bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON ANTIBODY PRODUCTION
Authors: Michaelides Maria C. , Coons Albert H.
Published: June 2004

Rabbits were injected into the hind foot with diphtheria toxoid and bovine serum albumin. Fragments of popliteal lymph node taken from them several months later were placed in plasma-clot cultures with Eagle's medium. When antigen was added to the culture fluid, anamnestic antibody responses occurred regularly. When the antigen was diphtheria, responsiveness remained for 4 days after the beginning of the culture. When it was bovine serum albumin, responsiveness lasted for about 8 days. Once an anamnestic response had begun, antibody formation continued for 4 weeks or more. High concentrations of bovine serum albumin (0.5 mg/ml) did not inhibit the response. When both antigens were used to stimulate the same culture, it was found that the two responses were independent.
STUDIES ON ANTIBODY PRODUCTION
Authors: O'Brien Thomas F. , Michaelides Maria C. , Coons Albert H.
Published: June 2004

The in vitro anamnestic antibody response of popliteal lymph node fragments to additions of antigen closely resembles the in vivo anamnestic antibody response in its sensitivity to antigen, in the time course of antibody production, and in the sequence of appearance and the morphology of the antibody containing cells.

Most of the cells responsible for antibody synthesis remain in the explant and do not migrate, although a few can be found in the outgrowing sheet of cells.

The smallest concentration of bovine serum albumin which stimulates an anamnestic response in vitro is about 1 x 10–9 gm/ml.
STUDIES ON ANTIBODY PRODUCTION
Authors: O'Brien Thomas F. , Coons Albert H.
Published: June 2004

Incorporation of 5-bromodeoxyuridine (BUDR) in the culture medium for the 2nd, 3rd, or 4th day after in vitro antigen stimulation of rabbit popliteal lymph node fragments suppressed the in vitro anamnestic antibody response described previously. Before or after this 3-day period, BUDR had no measurable effect. The results suggest that the antibody response in this in vitro system depends upon cell multiplication during this period.
STUDIES ON ANTIBODY PRODUCTION
Authors: Ambrose Charles T. , Coons Albert H.
Published: June 2004

When lymph node fragments from previously immunized rabbits were stimulated in vitro to produce a secondary response, the continuous presence of 50 µg/ml (0.15 mM) of chloramphenicol in the medium during the entire incubation period of 15 to 21 days produced nearly complete suppression of the response. Concentrations as low as 5 µg/ml (0.015 mM) produced approximately 80 per cent suppression of the response.

When 50 µg/ml of chloramphenicol was present during only the first 6 days of culture, the secondary response was reduced 90 per cent. When it was absent for the first 6 days but present for the next 9 to 15 days, the response was reduced only 40 per cent. Since over 95 per cent of the antibody of the secondary response in most experiments appeared in the medium after the 6th day, chloramphenicol apparently inhibits antibody production by interfering with some early phase of the response. It is suggested that this interference involves messenger RNA and that animal cells have appeared resistant to this drug only because their complement of messenger RNA present when the drug has been added is stable over the short periods during which protein synthesis has usually been studied.
PROPERTIES OF GUINEA PIG 7S ANTIBODIES
Authors: Ovary Zoltan , Benacerraf Baruj , Bloch Kurt J.
Published: June 2004

Guinea pig 7Sγ1 antibodies were demonstrated to mediate passive systemic or cutaneous anaphylaxis; guinea pig 7Sγ2 antibodies were unable to mediate these reactions. Gamma-2 antibodies specifically inhibited passive cutaneous anaphylactic reactions provoked by gamma-1 antibodies by competing for antigen. However, gamma-2 antibodies were unable to inhibit passive cutaneous sensitization of guinea pigs by a heterologous antibody system. Guinea pig 7Sγ2 antibodies appear to lack receptors for fixation to guinea pig tissues and do not compete with sensitizing antibody for receptor sites.
THE EFFECT OF EXCESS VITAMIN A ON THE EMBRYONIC RAT OESOPHAGUS IN CULTURE
Authors: Lasnitzki Ilse
Published: June 2004

The effect of excess vitamin A on the oesophageal epithelium of late foetal rats has been studied in organ culture.

In explants kept in normal medium the epithelium is, at first, higher and the keratinisation increased as compared with the development of the organ in vivo. At the later stages of growth, the acceleration of keratinisation leads to an extreme thinning of the epithelium.

Excess vitamin A completely inhibits keratinisation and induces a transformation of the cells lining the oesophageal lumen into mucin-secreting elements. In vitamin A-treated cultures the epithelium remains high throughout the whole period of cultivation.

The amount of secretory matter and the height of the epithelium seem to depend on an adequate supply of oxygen and carbon dioxide to the cells.
COMPARISONS OF BENCE-JONES PROTEINS AND L POLYPEPTIDE CHAINS OF MYELOMA GLOBULINS AFTER HYDROLYSIS WITH TRYPSIN
Authors: Schwartz J. H. , Edelman G. M.
Published: June 2004

L polypeptide chains of myeloma globulin and Bence-Jones protein isolated from the same patient were found to be identical after comparison of their tryptic hydrolysates by two-dimensional high voltage electrophoresis. The patterns of peptides from proteins belonging to antigenic group I differed markedly from those of proteins in antigenic group II. A partially purified H chain fraction was compared with L chains from the same myeloma protein. The tryptic hydrolysates yielded dissimilar patterns of peptides.

