bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ENHANCING EFFECT OF THE MICROBIAL FLORA ON MACROPHAGE FUNCTION AND THE IMMUNE RESPONSE
Authors: Bauer Heinz , Paronetto Fiorenzo , Burns Willard A. , Einheber Albert
Published: June 2004

The immune response to bacteria and to a soluble protein was compared in germfree and conventionalized mice. Sixty germfree and 59 conventionalized mice received a suspension of killed Serratia marcescens into one front foot-pad and sterile horse ferritin into the other and were sacrificed in groups from 2 hr to 14 days after inoculation. All mice had no pre-existing antibody to either antigen and the flora of the conventionalized mice never contained Serratia. Lymphatic tissue changes and the fate of the antigens were followed in axillary lymph nodes and the spleens by histologic, fluorescent antibody, and autoradiographic techniques after tritiated thymidine injection. Individual serum antibody titers for both antigens were determined at each time period.

The cellular and serologic responses were slightly delayed in the germfree mice but later equaled and sometimes exceeded those of the conventional animals. In all animals, lymph nodes draining the site of Serratia injection showed a more vigorous response than those on the ferritin-injected side but the reaction was qualitatively the same for both antigens. All lymph nodes contained the antigens by 2 hr after foot-pad injection. With time, both antigens lost their particulate nature sooner in conventionalized than in germfree macrophages. In the latter, both antigens persisted throughout the study while no longer demonstrable with fluoresceinated antiserum in conventional macrophages after the first week.

While phagocytosis is equal in germfree and conventional mice, a greater digestive capacity of macrophages for antigens seems to result from the continuous exposure of conventional animals to the immunologic effects of the microbial flora. Conversely, the lack of substantial antigenic stimulation of lymphatic tissue in germfree animals fails to develop these macrophage functions beyond their basic ability to degrade foreign substances. Although the onset of the immune response is delayed in germfree mice, the relatively prolonged antigen digestion and the presumably slower release of immunogenic antigen fragments result in a more sustained and sometimes greater response than in conventional animals. This modifying effect of the microflora on the function of macrophages during the immune response is independent of previous experience with, or the nature of, the antigen.
AUTOIMMUNE DISEASE IN NZB/BL MICE
Authors: Mellors Robert C.
Published: June 2004

The transplantation of spleen cells from old NZB/Bl mice with renal disease induced both the structural and the functional changes of membranous glomerulonephritis in young NZB/Bl mice within a few weeks and well in advance of its usual spontaneous occurrence. The development of hypergammaglobulinemia and lymphoid cell hyperplasia in the young mice indicated that immunologically competent cells, derived from either the transplant or the recipient, proliferated during this process. These experiments, together with other findings, provide further support for the view that membranous glomerulonephritis in NZB/Bl mice is produced by immunological, and probably autoimmune, mechanisms and that the renal disease is apparently almost wholly unrelated to the hemolytic process.
CRYSTAL-INDUCED INFLAMMATION IN CANINE JOINTS
Authors: Phelps Paulding , McCarty Daniel J.
Published: June 2004

In an experimental model, the polymorphonuclear leukocyte was found to be necessary to the inflammation induced by crystals.

This conclusion is based on (a) the invariable migration of polymorphonuclear leukocytes into the synovial fluid of canine joints injected with urate crystals, (b) the experimental suppression of the synovitis by the depletion of polymorphonuclear leukocytes in animals treated with vinblastine, (c) the dependence of the degree of suppression on the degree of leukocyte mobilization into the joint space, and (d) the restoration of the inflammatory response in a leukopenic animal by perfusion with normal blood.
AN ANTIVIRAL SUBSTANCE FROM PENICILLIUM FUNICULOSUM
Authors: Shope Richard E.
Published: June 2004

1. Helenine prevents the establishment in mice of passive viral immunity by anti-Semliki serum of swine, rabbit, or guinea pig origin.

2. A period of 12 days must elapse, between the antiviral serum administration and challenge with virus, for prevention of the establishment of passive immunity to become apparent. This period is believed to correspond to that in which injected antibody persists in circulation in the injected host.

3. Helenine is effective in preventing the establishment of passive viral immunity by heterologous antiviral sera when it is administered any time during a period of 6 days, extending from 4 days before to 2 days after injection of the antiviral serum.

4. Helenine does not prevent the establishment of passive viral immunity by antiviral sera of mouse origin (homologous).

5. Evidence is presented to indicate that the phenomenon of the prevention of the establishment of passive viral immunity by heterologous antiviral sera is not effected directly, but rather is mediated through some substance that helenine induces the injected host to elaborate.

6. The capacity to prevent the establishment of passive viral immunity could not be exhausted by repeated preceding injections of helenine at 2- or 3-day intervals.

7. Evidence is presented to indicate that the helenine-induced material does not act upon antiviral antibody per se but rather on heterologous foreign protein that happens to be labeled as Semliki Forest virus antibody. This helenine-induced material, whatever its nature, appears to enhance the capacity of the injected host to recognize and dispose of foreign protein.

8. Statolon, a material that like helenine is a known inducer of interferon, is, like helenine, also capable of preventing the establishment of passive viral immunity by heterologous antiviral sera.

9. Experiments designed to determine whether the induced material responsible for the antipassive immunity effect of helenine is interferon have yielded inconclusive answers thus far.
ONTOGENY OF THE IMMUNE RESPONSE
Authors: Williams G. M.
Published: June 2004

The development of the ability of young rats to generate a prompt primary antibody response to polymerized flagellin, with IgM to IgG transition, is correlated in time with the development of structures in the cortex of lymph nodes that localize antigen to spherical areas which subsequently become primary lymphoid follicles.

