bluuebunny/crossref_metadata_2025 huggingface dataset:
COLLAGEN METABOLISM IN THE NORMAL AND LATHYRITIC CHICK
Authors: Tanzer Marvin L. , Gross Jerome
Published: June 2004

1. Radioisotope incorporation studies of normal and lathyritic chick embryo bone collagen do not demonstrate any interference by lathyrism with collagen synthesis or fibril formation.

2. The results indicate that a portion of the extractable collagen from lathyritic chick embryo bone represents newly synthesized protein. Evidence from a double labeling experiment and from analysis of isotope flow between the extractable and non-extractable pools suggests the extractable lathyritic collagen is heterogeneous. We propose that the lathyritic process affects collagen in all states of aggregation, probably in varying degree.

3. Puromycin, administered intravenously, reduces the amount of extractable collagen in both normal and lathyritic chick embryo bone, and diminishes the incorporation of labeled proline into collagen.

4. Marked fluctuations in incorporation of labeled amino acids into chick embryo bone collagen suggests the occurrence of wide fluctuations in metabolism of this protein.
THE APPLICATION OF TISSUE CULTURE TO THE STUDY OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
Authors: Appel Stanley H. , Bornstein Murray B.
Published: June 2004

1. In the presence of a source of complement, the gamma 2 globulin fraction of rabbit EAE serum results in complete demyelination of myelinated cultures of rat cerebellum. Exposure of the serum to homologous or heterologous brain specifically removes the myelinotoxic activity whereas exposure to non-nervous tissue does not. Polylysine has no effect upon the cultures or upon the demyelinative potency of EAE, whereas heparin inhibits activity presumably through an effect on complement.

2. With the fluorescent antibody technique, the EAE globulins are specifically localized to the myelin sheaths and glial cell membranes during the process of demyelination. As demyelination proceeds, the globulins become localized within the neuroglia in a homogeneous manner which contrasts sharply with the punctate pattern observed in control experiments.

3. The "delayed sensitivity" and classical antibody interpretations of experimental allergic encephalomyelitis are discussed. It is suggested that several factors may be responsible for the pathogenesis of EAE, one of which may well be a myelinotoxic antibody.
PORCINE CONTAGIOUS PLEUROPNEUMONIA
Authors: Shope Richard E.
Published: June 2004

An acute frequently rapidly fatal respiratory illness occurring as an epidemic disease in Argentine swine has been shown to have a bacterium of the genus Hemophilus as its causative agent. This organism, for which the name Hemophilus pleuropneumoniae is suggested, causes a singular, fulminating pleuropneumonia in experimental swine. The very marked effectiveness of H. pleuropneumoniae as a respiratory pathogen contrasts strikingly with the relatively mild pathogenicity of the well known swine Hemophilus, H. influenzae suis, which, in concert with a virus, causes a less highly fatal respiratory ailment, swine influenza. Porcine contagious pleuropneumonia (PCP) is contagious under experimental conditions. In the pathogenesis of the disease, histopathological studies of early cases suggest that the lymphatics of the lung and pleura may be primarily involved and that the pneumonia and pleuritis then proceed from these initial sites of reaction.
PORCINE CONTAGIOUS PLEUROPNEUMONIA
Authors: Shope Richard E. , White David C. , Leidy Grace
Published: June 2004

Hemophilus pleuropneumoniae is highly pathogenic for swine when given intranasally. As few as 100 organisms induce characteristic porcine contagious pleuropneumonia (PCP) and, when as many as one-half million are given, the infection usually proceeds to a fatal termination. While the organism is highly pathogenic when introduced by way of the respiratory tract, it is innocuous when given subcutaneously even in large numbers. Swine that have been inoculated subcutaneously are rendered solidly immune to infection with H. pleuropneumoniae intranasally. The marked pathogenicity of H. pleuropneumoniae for swine has been contrasted with the lack of pathogenicity of another swine Hemophilus, H. influenzae suis. It has been pointed out that, in its high degree of pathogenicity, in its pneumotropism, and in its immunogenicity by a non-respiratory route of inoculation, H. pleuropneumoniae appears to resemble certain viruses more than it does a bacterium.
THE PRESENCE OF RENIN ACTIVITY IN BLOOD VESSEL WALLS
Authors: Gould Anne B. , Skeggs Leonard T. , Kahn Joseph R.
Published: June 2004

The preparation, of an extract of hog blood vessels and organs containing renin activity has been described. The extract hydrolyzes natural or synthetic renin substrate to form a vasopressor material. This reaction could not be distinguished from the hydrolysis of renin substrates by kidney renin. The activation energy, effect of substrate concentration on velocity, inhibition by antirenin, and pH optimum of the extract and of kidney renin are the same. Renin activity is found in the adventitia and media of the aorta, the liver and, to a lesser extent, in other vascular organs.
DIFFERENCES IN THE ELECTROPHORETIC MOBILITIES OF GUINEA PIG 7S ANTIBODIES OF DIFFERENT SPECIFICITIES
Authors: Nussenzweig Victor , Benacerraf Baruj
Published: June 2004

