bluuebunny/crossref_metadata_2025 huggingface dataset:
LOCALIZATION AND FATE OF ESCHERICHIA COLI IN HEMATOGENOUS PYELONEPHRITIS
Authors: Sanford Jay P. , Hunter Betty W. , Donaldson Paul
Published: June 2004

1. Hematogenous E. coli pyelonephritis was produced in rats. The localization of the organisms and the persistence of bacterial antigens was followed by fluorescent antibody techniques as well as by standard histological and bacteriological methods.

2. Salient sequential features were as follows: Single organisms passed through vessel walls into the renal interstitium and began multiplication and subsequently evoked a leucocytic response. Bacterial multiplication did not occur in glomeruli or renal tubular cells. Bacteria did not appear within renal tubular lumina until microabscesses were well developed in the renal interstitium. Bacteriuria appeared late and represented secondary invasion rather than filtration of organisms. The infection healed spontaneously but, while sterile, the parenchymal scars contained large amounts of residual bacterial antigen. The persistence of bacterial antigen did not result in continuing inflammatory changes or progressive scarring.

3. The persistence of bacterial antigens is postulated to constitute a major antigenic stimulus responsible for active immunity in experimental hematogenous pyelonephritis.
EXPERIMENTAL HYPERGAMMAGLOBULINEMIA IN MINK
Authors: Henson James B. , Gorham John R. , Leader Robert W. , Wagner Bernard M.
Published: June 2004

Hypergammaglobulinemia in mink was produced by the injection of crude tissue suspensions from mink with spontaneous Aleutian disease. The initiating factor was found to be resistant to 0.3 per cent formalin for 2 weeks but not 40 weeks at 5°C. Foreign antigens as well as formalinized normal mink tissue from homologous and heterologous genotypes did not cause a detectable change in the serum protein values.

Mink homozygous recessive for the Aleutian gene were found to be significantly more susceptible to the experimental disease.

Possible pathogenetic mechanisms as well as similarities between the mink disease and certain immunologic and connective tissue diseases of man are discussed.
CELLULAR RESISTANCE TO INFECTION
Authors: Mackaness G. B.
Published: June 2004

The mouse was found to be natively susceptible to Listeria monocytogenes. Its susceptibility was attributed to the capacity of the organism to survive and multiplying in host macrophages. During the first 3 days of a primary infection the bacterial populations of spleen and liver were found to increase at a constant rate. On the 4th day of infection the host became hypersensitive to Listeria antigens and at the same time bacterial growth ceased. A rapid inactivation of the organism ensued.

Convalescent mice were resistant to challenge, but no protective factor could be found in their serum. Histological evidence suggested that acquired resistance was the result of a change occurring in the host's mononuclear phagocytes. When challenged in vitro, the macrophages of convalescent mice were found to resist infection with Listeria monocytogenes. Listeria-resistant cells appeared during the course of infection at a time which corresponded with the development of the antibacterial mechanism in the spleen. They persisted for as long as the antibacterial mechanism remained intact in this organ.

This period of absolute resistance to Listeria lasted about 3 weeks. Thereafter, the host remained hypersensitive but unable to inactivate a challenge inoculum of Listeria. However, it remained capable of producing an accelerated response to reinfection. This was thought to depend upon an ability to generate a new population of resistant cells from a residuum of specifically sensitized macrophages or macrophage precursors still surviving in the tissues as a result of the immunological activation which occurred during the primary infection.
REDUCTION OF SERUM COMPLEMENT IN RABBITS AFTER INJECTION OF ENDOTOXIN
Authors: Gilbert Verne E. , Braude Abraham I.
Published: June 2004

Injection into rabbits of a consistently lethal dose of endotoxin regularly produced a rapid and sustained fall of complement levels and lowered the titers of antibody to endotoxin. Doses of endotoxin below the LD50 lowered complement levels sporadically but not the titers of antibody to endotoxin. The possibility is discussed that complement may be involved in the mechanisms responsible for the lethal action of endotoxin.
INHIBITION OF SYNTHESIS OF SULFATED MUCOPOLYSACCHARIDES BY ESTRADIOL
Authors: Priest Robert E. , Koplitz R. Marlene
Published: June 2004

The influence of estradiol upon incorporation of isotopes into the sulfated acid mucopolysaccharides of connective tissues of the rat has been studied.

Administration of the hormone for 3 weeks significantly reduces the in vitro incorporation of S35-sulfate into cartilage and thoracic aorta without significantly altering the amount of hydrolyzable sulfate in these tissues.

The reduction of sulfate incorporation into these tissues by estradiol represents reduced synthesis since the hormone reduces incorporation of sulfate into the acid mucopolysaccharides of the tissue to the same extent and since reduction in incorporation of C14-glucose also parallels S35-sulfate incorporation into acid mucopolysaccharides.

The rate of synthesis of sulfated acid mucopolysaccharides is greater in thoracic aorta than abdominal aorta or cartilage. Since the amount of hydrolyzable sulfate is the same in these two portions of aorta, the turnover is also more rapid in the thoracic aorta.
IMMUNOLOGIC RESPONSE OF NEONATAL AND OLDER RABBITS TO ANTIGENS OF RABBIT LEUCOCYTES
Authors: Harris T. N. , Harris Susanna , Farber Miriam B.
Published: June 2004

The immunologic response of neonatal and of older rabbits to the tissue (transplantation) antigens of pooled rabbit leucocytes was studied, the test system being the suppression of formation of agglutinin to Shigella paradysenteriae by transferred lymph node cells which had been incubated with Shigella antigen.

