bluuebunny/crossref_metadata_2025 huggingface dataset:
A LABILE INTRANUCLEAR RNA ASSOCIATED WITH THE DEVELOPMENT OF ADENOVIRUSES
Authors: Mayor Heather Donald
Published: June 2004

The nucleic acids produced intracellularly during the replication cycles of both DNA and RNA viruses can now be identified rapidly using a sensitized procedure based on staining with the fluorochrome acridine orange. Cellular DNA, viral DNA (both single and double stranded forms), cellular RNA, and RNA arising as a result of viral stimulus can be differentiated.

The intracellular development of virus specific DNA, RNA, and protein has been studied in monkey kidney cells infected with adenoviruses types 3 and 7. It has been possible to detect a labile RNA in the nucleus from 16 to 20 hours after inoculation. When the cultures are treated with puromycin at this time, this RNA can be accumulated under certain conditions in the nucleus and demonstrated cytochemically. At the same time the production of specific viral protein as determined by staining with fluorescein-labeled antibodies is markedly inhibited. However, intranuclear double stranded DNA continues to be formed for a time. When puromycin is added to the system early in the eclipse period virus-specific DNA and labile RNA cannot be detected.
STUDIES ON HUMAN ANTIBODIES
Authors: Edelman G. M. , Kabat Elvin A.
Published: June 2004

Specific precipitates and purified human antibodies were reduced and alkylated and subjected to starch gel electrophoresis in 8 M urea to dissociate and separate the L and H polypeptide chains. Dissociated antibodies to dextran, levan, teichoic acid, blood group A substance, and tetanus toxoid showed sharp bands corresponding to L polypeptide chains. The patterns differed for antibodies of different specificities. Some differences were also seen among antibodies of the same specificity from different individuals. Purified antidextran antibodies showed particularly simple patterns resembling those of purified human γ myeloma proteins. In some cases only one L chain band was present.
GAMMA GLOBULIN TURNOVER IN RABBITS BEFORE AND DURING HYPERIMMUNIZATION
Authors: Andersen Stig Bryde , Bjørneboe Mogens
Published: June 2004

The turnover of 131I-labeled gamma globulin has been determined in rabbits before and during (8 weeks later) hyperimmunization with pneumococcic vaccine, which increased the gamma globulin concentration 5 to 10 times. Before immunization fractional turnover rate was an average of 36 per cent of the plasma pool per day, and the rate of catabolism was 133 mg/kg/day. During hyperimmunization fractional turnover rate was an average of 37 per cent per day, and the rate of catabolism was 1160 mg/kg/day. The observation that the fractional turnover rate is independent of the concentration suggests that the rate of breakdown should have the characteristic of a first order process.
ANTIGENIC VARIANTS OF EASTERN EQUINE ENCEPHALITIS VIRUS
Authors: Casals Jordi
Published: June 2004

A study by hemagglutination-inhibition test showed that 19 strains of eastern equine encephalitis virus grouped themselves in two main types, which have been designated North American and South American. The former consists of ten strains from the eastern half of the United States, from Massachusetts to Florida; Jamaica, the Dominican Republic, and, subject to confirmation, Thailand. The South American type comprises nine strains from Panama, Trinidad, British Guiana, Brazil, and Argentina. The strains were isolated from different natural hosts over a period of 30 years.
IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS
Authors: Kaplan Melvin H. , Suchy Mary Louise
Published: June 2004

Further evidence of a cross-reactive relationship between a cell wall antigen of certain Group A streptococcal strains and mammalian heart tissue is provided by the demonstration that goat antisera to washed human or rabbit heart tissue homogenates exhibit precipitation with cell wall extract preparations. A single line of precipitation was observed in agar gel diffusion tests. Precipitating activity of goat antiheart sera was related to the γ-globulin fraction in zone electrophoresis. The cell wall antigen was demonstrated in cell wall extracts of a Type 5 and Type 19 but not of a Type 12 strain. Antigenic activity was concentrated in the same neutral salt and chromatographic fractions of acid extracts of cell wall previously reported to exhibit this activity by immunofluorescent inhibition of the cross-reaction of antistreptococcal serum with heart tissue.
THE ROLE OF TEMPERATE BACTERIOPHAGE IN THE PRODUCTION OF ERYTHROGENIC TOXIN BY GROUP A STREPTOCOCCI
Authors: Zabriskie John B.
Published: June 2004

Non-lysogenic, non-toxinogenic Group A streptococci when infected by temperate bacteriophages isolated from known scarlatinal toxin-producing strains acquire the capacity to form erythrogenic toxin. This toxin causes a characteristic erythematous reaction in the skin of rabbits and is readily neutralizable by standard scarlatinal antitoxins.