The electrophoretic mobilities of guinea pig γ1 and γ2 antibodies bearing different specificities were compared in agar gel at pH 8.2. Specifically purified antibodies bearing the same immunological specificity showed the same electrophoretic mobility, but significant differences in mobility were observed when antibodies with certain selected different specificities were compared. The specificity of the carrier protein appeared not to affect the mobilities of antihapten antibodies. Differences in mobility have also been shown between γ1 antihapten antibodies produced by individual guinea pigs immunized concomitantly with 2,4-dinitrophenyl bovine gamma globulin and arsanilic acid azo guinea pig albumin. The differences in the net electrophoretic charge between antibodies with different specificities roughly paralleled that of their S fragments produced by papain digestion.
IMMUNOCHEMICAL IDENTIFICATION OF PARATHYROID HORMONE IN NON-PARATHYROID NEOPLASMS ASSOCIATED WITH HYPERCALCEMIA
Authors: Tashjian Armen H. , Levine Lawrence , Munson Paul L.
Published: June 2004

1. Immunochemical cross-reactivity, but not identity, has been demonstrated between bovine parathyroid hormone and an antigen in biologically active extracts of human parathyroid tissue by quantitative C' fixation and C' fixation inhibition.

2. An antigen that fixes C' with rabbit antibody to bovine parathyroid hormone has been found in urea extracts of six human non-parathyroid neoplasms associated with a hypercalcemic syndrome mimicking primary hyperparathyroidism. Comparable extracts of control tissues and other tumors were serologically negative.

3. It is concluded that the tumor antigen is parathyroid hormone or a very closely related protein, and that its production by these neoplasms was the cause of the hypercalcemic syndrome in these six patients.
THE HISTOLOGICAL DISTRIBUTION OF THE BLOOD GROUP SUBSTANCES IN MAN AS DISCLOSED BY IMMUNOFLUORESCENCE
Authors: Szulman Aron E.
Published: June 2004

The ABH antigens have been mapped out in the tissues of embryos and fetuses, 18 to 125 mm crown to rump length, 6 to 14½ weeks ovulation age.

Both the H and A,B antigens have the same distribution, and their spatial and temporal parallel obtains in intrauterine as well as extrauterine phases of life.

The cell wall antigens are present in their maximal distribution in the youngest specimens available. They outline the endothelium of the cardiovascular system, and the cells of most of the epithelia throughout the body. The exceptions are the liver, the adrenal, and the nervous system, presumed to have lost the epithelial antigens at stages antedating the youngest specimens here described.

The antigens of the stratified epithelia (and of the simple epithelia of the renal collecting tubules), together with the endothelial antigens, are permanent and persist into and throughout adult life. All other cell wall antigens disappear at a time characteristic for each organ. The antigenic recession coincides with recognizable steps of morphological advancement and often with assumption of function by the organ concerned; it is completed at about the end of the first trimester of pregnancy.

The secretion-borne antigens first appear at the 35 to 40 mm stage (8 weeks ovulation age) in the salivary glands and in the stomach, to be followed in a constant sequence by the rest of the gastrointestinal tract, respiratory system, and pancreas. The secretion of these antigens persists throughout life.

The early presence and wide distribution of the cell wall A,B antigens render them likely potential targets for maternal anti-A,B antibodies in heterologous pregnancies; the advent of the water-soluble substances at 8 weeks ovulation age may be providing a buffer shielding the fetal cell wall antigens by mopping up the maternal isoagglutinins.
IMMUNE MECHANISMS IN PARABIOSIS INTOXICATION
Authors: Hilgard Henry R. , Cornelius Eugene A. , Dalmasso Agustin P. , Martinez Carlos , Good Robert A.
Published: June 2004

When A strain mice are placed in parabiotic union with (A x C57Bl/1)F1 hybrid partners, the parental strain partners are polycythemic and the hybrids anemic from the 5th through the 16th parabiosis days. All hybrids develop clinical intoxication between the 7th and the 12th days, and no pairs survive to 1 month.

Long-term survival of parabiotic pairs can be achieved if lethally irradiated or specifically tolerant parental strain mice are united to hybrid partners. Production of tolerance by either of these methods results in elimination of anemia-polycythemia by the 12th parabiosis day and prevents intoxication in the hybrid partners.

Preimmunization of the parental strain partners against the C57Bl/1 component of the hybrid leads to a considerable intensification of day 5 anemia-polycythemia. Intoxication develops in the hybrid partners between the 4th and the 6th days after union. It is concluded that anemia is primarily responsible for the syndrome of clinical intoxication.

Early anemia-polycythemia on day 5 does not depend upon an immunological mechanism, but the late anemia-polycythemia appearing between days 12 and 16 is a function of the ability of the parental strain mouse to react immunologically against its hybrid partner.

When neonatally thymectomized A strain mice are joined to hybrid partners, anemia-polycythemia is sustained through the 16th day and the hybrid partners develop clinical intoxication. On the other hand, when both partners are neonatally thymectomized, late anemia-polycythemia is considerably reduced, and the hybrid partners apparently do not develop clinical intoxication. It is concluded that normal hybrid mice are capable of reconstituting the immunological capacity of their thymectomized partners, whereas thymectomized hybrid mice do not have this restorative capacity.