In the active induction of the suppressive effect on the transferred cells it was found that neonatal rabbits reacted as vigorously as 1 kg rabbits to the prior injection of a given number of rabbit leucocytes pooled from prospective donors of lymph node cells. The suppressive effect was dose-related, and within the range of number of leucocytes used was similar for both age groups of recipients. An attempt to detect a difference in the response during the first few days after leucocyte injection, before the full suppressive effect is reached, failed to show any difference between rabbits of the two age groups.

Since it had been found possible to transfer the suppressive effect passively with sera obtained from older rabbits injected with rabbit leucocytes, attempts were made to do so with sera obtained from neonatal rabbits injected with similar numbers of pooled adult rabbit leucocytes. No consistent suppression of transferred lymph node cells was observed with sera from neonatal rabbits, even with relatively large amounts of such serum. In sera of rabbits which had been injected with rabbit leucocytes at the age of 4 to 6 weeks, suppressive antibody could be detected. When anti-rabbit-leucocyte serum obtained in adult rabbits was injected into neonatal and 1 kg recipients at a given volume per gram of animal weight the suppressive effect of the serum was of similar extent in the two groups of recipients.

In the adoptive transfer of the lymph node cell suppressive effect, by cells of lymph nodes draining the sites of injection of pooled rabbit leucocytes, it was found that the popliteal lymph node cells of neonatal rabbits were as effective as those of 1 kg rabbits. Splenic cells of neonatal rabbits were also effective, when an adequate number of rabbit leucocytes had been injected intravenously.

Thus, in conferring adoptive immunologic response, as in active immunization, the neonatal rabbits were as effective as the older rabbits in their response to homotransplantation antigens, in contrast to the considerable difference in concentration of the suppressive antibody in sera of neonatal and older rabbits injected with rabbit leucocytes.
FACTORS RELATING TO THE VIRULENCE OF STAPHYLOCOCCI
Authors: Koenig M. Glenn , Melly Marian Ann , Rogers David E.
Published: June 2004

Antitoxic and antibacterial immunity have been clearly differentiated in the experimental mouse infection produced by the diffuse colonial variant of the Smith strain of Staphylococcus aureus.

Immunization with crude toxoid protected mice from otherwise lethal doses of alpha hemolysin, but did not alter mortality following intraperitoneal infection with living staphylococci. Conversely, animals immunized with heat killed vaccines were readily killed by culture supernates containing alpha hemolysin, but were strikingly protected from otherwise fatal intraperitoneal infection with viable staphylococci.

Protection was directly related to the ability of the immunizing substance to promote early intraperitoneal phagocytosis of the infecting inoculum. In these studies with the Smith diffuse variant, rapid intraperitoneal phagocytosis was induced by vaccination with whole cell bacterial vaccines but not by alpha hemolysin toxoid.
THE ANTIGENIC STRUCTURE OF THE POLYPEPTIDE CHAINS OF HUMAN γ-GLOBULIN
Authors: Olins D. E. , Edelman G. M.
Published: June 2004

The antigenic properties of the polypeptide chains of human 7S γ-globulin have been related to two major non-cross-reacting antigenic determinants of the whole molecule. These determinants, called S and F, were obtained by hydrolysis of γ-globulin with papain. Antisera against whole γ-globulin and against S and F fragments were used in techniques of immune diffusion. Light (L) chains of γ-globulin showed reactions of partial identity with S fragments, and thus are antigenically deficient with respect to these fragments. Antisera directed against F determinants did not react with L chains but did react with heavy (H) polypeptide chain preparations. In addition, the major component of H chain fractions did not appear to contain determinants in common with the S fragments.

L chains of a γ-myeloma protein were shown to be antigenically deficient with respect to the whole myeloma molecule, and antigenically identical with the Bence-Jones protein of the same patient.

Correlation of these results with those of previous investigations have led to the conclusions that the S fragment which is known to contain the combining region of antibody molecules, consists in part of L chains or portions of L chains, and that the F fragment, which mediates several other functions of the whole molecule, is composed in part of portions of H chains.
THE PRODUCTION OF RUNT DISEASE IN RATS THYMECTOMIZED AT BIRTH
Authors: Aisenberg Alan C. , Wilkes Barbara , Waksman Byron H.
Published: June 2004

Thymectomy of Sprague-Dawley rats on the 3rd day of life failed to influence the time of onset, incidence, clinical, or histologic picture of runt disease produced by the intraperitoneal injection of adult Long-Evans spleen cells. The fact that severe immunologic impairment of the host by thymectomy does not modify runt disease was felt to be consistent with the current view that the if direction of the immunologic event in this syndrome is graft versus host.

Following the injection of 800 to 1000 million Long-Evans spleen cells into adult Sprague-Dawley rats, a severe illness comprised of dermatitis, gastrointestinal bleeding, arthritis, weight loss, and death ensued in 37 per cent of adults thymectomized neonatally and 13 per cent of normal controls. Histologic lesions were observed in 69 per cent of adequately thymectomized animals and 17 per cent of normal controls, and involved lymph nodes, spleen, liver, lungs, kidneys, joints, heart, and skin. The time of onset and the histologic and clinical pictures are consistent with the adult disease being a typical graft versus host reaction.
THE ROLE OF THE THYMUS IN DEVELOPMENT OF IMMUNOLOGIC CAPACITY IN RABBITS AND MICE
Authors: Good Robert A. , Dalmasso Agustin P. , Martinez Carlos , Archer Olga K. , Pierce James C. , Papermaster Ben W.
Published: June 2004

In rabbits, complete thymectomy before the age of 5 days produced immunologic deficiency in the adult animals, as indicated by reduced antibody production to bovine serum albumin and bacteriophage T2. Homotransplantation immunity was unaffected, however.