The production of toxin appears to be related to the synthesis of mature phage particles since ultraviolet enhancement of phage production results in a concomitant increase in toxin titer. In contrast, there is no increase in the production of another extracellular product, deoxyribonuclease, by these lysogenized streptococci. Furthermore, cellular disruption studies indicate that the toxin probably does not exist in a preformed state within the cell.

Double diffusion reactions in agar indicate that a newly formed protein appears in the lysogenic culture filtrate and is absent in the non-lysogenic filtrates.
RECONSTITUTION OF 7S MOLECULES FROM L AND H POLYPEPTIDE CHAINS OF ANTIBODIES AND γ-GLOBULINS
Authors: Olins D. E. , Edelman G. M.
Published: June 2004

Admixture of separated L and H polypeptide chains of 7S γ-globulins under appropriate conditions has been found to result in the reconstitution of 7S molecules. The chains were mixed in 0.5 N propionic acid and when dialyzed into neutral aqueous buffers interacted to form reconstituted material in greater than 30 per cent yield. This material had sedimentation coefficients of 6S to 7S, a weight average molecular weight of 160,000, and its antigenic structure and electrophoretic properties were the same as those of 7S γ-globulin.

By the use of I131 and I125 labels on the different types of chains, combined with ultracentrifugation of chain mixtures in sucrose density gradients, the 7S product was found to contain both isotopes in ratios consistent with the presence of two L and two H chains. After hydrolysis with papain, the reconstituted material yielded products resembling S and F fragments. All of the isotope corresponding to L chains was found in the counterpart of the S fragment; the isotope corresponding to the H chain fraction was present in both fragments. The activity reconstituted from chains of a purified guinea pig antibody to f1 phage was found to be associated mainly with the 7S material. Hybrid molecules containing rabbit L chains and human H chains and of human L chains and rabbit H chains were formed by the same techniques of reconstitution.

It was found that the interchain disulfide bonds of native 7S γ-globulins could be broken and reoxidized, as could those of reconstituted 7S material. Reduced L and H chains mixed in propionic acid, dialyzed against neutral buffers containing mercaptan, then against neutral buffers in the absence of mercaptan, formed stable 7S molecules of molecular weight 160,000, which were dissociable only after reduction.
STUDIES ON THE RECOVERY OF THE IMMUNE RESPONSE IN IRRADIATED MICE THYMECTOMIZED IN ADULT LIFE
Authors: Cross A. Marjorie , Leuchars Elizabeth , Miller J. F. A. P.
Published: June 2004

Experiments performed on CBA mice thymectomized in adult life, exposed to lethal doses of irradiation and given tissue therapy are described. Marrow, foetal liver, or spleen cells from syngeneic donors could protect the mice against the lethal effects of irradiation. Between 30 and 70 days' postirradiation, however, marrow-treated, thymectomized irradiated mice showed evidence of trophic disturbances, such as failure to gain weight, in contrast to sham-operated, irradiated, marrow-treated controls. The immune responses of experimental and control mice were tested up to 150 days' postirradiation by challenging with sheep erythrocytes and allogeneic skin grafts. Sham-operated irradiated controls, whether protected with marrow, foetal liver, or spleen cells, produced normal immune responses when challenged at 28, 60, or 150 days after irradiation. Neither foetal liver cells nor marrow cells, in doses of up to 40 million cells per mouse, enabled thymectomized irradiated mice to recover normal immune functions. Spleen cells, from normal donors but not from neonatally thymectomized donors, restored immunological capacity in such mice. It is concluded that immunologically competent cells are present in the spleen of normal adult donors and can function in the absence of the thymus. Bone marrow, on the other hand, does not contain an adequate population of such cells but has lymphoid precursor cells, the descendants of which can become immunologically competent only in the presence of a functioning thymus mechanism.
A SYNTHETIC ACYL POLYSACCHARIDE AND THE HEMAGGLUTINATION ACTIVITY
Authors: Tsumita Toru , Ohashi Masako
Published: June 2004

From Mycobacterium tuberculosis, a serologically specific polysaccharide was purified. It contained mannose, arabinose, and a trace of glucose. It was not active in hemagglutination (HA) reaction.

Partial acylation of the polysaccharide was carried out with palmitoylchloride, and the synthetic lipopolysaccharide contained 15.1 per cent of esterified palmitic acid.

The synthetic lipopolysaccharide had hemagglutination activity and 0.5 µg was able to sensitize 1 ml of 2 per cent erythrocyte suspension; it had the same activity as the natural antigenic lipopolysaccharide.

The same antibody in the antiserum was involved in the hemagglutination reaction with both the synthetic and natural lipopolysaccharides.

The sensitizing activity of the synthetic lipopolysaccharide was completely neutralized by cholesterol.