These findings are discussed in terms of their possible application to the problem of the induction of immunological tolerance in adult mice by the parabiosis procedure.
INFLUENCE OF NEOMYCIN AND INGESTED ENDOTOXIN IN THE PATHOGENESIS OF CHOLINE DEFICIENCY CIRRHOSIS IN THE ADULT RAT
Authors: Broitman Selwyn A. , Gottlieb Leonard S. , Zamcheck Norman
Published: June 2004

Two groups of adult rats fed a choline-deficient diet supplemented with neomycin in their drinking water for 250 or 350 days were protected against the development of liver fibrosis and cirrhosis. At the termination of the study these animals weighed more than others not receiving neomycin. This difference in weight did not appear to be caused by a growth-promoting effect of neomycin but rather reflected the increased severity of liver disease and a resultant weight loss in animals not receiving neomycin. Protection by neomycin was cancelled when Salmonella typhosa endotoxin was added to the drinking water. It was concluded that the protective effect of neomycin was mediated by an alteration in the intestinal microflora resulting in a reduction in the numbers of organisms contributing to intraluminal endotoxin. In the presence of choline deficiency, absorption of intraluminal endotoxin may contribute to the development of fibrosis and cirrhosis.
APPLICATION OF A LOCALIZED HEMOLYSIN REACTION FOR SPECIFIC DETECTION OF INDIVIDUAL ANTIBODY-FORMING CELLS
Authors: Ingraham Joseph S. , Bussard Alain
Published: June 2004

A technique is described which makes it possible to detect individual antibody-forming cells using a localized hemolysis reaction in a thickened culture medium containing sheep erythrocytes and guinea pig complement. This technique has the advantage over single cell isolation in that it is technically feasible to survey large populations in order to detect a very small active fraction. The cells can be observed continuously during the time of antibody release, and it appears that an estimate of the relative antibody-forming activity can be made from the size of the areas of lysis. Experiments with metabolic inhibitors indicate that active synthesis is occurring rather than release of preformed antibody. Some experiments on the detection of antibody other than anti-red cell antibodies are reported.

This technique has been applied to a study of the induction period of the primary response of rabbits to sheep red blood cells. The results of this experiment are consistent with an induction period of 2 to 3 days during which there is no increase in the number of active cells in spleen and lymph node reflecting the lag in appearance of detectable serum antibody followed by an abrupt rise of 50- to 100-fold between the 3rd and 5th day. However, the present data are not sufficient to exclude various other mechanisms.
STUDIES ON ANTIBODY PRODUCTION
Authors: Wellensiek Hans-Jobst , Coons Albert H.
Published: June 2004

The physical presence of the antigen used to stimulate a secondary antibody response was demonstrated in the cells of popliteal lymph nodes. Rabbits previously injected with apoferritin (containing no iron), which was prepared from recrystallized horse ferritin, were given an injection of ferritin 5 weeks later. The antigen was traced by means of the Prussian blue reaction, by specific fluorescent antibody, and by electron microscopy. Antiferritin antibody was localized by immunofluorescence, though it was not possible to test cells simultaneously for antigen and antibody. Horse ferritin induces a rather weak primary antibody response, but a brisk secondary response characterized by the appearance in the medullary cords of numerous plasma cells containing antiferritin. Many intact ferritin molecules were found in the nucleus and cytoplasm of numerous reticular and other phagocytic cells in the sinuses. In decreasing amount, ferritin molecules were also clearly demonstrated in hemacytoblasts (plasmoblasts), and immature and mature plasmocytes.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Berlin Richard D. , Wood W. Barry
Published: June 2004

1. Phagocytosis promotes the release of endogenous pyrogen from polymorphonuclear leucocytes.

2. The release of pyrogen, though initiated by the phagocytic event, is not synchronous with it.

3. The postphagocytic release mechanism is not inhibited by sodium fluoride and, therefore, appears not to require continued production of energy by the cell.

4. The release process, on the other hand, is inhibited by arsenite, suggesting the participation of one or more sulfhydryl-dependent enzymes in the over-all reaction.

5. Particle for particle, the ingestion of heat-killed rough pneumococci causes the release of approximately 100 times as much pyrogen as the ingestion of polystyrene beads of the same size.

6. The pyrogen release mechanism of polymorphonuclear leucocytes separated directly from blood, unlike that of granulocytes in acute inflammatory exudates, is not readily activated by incubation of the cells in K-free saline. Despite this difference, both blood and exudate leucocytes following phagocytosis release large amounts of pyrogen, even in the presence of K+. The fact that the postphagocytic reaction is uninhibited by the concentrations of K+ which are present in plasma and extracellular fluids, suggests that this mechanism of pyrogen release may well operate in vivo.

7. As might be expected from the foregoing observations, the intravenous injection of a sufficiently large number of heat-killed pneumococci causes fever in the intact host. Intravenously injected polystyrene beads, on the other hand, are significantly less pyrogenic. Evidence is presented to support the conclusion that the fever in both instances is caused by pyrogen released from the circulating leucocytes which have phagocyted the injected particles.

8. The possible relationships of these findings to the pathogenesis of fevers caused by acute bacterial infections are discussed.
IMMUNOLOGIC STUDIES IN HUMAN ORGAN TRANSPLANTATION
Authors: Kirkpatrick Charles H. , Wilson W. E. C. , Talmage David W.
Published: June 2004

Twenty-eight patients with chronic renal diseases and uremia were investigated with respect to their cutaneous responsiveness to a panel of antigens expected to elicit immediate and delayed hypersensitivity reactions. Compared to a control group, there was a marked decrease in the incidence of responses of both types.

Eighteen patients received renal allografts from members of the control group and were available for restudy in the postoperative period prior to the institution of adrenal steroid therapy. Each recipient acquired delayed responsiveness with specificity identical with that of the kidney donor. The donor group was reactive to 49 antigens to which the recipients were non-reactive preoperatively. Postoperatively, 40 of these reactivities were observed in the recipients.