In an inbred strain of mice, complete neonatal thymectomy resulted in complete inability of the 60-day-old animals to form antibody to bacteriophage T2.

Inbred mice, completely thymectomized at birth, had a deficient homograft response, indicated by acceptance of skin homografts from strains differing in both the weaker and stronger (H-2) histocompatibility antigens. Tumor transplants (mammary adenocarcinoma) were also successful across the H-2 genetic barrier in mice thymectomized at birth. Neonatal thymectomy also eliminated the Eichwald-Silmser phenomenon, rendering female mice capable of accepting isografts of male skin.

Transplantation immunity in mice was also affected by later thymectomy, at 30 days of age, in certain strain combinations involving weak histocompatibility differences.

Spleen and lymph node cells from mice thymectomized at birth or at 6 days of age, and sacrificed 2 months later, did not produce a graft versus host reaction in appropriate F1 hybrid recipients, indicating that such cells are immunologically inactive.

Neonatal thymectomy of F1 hybrid mice, and in one strain combination thymectomy at 40 days of age, produced animals with inordinate susceptibility to runt disease (homologous disease) following injection of parent strain spleen cells 35 days (neonatal surgery) and 10 days (surgery at 40 days) later.

Mice thymectomized at birth also showed growth failure and were short-lived.

Studies of newborn mice indicated that they have true lymphocytes only in the thymus, and lack such cells in the spleen, lymph nodes, and gut. In normal mice, adult lymphoid structure develops gradually, beginning during the 1st week of life and continuing for the next month. In contrast, mice thymectomized at birth do not develop mature lymphoid structure: the lymph nodes and spleens tend to be small and poorly organized, and show a quantitative deficiency in lymphoid cells.

It is our current working hypothesis that the thymus makes a major contribution toward the centrifugal distribution of lymphoid cells which, in turn, is essential to the full expression of immunologic capacity.
COMPARATIVE STUDIES OF THE ISOZYMES OF LACTIC DEHYDROGENASE IN RABBIT AND MAN
Authors: Vesell Elliot S. , Philip John , Bearn Alexander G.
Published: June 2004

During development of rabbit tissues, characteristic sequential alterations in the LDH isozyme pattern occur, and consist for liver and muscle in loss of the most rapidly migrating anodal bands, and increased activity in the cathodal bands and slower migrating anodal bands. In heart the reverse changes were observed. Comparison of the isozyme patterns observed in various fetal and adult human tissues suggests that these same sequential alterations probably occur.

A species-specific isozyme pattern is obtained in long term culture of rabbit, chick, and human cells. The alterations in tissue culture are characterized by a gradual redistribution of total LDH activity in which there is decreased intensity of rapidly migrating anodal bands. These sequential alterations are independent of the organ of origin. The number of bands observed in the starch gel is partly dependent upon the total activities applied.

Isozymes may provide a convenient method for determining the species of origin of cell lines in common use and for investigating the effects of various alterations in the in vitro environment on cells grown in tissue culture.
CLASSIFICATION OF MYELOMA PROTEINS, BENCE JONES PROTEINS, AND MACROGLOBULINS INTO TWO GROUPS ON THE BASIS OF COMMON ANTIGENIC CHARACTERS
Authors: Mannik Mart , Kunkel Henry G.
Published: June 2004

Antisera to normal 7S γ-globulin and to Bence Jones proteins permit the grouping of myeloma proteins (gamma and beta 2A types), Bence Jones proteins, and the Waldenström type macroglobulins into two fundamental antigenic groups. The antigenic determinants responsible for this grouping are common to all these proteins which fall in the general category of immunoglobulins. Antisera to Bence Jones proteins were particularly useful for this classification since they failed to react with the proteins of the opposite group. These antisera also permit the grouping of normal 7S γ-globulin into two major types.

The Bence Jones proteins from individual patients were found to correspond in antigenic group to that of the serum myeloma protein. Studies with antisera to 7S γ-globulin and to Bence Jones proteins indicated that the Bence Jones proteins were antigenically identical to a portion of the corresponding multiple myeloma protein molecules.
THE STIMULATION OF NON-SPECIFIC HOST RESISTANCE TO INFECTION BY CHEMICALLY MODIFIED ENDOTOXIN
Authors: Sultzer Barnet M. , Freedman Henry H.
Published: June 2004

An acetylated derivative prepared from Salmonella typhosa O-901 endotoxin has been found to retain the ability to stimulate non-specific host resistance to a variety of bacterial infections. Relative to the parent endotoxin, the derivative has been reduced in the gross in its pyrogenicity to rabbits and lethality to mice. With the use of this chemically modified preparation under a variety of conditions, the direct dissociation of the toxic properties of endotoxin from its protective capacity appears evident.