Model experiments showed that the lipid moiety of hemagglutination antigen was essential for the sensitization of erythrocytes. The mechanism of the hemagglutination reaction is discussed.
FETAL RESPONSE TO ANTIGENIC STIMULUS
Authors: Silverstein Arthur M. , Prendergast Robert A. , Kraner Keith L.
Published: June 2004

The fetal lamb was found to reject orthotopic skin homografts applied at any time after the 77th day of gestation. Prior to this, grafts remained in place without stimulating any detectable immunologic response. Once the fetus achieves the ability to reject the graft, the process occurs with the same competence and rapidity as in the adult. Graft rejection in the fetal lamb is unaccompanied by formation of plasma cells or by the production of typical immunoglobulins, thus supporting the suggestion that circulating antibody does not play an obligatory role in the process.
IMMUNOCHEMICAL STUDIES ON THE SPECIFIC CARBOHYDRATE OF GROUP G STREPTOCOCCI
Authors: Curtis Stephen N. , Krause Richard M.
Published: June 2004

Group G hemolytic streptococcal cell walls which have been treated with trypsin are composed of a group-specific polysaccharide moiety and a mucopeptide matrix. The mucopeptide contains N-acetylglucosamine, N-acetylmuramic acid, alanine, glutamic acid, lysine, and glycine, a composition similar to that of other groups of streptococci. The Group G carbohydrate is composed of rhamnose, N-acetylgalactosamine, and galactose. Serological studies suggest that the monosaccharide of L-rhamnose is a major component of the determinant of antigenic specificity.
PORCINE CONTAGIOUS PLEUROPNEUMONIA
Authors: White David C. , Leidy Grace , Jamieson James D. , Shope Richard E.
Published: June 2004

Hemophilus pleuropneumoniae, the causative agent of porcine contagious pleuropneumonia (PCP) is an encapsulated organism that has the metabolic features of the parainfluenza group of Hemophilus in that it requires DPN but not hemin for growth. Its formation of nitrate reductase cytochrome a1 and non-physiologically reducible cytochrome c1 in the stationary phase, together with its requirement of electron transport through oxidases for growth are typical of non-hemin-requiring Hemophilus species. It has the closest genetic homology, judged from the capacity of its DNA to induce transformation to streptomycin resistance, with H. parasuis but can be differentiated from this organism on the basis of its growth in defined medium and its marked and characteristic pathogenicity for swine.
THE SEDIMENTATION PROPERTIES OF THE SKIN-SENSITIZING ANTIBODIES OF RAGWEED-SENSITIVE PATIENTS
Authors: Andersen Burton R. , Vannier Wilton E.
Published: June 2004

The sedimentation coefficients of the skin-sensitizing antibodies to ragweed were evaluated by the moving partition cell method and the sucrose density gradient method. The most reliable results were obtained by sucrose density gradient ultracentrifugation which showed that the major portion of skin-sensitizing antibodies to ragweed sediment with an average value of 7.7S (7.4 to 7.9S). This is about one S unit faster than γ-globulins (6.8S). The data from the moving partition cell method are in agreement with these results. Our studies failed to demonstrate heterogeneity of the skin-sensitizing antibodies with regard to sedimentation rate.
INHIBITION OF PROTEIN SYNTHESIS IN MAMMALIAN CELL-FREE SYSTEMS BY CHLORAMPHENICOL
Authors: Weisberger Austin S. , Wolfe Sidney , Armentrout Steven
Published: June 2004

Chloramphenicol can inhibit protein synthesis in mammalian cell-free systems as effectively as it inhibits protein synthesis in analogous microbial systems. Significant inhibition in mammalian systems was obtained only when protein synthesis was stimulated by the addition of template RNA to the system, there being comparatively little inhibition of protein synthesis by ribosomes in the absence of stimulatory RNA. It is postulated that chloramphenicol may inhibit the function of messenger or template RNA by successfully competing for ribosomal binding sites, thereby preventing the attachment of RNA to ribosomes.

The apparent discrepancy in the sensitivity of mammalian and microbial cells to chloramphenicol may be related to differences in turnover or stability of ribosomal template RNA rather than to intrinsic differences in mechanism of protein synthesis.

These observations are in accord with the suggestion that protein synthesis in intact mammalian cells may be susceptible to chloramphenicol inhibition only at the time that new messenger or template RNA is being deposited on ribosomes and that more mature cells may be resistant because informative RNA already deposited on ribosomes is not accessible to chloramphenicol inhibition. The inhibitory effect of chloramphenicol on protein synthesis in proliferating cells may be an important factor in hematologic toxicity attributable to chloramphenicol.
SUPPRESSION OF ANTIBODY SYNTHESIS AND PROLONGATION OF HOMOGRAFT SURVIVAL BY CHLORAMPHENICOL
Authors: Weisberger Austin S. , Daniel Thomas M. , Hoffman Allan
Published: June 2004