This successful demonstration of the transfer of immunologically competent tissue in association with renal transplantation indicates that the cause of depressed cutaneous hypersensitivity in uremia is not an inability of the skin per se to react.
STUDIES ON ANTIBODY PRODUCTION
Authors: Sainte-Marie Guy , Coons Albert H.
Published: June 2004

Cells from lymph nodes of rabbits injected repeatedly with bovine serum albumin were transferred subcutaneously to previously irradiated rabbits, and the recipients were immediately injected with bovine serum albumin. A good antibody response resulted. In a series of such animals killed on successive days, skin samples at sites of cell deposition were removed and examined by immunofluorescence and by light microscopy. In these tissues abundant plasmocytes were found to have multiplied and differentiated in a regular progression from immature, to medium, to mature plasmocytes. During the 6 days of the experiment the small plasmocytes accumulated until they reached 85 per cent of the total plasmocytic population.

The mitotic index of the large and medium plasmocytes averaged 11 per cent, implying a generation time of 6.3 hours on the basis of a 1 hour mitotic time. This rate of growth is sufficiently rapid to account for all the plasmocytes on the 6th day as deriving from less than 1 per cent of the population initially transferred. This rate and the orderly progression in the evolution of the plasmocytic population, make it highly improbable that plasmocytes arise from transformation of lymphocytes, but rather indicate that they spring from specific precursors already present among the transferred cells.
THE SPECIFICITY OF ALLERGIC REACTIONS
Authors: Salvin S. B. , Smith R. F.
Published: June 2004

Adult guinea pigs were made unresponsive to a heterologous protein (e.g. bovine gamma globulin, or BGG) or a hapten-protein conjugate (e.g. p-aminobenzoic acid-bovine gamma globulin, or PABAγmiddot;BGG) by intraperitoneal injection of 80 mg cyclophosphamide and the specific antigen. This immunologic unresponsiveness developed to the specific antigen administered simultaneously with the cyclophosphamide, and not to any variants. Thus, animals unresponsive to PABAγmiddot;BGG remained unresponsive to the original antigen on challenge with a variant, but formed delayed hypersensitivity and circulating antibody to the variant. The specificity of immunologic unresponsiveness, therefore, seems more closely related to the whole antigen molecule than does delayed hypersensitivity.
ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS)
Authors: Maurer Paul H. , Gerulat Bernard F. , Pinchuck Paul
Published: June 2004

A new group of synthetic random polymers of α-L-amino acids has been studied for immunogenicity. With the glutamic acid and alanine copolymers, those consisting of almost equimolar amounts of the two (G60A40 and G40A60) were effective antigens in rabbits whereas those with higher glutamic acid contents (G75A25, G90A10) were poor antigens. The substitution of alanine by valine or leucine (G75V25 and G80Leu20) produced copolymers which were poor antigens in rabbits but effective in guinea pigs. L70A30, although capable of "non-specifically" precipitating serum proteins, was shown not to be antigenic in either rabbits or guinea pigs. The introduction of alanine into glutamic acid and lysine polymers (GLA series) enhanced the immunogenicity of the terpolymers, i.e., GLA30 > GLA20 > GLA10 > GL. The mechanism by which this may be accomplished is discussed as possibly being related to the reduction of the interactions between glutamyl and lysyl residues which allows the carboxyl groups to act as strong immunogenic determinants.
THE ROLE OF IMMUNITY IN THE PATHOGENESIS OF EXPERIMENTAL RETROGRADE PYELONEPHRITIS
Authors: Hunter Betty W. , Akins Lona L. , Sanford Jay P.
Published: June 2004

Retrograde pyelonephritis was produced in rats by the intravesical injection of Proteus mirabilis. When animals were preimmunized against Proteus mirabilis by (a) prior infection, (b) administration of antigen, or (c) passively transferred antiserum, they were resistant to infection by proteus when challenged by the retrograde route.

The protective effect of specific preimmunization in retrograde pyelonephritis indicates that a major site of action is retardation of bacterial growth within the parenchyma of the kidney.
EFFECT OF ACTINOMYCIN D ON RNA SYNTHESIS AND ANTIBODY FORMATION IN THE ANAMNESTIC RESPONSE IN VITRO
Authors: Smiley J. Donald , Heard John G. , Ziff Morris
Published: June 2004

Antibody synthesis in anamnestic lymphoid cells, measured by incorporation of leucine-C14 into specific antibody, was inhibited at moderate concentrations of actinomycin D. This was accompanied by marked inhibition of synthesis of RNA as measured by incorporation of H3-cytidine monophosphate. However, at low concentrations of actinomycin D, antibody synthesis was unaffected or even increased while RNA synthesis continued to be inhibited. The results obtained suggest that messenger RNA for antibody synthesis, either because it is relatively stable or present in excess, does not become a limiting factor until its synthesis is maximally inhibited.

Puromycin, an inhibitor of amino acid coupling, abolished antibody synthesis in low concentration. 6-Mercaptopurine had no effect on the synthesis of antibody or RNA even at high concentration.

The data obtained support the view that antibody synthesis follows pathways similar to those utilized for the formation of other types of proteins.
INDUCED PROTECTION OF ADRENAL CORTEX AGAINST 7,12-DIMETHYLBENZ[a]ANTHRACENE
Authors: Huggins Charles , Fukunishi Ryo
Published: June 2004

7,12-Dimethylbenz[a]anthracene (7,12-DMBA) exerts adrenocorticolytic effects which set it apart from all other polynuclear aromatic hydrocarbons and aromatic amines which have been investigated. Adrenal damage by this compound appears to be due to its steric and electronic properties together with its unusually high solubility in lipides.