Throughout development the increased magnitude of the antibody response parallels the increased ability of lymphoid structures to retain antigen.

During the first week of life primitive lymphoid tissue appears capable of undergoing the initial steps in differentiation toward antibody production in response to neonatal injections of polymerized flagellin. However, further maturation appears to be blocked resulting in a complex immunological state at the age of 2 weeks characterized by increased IgM and decreased IgG antibody response to antigenic challenge at this time.

The possible relationship between the block in cellular differentiation toward antibody formation and the ease of tolerance induction is discussed.
CONCOMITANT ANAPHYLACTIC SENSITIZATION AND CONTACT UNRESPONSIVENESS FOLLOWING THE INFUSION OR FEEDING OF PICRYL CHLORIDE TO GUINEA PIGS
Authors: Pomeranz Jerome R. , Norman Philip S.
Published: June 2004

Guinea pigs receiving one large dose of picryl chloride by the intravenous or oral routes commonly develop circulating antibody demonstrable by passive cutaneous anaphylaxis or by active anaphylaxis. They often concommittantly become unresponsive to the induction of delayed contact hypersensitivity by intracutaneous injections. Erythrocytes obtained from guinea pigs after infusion or feeding of picryl chloride may be used to sensitize other animals when injected with adjuvant.

It is concluded that guinea pigs may be anaphylactically sensitized to simple chemicals by the intravenous and oral routes if a sufficient dose is administered.
STUDIES ON THE IMMUNOCHEMISTRY OF STREPTOCOCCAL MUCOPEPTIDE
Authors: Karakawa Walter W. , Krause Richard M.
Published: June 2004

Streptococcal mucopeptide, solubilized by either ultrasonic treatment or lysozyme, gave a precipitin reaction with rabbit antimucopeptide serum. A haptenic inhibitor of this reaction, which was composed of alanine, glutamic acid, and lysine in a mole ratio of 4:1:1, was isolated from a Streptomyces albus enzymes digest of Group D cell walls by ion exchange chromatography. When selected antisera were employed, greater than 90% inhibition of the mucopeptide quantitative precipitin reaction was achieved with 2 mg/ml of this inhibitor, whereas a hexosamine fraction with minimal concentrations of amino acid residues was inactive in this respect. These results suggest that the peptide moiety is an antigenic determinant of mucopeptide.

Preliminary results indicate that the hexosamine polymer of the mucopeptide is a secondary antigenic determinant.
MECHANISMS OF IMMUNOLOGIC INJURY OF RAT PERITONEAL MAST CELLS
Authors: Becker Elmer L. , Austen K. Frank
Published: June 2004

The ability of a number of p-nitrophenylethyl, alkyl phenylalkyl, chloroalkyl, and aminoalkyl phosphonates to inhibit the homocytotropic antibody-mediated release of histamine from rat peritoneal mast cells has been tested. The effectiveness of these same phosphonates against the activated first component of rat complement (C'1a) has also been investigated.

The rat mast cell esterase activated by the reaction of antigen and homocytotropic antibody resembles chymotrypsin in its reactivity with the phenylalkyl and chloroalkyl phosphonate, but is unlike this protease in its greater responsiveness to the 5-aminopentyl phosphonate relative to the pentyl phosphonate. The antigen-homocytotropic antibody-activated mast cell esterase and chymotrypsin, thus, appear to be similar, but different enzymes; i.e., they are parazymes (see reference 4, p. 501).

There are distinct differences in the pattern of inhibition given by the phenylalkyl and aminoalkyl and alkyl phosphonates of the homocytotropic antibody-mediated histamine release from rat peritoneal mast cells and from guinea pig lung slices. On the basis of these differences it is concluded that the esterases activated by the combination of antigen and homocytotropic antibody on the mast cells of the two species are not the same.

The arithmetic dose response curve found for the action of the phosphonates on the antigen-induced histamine release from rat peritoneal mast cells contrasted sharply with the logarithmic relationship found when these same inhibitors acted on the guinea pig lung system. This suggests that in addition to the antigen-antibody-activated esterases being unlike, the detailed mode of histamine release from the mast cells of the guinea pig lung differs from that of the mast cells of the rat peritoneum.

Distinct and large differences were found in the pattern of inhibition of histamine release from rat peritoneal mast cells and of rat C'1a given by the phenylalkyl, and chloroalkyl and alkyl phosphonates implying that esterase activated by the combination of antigen with the sensitized rat peritoneal mast cells is not C'1a. Thus, the results with the peritoneal mast cells lead to the same conclusion as the previous work with guinea pig lung slices; i.e., the antigen-antibody-activated esterase involved in the homocytotropic antibody-mediated release of histamine is not part of the complement system.
TRANSFER OF OVINE EXPERIMENTAL ALLERGIC GLOMERULONEPHRITIS (EAG) WITH SERUM
Authors: Lerner Richard A. , Dixon Frank J.
Published: June 2004

Serum globulin from donor sheep made nephritic by immunization with glomerular basement membrane and subsequently nephrectomized contained specific kidney-fixing antibody and was capable of inducing an immediate, although transient, glomerulonephritis when injected into unilaterally nephrectomized lambs. This nephritis was characterized by immediate proteinuria, PMN infiltration into the glomerulus, and localization of γG- and ß1C-globulins in a linear fashion along the recipients' glomerular capillary walls. The nephritogenic property of the serum could be absorbed in vitro with isolated sheep glomerular basement membranes.
STUDIES ON HUMAN LEUKOCYTE MOTILITY
Authors: Bryant Richard E. , DesPrez Roger M. , VanWay Margery H. , Rogers David E.
Published: June 2004