In young male mice, the endotoxin and its derivative produced a leucocytosis but no leucopenia. However, no direct correlation could be found with the level of the peripheral white blood cells and resistance to infection with Escherichia coli. Furthermore, under the conditions employed, passive transfer of early resistance to infection by serum or plasma was not detectable.
ACCESSORY PLASMA FACTORS INVOLVED IN THE BACTERICIDAL TEST FOR TYPE-SPECIFIC ANTIBODY TO GROUP A STREPTOCOCCI
Authors: Stollerman Gene H. , Rytel Michael , Ortiz Jesse
Published: June 2004

A study was made of the nature of the thermolabile plasma factors in human blood which promote the phagocytosis of Group A streptococci in vitro in the presence of optimal amounts of type-specific M antibody. The plasmas of individuals with strong opsonic activity (normal) were compared with those of some individuals whose opsonic activity was consistently weak (deficient).

A general relationship was established between encapsulation of streptococci and the opsonic requirement for thermolabile plasma factor(s). Marked differences in phagocytosis of Group A organisms by human bloods were demonstrated with encapsulated strains only. Human bloods deficient in the cofactor required for opsonization of encapsulated streptococci (coopsonin) showed a normal rate of phagocytosis against all other organisms and particles studied. Furthermore, coopsonin-deficient bloods contained normal levels of four components of complement, of properdin, of lysozyme, and of direct bactericidal activity against several species of Gram-negative organisms and of E. coli bacteriophage.

The independence of the streptococcal coopsonin from complement was also demonstrated by absorption of plasma with bentonite and with zymosan. Under appropriate conditions, the coopsonin was reduced without significant loss of complement.

The data support the concept that the capsule of the streptococcus imposes an opsonic requirement for a plasma factor(s) which is present in varying amounts in human bloods and which appears to be independent of the complement system. The possibility that it is accessory to the latter components has not been excluded.
THE EFFECT OF RHEUMATOID FACTORS AND OF ANTIGLOBULINS ON IMMUNE HEMOLYSIS IN VIVO
Authors: Kaplan Manuel E. , Jandl James H.
Published: June 2004

Studies were undertaken in man and in the rat comparing the effects of rheumatoid factors and immune antiglobulins on red cells sensitized with incomplete antibodies.

The interaction of immune antiglobulins with sensitized red cells produced (a) agglutination in vitro and (b) an accelerated sequestration of the sensitized cells in vivo. In contrast, rheumatoid macroglobulins, although capable of agglutinating Rh-sensitized red cells in vitro, did not modify their destruction in vivo. The failure of rheumatoid factors to function as antiglobulins in vivo appears to reflect their non-reactivity with sensitized cells in whole serum.

It is suggested: (a) that the native (7S) gamma globulins of plasma competitively inhibit rheumatoid factors from reacting with fixed antibody in the blood stream; (b) that if these macroglobulins do indeed have pathogenetic activity, this may be limited to body fluids of low protein content.
STUDIES ON THE DIMENSIONS OF THE RABBIT ANTI-BENZYLPENICILLOYL ANTIBODY-COMBINING SITES
Authors: Levine Bernard B.
Published: June 2004

Rabbit antisera prepared against conjugates of the benzylpenicilloyl (BPO) bifunctional haptenic group were analyzed to determine whether the antibodies are adapted to only a portion of the large BPO molecule, or to the entire molecule, and whether specificity extends to the lysine side chain and adjoining structures of the immunizing carrier protein.

No antibodies adapted to the phenylacetylamine portion of the BPO group could be detected in a pooled rabbit anti-BPO serum globulin fraction by PCA and quantitative precipitin analysis using several phenylacetylamine-protein conjugates as antigens. No antibodies adapted only to the thiazolidine carboxylic acid portion of the BPO molecule were detected in the anti-BPO globulin fraction using quantitative precipitin and hapten inhibition methods. At least the bulk of the anti-BPO antibodies was found to be adapted to the entire BPO haptenic group.

By quantitative hapten inhibition of precipitation of the anti-BPO globulin fraction, the anti-BPO antibodies were found to show specificity for a 6 carbon amide side chain corresponding to the lysine side chain through which BPO groups are bound predominantly to protein. The contribution of this 6 carbon chain to antibody-hapten binding was small; (–ΔF°) was calculated to be 460 calories per mole (average).

Rabbit anti-BPO antibodies prepared against BPO-rabbit serum albumin conjugates showed specificity also toward structures of the immunizing carrier protein, and possibly toward secondary or tertiary structural configurations. Penicilloyl conjugates of rabbit serum albumin precipitated from 3 individual rabbit antisera more anti-BPO antibodies than did penicilloyl conjugates of heterologous carriers (poly-L-lysine, human serum albumin, and human γ-globulin).

Anti-BPO antibodies demonstrated heterogeneity with regard to closeness of fit to the haptenic group, or with regard to the dimensions of the combining sites, or both.

It was concluded that at least a large part of anti-BPO antibodies are specifically adapted to a large antigenic unit comprised of the entire BPO group, the lysine side chain, and structural configurations of the immunizing carrier protein.
THE FATE OF BACTERIA WITHIN PHAGOCYTIC CELLS
Authors: Cohn Zanvil A.
Published: June 2004

The intraleucocytic fate of a variety of P32- and C14-labeled bacteria has been studied in both polymorphonuclear leucocytes and macrophages. Both cell types brought about extensive degradation of bacterial lipids, nucleic acids, and proteins. Intracellular breakdown was primarily dependant upon the composition of the ingested particle rather than on the type or source of the phagocyte. Evidence is presented for the reincorporation of bacterial constituents into leucocyte lipid. More than 50 per cent of the acid-soluble degradation products of P32-labeled bacteria appear as inorganic phosphate. Bacterial RNA is degraded more readily than DNA.