These data indicate that γ-myeloma proteins contain two kinds of polypeptide chains, Hγ chains and either LI or LII chains. The L chains appear to be identical with those comprising the Bence-Jones protein from the same patient.
INSULIN ANTIBODY VARIATIONS IN RABBITS AND GUINEA PIGS AND MULTIPLE ANTIGENIC DETERMINANTS ON INSULIN
Authors: Arquilla Edward R. , Finn Jack
Published: June 2004

1. A method is presented for measuring the degree to which insulin antibodies in one antiserum react with an insoluble insulin complex saturated with antibodies from a different antiserum.

2. Many rabbits produce antibodies which bind to portions of the insulin molecule to which antibodies from guinea pigs or other rabbits cannot bind.

3. Occasional guinea pigs produce antibodies which bind to portions of the insulin molecule to which antibodies from rabbits or other guinea pigs cannot bind.

4. Studies with labeled antisera and repeated incubations of test antisera with antibody insulin complexes demonstrate the individual antibody variations to be due to antibodies directed to different determinants and not to dissociation of antibodies from the same determinant on the insulin molecule.

5. More than one antibody molecule can simultaneously bind to an insulin molecule.

6. Insulin has a multiplicity of antigenic determinants.

7. The relationship between antigenic determinants, insulin antibodies, and neutralization of insulin by antisera is discussed.

8. The determinants to which insulin antibodies are directed appear to be characteristic for the individual rabbit or guinea pig immunized. It is postulated therefore that genetic factors direct antibody production toward specific determinants when insulin is the antigen.
ACUTE INFLAMMATION AND TISSUE MAST CELLS IN ADRENALECTOMIZED RATS WITH CUTANEOUS MUCORMYCOSIS
Authors: Paplanus Samuel H. , Sheldon Walter H.
Published: June 2004

The effects of the absence of adrenal tissues on the inflammatory reaction and on the relationship of the tissue mast cells to the inflammatory process have been studied histologically in rats with cutaneous Rhizopus oryzae infection. Degranulation and regranulation of the tissue mast cells at the site of injury have been found to correlate respectively with the onset and subsidence of the exudative cellular phase of inflammation. In the adrenalectomized animals regranulation of these cells and correspondingly termination of the exudative phase are delayed. In the lesions of these rats the numbers of eosinophiles are increased. The proliferative cellular processes of inflammation, although delayed in onset, progress in essentially normal manner but result in some increased collagen deposition. The lack of adrenal secretions does not enhance fungus proliferation and is not associated with spread of the infection. In the present experiments the effectiveness of inflammation does not differ in normal and adrenalectomized rats.
IMMUNOLOGICAL IDENTIFICATION OF FOOT-PAD ISOLATES AS MYCOBACTERIUM LEPRAE BY LEPROMIN REACTIVITY IN LEPROSY PATIENTS
Authors: Shepard Charles C. , Guinto R. S.
Published: June 2004

Lepromin, a product containing Mycobacterium leprae from patients' tissues, fails to elicit skin reactions in lepromatous patients; this non-reactivity was utilized as a means of identifying the mycobacterium isolated in mouse foot-pads from leprosy patients. To do this a suspension of acid-fast bacilli prepared from mouse foot-pads infected with a typical isolate was compared to human lepromin. The isolate was in fourth passage, and the multiplication since first isolation had diluted the original inoculum to insignificant levels. Three preparations were tested: A, A foot-pad preparation containing 1.6 x 107 organisms/ml, B, lepromin diluted to the same bacillary content, and C, undiluted lepromin containing 4.2 x 107 organisms/ml.

The reactions were compared in 34 lepromatous and 30 tuberculoid patients. All 34 lepromatous patients were negative in both early (Fernandez) and late (Mitsuda) reactions to all 3 antigens. In the tuberculoid patients the late reactions were positive in 66.7, 70.0 and 90.0 per cent to antigens A, B, and C, respectively. The size of the reactions to A and B were closely correlated in the individual patients.

Experience in leprosy patients with suspensions prepared from 16 other mycobacterial cultures is reported or reviewed. None of them produced reactions that correlated with those of lepromin. Thus the lack of reactivity to lepromin of lepromatous patients appears to be a specific phenomenon.

The results provide evidence that the foot-pad isolates and M. leprae are immunologically identical.
STUDIES ON LYSOSOMES
Authors: Weissmann Gerald , Keiser Harold , Bernheimer Alan W.
Published: June 2004

Streptolysins O and S from hemolytic streptococci have been added to granular fractions of tissue homogenates in 0.25 M sucrose prepared from rabbit liver, heart, spleen and lymph nodes. At concentrations ranging from 0.65 µg/ml to 2.0 mg/ml of streptolysin S, and from 10 µg/ml to 1.0 mg/ml of streptolysin O, two lysosomal enzymes (beta glucuronidase and acid phosphatase) and, to a lesser degree, one mitochondrial enzyme (malic dehydrogenase) were released into the supernatants of the reaction mixture. Although the hemolytic action of each lysin paralleled the effect on lysosomes, at equivalent levels of hemolytic activity, SLS was approximately 10 times more active on lysosomes than SLO. SLO was inhibited by cholesterol, cortisol, and specific antibody in vitro; pretreatment of animals with cortisone decreased the susceptibility of their isolated lysosomes to SLO. These agents failed to prevent SLS action on lysosomes. SLO had a pH optimum of 6.5 against lysosomes while SLS was maximally active at 7.5. No other streptococcal extracellular products were as active on lysosomes as the streptolysins, although activated streptococcal proteinase precursor released some hydrolases from the granules. Similarities between the actions of SLO and SLS on red cells and lysosomes suggested that the membranes bounding lysosomes and erythrocytes have common properties.
MOTION PICTURE STUDY OF THE TOXIC ACTION OF STREPTOLYSINS ON LEUCOCYTES
Authors: Hirsch James G. , Bernheimer Alan W. , Weissmann Gerald
Published: June 2004

The initial morphologic alteration in rabbit polymorphonuclear leucocytes exposed to streptolysin is rapid and extensive lysis of cytoplasmic granules. The granules appear to rupture directly into the cell sap. Within a few minutes following degranulation, the leucocyte rounds up, filamentous processes appear on the cell membrane, the cytoplasm liquefies, and finally the nuclear lobes swell and fuse.