Leukocyte migration was studied in a microhematocrit system which permitted evaluation of the separate effects of leukocyte adhesiveness, intrinsic cell motility, and leukocyte clumping. Leukocyte adhesion to glass required the presence of magnesium ion, was totally independent of calcium ion, and was partially dependent on heat-labile plasma factors. Leukocyte migration was unimpaired by marked acidosis or by wide variations in sodium, potassium, or calcium concentrations. Marked impairment of individual leukocyte motility and increased leukocyte aggregation were observed after phagocytosis of particulate matter, suggesting a mechanism facilitating recruitment and retention of leukocytes at areas of microbial invasion.
ON THE ROLE OF THE RESPONSE OF THE CELL MEMBRANE IN DETERMINING VIRUS VIRULENCE
Authors: Holmes Kathryn V. , Choppin Purnell W.
Published: June 2004

The simian myxovirus SV5 multiplies in a continuous line of baby hamster kidney (BHK21-F) cells causing extensive cell fusion, followed by cell death. After inoculation of 15 PFU/cell, the latent period was 7 hr, the doubling time approximately 60 min, and the yield 7 PFU per cell. Giant cell formation began about 6 hr after infection and rapidly progressed to the formation by 14 to 18 hr of a single syncytium which disintegrated by 24 to 36 hr. In contrast, SV5 multiplies in primary rhesus monkey kidney cells for long periods of time producing high yields of virus with little cytopathic effect.

High multiplicities of SV5 induced cell fusion in BHK21-F cells within 1 hr in the absence of virus multiplication but had no visible effect on monkey kidney cells.

Time-lapse photomicrography has demonstrated that giant cells form by fusion of infected cells, and that some polykaryocytes divide. During aberrant division of polykaryocytes giant nuclei are formed from the nuclear material of several parent nuclei.

The cytoplasmic development of viral antigens as demonstrated by immunofluorescence is similar in BHK21-F and monkey kidney cells. Synthesis of cellular DNA, RNA, and protein in monkey kidney cells is not shut off by SV5-infection, and in BHK21-F cells synthesis of these macromolecules is not inhibited until after extensive cell fusion has occurred 12 to 15 hr after infection. Persistently infected BHK21-F and monkey kidney cells have been serially carried through 11 and 28 cell passages, respectively.

The results suggest that whether SV5 acts as a moderate virus, as in monkey kidney cells, or a virulent virus, as in BHK21-F cells, depends on the response of the cell membrane to the virus.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Bonventre Peter F. , Imhoff John G.
Published: June 2004

The effect of crystalline diphtheria toxin on protein synthesis in vivo was evaluated in guinea pigs and mice. By two independent methods of analysis (microdensitometry of tissue radioautograms and radioactivity of tissue proteins), it was established that inhibition of protein synthesis was not a widespread metabolic effect of diphtheria toxin. In the sensitive guinea pig, only the heart and the pancreas showed any demonstrable reduction in the quantity of tritiated leucine incorporated into proteins following challenge of the animals with the crystalline toxin. No such inhibition was noted in mice which are resistant to the action of diphtheria toxin.

The effect on the pancreas involved a decrease in the synthesis of pancreatic enzymes and their subsequent secretion. For reasons discussed, it was concluded that this lesion was not as significant as the inhibition of protein synthesis in the heart tissues. Although the rate of protein turnover in heart muscle is relatively low, an inhibition of 73% was noted when the exchange period with the tritiated leucine was 6 hr.

It was suggested that the inhibition of protein synthesis in heart tissues could provide a biochemical rationale for the site and mode of action of diphtheria toxin in the sensitive mammalian host. An attempt was also made to correlate the biochemical heart lesion described here with past clinical evidence of cardiac failure and tissue pathology noted in many cases of fatal diphtheria infections of humans.
DEFICIENCY OF THE FIFTH COMPONENT OF COMPLEMENT IN MICE WITH AN INHERITED COMPLEMENT DEFECT
Authors: Nilsson Ulf R. , Müller-Eberhard Hans J.
Published: June 2004

The inherited complement deficiency of certain inbred strains of mice was shown to be due to an isolated lack of the fifth component of complement. The protein MuB1 (or hc'), which is present in normal mouse serum but absent from the serum of complement-deficient mice, was shown to be immunochemically related to the fifth component of human complement (C'5). C'5 hemolytic activity was specifically inhibited in human serum by mouse anti-MuB1 and in normal mouse serum by mouse antiserum to human C'5. Highly purified human C'5 reconstituted the hemolytic activity of complement-deficient mouse serum. It was, therefore, concluded that he', or MuB1, constitutes the murine analogue of the fifth component of human complement.