Following phagocytosis, labeled bacteria lose their pool of small molecular weight intermediates. This is followed by the degradation of acid-insoluble constituents. The majority of bacterial breakdown products are then excreted by the leucocyte and appear in the medium.

Heat-killed bacteria were more readily broken down than viable organisms. Only small amounts of C14-labeled bacteria were completely oxidized by leucocytic enzymes to C14O2.

Acid extracts of polymorphonuclear leucocyte granules, which were highly bactericidal, liberated the acid-soluble constituents of labeled bacteria but did not significantly degrade bacterial macromolecules.
METABOLISM IN INFECTION: STUDY ON THE ENZYMATIC DAMAGE IN KIDNEY OF GUINEA PIG INFECTED WITH MYCOBACTERIUM TUBERCULOSIS
Authors: Chaudhuri S. N. , Suter Elsi , Shah N. S. , Martin S. P.
Published: June 2004

Malic dehydrogenase activity of the kidney homogenate from the normal and the tuberculous guinea pigs has been estimated. A defect in the electron transport chain has been detected at the level of flavoprotein-diaphorase system. A significantly high DPNase activity of kidney homogenate has also been found in the infected group. Niacin and phenazine methochloride could correct both the defects and improve the tetrazolium reduction of the homogenate in the infected group to the level of the normal activity. Oxidative phosphorylation by the kidney mitochondria from the tuberculous guinea pigs was found to be low and could not be improved by niacin and phenazine methochloride, unlike their effects on the reduction of tetrazolium. Results have been discussed in the light of the over-all intercellular economy and its relation to the symptom complexes in tuberculosis.
ANTIGENIC RELATIONSHIPS OF BENCE JONES PROTEINS, MYELOMA GLOBULINS, AND NORMAL HUMAN γ-GLOBULIN
Authors: Migita Shunsuke , Putnam Frank W.
Published: June 2004

By means of immunodiffusion and immunoelectrophoresis study has been made of antigenic relationships of Bence Jones proteins, and the three classes of normal and pathological immunoglobulins, 7S γ, ß2A, and ß2M. All thirty-nine Bence Jones proteins studied could be classified into either one of two distinct antigenic types, A or B. Both types are related to the immunoelectrophoretically slow (S) fragment of a papain digest of normal γ-globulin; B is related more closely than A, but neither has antigenic determinants in common with the fast (F) fragment. The 7S γ myeloma globulins were either immunological type I or II. The papain digests of these proteins produced the S and F precipitin lines in immunoelectrophoresis but multiple bands in starch gel electrophoresis, especially in the F region. The S fraction of type I myeloma globulins is antigenically similar to Bence Jones protein of type B, and the S component of type II myeloma globulins has antigenic determinants in common with type A Bence Jones protein. Correspondingly, myeloma patients with type I globulins and proteinuria usually excrete type B Bence Jones proteins, whereas patients with type II excrete type A proteins. The F fragment is the part common to normal 7S γ-globulin and types I and II myeloma globulins but is absent in ß2A and ß2M pathological globulins and in both types of Bence Jones proteins. Papain digests of ß2A myeloma globulins produced a single precipitin line in immunoelectrophoresis. ß2A myeloma globulins appeared to have two antigenic units, one in common with type B Bence Jones protein and normal γ-globulin, and another specific to ß2A. The ß2A myeloma patients excreted type B Bence Jones protein. The papain digest of a macroglobulin produced two precipitin lines, the faster of which had antigenic determinants in common with type B Bence Jones protein, the slower seemed specific for the macroglobulin. Five serum micromolecular globulins proved to be either type A or B Bence Jones proteins. From the above results, an antigenic map was constructed showing which determinants are shared and which are specific for normal 7S γ-globulin, types I and II myeloma globulins, ß2A myeloma globulins, a macroglobulin, and types A and B Bence Jones proteins.
MULTIPLE ENZYME CHANGES IN THE PLASMA OF NORMAL AND TUMOR-BEARING MICE FOLLOWING INFECTION WITH THE LACTIC DEHYDROGENASE AGENT
Authors: Notkins Abner Louis , Greenfield Robert E. , Marshall Diana , Bane Louisa
Published: June 2004

Within 72 hours after injection of the LDH agent into normal mice, five (LDH, ICDH, MDH, PHI, and GOT) out of the seven plasma enzymes studied were elevated. This elevation persisted for the duration of the experiment. Alkaline phosphatase and aldolase were not elevated.

Plasma from mice bearing tumor SS-70429 and infected with the LDH agent showed 7 times more LDH, 8 times more ICDH, and 4 times more MDH activity than the plasma from mice with the same tumor but uninfected. The plasma aldolase activity from the infected tumor-bearing animal was approximately the same as that from the uninfected tumor-bearing animal. Somewhat similar results, but lower in magnitude, were found with mice bearing mammary carcinoma C3HBA.

The early rise in plasma enzyme activity (LDH, MDH, ICDH) prior to the actual appearance of the tumor was shown to be due not to the tumor, but to the LDH agent. Uninfected tumor-bearing mice showed a late increase in plasma enzyme activity which appeared to be related to tumor growth.