Many compounds given prior to 7,12-DMBA induced protection of adrenal. The most efficient inducers of protection are flat condensed aromatics possessing 4 or 5 rings; very small doses of these compounds were required to induce protection. Other compounds devoid of these properties induced protection but large or repeated doses were necessary. All inducers of protection had to be given prior to 7,12-DMBA to prevent adrenal necrosis; when given simultaneously with, or later than, this compound adrenal apoplexy resulted.

Protective aromatics and 7,12-DMBA as well induced synthesis of menadione reductase in liver. 3-Methylcholanthrene (3-MC) induced this enzyme in many normal organs including liver, lung, adrenal, and in mammary cancer as well. dl-Ethionine under appropriate conditions of time and dosage eliminated the adrenal protection induced by aromatics and also delayed the induction of menadione reductase while depressing the amount of this enzyme which was synthesized.

7,12-DMBA caused a greatly reduced incorporation of tritium from thymidine-H3 into washed acid-insoluble residue of adrenal. 3-MC given in advance mitigated the drastic effect of 7,12-DMBA on DNA synthesis and increased considerably the amount of tritium which was incorporated.

The specific damage to adrenal by 7,12-DMBA is a direct effect on cells. Protection of adrenal is a secondary effect which requires induction of protein synthesis and it results in improvement in synthesis of DNA.
SPECIFIC FRACTIONATION OF HUMAN ANTIDEXTRAN ANTIBODIES
Authors: Gelzer Justus , Kabat Elvin A.
Published: June 2004

Human antidextran of one individual, absorbed specifically on sephadex, was fractionated into two populations of antibody molecules by successive elution with oligosaccharides of the isomaltose series of increasing size. The purified antibody fractions and some whole antidextran sera were found to fix complement with dextrans of molecular weight of 195,000 and above.

It could be demonstrated by quantitative microcomplement fixation inhibition assays that the antibody eluted with isomaltotriose had a higher affinity for smaller oligosaccharides relative to isomaltohexaose, indicating a high content of antibody molecules with smaller combining sites, while with the second fraction, eluted with isomaltohexaose, the small haptens were very poor inhibitors and the larger oligosaccharides inhibited readily, presumably due to a higher proportion of molecules with larger combining site size. Assays of similarly prepared fractions, obtained from earlier bleedings of the same individual (1), with inhibition of complement fixation were in good agreement with those obtained by inhibition of precipitation.

The two purified antidextran fractions were shown to differ with respect to their complement-fixing capacity. The fraction with molecules with smaller size-combining sites fixed only about half as much complement per unit antibody N as did the fraction containing largely molecules with larger combining sites suggesting that the strength of complement fixation is affected by the strength of the antigen-antibody interaction.
THE IMMUNOLOGICAL BASIS OF ACQUIRED CELLULAR RESISTANCE
Authors: Mackaness G. B.
Published: June 2004

The resistance developed by mice during infection with Listeria monocytogenes, Brucella abortus, or Mycobacterium tuberculosis is not specifically directed against the infecting organism. The processes involved in the induction of acquired resistance, however, are highly specific and seem to depend upon two factors: a state of immunological reactivity of the host and the presence of the specific microbial antigens to which the host has become reactive. When these two coexist in the tissues the host is found to be non-specifically resistant. It is suggested that resistance, which was shown to depend upon an altered state of host macrophages, may be due to the interaction of antigen and a specific antibody adsorbed to the surface of host macrophages; and that the antibody involved in the reaction is perhaps identical with the antibody which confers the state of delayed-type hypersensitivity. The results are discussed in relation to the question of latent infection and infection immunity.
PATHOGENESIS OF INFLAMMATION
Authors: Moses John M. , Ebert Robert H. , Graham Richard C. , Brine Katherine L.
Published: June 2004

Material obtained from the in vitro incubation of granulocytes from saline-induced peritoneal exudates of rabbits has been shown to produce inflammation and fever in rabbits. The supernatant material from cells incubated in saline has been termed granulocytic substance (GS) and is heat-labile. Its production is temperature dependent, occurring at 37°C but not at 4°C, requires viable cells, and is inhibited by potassium ions. A similar material is liberated when cells are incubated in a more physiologic medium. Freezing and thawing of granulocytes does not release GS and the active principle cannot be obtained from the incubation of lymphocytes.

GS produces a delayed inflammatory response as measured by leucocyte sticking and emigration in the rabbit ear chamber and the leakage of protein-conjugated dye at the site of intradermal injection. The former response can be accurately quantitated by calculation of the inflammatory index from reactions observed in the ear chamber. The inflammatory reaction and the properties of GS distinguish it from a variety of previously described mediators of inflammation, but GS appears to be identical with leucocytic pyrogen. The possible role of GS in delayed and protracted inflammation and its relationship to the pathogenesis of fever are discussed.
HETEROGENEITY OF THE INHERITED GROUP-SPECIFIC COMPONENT OF HUMAN SERUM
Authors: Bearn Alexander G. , Kitchin F. David , Bowman Barbara H.
Published: June 2004

Heterogeneity of the group-specific (Gc) components in normal human serum has been demonstrated by the use of a lithium borate buffer system in conventional vertical starch gel electrophoresis and by prolonged immunoelectrophoresis in agar gel. In both Gc 1-1 and Gc 2-2 phenotypes a protein component migrates ahead of the main band. Immunological evidence indicates that the faster migrating band contains Gc specificity. The possibility that the two electrophoretically distinct Gc components share a common polypeptide chain is discussed.
DETECTION OF SPECIFIC ANTIGEN IN SV40-TRANSFORMED CELLS BY IMMUNOFLUORESCENCE
Authors: Pope John H. , Rowe Wallace P.
Published: June 2004

With an immunofluorescent technique involving the use of serum of hamsters with SV40 tumors, nuclear fluorescence was detected in each of five cell lines, derived from four mammalian species, transformed by SV40 virus. Essentially all nuclei, including those of multinuclear cells, were fluorescent-stainable. Serum of hamsters bearing SV40 tumors was also found to give nuclear fluorescence in susceptible cells (AGMK or BSC-1) acutely infected with SV40 virus.