The MuB1 concentration in normal mouse serum was found to be subject to a sex-related variation. By quantitative precipitin analysis it was demonstrated that serum from male mice contains twice as much MuB1 as that of female mice. This difference in C'5 concentration was also detected by hemolytic assay. In addition, C'6 and C'7 were also found to be subject to sex-related variations.
EXPERIMENTAL ALLERGIC GLOMERULONEPHRITIS INDUCED IN THE RABBIT WITH HETEROLOGOUS RENAL ANTIGENS
Authors: Unanue Emil R. , Dixon Frank J.
Published: June 2004

Rabbits immunized to different heterologous renal antigens developed antibodies some of which are fixed to their own glomeruli (autoantibodies). These autoantibodies, reacting with the host's kidneys, were directed to those antigenic determinants which were present in identical or cross-reactive form in both the immunizing antigen and the kidneys of the host. Glomerulonephritis developed in some of the rabbits immunized to heterologous mammalian kidneys, but in none of those immunized to nonmammalian kidneys. The development of glomerulonephritis in the immunized rabbits appears to depend upon two factors: (a) the amount of autoantikidney antibody made to the common renal antigens; and (b) the quantity of the common antigens available in the host's kidneys. An amount of common antigen sufficient to fix a nephritogenic amount of antibody is essential for the development of disease.
SUPPRESSION OF MURINE LEUKEMIAS BY L-ASPARAGINASE
Authors: Boyse Edward A. , Old Lloyd J. , Campbell H. A. , Mashburn Louise T.
Published: June 2004

A survey of 109 recently derived leukemias of the mouse revealed that sensitivity to suppression by guinea pig serum is a common property of transplanted leukemias of certain classes. The sensitive leukemias included five that arose spontaneously in mice of strains with a low incidence of leukemia and 21 that were induced by X-radiation.

Two GPS-sensitive leukemias were not more sensitive than a GPS-resistant leukemia to a range of standard chemotherapeutic agents.

The effectiveness of L-asparaginase EC-2 from Escherichia coli in suppression of the GPS-sensitive leukemia EARAD1 depends upon the conditions of assay. Whereas it is not inhibitory when administered as a single dose at the time of inoculation of the leukemia it is considerably more effective than GPS when used in the treatment of established leukemia.

Permanent cures of 7-day generalized transplants of EARAD1 can be effected by the administration of 2000 or more units of EC-2. Immunological factors apparently do not contribute to cure as treated survivors are fully susceptible to rechallenge with minimal numbers of cells from the same leukemia. Reinoculated survivors with progressively growing transplants have been successfully retreated with EC-2.

The blood clearance of EC-2 L-asparaginase injected into mice is much more rapid than that of GPS L-asparaginase. After intraperitoneal inoculation of the EC-1 L-asparaginase, which does not have leukemia-inhibitory activity, only very low levels of enzyme activity could be detected in the serum.

The effectiveness of EC-2 from E. coli and its availability from a virtually limitless source will make it possible to extend the study of inhibition of leukemias and other tumors by L-asparaginase to species other than small rodents.
IN VIVO TRANSMISSION OF DRUG RESISTANCE FACTORS BETWEEN STRAINS OF STAPHYLOCOCCUS AUREUS
Authors: Novick Richard P. , Morse Stephen I.
Published: June 2004

1. Multiply resistant strains of Staphylococcus aureus often harbor one or more extrachromosomal drug resistant factors as well as temperate prophages capable of mediating generalized transduction.

2. Spontaneous transduction occurs in mixed cultures of such staphylococcal strains, and the extrachromosomal resistance factors are involved more frequently than are chromosomal genes.

3. Spontaneous transduction of extrachromosomal determinants of erythromycin resistance and of linked penicillin-erythromycin resistance occurs in the kidneys of mice in which mixed infection has been induced.
FORMATION AND FUNCTIONAL SIGNIFICANCE OF A MOLECULAR COMPLEX DERIVED FROM THE SECOND AND THE FOURTH COMPONENT OF HUMAN COMPLEMENT
Authors: Müller-Eberhard Hans J. , Polley Margaret J. , Calcott Mary Ann
Published: June 2004

A functional unit of the human complement system has been delineated. It is composed of two subunits which are derived from the second (C'2) and from the fourth (C'4) component of complement. Purified C'2 and C'4 were found to interact in free solution and to form a reversible protein-protein complex. When acted upon by C'1 esterase in the presence of Mg ions, the reversible complex acquires stability and the ability to act enzymatically on the third component of complement. The trivial name C'3 convertase has been selected to denote the enzyme. Molecular weight determinations suggest that the entire C'4 molecule, but probably only a fragment of the C'2 molecule, are incorporated into C'3 convertase. Prior treatment of C'2 with iodine led to enhanced stability and activity of the enzyme. It was shown that the cell-bound form of C'3 convertase is cytolytically active and that the free enzyme is able to induce lysis from the fluid phase of erythrocytes from patients with paroxysmal nocturnal hemoglobinuria. Evidence was presented that action of C'3 convertase on C'3 results in fragmentation of the molecule.
STUDIES ON THE CONSERVATION OF EPIDERMAL SPECIFICITIES OF SKIN AND CERTAIN MUCOSAS IN ADULT MAMMALS
Authors: Billingham R. E. , Silvers Willys K.
Published: June 2004

To determine whether the factor(s) responsible for the conservation of epidermal specificities in adult guinea pigs and hamsters resides in the germinal layer of the epidermis or in the dermis, thin grafts of skin, possessing qualitatively distinct regional characteristics, were separated into their superficial epidermal and dermal components with the aid of trypsin. Dermis of one type was combined with epidermis of another to produce "recombinant" grafts which were then transplanted to small, full thickness cutaneous sites on the thorax of geneticaily compatible hosts. A variant of this procedure involved transplanting sheets of superficial epidermis of various types to shallow split thickness recipient areas in the skin of the thorax. All grafts were maintained for 100 days before they were excised and examined histologically.