The findings reported above suggest that contamination with the LDH agent may have been responsible for much of the increased plasma enzyme activity previously attributed to the tumor.
IN VITRO STUDIES OF MAMMALIAN SOMATIC CELL VARIATION
Authors: Cann Howard M. , Herzenberg Leonard A.
Published: June 2004

The isoantigenic phenotype of the H-2 locus has been detected by isohemagglutinin absorption in a line of mouse lymphoma cells growing continuously in culture for 6 years and in two established lines of fibroblastic mouse cells growing continuously in culture for 1 year. Quantitative absorption studies suggest that the concentration of H-2 isoantigens is higher in the cultured lymphoma cells than in the other two fibroblastic cell lines.
PROPERTIES OF A BACTERIOPHAGE DERIVED FROM ESCHERICHIA COLI K235
Authors: Jesaitis Margeris A. , Hutton John J.
Published: June 2004

A temperate bacteriophage was isolated from the colicinogenic strain of Escherichia coli K235 and characterized. This phage, termed PK, is related to P2 virus morphologically, serologically, and, possibly, genetically and it bears no relationship to the T-even phages. It was also demonstrated that PK virus and colicine K differ both in their host range and in their immunological specificity, and that PK prophage does not induce the colicinogenesis in its host bacterium. It was concluded that the formation of colicine K. and PK phage in E. coli K235 are controlled by different genetic determinants.
THE ANTIBODY RESPONSE OF RATS DEPLETED OF LYMPHOCYTES BY CHRONIC DRAINAGE FROM THE THORACIC DUCT
Authors: McGregor D. D. , Gowans J. L.
Published: June 2004

The chronic drainage of lymph and cells from a thoracic duct fistula in rats results in a reduction in the weight of all the lymph nodes and of their content of small lymphocytes. The primary immune response to tetanus toxoid or sheep erythrocytes is severely depressed or abolished in such animals. This unresponsive state is related to the loss of lymphocytes from the thoracic duct fistula and, not to stress factors ensuing from the trauma of operation and restraint; it can be reversed by injecting inocula which contain almost exclusively small lymphocytes. In contrast to the severe impairment of the primary immune response in lymphocyte-depleted rats, such animals show a normal response to a second injection of tetanus toxoid. The mechanism by which small lymphocytes mediate the primary immune response is discussed.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Bornstein Donald L. , Bredenberg Carl , Wood W. Barry
Published: June 2004

Although the absolute febrile responses of trained individual rabbits injected intravenously with small to moderate doses of leucocytic pyrogen vary over an appreciable range, the relative responses of each rabbit to changes in dosage are satisfactorily reproducible.

The quantitative dose-response relationship is characterized by a hyperthermic ceiling at which the intensity of the febrile reaction is relatively constant over a wide dosage range. Only at lower dose levels, where the dose-response curve is reasonably steep, is the magnitude of the fever produced proportional to the amount of pyrogen injected.

When sufficiently large doses of LP are injected, the hyperthermic ceiling is exceeded. The fevers thus induced are biphasic in character and, in this way, resemble the usual response to bacterial endotoxin.

Similar biphasic fevers result from continuous infusions of relatively low concentrations of LP at a constant rate.

Repeated intermittent injections of moderate doses of LP likewise cause prolonged biphasic fevers, but, once the fever has become established, the reaction to each individual injection becomes markedly depressed.

When large doses of LP are injected at daily intervals, the characteristic biphasic response occurs only following the first injection. Thereafter a state of tolerance intervenes in which the late secondary rise in temperature fails to occur. This form of tolerance lasts as long as the daily injections are continued but subsides within a few days after the injections are stopped.

During the transient tolerance the rabbit's responsiveness to small doses of LP (in the sensitive range of the dose response curve) is depressed. In addition, the amount of endogenous pyrogen mobilized from the tissues by a large dose of LP is not as great as that generated in a normal rabbit.

The relations of these findings to biphasic fevers, tolerance, and the accuracy of the conventional method of pyrogen assay are briefly discussed.
STUDIES OF L FORMS AND PROTOPLASTS OF GROUP A STREPTOCOCCI
Authors: Freimer Earl H.
Published: June 2004

Intact bacterial membranes have been isolated from protoplasts prepared from Group A streptococci by a cell wall-dissolving enzyme. A membrane fraction with identical chemical and serological properties has been obtained by differential centrifugation of mechanically disrupted streptococci. The membrane is chemically distinct from the cell wall and is composed of 72 per cent protein, 26 per cent lipid, and 2 per cent carbohydrate. Capillary precipitin tests and analysis by microdiffusion have demonstrated that the membrane contains antigens distinct from those of the cell wall and from those of the cytoplasm which it envelops. Evidence is presented which demonstrates that this antigenic material is common to the membranes of Group A streptococci, and that it can be distinguished by immunodiffusion from related antigenic substances present in membranes of several other serological groups of hemolytic streptococci. This antigenic material does not cross-react with the membrane antigens of other Gram-positive cocci.
ACQUIRED TOLERANCE TO SKIN HOMOGRAFTS IN MICE
Authors: Argyris Bertie F.
Published: June 2004

Acquired tolerance to CBA skin homografts is lost in a large number of C3H mice neonatally injected with CBA spleen cells. The skin homografts persist for at least 2 months but then exhibit a chronic rejection pattern which may last up to 7 months. Histological analysis of the lymphoid tissues reveals the onset of an immune response in the axillary lymph nodes of many 4-month-old tolerant mice. This immune response which appears before external indications of graft rejection are evident, is manifested as an increase in number of germinal centers and plasma cells in the cortex and medulla, respectively. In older tolerant mice, an even larger proportion show these histological indications of immunological activity. During graft contraction and shortly after graft rejection, the immune response is still limited to the lymph nodes. After rejection of a second graft by post-tolerant mice, histological indications of an immune response are not only found in lymph nodes but also in spleen.