These findings provide further evidence that cellular incorporation of the SV40 viral genome, with partial expression of the genome by synthesis of at least one virus-specific antigen, is an integral property of all SV40 transformed cells.
THE IMMUNOGLOBULINS OF MICE
Authors: Fahey John L. , Wunderlich John , Mishell Robert
Published: June 2004

Two classes of 7S γ-globulins are identified in normal mouse serum and are designated 7S γ2-globulins and 7S γ1-globulins. These two immunoglobulin classes are similar in size. They differ in range of electrophoretic mobility, in specific antigenic determinants, and in genetically determined isoantigens.

Four classes of immunoglobulins in mouse serum, i.e. 7S γ2-, 7S γ1-, γ1A (ß2A), and γM-globulins, were shown to have antibody activity. Each class was characterized and shown to have distinctive immunochemical and physicochemical properties. The genetically determined isoantigens, Iga-1 and Iga-2, were shown to be present only on 7S γ2-globulin molecules.
THE IMMUNOGLOBULINS OF MICE
Authors: Fahey John L. , Wunderlich John , Mishell Robert
Published: June 2004

Two subclasses of mouse 7S γ2-globulins are identified, and are designated γ2a- and γ2b-globulins. They are distinguished from 7S γ1-globulins, γ1A (ß2A)-globulins, and γ1M-globulins of mouse serum. Antibody activity was detected among the γ2a-globulins and γ2b-globulins of hyperimmune mouse serum.

γ2a- and γ2b-myeloma proteins were identified. The genetically determined isoantigen, Iga-1, was present on γ2a-myeloma proteins, but not on γ2b-myeloma proteins.

These findings indicate a complexity among the 7S γ2-globulins which must be taken into account in structural, functional, and genetic studies of immunoglobulins.
IMMUNOLOGIC TOLERANCE AFTER SPECIFIC IMMUNIZATION
Authors: Dorner Marianne M. , Uhr Jonathan W.
Published: June 2004

Specific immunologic tolerance to bovine serum albumin (BSA) was induced in approximately one-half of the rabbits that had been primarily immunized and were prepared for a secondary antibody response to BSA. The state of tolerance lasted for several months in the majority of rabbits and was not easily terminated by immunization with human serum albumin followed by BSA.
STUDIES ON THE MECHANISMS OF HYPERSENSITIVITY PHENOMENA
Authors: Lichtenstein Lawrence M. , Osler Abraham G.
Published: June 2004

Human leukocytes, isolated from the blood of ragweed-sensitive donors, release histamine upon reaction with a purified protein antigen derived from this pollen. The release process has been studied with washed cells suspended in a defined, serum-free medium. Physiologic levels of pH, ionic strength, and temperature, as well as both calcium and magnesium, are required for optimal cellular reactivity. The level of cellular sensitivity of approximately 200 ragweed-sensitive donors has been ascertained, and the kinetics of the release process studied. The rate of histamine release is a function of antigen concentration, but even with a large excess of this reagent it is impossible to abolish a lag phase. Chelation of the divalent cations or a decrease in the reaction temperature may be utilized to stop the reaction. These measures are effective both before and after the initiation of histamine release. Diminished cellular reactivity (desensitization) has been achieved by several procedures. These have in common the addition of antigen to cells in an environment deficient in but a single respect, followed by a restoration of optimal conditions.

The significance of these data has been discussed and it has been proposed that immunologically induced histamine release is an active, enzymatically mediated process which occurs as a multistep response of viable cells to a specific antigenic stimulus.
THE ROLE OF DISULFIDE BONDS IN THE COMPLEMENT-FIXING AND PRECIPITATING PROPERTIES OF 7S RABBIT AND SHEEP ANTIBODIES
Authors: Schur Peter H. , Christian Gary D.
Published: June 2004

The number of total disulfide bonds in rabbit and sheep 7S gamma globulin, before and after treatment with 2-mercaptoethanol, has been measured by amperometric titration.

Mercaptan reduction could diminish the complement-fixing efficiency of 7S rabbit gamma globulin by no more than 90 per cent without any significant decrease in maximal complement-fixing ability. This was associated with the reduction of only 7 disulfide bonds, including 1 interchain disulfide bond [S—S(1)].

The reduction of 7 disulfide bonds in 7S sheep gamma globulin was associated with a 64 per cent decrease in complement-fixing efficiency, while reduction of 10 to 11 disulfide bonds decreased the complement-fixing efficiency by 90 per cent. Reduction of more disulfide bonds was not associated with any further decrease in complement-fixing efficiency, nor of any decrease in maximal complement-fixing ability.