Streptolysin O causes these changes in intact leucocytes when added in concentrations only slightly higher than those required for release of hydrolases from isolated liver lysosomes, and furthermore exerts its action on granulocytes promptly. On the other hand streptolysin S acts on white cells only after a 15 to 30 minute delay, and the levels necessary to disrupt granules in leucocytes are considerably higher than those which act on lysosome suspensions.

Exposure of rabbit alveolar macrophages to streptolysin O also results in lysis of granules, soon followed by alterations in the cytoplasm and membrane.

The observations are in accord with the hypothesis that streptolysins penetrate the leucocyte membrane and bring about lysis of granules. Autolytic enzymes released from the granules might then be responsible for the subsequent damage seen in various other cell structures.
EXPERIMENTAL TRANSMISSION OF INFLUENZA VIRUS INFECTION IN MICE
Authors: Schulman Jerome L. , Kilbourne Edwin D.
Published: June 2004

An experimental model has been developed for the reproducible transmission of influenza virus infection from experimentally infected mice to uninfected cage mates. Infector mice transmit influenza virus infection most readily during the period 24 to 48 hours after initiation of their infection. This restricted period of transmission is not due to declining titers of infective virus in the nose, trachea, or lungs of infector mice after 48 hours of infection, since peak titers in these tissues are maintained for another 48 hours.

A mouse-adapted strain of A2 virus was found to be more readily transmitted than the mouse-adapted CAM strain of influenza A1 virus, although the CAM strain induced higher pulmonary virus titers and more extensive lung lesions.
MOTION PICTURE STUDIES ON DEGRANULATION OF HORSE EOSINOPHILS DURING PHAGOCYTOSIS
Authors: Archer Gordon T. , Hirsch James G.
Published: June 2004

Horse eosinophil function has been studied in vitro by means of phase contrast cinemicrophotography.

Locomotion of horse eosinophils was inhibited by serum factors reacting with glass surfaces. Under appropriate conditions which eliminated this inhibitory effect, eosinophils moved about and ingested some particles as rapidly as did neutrophils.

Eosinophils were attracted to and readily engulfed such diverse materials as yeast cell walls, foreign erythrocytes, and antigen-antibody precipitates. Specific antibody was required for phagocytosis of red cells, and greatly accelerated the uptake of yeast cell walls.

Horse eosinophil granules situated adjacent to material being engulfed disrupted with discharge of granule contents into or alongside the phagocytic vacuole. Granule disruption resulted in a clear zone and deposition of amorphous, phase-dense material.

A heat-labile serum factor was required for degranulation of eosinophils ingesting foreign red cells, but not for degranulation during engulfment of yeast cell walls or antigen-antibody precipitates.

Horse eosinophils were incapable under these conditions of engulfing an entire human red cell. The eosinophil commonly put out a large pseudopod to surround about half the red cell, and then appeared to constrict this pseudopod distally to cut the erythrocyte in half.

It is concluded that eosinophils are phagocytic cells, resembling neutrophils in many of their properties. Any specific functions of eosinophils, distinguishing them from other phagocytes, remain to be discovered.
PLASMA PROTEIN FORMATION IN VITRO BY TISSUES FROM MICE INFECTED WITH STAPHYLOCOCCI
Authors: Williams Curtis A. , Asofsky Richard , Thorbecke G. Jeanette
Published: June 2004

Isotopic labeling of plasma proteins in vitro by tissues from staphylococcal-infected and control mice was examined, using autoradiography of immunoelectrophoretic patterns. The results indicate that in infected animals there is hyperactivity of liver tissue in producing albumin, α- and ß-globulins, and of spleen tissue in producing immune globulins. The observed increase in labeling of some proteins by tissues from infected mice is to a large extent correlated with an increase of these proteins in the serum.
THE STRUCTURE OF ANTIGEN-ANTIBODY COMPLEXES
Authors: Almeida June , Cinader Bernhard , Howatson Allan
Published: June 2004

Negatively stained aggregates of antigen (polyoma or verruca vulgaris virus) and antibody (from rabbit or goat) were examined in the electron microscope. The antibody molecules appeared as cylindrical rods (often, but not always, showing a beaded appearance) with a long axis of 250 to 270 A and a short axis of 35 to 40 A. The combining sites were at the opposite short ends of the antibody molecules separated by the length of 250 to 270 A of the antibody molecule.

Aggregates of antigen and antibody showed regions of orderly arrangements and frequently ring structures of five or more linked virus particles. Sometimes a virus particle in the center of these ring structures was linked to the peripheral particles. In extreme antibody excess, cross-linking was only rarely observed and virus particles were surrounded by a dense aura of antibody molecules.