The results indicate that, whereas the dermis determines the kind of epidermis produced in recombinant grafts involving the ear, the sole of the foot, and the trunk, this is not the case in recombinants which include tongue, esophageal, or cheek pouch epithelia. The one exception to this occurred when tongue or esophagus epithelia were transplanted to split thickness beds in trunk skin. Here they appeared to produce an epidermis characteristic of their new location. It is believed that this exception is probably due to the fact that the native follicular epidermis present in trunk dermis made such a substantial contribution to the new superficial epidermis that it behaved overtly as body skin epidermis.

Taken together, these results suggest that basal layer cells of the superficial epidermis of sole of foot skin, ear skin, and the hair-bearing skin of the general integument behave as if they are equipotential, and that in adult life maintenance of these particular epidermal specificities is the outcome of persistent specific inductive stimuli from the underlying dermis.

The results of subsidiary experiments are reported which indicate that the epithelial component of mammary gland tissue is also pluripotential, being capable of producing, under appropriate conditions, a normal-looking, fully stratified superficial epidermis.
COMPARATIVE STUDIES BETWEEN PATHOGENESIS OF STREET AND FIXED RABIES INFECTION
Authors: Miyamoto Kaneatsu , Matsumoto Seiichi
Published: June 2004

Comparative neuropathology of Ammon's horn caused by both the street and fixed rabies infection was studied by combined light and electron microscopy. Neurons containing Negri bodies appeared comparatively little damaged. In striking contrast, in the case of fixed virus infection, neurons showed the following variety of degeneration. Lightly damaged neurons showed an increase in the number of small vesicles throughout the cytoplasm. A considerable number of lysosomes were also encountered within these nerve cells. Severe necrotic alteration involving the nucleus as well as the cytoplasm was found in the nerve cell band. The characteristic homogeneous foci (matrices) were discernible within these neurons. It appears that the matrix is morphologically identical with the ground substance of the Negri body, though its size is smaller than that of the Negri body. This evidence suggests a possibility that fixed virus injures neurons so extensively that they cannot bring about the full development of the characteristic matrix of the Negri body recognizable by the light microscope. Selective vulnerability was demonstrated among different groups of neurons in respect of cytopathogenesis of both street and fixed virus infection.
EXPERIMENTAL TRANSMISSION OF INFLUENZA VIRUS INFECTION IN MICE
Authors: Schulman Jerome L.
Published: June 2004

A mouse-adapted Jap. 305 strain of influenza A2 virus was found to be much more readily transmitted from one mouse to another than the NWS strain of influenza A0 virus although the two viruses were equally pathogenic for mice as judged by pulmonary virus titers and lung lesions. The survival of artificially created aerosols of virus and the quantity of airborne virus required to initiate infection in mice were identical for the two viruses. The difference in transmissibility was associated with the recovery of infectious airborne virus in the environment of mice infected with the Jap. 305 strain during the period of their maximum infectiousness, but not in the environment of mice infected with the NWS strain.
THE EFFECT OF 5-HYDROXYTRYPTAMINE ON THE COTTON PELLET LOCAL INFLAMMATORY RESPONSE IN THE RAT
Authors: Bianchine Joseph R. , Eade Norman R.
Published: June 2004

The cotton pellet technique was used to evaluate the effect of 5-HT and certain related compounds on granuloma formation in the rat. 5-HT (10 mg/kg) significantly decreased granuloma formation, significantly increased adrenal weight, and significantly decreased thymus weight in normal rats, and significantly decreased granuloma formation and thymus weight in sham-operated rats. On the other hand, 5-HT (10 mg/kg) significantly increased granuloma weight in adrenalectomized rats.

Methysergide (1 mg/kg) blocked the inhibitory effect of 5-HT on granuloma formation as well as the changes in weight of adrenal and thymus glands.

5-HIAA (11 mg/kg) and 5-HTP (13 mg/kg) failed to alter granuloma formation.
CELLULAR LOCALIZATION OF ANTI-DNP-PLL AND ANTICONVEYOR ALBUMIN ANTIBODIES IN GENETIC NONRESPONDER GUINEA PIGS IMMUNIZED WITH DNP-PLL ALBUMIN COMPLEXES
Authors: Green Ira , Vassalli Pierre , Benacerraf Baruj
Published: June 2004

Genetic nonresponder guinea pigs incapable of an immune response to DNP-PLL alone were immunized with DNP-PLL complexed to ovalbumin or bovine serum albumin. Under these circumstances the animals produce both anti-DNP-PLL antibodies and antibodies directed against the conveyor albumin. Thus immune response to DNP-PLL complexed to conveyor albumin molecules can serve as a simple model of hapten-carrier relationships. To explore these relationships the question whether these two types of antibody are synthesized by the same or by different plasma cells was investigated by a combination of a double immunofluorescent technique and radioautographic localization of radioactive antigen.

It was shown that the anti-DNP-PLL antibodies and the antibodies against the carrier albumin molecule were produced in separate cells. No cell-producing antibodies with both specificities were detected out of 526 cells studied.
MOUSE ISOANTIGENS: SEPARATION OF SOLUBLE TL (THYMUS-LEUKEMIA) ANTIGEN FROM SOLUBLE H-2 HISTOCOMPATIBILITY ANTIGEN BY COLUMN CHROMATOGRAPHY
Authors: Davies D. A. L. , Boyse E. A. , Old L. J. , Stockert Elisabeth
Published: June 2004

Mouse H-2 histocompatibility antigen has been extracted, solubilized, and partly purified from the cells of an A strain spontaneous leukemia carrying TL (thymus-leukemia) antigens. H-2 and TL. 1, 2, 3 activities were measured by inhibition of the cytotoxic effect of the corresponding isoantibodies.