The data suggest the development of a host versus graft reaction in seemingly tolerant C3H mice, which increases in severity with the age of the animal. The results are discussed from the point of view that tolerance is dependent upon a critical balance between the immune potential of the host and the population of donor cells. As mice mature, their immune potential may increase. The resulting host versus graft reaction increases, culminating in the rejection of skin graft and donor lymphoid cells.
THE ASSOCIATION OF SKIN-SENSITIZING ANTIBODY WITH THE ß2A-GLOBULINS IN SERA FROM RAGWEED-SENSITIVE PATIENTS
Authors: Fireman Philip , Vannier Wilton E. , Goodman Howard C.
Published: June 2004

1. The removal of the ß2A-globulins from three sera from treated ragweed-sensitive individuals by immune absorption was associated with the loss of all detectable skin-sensitizing antibody activity as demonstrated by Prausnitz-Küstner testing.

2. Gel filtration studies, with sephadex G-200, indicated that the fractions containing only macroglobulins were devoid of all detectable skin-sensitizing antibody activity.

3. The immune absorption of the γ-globulins from a serum fraction containing ß2A-globulins, γ-globulins, and a trace of ß2M-globulins had no detectable influence on the skin-sensitizing antibody activity.

4. The removal of a portion of the albumin from the allergic sera by immune absorption, with retention of the skin-sensitizing activity, indicated that the loss of skin-sensitizing antibody was not due to non-specific absorption on an antigen-antibody precipitate.

5. No inhibition of the Prausnitz-Küstner reaction was observed when sheep serum, normal human serum, or normal human γ-globulins were tested in concentrations described.

6. We conclude that the skin-sensitizing antibody activities in the three sera from treated ragweed-sensitive individuals studied were associated with the ß2A-globulins.
INHIBITION OF THE LESIONS OF PRIMARY VACCINIA AND OF DELAYED HYPERSENSITIVITY THROUGH IMMUNOLOGICAL TOLERANCE IN RABBITS
Authors: Flick John A. , Pincus William B.
Published: June 2004

In order to gain insight into the pathogenesis of the vesicular lesion of local primary vaccinia infection, newborn rabbits were injected with 0.5 mg of purified inactivated vaccinia virus in an attempt to render them immunologically tolerant. Within a few days these, and control normal rabbits of the same age, were infected on the skin with active vaccinia virus. Most of the tolerant-prepared rabbits failed to develop a local lesion of vaccinia but some developed a very atypical lesion. Successful virus isolation from some, and the presence of inclusions in the tissues of others, indicated successful infection with the virus. Skin allergy to the active virus failed to develop in the test animals but did in the controls. Thus, there was a high degree of correlation between inability to produce delayed hypersensitivity to the viral antigens and failure to develop a vaccinial skin lesion, indicating the probable allergic nature of the primary lesion.

There was also a high mortality rate in the group of tolerant-prepared, infected animals. It was associated with a spreading of the virus from the site of infection to the organs, suggesting that generalized vaccinial infection was the cause of death. The observations were compatible with the hypothesis that death was due to viral toxicity.

The observations also suggest that, in the animal possessing normal immunological function, active immunity develops rapidly, perhaps at the level of the draining lymph node, to prevent appreciable virus from leaving the site of infection.

The absence of detectable immunological activity toward vaccinia virus early in the tolerant-prepared animals and even after 1 month in some of the survivors, indicates that a high degree of immunological tolerance was produced against these microbial antigens.
ANTIBODY RESPONSE TO HOMOGRAFTS
Authors: Terasaki Paul I. , McClelland John D.
Published: June 2004

Antigenic differences between certain inbred strains of mice which could not be revealed by hemagglutination techniques were readily disclosed by lymphocyte cytotoxicity. With an improved cytotoxicity test lymphotoxic titers were as high as 1:512 with non-hemagglutinating A anti CBA antisera. In other mouse strain combinations, a close parallel of both types of antibody activity was obtained. Though both activities were absorbed from antisera proportionally by erythrocytes and lymph node cells, 100 to 1000 times as many erythrocytes as lymphocytes were necessary to produce an equivalent reduction in antibody activity. These findings suggest that erythrocytes may possess only subthreshold quantities of certain antigens which are present in readily detectable levels on lymphocytes. Lymphocyte cytotoxicity therefore may assay a wider range of allogenic antigens than hemagglutination.
IN VITRO STUDIES OF ULCERATIVE COLITIS
Authors: Perlmann Peter , Broberger Ove
Published: June 2004

Freshly isolated fetal human colon cells were labeled with 32P-orthophosphate or 14C-amino acids and exposed to white blood cells from children with ulcerative colitis or from healthy controls. Exposure of the colon cells to patients' white cells led to a rapid isotope release, significantly higher than that obtained with normal white cells. After 150 minutes of incubation, 75 per cent of the total isotope present was found in the media of the colitis samples but only 40 per cent in those of the controls. Consistent results were obtained with white blood cells from 14 patients and 18 healthy individuals. Similar results were obtained with either fresh white cells or with white cells aged for 12 to 18 hours and consisting to 60 to 70 per cent of lymphocytes and to 20 to 30 per cent of large mononuclear cells.