The specificity of the two combining sites of most antibody molecules is identical. This was utilized to examine the antigenic relation between the normal (icosahedral) and aberrant forms of polyoma virus.
SPECIFICITY OF PASSIVELY TRANSFERRED DELAYED HYPERSENSITIVITY
Authors: Najarian John S. , Feldman Joseph D.
Published: June 2004

Guinea pigs were injected intravenously with lymphoid cells sensitized to tubercle bacilli (TBC cells) and with lymphoid cells sensitized by contact to a simple chemical, dinitrofluorobenzene (DNFB cells). In each transfer, either the TBC cells or the DNFB cells were labeled with H3-thymidine. Immediately after transfusion, each recipient was skin tested with PPD and DNFB. 24 hours later these lesions were removed for determination of total radioactivity and for autoradiographic analysis. When TBC cells labeled with H3-thymidine were transferred with DNFB cells without an isotopic marker, the total radioactivity and the concentration per gram of skin lesion were greater in the PPD test sites. In the reciprocal arrangement, when DNFB cells labeled with H3-thymidine were transfused with TBC cells without an isotopic tag, the total radioactivity and the concentration per gram of skin lesion were greater in the DNFB test site. Similar results were obtained in guinea pigs which were actively immunized by tubercle bacilli and passively by transfer of DNFB cells. Autoradiographic analysis of test sites from guinea pigs passively transferred with both types of sensitized cells confirmed these findings.

By calculation, only a very small number of transferred sensitized cells reached the specific test lesion. Most of the cellular infiltrate was derived from the responding host. The specificity of the reaction of delayed hypersensitivity was apparently achieved by retention of the sensitized cells after they had arrived by chance at the specific antigen depot and was not due to a non-specific stickiness of sensitized or inflamed lymphoid cells.
THE ASSAY OF GALACTOKINASE AND GALACTOSE-1-PHOSPHATE URIDYL TRANSFERASE ACTIVITY IN HUMAN ERYTHROCYTES
Authors: Robinson Arthur
Published: June 2004

A simple, rapid, and direct method for measuring the activities of the galactokinase and Gal-1-P uridyl transferase enzymes in human erythrocytes is presented.

The method has been applied to measurement of enzyme activities in a group of 37 presumably normal persons, 3 patients with galactosemia, 6 known heterozygous carriers of the defect, and 9 relatives of carriers. In every case the test unambiguously identified the individual's status as normal, heterozygotic carrier, or homozygously defective.

Use of the test in genetic counseling and genetic epidemological studies is discussed.
MODIFICATION OF HOST RESPONSES TO BACTERIAL ENDOTOXINS
Authors: Watson Dennis W. , Kim Yoon Berm
Published: June 2004

Evidence is presented suggesting that the apparent non-specificity of pyrogenic tolerance observed with Gram-negative bacterial endotoxins is due to related antigenic determinants associated with the macromolecular toxins. This is based on results obtained in rabbits from pyrogenic cross-tolerance tests with selected endotoxins. In these tests, purified endotoxins from Escherichia coli (COO8) and Chromobacterium violaceum (CV) gave results one might expect with non-reciprocal cross-reacting antigens in classical immune systems. Additional evidence for an immune mechanism in tolerance is suggested by the highly significant anamnestic response observed.

Lipid A, a toxic derivative of the purified COO8 endotoxin, failed to induce pyrogenic tolerance against the parent toxin. These results are explained by assuming that endotoxins have two interdependent activities associated with different portions of the macromolecule; one is assumed to be responsible for the primary toxicity, and the other is involved in secondary toxicity. The latter is dependent on the hypersensitive state of the host. Additional evidence for the role of hypersensitivity in secondary toxicity is based on the observation that adult rabbits are highly sensitive to the pyrogenic, lethal, and skin-reacting activities of endotoxin in contrast to young animals which are more resistant to all of these attributes of toxicity.

In adults, the host responses to pyrogenicity, lethality, and skin reactivity could be partially inhibited by the early exposure of the animals to massive doses of endotoxin equivalent to a LD50. The pyrogenic tolerance shown in these animals was specific indicating that the inhibition of the hypersusceptibility to endotoxin involved an immunological mechanism.

A mechanism of endotoxin tolerance is proposed and discussed based on the induction of specific antibodies capable of assisting the RES in the clearance and destruction of endotoxin.

It is suggested that the present inconsistencies relative to the chemical nature and biological activities of endotoxins might be explained on the basis of these two activities and the failure to recognize the importance of the immunological state of the host in which the toxins are tested.
STUDIES ON THE LOCALIZATION OF CIRCULATING ANTIGEN-ANTIBODY COMPLEXES AND OTHER MACROMOLECULES IN VESSELS
Authors: Cochrane Charles G.
Published: June 2004

A short term model in which circulating antigen-antibody complexes and host complement localized in vessel walls of guinea pigs was analyzed. Localization was accomplished by subjecting the animals to anaphylactic shock.

The circulating macromolecules, such as antigen-antibody complexes, appeared to localize by being trapped in the vessel wall along the basement membrane that acted as a filter during a state of increased permeability of the vessel.

It was suggested that this point of localization between the endothelial cell and the basement membrane may well represent the earliest focus of inflammation in diseases caused by the deposition of injurious macromolecules such as soluble antigen-antibody complexes from the blood stream.

Complexes localized in the vessel walls did not provoke Arthus-type vasculonecrotic reactions even though in both these vessels and in cutaneous Arthus reactions antibody, antigen, and host complement (C'3c) were deposited in the vessel walls. The possibility was presented that since circulating macromolecules and probably complexes deposited in (a) relatively small amounts, and (b) in a position beneath endothelial cells, they were not strongly chemotactic toward circulating polymorphonuclear leukocytes. Vasculonecrotic reactions, therefore, were not observed. It was brought out that this may be similar to the situation in glomerulonephritis induced by localized immune complexes, in which severe necrosis is not observed.