TL activity was associated with the H-2 active fraction obtained by solubilization and fractionation by gel filtration. TL specificity was largely separated from H-2 antigen by subsequent chromatography on DEAE Sephadex as an adjacent component in a series of fractions.

The soluble H-2 antigen prepared from the leukemia cells was tested for most of the specificities determined by H-2a with no exceptional results.

TL. 1, 2, 3 activities, measured as each component separately, were located in approximately the same position; there is no clear indication yet whether the three TL specificities are separable from one another.

It appears that in addition to the close genetic linkage between the H-2 and TL loci, and their reciprocal interaction in producing H-2 and TL antigens, these antigens exhibit some similarity at the chemical level.
THE ROLE OF PENICILLIN-INDUCED BACTERIAL VARIANTS IN EXPERIMENTAL PYELONEPHRITIS
Authors: Winterbauer Richard H. , Gutman Laura T. , Turck Marvin , Wedgwood Ralph J. , Petersdorf Robert G.
Published: June 2004

1. After injection into the renal medulla of rats Escherichia coli 06 variants reverted rapidly in vivo in the absence of penicillin. These variants had previously been shown to be stable in vitro.

2. Variants failed to survive following intramedullary injection when animals were receiving penicillin.

3. Late reversion of variants also failed to occur in animals treated with penicillin for only 1 or 2 days.

4. Variants survived and reverted more readily when injected in the renal medulla, compared with liver and spleen. Classical bacteria injected into the kidney, liver, and spleen were recovered in approximately equal numbers.

5. The histologic response to nonreverting variants, medium not containing variants, and killed variants was similar and was characterized by a fibrotic reaction with moderate round cell infiltration.

6. In contrast, the histologic response to reverting variants and to classical E. coli was characterized by an intense, acute, polymorphonuclear leukocytosis typical of acute pyelonephritis.
STUDIES ON THE LEUKOCYTOSIS AND LYMPHOCYTOSIS INDUCED BY BORDETELLA PERTUSSIS
Authors: Morse Stephen I. , Riester Sallie K.
Published: June 2004

The 24 hr volume flow, cell concentration, and total cell output of thoracic duct fluid from mice with pertussis-induced hyperlymphocytosis were markedly reduced when compared with values obtained in normal animals.

An increase in the number of circulating lymphocytes occurred in several of the pertussis-treated mice despite the presence of an indwelling thoracic duct cannula. The drainage from such animals also showed a reduced cell concentration and total cell output.

It is suggested that lymphocyte recirculation may be minimal in pertussis-induced lymphocytosis, and the evidence obtained also suggests that lymphocytes may enter the blood stream by direct routes during the course of the reaction.
IN VITRO TRANSFORMATION BY THE ADENOVIRUS-SV40 HYBRID VIRUSES
Authors: Black Paul H. , White Beverly J.
Published: June 2004

Primary weanling hamster kidney cultures were transformed with the adeno 2-SV40, adeno 3-SV40, and adeno 12-SV40 hybrid viruses and with adenovirus type 12. The transformed cell lines which were established were characterized with respect to morphology, virus and antigen content, and chromosome aberrations. The adeno 2 and adeno 3-SV40 hybrid transformed cells had the morphology and T antigen content characteristic of SV40 transformations; cells transformed by the former hybrid had cytogenetic changes typical of SV40-transformed cells as well. The adeno 12-SV40 transformed cells were similar morphologically to adeno 12-transformed cells, contained both the SV40 and adeno T antigens and demonstrated the karyotypic instability of SV40-transformed cells, indicating that both viral genomes are operative in these cells. Although the results indicate that the SV40 genome in hybrids derived from the moderately or nononcogenic adenoviruses supplies the determinants for most of the characteristics investigated, and perhaps for oncogenesis, evidence was presented which suggests that a portion of a nononcogenic adenovirus genome may be integrated in adeno 2-SV40 transformed cells and directs the synthesis of adenovirus T antigens.
IN VITRO TRANSFORMATION BY THE ADENOVIRUS-SV40 HYBRID VIRUSES
Authors: Igel H. J. , Black P. H.
Published: June 2004

Tumors induced with hamster kidney cells transformed by the adeno 2-, adeno 3-, adeno 7-, and adeno 12-SV40 hybrid viruses, and by adenovirus type 12, were examined histologically. The tumors induced with adeno 2-, adeno 3-, and adeno 7-SV40-transformed cells were similar to tumors induced with SV40-transformed hamster kidney cells but contained cells intermediate in morphology between SV40 and adenovirus tumor cells and occasionally contained nests of adenovirus-like cells. Cells transformed by the adeno 12-SV40 hybrid and by adenovirus type 12 gave rise to morphologically similar tumors.

The results suggest that both viral genomes are operative in hybrid-transformed cells but that one genome is apparently responsible for the predominant morphology of the tumor. Evidence that the morphology of a single transformed target cell is determined by the transforming genome was discussed.
MOUSE COMPLEMENT: THE EFFECT OF SEX HORMONES AND CASTRATION ON TWO OF THE LATE-ACTING COMPONENTS
Authors: Churchill Winthrop H. , Weintraub Ronald M. , Borsos Tibor , Rapp Herbert J.
Published: June 2004

The titer of late-acting complement components in sera from male mice is 8–10 times higher than the titer of sera from female mice. Using assays developed to measure the serum content of two of the late-acting components, we have shown that this difference is due to the effect of androgen and estrogen on these two late-acting complement components. These two components have been tentatively identified as C'5 and C'6. Androgen and estrogen have greater effect on C'6 than on C'5. The possibility has not been excluded that still other of the late-acting complement components are affected by androgens and estrogens.

