications concerning the pathogenesis of erythrocyte autosensitization.
ONSET AND DURATION OF DNA SYNTHESIS IN ANTIBODY-FORMING CELLS AFTER ANTIGEN
Authors: Cohen Edward P. , Talmage David W.
Published: June 2004

Within 5 hours after the intravenous injection of particulate antigen into the primarily immunized mouse, precursors of antibody-forming cells began DNA synthesis as shown by the incorporation of tritium-labeled thymidine. DNA synthesis continued for at least 24 hours and essentially stopped by 48 hours. No DNA synthesis in antibody-forming precursor cells occurred before the injection of antigen.
STUDIES ON THE LYMPHOCYTOSIS INDUCED IN MICE BY BORDETELLA PERTUSSIS
Authors: Morse Stephen I.
Published: June 2004

1. Intravenous injection into mice of phase I Bordetella pertussis vaccine resulted in a striking hyperleucocytosis with a predominating lymphocytosis. Intraperitoneal inoculation was less effective, and subcutaneous administration was inactive.

2. Active immunization prevented the hyperleucocytosis; passive immunization was less effective.

3. Reticuloendothelial blockage reduced the effect of the vaccine.

4. Extirpation of the spleen or thymus did not alter the leucocyte response.

5. Histologic studies suggested that the increase in circulating lymphocytes resulted from release of cells from lymphoid organs, including the thymus.
RELATIONSHIP OF DONOR AGE TO IN VITRO PRODUCTION OF FOOT-AND-MOUTH DISEASE VIRUS BY MOUSE KIDNEY CELLS
Authors: Campbell Charles H.
Published: June 2004

Multiplication of foot-and-mouth disease virus (FMDV) was compared in kidney cells from 7- to 35-day-old mice representing various degrees of age resistance to this virus. Three types of cell preparations were used: primary monolayer cultures, suspensions of dispersed cells, and suspensions of minced tissue.

Virus multiplication in the two types of cell suspensions was related to the age of the donors both in regard to time when multiplication first became evident and to the amount of virus produced. While adsorption rates were similar in the cells from all age groups, virus multiplication began earlier in cells from younger mice and more virus was produced by these cells than by cells from older animals. There was no significant difference in the virus growth rates in the primary monolayer cultures of cells.

The results indicate that kidney cells from mice 7 to 35 days old vary in their ability to produce virus in relation to the degree of susceptibility of the cell donors. After propagation of the cells in primary monolayer cultures, however, this difference no longer exists probably because of cell selection under the cultural conditions.
ENDOTOXEMIA AND ADRENAL HEMORRHAGE
Authors: Levin Jack , Cluff Leighton E.
Published: June 2004

An experimental model that produces adrenal cortical hemorrhage with endotoxin has been described. When stimulated by thorotrast, endotoxin, or its tropic hormone (ACTH), the adrenal cortex is susceptible to the development of a hemorrhagic reaction during endotoxemia. The hemorrhagic reaction resembles that described in the Waterhouse-Friderichsen syndrome.

A pathophysiologic mechanism for the occurrence of adrenal hemorrhage occurring during acute sepsis is presented. Increased metabolic activity associated with the production of corticosteroids seems to make the adrenal cortex susceptible to endotoxin-induced hemorrhage. Adrenal hemorrhage observed during sepsis, as in the Waterhouse-Friderichsen syndrome, may be attributable to endotoxemia occurring during or shortly after stimulation of the adrenal cortex by infection.

Significant differences between adrenal cortical hemorrhage and the Shwartzman phenomenon are described.