In the Arthus vascular reaction, host complement was found microscopically accumulated with the immune reactants in affected vessel walls.
CONVULSIVE SYNDROME IN RABBITS INJECTED WITH FAT EMULSION AND HEPARIN
Authors: Van den Bosch Jozef , Billiau Alfons
Published: June 2004

Functionally hepatectomized rabbits showed convulsions and coma within 2 hours after the intravenous injection of fat emulsion and heparin.

Intravenous injection of the detergent triton prevented this syndrome, if given before the fat emulsion and heparin, and reversed it if given subsequently.

Extremely high plasma non-esterified fatty acid levels were noted in rabbits showing the convulsive syndrome, but not in animals that received the detergent.

The mechanism of the convulsions probably includes the toxicity of high amounts of non-esterified fatty acids.
ISOLATION AND PARTIAL CHARACTERIZATION OF THE TWO PRINCIPAL INHERITED GROUP-SPECIFIC COMPONENTS OF HUMAN SERUM
Authors: Cleve Hartwig , Prunier John H. , Bearn Alexander G.
Published: June 2004

The group-specific component (Gc), an α2-globulin of human plasma with inherited variations in relative electrophoretic mobility, has been isolated from plasma and partially characterized.

The isolation procedure combines ammonium sulfate fractionation, anion exchange chromatography, preparative zone electrophoresis, and gel filtration. The method is suitable for the isolation and purification of the group-specific components. The Gc proteins representing the gene products of the two common homozygous Gc-types) Gc 1-1 and Gc 2-2, have been prepared. Gc belongs to the group of α2-globulins of relatively low molecular weight (4.1S, molecular weight 50,800) and relatively low carbohydrate content (3.3 per cent). The total amino acid composition of the two homozygous group-specific components is very similar; treatment with reducing agents and alkylation provides no evidence for the presence of more than a single polypeptide chain in the Gc molecule.
COMPONENTS OF GUINEA PIG COMPLEMENT
Authors: Nishioka Kusuya , Linscott William D.
Published: June 2004

Employing sheep erythrocytes sensitized by antibody and the first and fourth components of complement (EAC'1,4), in such a manner as to prevent the development of immune adherence (I-A) reactivity during preparation, four separate substances required for the conversion of EAC'1,4,2 to the final damaged state (E*) were identified in whole guinea pig serum by cellulose chromatography, and tentatively termed C'3c, C'3b, C'3a, and C'3d.

I-A reactivity was induced in EAC'1,4,2 after interaction with only one of these four substances, C'3c. A detailed comparison of the effects of heat, hydrazine, low pH, freezing, absorption by immune complexes, and elution from cellulose columns indicated that this same substance which was capable of imparting I-A reactivity to EAC'1,4,2 was also essential for immune hemolysis. Other experiments showed that I-A-reactive cells prepared either by treating EA with different concentrations of whole C' at 0°C, or by treating EAC'1,4,2 with C'3c, underwent lysis by C'2 + C'3b + a + d in proportion to the amount of whole C' or of C'3c used to make the cells reactive in I-A. These data provide strong evidence that a single factor, C'3c, is required both for the conversion of EAC'1,4,2 to an I-A-reactive complex (EAC'1,4,2,3c) and for the lysis of EAC'1,4,2 by C'3b + a + d.

C'3c is the only one of the components studied which can induce I-A reactivity, and is the first to react with EAC'1,4,2. Formation of EAC'1,4,2,3c proceeds even at 0°C, but is much more rapid at elevated temperatures, showing a maximum in from 5 to 15 minutes at 37° or 30°C respectively. Prolonged incubation at these temperatures results in a decline in hemolytic reactivity without a noticeable effect on I-A. This loss was resolved into three phenomena: (a) a rapid loss of ability of SAC'1,4,2,3c to react with C'3b, presumably as a result of decay of the C'2 moiety in the complex, which is readily reversed by addition of fresh C'2; (b) a slow, irreversible spontaneous inactivation of SAC'1,4,2,3c; (c) a moderately rapid, irreversible inactivation of SAC'1,4,2,3c by some factor present in C'3c preparations.
COMPONENTS OF GUINEA PIG COMPLEMENT
Authors: Linscott William D. , Nishioka Kusuya
Published: June 2004

The elution characteristics from DEAE cellulose are presented for four components of guinea pig serum, which are capable of interacting sequentially with sheep erythrocytes sensitized with antibody and the first, fourth, and second components of complement (EAC'1,4,2) to cause immune hemolysis, and information is given regarding some of the properties of these components, termed C'3c, C'3b, C'3a, and C'3d. All can react in the presence of ethylene-diaminetetraacetate, and are non-dialyzable. C'3c is quite stable at 56°C, but is rapidly inactivated at low pH or by contact with hydrazine or ammonium hydroxide. C'3b is moderately heat-stable, quite susceptible to low pH, and less readily destroyed by hydrazine. C'3a is very heat-labile, but relatively stable at low pH, while C'3d is heat-labile, sensitive to low pH, and insensitive to bydrazine.

EAC'1,4,2 reacts with C'3c to form EAC'1,4,2,3c, which reacts then with C'3b to give the intermediate, EAC'1,4,2,3cb. The following reaction with C'3a yields EAC'1,4,2,3cba, which reacts finally with C'3d to give EAC'1,4, 2,3cbad (E*). The first and last reactions proceed moderately well at 0°C, but more rapidly at 30–37°C. The reaction with C'3b is almost completely inhibited at 0°C, while that involving C'3a proceeds almost as rapidly at 0°C as at higher temperatures. EAC'1,4,2,3cba cells have an increased fragility as compared with the other intermediate forms.