The reduction of more than 10 to 11 disulfide bonds in 7S rabbit and sheep gamma globulins was associated with a decrease in precipitating ability.

The disulfide bonds which are more labile to mercaptan reduction appear to be associated with complement-fixing efficiency while the disulfide bonds which are more resistant to mercaptan reduction appear to be associated with precipitating ability.

The measurement of interpolypeptide chain disulfide bonds has been discussed. One easily reduced interchain disulfide bond [S—S(1)] appears to be important for the complement-fixing efficiency of 7S rabbit antibody. The integrity of this same bond is essential for the precipitating ability of 5S rabbit antibody and may also be important for its complement-fixing ability.
PASSIVE TRANSFER OF ADJUVANT ARTHRITIS BY LYMPH NODE OR SPLEEN CELLS
Authors: Pearson Carl M. , Wood Fae D.
Published: June 2004

All adjuvant-induced arthritis has been passively transferred in a highly inbred strain of rats by transfer of viable lymph node or spleen cells, but not thymus cells, to normal recipients. After an interval averaging 4.3 days recipients developed arthritis, whereas animals actively sensitized with adjuvant never developed disease before the 9th day (average 11.3 days). The transferred disease had all of the gross and pathological characteristics of primary disease, except for a lesser severity. Control studies using non-viable cells either of lymphoidal or other tissue origin were always negative. It is concluded that adjuvant arthritis is the result of an immunologic reaction which is perhaps similar to delayed hypersensitivity. The antigen in this reaction so far remains obscure.
EQUINE ANTIHAPTEN ANTIBODY
Authors: Rockey John H. , Klinman Norman R. , Karush Fred
Published: June 2004

Anti-p-azophenyl-ß-lactoside (Lac) antibody has been isolated from equine antiserum by specific precipitation with Lac-HSA (human serum albumin) and Lac-Hy (hemocyanin). Antibody was separated from antigen by chromatography on DEAE cellulose and zone electrophoresis in solvents containing lactose. Six antigenically distinct immunoglobulins have been identified in purified equine anti-Lac antibody: 7S ß2A-globulin, 19S γ-globulin, a 10S γ1 globulin, and three antigenically distinct 7S γ-globulins. The specific hapten-binding activity of the 7S ß2A-antibody and of the 10S γ1-antibody has been demonstrated by equilibrium dialysis and by analytical ultracentrifugation using a combination of schlieren and absorption optics. The 10S γ1-globulin antibody may be representative of a hitherto undescribed class of immunoglobulins.
IMMUNOLOGICAL AND BIOCHEMICAL STUDIES ON SERUM HAPTOGLOBIN
Authors: Shim Bong-Sop , Bearn Alexander G.
Published: June 2004

Antibody to purified type 1-1 human serum haptoglobin was obtained in rabbits. Using this antiserum it was demonstrated that the antigenic determinants of the haptoglobin molecule reside in both α- and ß-chains. No immunological difference between the normal α1F- and α1S-chains of haptoglobin could be detected.

A number of healthy individuals whose haptoglobin pattern appeared normal by starch gel electrophoresis were shown to possess a haptoglobin which could be distinguished immunologically from the common haptoglobin types. These immunological atypical haptoglobins have been observed in individuals of types 1-1, 2-1, and 2-2. Combined immunological and chemical studies of purified haptoglobin have enabled the construction of a tentative model for the structure of human type 1-1 haptoglobin.
SEROLOGIC STRAIN DIFFERENTIATION IN TRACHOMA
Authors: Nichols Roger L. , McComb Dorothy E.
Published: June 2004

An in vitro test for the differentiation of trachoma strain isolates was described. The method was based on absorption of trachoma antiserum followed by immunofluorescent staining of individual trachoma strains.

Nineteen trachoma strains were studied; two main types were identified. Evidence for quantitative and qualitative antigenic variation between the two types was presented. The limitations in practice and in theory of the test were emphasized.
A STUDY OF RABBIT γ-GLOBULIN ALLOTYPY BY MEANS OF HETEROIMMUNIZATIONS
Authors: Bornstein Paul , Oudin Jacques
Published: June 2004

Representatives of two species, the chicken and the goat, were immunized by injection with Freund's adjuvant, of specific precipitates prepared from the antisera of rabbits with various allotypic specificities. The precipitation reactions of the resulting antisera with normal rabbit sera were studied in liquid and in gellified media. In these reactions the isotypic specificity and often one or the other of the allotypic specificities of rabbit γ-globulin were involved.

It was always easier to obtain antibodies against the specificities controlled by the alleles of locus b (Ab4, Ab5, Ab6) than of locus a (Aa1, Aa2, Aa3). The precipitation reaction of antibodies against a specificity of the a series could always be inhibited by an excess (nearly always moderate) of a serum lacking this specificity. A similar inhibition of the antibodies against the specificities of the b series was often impossible, especially if the antiserum had been collected after a second injection of immunizing material.

The reactions of 58 Ab4+ sera with a goat anti-Ab4 serum and of 28 Ab5+ sera with a chicken anti-AbS serum were studied in gel tubes (simple diffusion). The constant observation of two precipitation zones due respectively to two types of molecules, Ab4+ and Ab4- (or Ab5+ and Ab5-), indicated the existence of an appreciable number of Ab4- or Ab5- molecules, even in supposed homozygotes. In the latter rabbits Ab4- or Ab5- molecules are b- molecules; i.e., molecules lacking the specificities of the b series. Measurements of the distances between the two zones in the reaction of 72 sera revealed significant differences between sera of individuals of the same phenotype, as well as systematic differences not only between sera of homozygotes and of heterozygotes, but also between heterozygotes of different genotypes. These measurements were used to evaluate the ratio of concentrations of the two types of molecules detected by each of the two antisera.