No specific cytotoxic activity could be conferred onto normal white cells by pretreating them with patients' serum containing antibodies against colon antigen. The cytotoxic action of the patients' white cells was immunologically specific, since no difference from the controls was found in the isotope release when cells from other organs or animals were similarly treated. Preliminary experiments suggested that the patients' white cells could be desensitized by pretreating them with colon extract. For obtaining a significant cytotoxic effect of the patients' white cells, the presence of 10 to 20 per cent of fresh guinea pig or human serum in the incubation medium was required.
SUPPRESSION OF ALLERGIC ENCEPHALOMYELITIS IN RATS BY MEANS OF ANTIBRAIN SERUM
Authors: Paterson Philip Y. , Harwin S. Martin
Published: June 2004

Rats regularly develop evidence of allergic encephalomyelitis (AE) 2 to 3 weeks following sensitization to nervous tissue plus adjuvant. Independent of the severity of AE which occurs, gradual recovery is the rule and by the 6th to 9th week after sensitization rats appear clinically well and microscopic lesions of AE have virtually disappeared.

Pooled serum collected from rats 3 or 6 weeks after sensitization contains complement-fixing (CF) antibrain antibodies. Such pooled serum exerts a striking suppressive influence on development of AE when passively administered to rats actively sensitized to nervous tissue. Serum pools which contain CF antibrain antibody suppress the disease. Serum pools lacking CF antibody do not suppress the disease. Serum containing CF antibrain antibody after treatment with 2-mercaptoethanol no longer fixes complement with brain antigen in vitro and no longer suppresses AE in vivo. The data suggest that transfer of protection against AE by passively administered antibrain rat serum is due to an antibrain antibody, possibly the CF antibodies. The meaning of these findings is discussed in terms of the role(s) of circulating antibrain antibody in the pathogenesis of AE.
THE CELLULAR NATURE OF GENETIC SUSCEPTIBILITY TO A VIRUS
Authors: Kantoch M. , Warwick A. , Bang F. B.
Published: June 2004

Using peritoneal macrophage cultures it was found that both PRI mice and their macrophages in culture were susceptible to mouse hepatitis virus and that C3H mice and macrophages were resistant. All F1 macrophages and some back-cross cell cultures were susceptible. The degeneration of F1 and back-cross macrophages obtained either from adult mouse peritoneal exudate or newborn mouse liver, occurred more slowly than PRI macrophages. Segregation of susceptibility occurred in the first back-cross generation. Tests of three back-cross generations from susceptible mice yielded about one-quarter of the mice shown to be susceptible either by direct test or test of their macrophages. A clear correlation between susceptibility in vivo and in vitro was established both in the test of the percentage segregation and in tests of individual back-cross mice. A small series of tests, however, indicated that 50 per cent of the back-cross mice had the genetic capacity to transmit susceptibility. Thus a hypothesis of two genes for susceptibility, although not excluded, may yield to a hypothesis of a single dominant gene, incompletely expressed.

Resistant cells were converted into susceptible cells by ingestion of a relatively large particle containing a heat-stable substance. This susceptibility, although complete, was temporary. The nature of the factor causing the change has been discussed.
RETROGRADE PROTEUS PYELONEPHRITIS IN RATS
Authors: Cotran Ramzi S.
Published: June 2004

Rats with retrograde proteus pyelonephritis were treated with antibiotics until their kidneys became sterile. Using fluorescent antibody techniques, specific P. mirabilis antigen was found in some sterile pyelonephritic kidneys 20 weeks after cessation of treatment and presumed renal sterilization. Persistent antigen was associated with interstitial chronic inflammation but not with acute inflammation or progressive scarring. Rat gamma globulin and proteus antibody were localized in plasma cells of the renal inflammatory infiltrates. It is suggested that persistent antigen in chronic pyelonephritis may lead to the continued local appearance of antibody-producing cells.
RESULTS OF EXPERIMENTAL INTESTINAL STRANGULATION OBSTRUCTION IN GERMFREE RATS
Authors: Amundsen Egil , Gustafsson Bengt E.
Published: June 2004

Experimental low ileal strangulation obstruction has been produced in germfree and conventional rats. The mean survival time was 240 hours in the germfree rats and 44 hours in the conventional controls. 4 of the 10 germfree rats survived 15 or more days, whereas the 10 conventional animals were all dead within 2½ days.

The strangulation obstruction fluid from the germfree animals was sterile and non-toxic when injected into mice even after a fourfold concentration. The same fluid from the conventional animals contained a great number of microorganisms and caused death within 24 hours when injected intraperitoneally into mice.
LOCALIZATION OF ANTIBODIES IN PLASMA CELLS BY ELECTRON MICROSCOPY
Authors: de Petris Stefanello , Karlsbad Gioanna , Pernis Benvenuto
Published: June 2004

The localization of antibody in the interior of plasma cells of lymph nodes of rabbits hyperimmunized with ferritin was studied by electron microscopy. The cells were incubated with the antigen (ferritin) which was allowed to penetrate into the cells by suitable methods. Antigen-antibody precipitates were localized in the cisternae of the endoplasmic reticulum and in the perinuclear space. No evident association was found between ferritin and ribosomes or ferritin and outer cell membrane. Cells from control animals immunized with an unrelated antigen, incubated with ferritin, exhibited no labeling. From direct counts of ferritin molecules in plasma cells, a lower limit was evaluated for the antibody concentration in the endoplasmic reticulum (12.2 mg/cm3) and for the total antibody content of a plasma cell (7.0 x 10–3 gm).