Depletion studies with purified fractions and appropriate intermediate complexes showed a high degree of depletion of C'3c, somewhat less of C'3b, and little or no depletion of C'3a from the fluid phase.

Examination of a beta1C globulin prepared from fresh human serum revealed high C'3c and C'3b activity, and very little C'3a or C'3d.
LOCALIZATION OF ANTIBODIES IN GROUP I AND GROUP II γ-GLOBULINS
Authors: Mannik Mart , Kunkel Henry G.
Published: June 2004

A wide assortment of antibodies has been analysed by qualitative and quantitative techniques for their content of group I- and group II-type γ-globulin molecules. These included Rh antibodies, isoagglutinins, thyroglobulin antibodies, dextran antibodies, and teichoic acid antibodies. All the antibodies studied showed the presence of both groups. However, the ratio of the two varied widely in different individuals and diverged markedly from the ratio in the total γ-globulin of the individual. Two antibodies isolated from the serum of the same individual showed different ratios for the two groups.
FACTORS CONTROLLING SERUM γ-GLOBULIN CONCENTRATION
Authors: Fahey John L. , Robinson Alan G.
Published: June 2004

Both synthetic and catabolic processes determine the serum γ-globulin level. The rate of γ-globulin synthesis appears to be the primary factor determining the amount of serum γ-globulin. Increase of γ-globulin synthesis (as may occur following immunization or development of plasma cell tumor) elevates the serum γ-globulin level. This, in turn, accelerates the fractional rate of γ-globulin catabolism. The change in catabolic rate reduces the dimensions of the serum change from that which would occur if synthesis alone determined the serum γ-globulin level. The present studies indicate the existence of a homeostatic mechanism controlling the rate of γ-globulin catabolism.

The mechanisms of γ-globulin catabolism are specific and selective. Marked serum increase of other immunoglobulin components (ß2A-globulins and γ1-macroglobulins) do not accelerate γ-globulin catabolism. Similarly, serum albumin increases do not influence γ-globulin catabolism.

The site determining γ-globulin catabolism is restricted to a part of the γ-globulin molecule; i.e., on the F piece obtained by papain digestion and, by inference, on the H chains obtained by reduction and alkylation of γ-globulin molecules.
IMMUNOLOGICAL UNRESPONSIVENESS TO SENSITIZATION WITH SIMPLE CHEMICAL COMPOUNDS
Authors: Battisto Jack R. , Chase Merrill W.
Published: June 2004

Guinea pigs fed picryl chloride to induce specific immunologic unresponsiveness cleared small amounts of venously infused antipicryl antibody at a rate equal to that of normal guinea pigs.

Catabolism of passively administered picryl-specific antibody did not alter the unresponsive state of picryl chloride-fed guinea pigs or the responsive state of normal guinea pigs.

Lymphoid cells of picryl chloride immunized guinea pigs produced equal amounts of picryl-specific antibody in picryl chloride-fed and normal animals.

Allergen-fed guinea pigs remained unresponsive to attempted sensitization with the allergen in excess of 10 months after the final feeding, though some became feebly sensitive between 9 and 11 months. Second attempts to make unresponsive animals hypersensitive were unsuccessful.

White blood cells of guinea pigs unresponsive to picryl chloride were unable to transfer delayed-type hypersensitivity for picryl chloride to normal recipients yet readily transferred tuberculin hypersensitivity.
GROUP-SPECIFIC CARBOHYDRATE OF GROUP C-VARIANT HEMOLYTIC STREPTOCOCCI
Authors: Araujo Paulo , Krause Richard M.
Published: June 2004

The trypsinized cell walls of Group C hemolytic streptococci are composed of the specific carbohydrate antigen and a mucopeptide matrix. Certain phage resistant strains of Group C streptococci, isolated from organisms which survive exposure to Group C bacteriophage also possess carbohydrate and mucopeptide fractions, but the carbohydrate gives a precipitin reaction with Group A-variant antiserum and not with Group C antiserum. These strains have been termed Group C-variant. The C-variant carbohydrate contains 86 per cent rhamnose and only 2 per cent galactosamine, and is thus chemically and immunologically similar to Group A-variant carbohydrate. The evidence suggests that the antigenic determinants of Groups A-variant and C-variant carbohydrates are rhamnose-rhamnose linkages. These results strongly support the hypothesis that the carbohydrates of Groups A and C streptococci are composed of a similar rhamnose moiety but that the determinant amino sugar terminal to the rhamnose-rhamnose linkages in the case of Group A is N-acetylglucosamine whereas that of Group C is N-acetylgalactosamine.
THE APPEARANCE OF A HEPATOTROPHIC VIRUS IN MICE THYMECTOMIZED AT BIRTH
Authors: East June , Parrott Delphine M. V. , Chesterman Frederick C. , Pomerance Ariela
Published: June 2004

Inbred (C57BL; C3H/Bi), hybrid (C57BL x C3H/Bi), and outbred (TO) mice thymectomized within 24 hours of birth develop wasting symptoms and die prematurely and a proportion of these animals have pathological changes in the liver. The incidence of the liver lesions varies according to the strain of mice used and the lesions tend to occur in animals dying comparatively late.