The occurrence of b- molecules in every one of the fairly large number of sera studied indicates a new aspect of the heterogeneity of γ-globulin. Although detected by means of allotypy, this heterogeneity is not dependent upon factors which vary with individuals.

These results are discussed in connection with what is known of the structure of γ-globulin.
NATURALLY OCCURRING HUMAN ANTIBODY REACTING WITH BENCE JONES PROTEINS
Authors: Epstein Wallace V. , Gross Dale
Published: June 2004

Agglutinating substances having characteristics of naturally occurring macroglobulin antibodies to human Bence Jones proteins have been identified in human sera. By means of hemagglutination and hemagglutination inhibition techniques, common determinants have been demonstrated on the light (L) polypeptide chains of pooled normal human γ2-globulin and on some Bence Jones proteins of group 1 but not of group 2. Individual human sera serve to delineate subgroups of the two major antigenic groups of the Bence Jones proteins by agglutinating cells coated by one but not another protein of the same antigenic group. The complexity of subgroups, especially of group 2, is established by testing a panel of Bence Jones proteins of the same group for their ability to inhibit hemagglutination. By this means it appeared that different sera recognized different group-specific determinants of cells coated with a single Bence Jones protein.

The capacity of the L polypeptide chains and proteolytic fragments of γ2-globulin to inhibit the hemagglutination reaction between Bence Jones protein or L chain-coated cells and human sera was examined. These studies demonstrated that the determinants, toward which agglutinators of human serum are directed, appear to be blocked in intact γ2-globulin and in all fragments in which H chain remains in proximity to L chain. It would appear that the presence of H chains bound to L chains by non-covalent bonds completely obstructs the reactivity of the involved L chain groups. The agglutinating capacity of a serum toward Bence Jones proteins or L chains of γ2-globulin appeared to be independent of its agglutinating capacity for cells coated with intact γ2-globulin. No correlation of the presence in serum of agglutinators for Bence Jones proteins or L chains with health or disease has been established.
RECOMBINATION OF ANTIBODY POLYPEPTIDE CHAINS IN THE PRESENCE OF ANTIGEN
Authors: Metzger Henry , Mannik Mart
Published: June 2004

Conditions were developed by which the separated H and L chains of gamma2 globulins recombined to form four-chained molecules in good yields.

In the absence of antigen, anti-2,4-dinitrophenyl (anti-DNP) H chains randomly reassociated with a mixture of antibody and non-specific gamma2 globulin L chains. In the presence of a specific hapten, however, the antibody H chains preferentially interacted with the anti-DNP L chains.

Antibody H chain-antibody L chain recombinants formed in the presence of hapten were more active than the corresponding recombinants formed in the absence of hapten.

Speculations are made regarding the possible mechanisms and biological significance of these effects.
RESISTANCE OF THE MOUSE'S INTESTINAL TRACT TO EXPERIMENTAL SALMONELLA INFECTION
Authors: Bohnhoff Marjorie , Miller C. Phillip , Martin William R.
Published: June 2004

Multiplication of Salmonella enteritidis was inhibited in vitro by buffered suspensions of fecal material freshly removed from the large intestine of normal mice. Most effective was material obtained from cecum and transverse colon. Inhibitory activity was not impaired by sterilization by heat or filtration. From such materials were isolated acetic and butyric acids in concentrations which inhibited Salmonella in vitro. The degree of inhibitory activity of suspensions of colon content and of mixtures of the two fatty acids was conditioned by pH and favored by anaerobiosis. Effective inhibition occurred at or slightly below the pH of colon content of most normal mice as determined in situ by direct measurement. Acetic and butyric acids were isolated from anaerobic cultures of several strains of Bacteroides previously demonstrated to be one of the most numerous inhabitants of the large intestine of the normal mouse.
RESISTANCE OF THE MOUSE'S INTESTINAL TRACT TO EXPERIMENTAL SALMONELLA INFECTION
Authors: Bohnhoff Marjorie , Miller C. Phillip , Martin William R.
Published: June 2004

Determinations of pH, Eh, and concentrations of acetic, butyric and lactic acids were made on the content of cecum and transverse colon of groups of mice killed 1, 3, and 5 days after oral administration of 50 mg streptomycin. Control observations on untreated mice are reported in the preceding communication. Heat-killed supenatants of suspensions of bowel content were tested in vitro for their ability to inhibit multiplication of our standard streptomycin-resistant strain of Salmonella enteritidis during aerobic and anaerobic incubation. Also tested in like fashion were series of cultures in broth buffered at various pH levels and containing acetic, butyric, and lactic acids in varying concentrations.

In colon content of mice on the 1st day after streptomycin treatment, the pH had risen and the concentrations of the fatty acids fallen, a combination of effects which adequately accounts for its inability to inhibit multiplication of Salmonella in vitro and in vivo. By the 3rd day after streptomycin treatment, pH and fatty acid concentrations had returned to normal levels. The susceptibility of mice to oral challenge on the 3rd day was explained by the finding that lactic acid had accumulated in colon content to levels which, in broth, effectively counteracted the activity of inhibitory concentrations of the fatty acids. Other cocarboxylic acids also antagonized the inhibitory activity of the fatty acids; glucose did not.