The course of homograft rejection was unchanged in mice deficient in C'5 and C'6.
STUDIES ON THE TRANSMISSION OF HUMAN VIRAL HEPATITIS TO MARMOSET MONKEYS
Authors: Deinhardt F. , Holmes A. W. , Capps R. B. , Popper H.
Published: June 2004

Inoculation of human serums or plasmas obtained during the early acute phase of viral hepatitis induced chemical and morphological hepatic disease in marmosets in two out of five experimental series. The disease was transmissible in series from marmoset to marmoset with an apparent increased virulence of the causative agent in later marmoset passages. The chemical evidence for the disease was elevation of the activity of SGOT and SICD and of serum bilirubin. In serial liver biopsy specimens interpreted under code, a hepatitis, exhibiting some of the characteristics of human viral hepatitis, was readily distinguishable from nonspecific changes. The morphological changes preceded the biochemical alterations and persisted after them.

The data reported in these studies indicate that marmosets may be susceptible to human hepatitis. If these observations are confirmed, these animals may provide good experimental models for this disease. Final proof that the hepatitis observed in marmosets is caused by agents of human viral hepatitis is still lacking.
IMMUNOFLUORESCENT STUDIES OF THE POTENTIATION OF AN ADENOVIRUS-ASSOCIATED VIRUS BY ADENOVIRUS 7
Authors: Blacklow Neil R. , Hoggan M. David , Rowe Wallace P.
Published: June 2004

A quantitative immunofluorescent procedure for detection of viral antigen was used to study the potentiation of AAV-1 by Ad.7. AAV viral antigen formed only when the cells were also infected with adenovirus, and only in cell culture systems in which the adenovirus infection proceeded to completion. Ad. 7 infection of AGMK. cell cultures did not potentiate AAV unless the Ad. 7 infection was itself potentiated by SV40. Dose-response studies indicated that a single AAV particle and a single infectious Ad. 7 particle sufficed to initiate AAV antigen synthesis.

Sequential inoculation studies showed that AAV antigen formed simultaneously with Ad. 7 viral antigen when the AAV was inoculated any time between 15 hr before to 10 hr after the Ad. 7, both antigens appearing about 15 hr after inoculation of Ad. 7. The AAV-1 antigen formation had a minimum latent period of 5 hr, as seen with Ad. 7 preinfection of 10 hr or more. When UV-irradiated Ad. 7 was used as helper, the AAV antigen still appeared simultaneously with the Ad. 7 viral antigen, even though the latter was delayed by 23 hr compared to nonirradiated virus.

When the early replicative events of both viruses were allowed to proceed in FUDR-inhibited cells, and then the FUDR inhibition was reversed, AAV antigen formed within 2 hr, which was 3 hr before the Ad. 7 viral antigen appeared.

It was inferred that the event in the adenovirus cycle that renders a cell competent to synthesize AAV occurs after the 10th hr and may be temporally associated with replication of the adenovirus DNA.
COMPLEMENT AS A MEDIATOR OF INFLAMMATION
Authors: da Silva W. Dias , Lepow Irwin H.
Published: June 2004

Interaction in free solution of highly purified preparations of human C'1 esterase, C'4, C'2, and C'3, in the presence of Mg2+, resulted in rapid generation of an activity indistinguishable by biological criteria from anaphylatoxin. The formation of anaphylatoxin was associated with immunoelectrophoretic conversion of C'3 to anodically faster migrating proteins and was unaffected by the presence or absence of added C'5.

The biological properties of human anaphylatoxin prepared in this manner include: contraction and desensitization of isolated guinea pig ileum, failure to contract isolated rat uterus, enhancement of vascular permeability in guinea pig skin, degranulation of mast cells in guinea pig mesentery preparations, and liberation of histamine from suspensions of rat peritoneal mast cells. The smooth muscle-contracting and permeability enhancing properties were fully blocked by an antihistaminic drug, triprolidine. No cross-desensitizing activity on guinea pig ileum was demonstrable between rat and human or guinea pig and human anaphylatoxins but a closer biological relationship between rat and guinea pig anaphylatoxins was observed.

It is concluded that anaphylatoxin is a product of the complement system. Its possible relationship to apparently similar activities currently being obtained in other laboratories has been discussed.
THE IMMUNE RESPONSE TO FOREIGN RED BLOOD CELLS AND THE PARTICIPATION OF SHORT-LIVED LYMPHOCYTES
Authors: Craddock C. G. , Winkelstein A. , Matsuyuki Y. , Lawrence J. S.
Published: June 2004

The sequence of morphological changes in the rat spleen following SRBC injection associated with hemolysin production has been correlated with estimates of proliferative activity by splenic lymphatic tissue. Formation of new, reactive germinal centers containing macrophages which engulf nuclear debris is a prominent feature of the response. This is prevented by pretreatment of the animal with cortisol. Indirect evidence is provided that short-lived lymphocytes produced in germinal centers may be a necessary component in the induction of other cells to proliferate and differentiate into hemolysin-producing cells. The reasons are discussed for considering short-lived lymphocytes, such as those produced in the thymus, bone marrow, and germinal centers, as differing from long-lived lymphocytes capable of antibody synthesis.
ON THE NATURE OF TRANSPLANTATION IMMUNITY IN THE ADENOVIRUS TUMOR SYSTEM
Authors: Berman Leonard D.
Published: June 2004