These lesions were shown, by passage of tissue suspensions and of cell-free liver extracts, to be due to a hepatotrophic virus probably mouse hepatitis virus-1 (MHV-1). The part played by the hepatotrophic virus in the premature death of thymectomized mice is discussed but, although neonatal thymectomy apparently alters a normally stable host-virus relationship, it is not thought that the virus is primarily responsible for the death of its host. The role of this virus in the production of the physical wasting is also considered to be problematic.
BRIDGE FORMATION AND CYTOPLASMIC FLOW BETWEEN PHAGOCYTIC CELLS
Authors: Aronson Moshe
Published: June 2004

A simple chamber was constructed for observation of cells at 37°C and under high magnification. Rabbit peritoneal histiocytes observed in this chamber manifested a constant interaction, which lasted as long as the preparation itself. This interaction consisted of formation of cytoplasmic bridges and flow of cytoplasm between the cells.

Lung macrophages formed bridges both between themselves, and with peritoneal histiocytes. On the other hand, no bridges were noticed between histiocytes and polymorphonuclears or fibroblasts. BCG bacteria were observed passing from one histiocyte to another.

Autoradiographic studies suggest that RNA may be transferred from one cell to another. The possible significance of these observations is discussed.
ADDITIONAL STUDIES ON THE TRANSFERRINS OF CORD SERUM AND CEREBROSPINAL FLUID
Authors: Parker W. Carey , Hagstrom Jack W. C. , Bearn Alexander G.
Published: June 2004

Serum transferrins have been examined in 392 samples from full-term infants and from premature infants at various stages of growth. The characteristic transferrin pattern of the infants by starch gel electrophoresis contained a single prominent iron-binding component accompanied by 4 faint, slower migrating components. An additional faint component was present in the sera of infants heterozygous for a transferrin variant. The faint components migrated slightly more rapidly than the corresponding components in the stepwise pattern produced by the action of neuraminidase in removing sialic acid from transferrin. The interpretation is presented that the faint components may represent the absence of multi-unit carbohydrate prosthetic groups on the transferrin molecule in the infant. A similar interpretation is possible for the slow migrating transferrins of cerebrospinal fluid.
THE PARTICULATE HYDROLASES OF MACROPHAGES
Authors: Cohn Zanvil A. , Wiener Edith
Published: June 2004

The contents of selected hydrolytic enzymes of oil-induced peritoneal, normal alveolar, and BCG-induced alveolar macrophages have been studied. On a per cell or nitrogen basis the normal alveolar cells contained considerably more acid phosphatase, cathepsin, acid ribonuclease, lysozyme, and lipase than peritoneal cells. The BCG-induced alveolar macrophage exhibited increased levels of acid phosphatase, lysozyme, and lipase as compared to alveolar macrophages from unstimulated rabbits. The morphological differences between these cells was discussed and electron micrographs of the BCG-induced macrophage presented.

Fractionation of the BCG-induced macrophage by differential centrifugation showed that 60 to 80 per cent of the total cell content of acid phosphatase, cathepsin, beta glucuronidase, acid ribonuclease, acid deoxyribonuclease, aryl sulfatase, lysozyme, and lipase were localized in a postnuclear fraction which sedimented at 15,000 g. This fraction also contained the majority of the mitochondria as evidenced by its content of cytochrome oxidase. Non-specific esterase was not localized to this fraction.

A separation of the hydrolase-containing particles and mitochondria was achieved by isopycnic sucrose gradient centrifugation. Under the conditions employed, the mitochondria distributed at densities of 1.19 to 1.20, whereas the hydrolase particles sedimented to a density of 1.26 to 1.27. Each of the hydrolases including acid phosphatase, beta glucuronidase, cathepsin, lysozyme, and acid ribonuclease exhibited maximum activities in the same gradient fraction.

The isolated granules exhibited enzymatic latency, and activation could be achieved by cycles of freezing and thawing or surface active agents. The majority of each of the hydrolytic enzymes could be liberated in a non-particulate form by mechanical trauma.

Macrophages which had been stained supravitally with neutral red were fractionated by differential and gradient centrifugation. More than 70 per cent of the dye could be recovered in the particulate hydrolase fraction. The isolated, stained granules resembled those seen in the intact cell.
THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY
Authors: Svehag Sven-Eric , Mandel Benjamin
Published: June 2004

Rapid formation of poliovirus-neutralizing antibody was observed in the rabbit. 19S type antibody was detectable 8 to 12 hours following a single intravenous virus injection and the induction period was of the order of 4 to 5 hours or less. The production of 7S antibody had a longer lag phase (1½ to 2 days) and it was formed at slower rate. The observed rate of early 19S and 7S antibody formation as well as the peak titers of the two antibodies were antigen dose dependent. Normal rabbit sera showed low neutralizing activity to several viral antigens in a sensitive assay system.

Following intravenous inoculation of poliovirus either transitory (⩽ 1 month) or enduring (¾ to 1½ year) antibody formation resulted depending upon the dose of antigen employed. In transitory responses, which could be induced by a single small antigen dose, only 19S antibody was demonstrable and there was an abrupt cessation of antibody synthesis on day 4 or 5. In enduring responses, both 19S and 7S antibody were formed and the minimum antigen dose required for initiation of such a response was equal to the dose needed for induction of 7S antibody formation. Thus, enduring antibody formation was an all-or-none phenomenon depending upon whether or not 7S antibody formation was induced.

The antigen dose requirement for induction of 7S antibody was much higher (by 50-fold or more) than that for 19S antibody. This allowed a determination of antigen dose regions, within which predictably transitory (19S) or enduring (19S + 7S) antibody formation was obtained. These pronounced differences in antigen dose requirement for induction and kinetics of formation of 19S and 7S antibody suggest that the same cells do not participate in the formation of the two antibodies.
ACUTE INFLAMMATION IN THE RENAL CORTEX AND MEDULLA FOLLOWING THERMAL INJURY
Authors: Rocha Heonir , Fekety F. Robert
Published: June 2004

As determined by serial histologic study, the leukocyte component of the acute inflammatory response to thermal injury in the medulla of the kidney of rabbits was markedly delayed and diminished in intensity when compared with the response of the cortex. Similar differences in granulocyte mobilization between cortex and medulla were seen following the inoculation of bacteria. Hydronephrosis produced by ureteral ligation had no discernible effect upon the inflammatory response in either cortex or medulla following thermal burns. The susceptibility of the cortex to E. coli infection was markedly enhanced during leukopenia induced by nitrogen-mustard. These results suggest that deficiencies in granulocyte mobilization play an important role in the increased susceptibility of the renal medulla to bacterial infection.
STUDIES RELATING TO THE SERUM RESISTANCE OF CERTAIN GRAM-NEGATIVE BACTERIA
Authors: Osawa Etsuko , Muschel Louis H.
Published: June 2004

Paracolobactrum ballerup, an organism considered completely insusceptible to the bactericidal action of the antibody-complement system, became extremely sensitive to immune serum and even to normal serum, in conjunction with complement, when cultivated at temperatures above 37°C. This conversion to serum sensitivity was associated with the loss of the organism's Vi antigen and its tendency to assume a rough state. It did not result in a genetic change in the organism, however, since reincubation of serum-sensitive P. ballerup at 37°C resulted in a restoration of its resistance. The loss of serum resistance as a result of cultivation temperatures above 37°C may be of significance as an example of the enhancement of host defense mechanisms induced by fever.

Special conditions of testing indicated that P. ballerup cultured at 37°C and S. paratyphosa C, organisms considered insusceptible to serum bactericidal action, were not entirely refractory to serum. These conditions included simply a relatively low ratio of the number of test organisms to serum volume and an extended incubation period of the organisms with serum bactericidal substances, or even without these substances, prior to the initiation of bactericidal action. It is likely, therefore, that an absolute distinction between serum-sensitive and serum-resistant Gram-negative organisms does not exist, but rather that there is a very broad distribution of serum sensitivity among these organisms.
POSSIBLE ROLE OF INTERFERON IN DETERMINING THE ONCOGENIC EFFECT OF POLYOMA VIRUS VARIANTS
Authors: Friedman Robert M. , Rabson Alan S.
Published: June 2004

1. Infection of newborn C3Hf/Bi mice with both the highly oncogenic S variant and the poorly oncogenic M variant of polyoma virus caused significantly fewer tumors than infection with the S variant alone

2. Infection of newborn C3Hf/Bi mice at birth with either M or S variant caused resistance to infection with a heterologous agent, encephalomyocarditis virus, but the M variant caused a somewhat greater degree of resistance.

3. Extracts of tissues of animals infected at birth with the M variant had measurable levels of interferon, reaching a peak on the 5th day after infection with the virus. Extracts of animals infected with the S variant showed no such activity.

4. The growth curves of the two variants in newborn C3Hf/Bi mice showed that the S variant grew to a 1000-fold greater titer than did the M variant at 5 days after infection. Samples tested at 10 days showed a 10-fold difference.

5. These findings suggested that the difference between the variants in oncogenic potential might have been due to the greater interferon production induced by infection with the M variant than by infection with the S variant.
IMMUNOLOGICAL STUDIES OF THE 11S PROTEIN COMPONENT OF THE HUMAN COMPLEMENT SYSTEM
Authors: Morse Jane H. , Christian Charles L.
Published: June 2004

Rabbit anticryoprotein and anticomplement antisera recognized a heat-labile antigen in normal human serum. This antigen best fitted the previously described US protein because of its presence in fresh human serum, euglobulin, and purified 11S preparations and its absence in heated serum, R11S, and pseudoglobulin preparations. The 11S hemolytic activity correlated well with the presence of this heat-labile antigen in the 11S region in sucrose density gradient ultracentrifugation and in the gamma globulin region on zone electrophoresis. It could be identified as a single component in the gamma globulin region in immunoelectrophoresis. The intermediate complex EAC'11S was lysed by R11S reagents and agglutinated by these antisera. The antisera also agglutinated a human complement-binding Rh-positive cell system if the 11S protein had been previously bound.
THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY
Authors: Svehag Sven-Eric
Published: June 2004

Rabbits injected intravenously with a single high dose of poliovirus (type 1) produced two major 19S and two 75 type neutralizing antibody populations, with different electrophoretic mobilities.

The first 2 to 2½ days after immunization the antibody was of the 19S type and migrated as a single component in the ß-region. In contrast, the major 19S antibody synthesized from day 3 on was a γ1-globulin. 7S type antibody, appearing on day 4, was contained only in the γ1-region, while 10 to 14 days following immunization the 7S antibody was associated with both γ1- and γ2-globulins. The electrophoretic distribution of antibody in 2-week sera revealed the presence of at least four antibody populations (19S ß, 19S γ1, 7S γ1, and 7S γ2).

Serum samples collected 1 or 2 weeks following antigenic stimulation often contained small amounts of antibody which sedimented at a rate (11S to 15S) intermediate to that of 7S and 19S antibodies.

The neutralizing activity of the 19S type antibodies and the intermediately sedimenting antibody was destroyed by incubation with 0.1 M (5 days) or 0.2 M (1 day) 2-mercaptoethanol at 3°C. The 7S antibody activity was un-affected by treatment with from 0.1 to 0.8 M mercaptan.