The existence of a virus-induced, virus-specific transplantation, antigen in adenovirus 12-induced CBA mouse tumors was demonstrated. The antigen is virus-specific, but not related to structural virion or T antigens. It is a weak antigen, and required immunization with whole, infectious adenovirus 12 to produce considerable immunity. Comparable immunity could not be achieved with homologous cellular or subcellular materials, but some indication of enhancement was produced with low tumor dose. Immunization required at least 2 wk and was mediated by immune lymphoid cells. Serum of immunized animals showed no demonstrable cytotoxicity or enhancement. Animals immunized with virus and Freund's adjuvant showed diminished transplantation immunity, although these animals were actively immunized against adenovirus type 12 structural virion antigens.
RESISTANCE OF LONG-LIVED LYMPHOCYTES AND PLASMA CELLS IN RAT LYMPH NODES TO TREATMENT WITH PREDNISONE, CYCLOPHOSPHAMIDE, 6-MERCAPTOPURINE, AND ACTINOMYCIN D
Authors: Miller John J. , Cole Leonard J.
Published: June 2004

The cells of the popliteal lymph nodes of rats were labeled for 4 days after a secondary immunological stimulus. 31 days after the last dose of tritiated thymidine, groups of rats were started on courses of daily, intraperitoneal injections of prednisone, cyclophosphamide, 6-mercaptopurine, or actinomycin D. The initially low doses of these agents were doubled in successive weeks until either lymphoid hypoplasia or death occurred. Rats from each group were killed weekly, and the percentages of persisting, labeled small lymphocytes in the popliteal nodes were determined. Sections of these nodes were examined for persisting, labeled plasma cells. The per cent of lymphocytes labeled increased while the total number of lymphocytes decreased during treatment with prednisone and cyclophosphamide. Prednisone decreased the numbers of long-lived plasma cells, but these cells were preferentially resistant to cyclophosphamide. Neither 6-mercaptopurine nor actinomycin D had an appreciable effect on lymphoid tissues histologically nor on the proportions of labeled, long-lived lymphocytes and plasma cells before causing the deaths of the rats receiving them. These results indicate that long-lived lymphocytes and plasma cells survive treatment with the immunolytic drugs studied, and that long-lived lymphocytes are specifically resistant to prednisone and cyclophosphamide. We believe these results have an application to the attempts to find drugs useful in the treatment of immunologic rejections of organ transplants, and for therapy of autoimmune diseases.
CELLULAR HETEROGENEITY IN THE PRODUCTION OF AN ANTI-HAPTEN ANTIBODY
Authors: Mäkelä O.
Published: June 2004

Single lymph node cells from rats immunized with a conjugate of 3-iodo-4-hydroxy-5-nitrophenyl acetic acid chloride (NIP) and chicken globulin were tested against either NIP or NNP conjugated with bacteriophage. NNP is related to NIP but has a nitro group instead of iodine. The conjugated phages were still infective but easily inactivated by anti-hapten sera at a serum concentration of 10–7. Phages carrying a related hapten were less sensitive to antibody than phages conjugated with the immunogenic hapten.

When NIP-T2 and NNP-T4 conjugates were incubated in microdrops containing a single lymph node cell from an anti-NIP animal, strong inactivation of either or both phages occurred in some cases. For the reasons given in the text this inactivation was considered to be due to anti-NIP antibody produced by the cell in the microdrop.

Inactivation of the two kinds of phages by the anti-NIP cells was highly nonrandom; some cells inactivated almost all of the 1700 or so NIP-T2 phages in the drop but left almost all NNP-T4 phages viable. Others had a very strong cross-reaction and inactivated equal proportions (up to 75%) of both phages. The remaining active cells exhibited an intermediate degree of cross-reaction.

Control experiments indicated that there was a true cellular heterogeneity in the specificity of the anti-NIP produced by different cells. They suggested that the observed heterogeneity of specificities was limited to the structure of the hapten and was not influenced by the structure of the carrier. As all the cells studied were induced by a single hapten, the observed cellular heterogeneity was probably not caused by a heterogeneous antigen. It seems more likely that latent heterogeneity was present in the cells before they were stimulated by the NIP hapten.
ALTERATION OF THE RESPONSE OF PLATELETS TO SURFACE STIMULI BY PYRAZOLE COMPOUNDS
Authors: Packham M. A. , Warrior E. S. , Glynn M. F. , Senyi A. S. , Mustard J. F.
Published: June 2004

Sulfinpyrazone and phenylbutazone block the aggregating action of collagen, antigen-antibody complexes, and gamma globulin-coated surfaces on blood platelets. These drugs do not block the action of ADP or thrombin. Inhibition of surface-induced aggregation appears to be the result of a decreased response of the platelets to surface stimuli, giving rise to diminished release of platelet constituents, such as ADP and serotonin. The intravenous infusion of these drugs produced results similar to those found in the in vitro experiments. Administration of phenylbutazone in doses sufficient to produce marked suppression of the platelet-collagen reaction impaired hemostatic plug formation at the ends of transected mesenteric vessels in rabbits. Since platelet function is considered a factor influencing platelet survival, the effect of phenylbutazone on platelet survival was examined. It was found that phenylbutazone prolonged platelet survival to more than twice the normal time and reduced platelet turnover by nearly 50%. These studies show that drugs which suppress platelet response to surface stimuli alter platelet function in vivo.