Chloramphenicol suppresses primary antibody synthesis in vivo without affecting the ability to develop a normal anamnestic response. Chloramphenicol also prolongs homograft survival in rabbits. The survival of homografts is related to the duration as well as to the amount of chloramphenicol administered. The mechanism of action of chloramphenicol in suppressing immune responses is correlated with its ability to inhibit protein synthesis in proliferating mammalian cells. These observations suggest that the inhibitory effect of chloramphenicol on protein synthesis may be applicable to mammalian cells in vivo as well as to cell-free systems and to intact mammalian cells in vivo.
FURTHER EXPERIMENTS ON THE CAUSE OF SEQUENTIAL NEOPLASTIC CHANGES
Authors: Henderson James S. , Rous Peyton
Published: June 2004

When crystalline 20-methylcholanthrene (MC) and the cells of tar-induced mouse papillomas (paps.) are injected together into the thigh muscles of mice the carcinogen exerts a marked promoting and chemotactic influence upon the cells while it is dissolving in the tissue fluid. Under such circumstances it strongly stimulates and attracts them, with result they surround and include the scattered crystals in small cysts that later coalesce to form a larger one from which the MC only very gradually escapes.

Because of these findings intramuscular tests were made to learn whether MC would hasten the occurrence or increase the number of cancers that now and again derive from paps.; but the tests were repeatedly marred by the extraordinary behavior of such cancerous cells as happened to be already present in the implanted material. They responded far more actively to MC than did the pap. cells and soon took over the growths. Some carcinomas which failed to grow when transplanted alone, or only gradually formed small, regressing nodules, gave rise rapidly to huge growths of similar sort when exposed to MC.

To exclude cancerous cells so far as possible from the later tests small grafts of pap. tissue with MC crystals adhering to them were implanted subcutaneously. The pap. cells promptly lined the graft pockets, encysting the crystals incidentally, and formed tumors that enlarged progressively by keratinizing inwards. While they did this their living layer of pap. tissue was continually bathed in dissolved MC throughout many weeks. Despite these apparently favorable conditions the carcinogen neither hastened the occurrence nor increased the number of visible epidermal cancers deriving from the paps. It also failed to bring about sequential malignant changes in the carcinomas.

These negative results accord with those already obtained through long exposure of the benign pulmonary adenomas of mice to urethane or methylcholanthrene, agents which rapidly induce these benign tumors yet which were found to be incapable of furthering the cancerous changes to which such growths are prone. They accord also with another previous finding, namely that MC fails to bring on the malignant changes of discontinuous, sequential sort that mammary mouse carcinomas often undergo "spontaneously."

Taken together these facts indicate that the change or changes whereby normal cells are converted into benign tumor cells differ in nature from those taking place when they become cancer cells, as also from those occurring when cancer cells undergo further, step-like, malignant changes.

A study has been begun to learn whether the widely various carcinomas deriving from benign papillomas differ from these latter and from one and other in their chromosomal content.
CORYNEBACTERIAL PSEUDOTUBERCULOSIS IN MICE
Authors: Pierce-Chase Cynthia H. , Fauve Robert M. , Dubos Rene
Published: June 2004

The susceptibility of mice to experimental infection with Corynebacterium kutscheri was studied by comparing the host response to this organism of mice obtained from 31 different colonies, representing 15 different genetic types.

A standardized infective dose, administered intravenously, made it possible to separate the animals into two sharply differentiated groups. All the animals of the following colonies died: Swiss Lynch, Swiss R/J, A/Jax, Princeton, RFVL, and CF1 (SPF). All the animals of the following colonies survived: CFW, ICR, Balb/C, BSVS, BRVR, RIII, YBR/He, DBA/2 (from 3 different colonies), and C57B1/6 (from 12 different colonies).

The two highly inbred strains, Swiss Lynch and C57Bl/6, were selected as prototypes of susceptible and resistant animals respectively, for more detailed studies.

Following injection of an infective dose of 0.2 x 10–4 ml of culture of C. kutscheri, all Swiss Lynch animals died within 3 to 11 days (the majority within 4 to 7 days); whereas all C57Bl/6 animals survived. The outcome of the infection in each strain was independent of age and sex of the animals.

In Swiss Lynch animals, the corynebacteria multiplied rapidly in lungs, liver, kidneys, and to some extent in the spleen. In C57Bl/6 mice, there was no increase of the corynebacterial population in the lungs, liver, or spleen, but multiplication occurred in the kidneys during the early phase of the infectious process with resultant abscess formation. However, the renal infection soon subsided leaving no residual pathology. C. kutscheri could not be recovered from any organs of C57Bl/6 mice sacrificed 16 days after infection.

Homogenates of organs from Swiss Lynch mice obtained while the infection was progressing contained only typical C. kutscheri. In contrast, the lungs and livers of similarly infected C57Bl/6 animals occasionally yielded large numbers of small translucent colonies distinctly different from those of typical corynebacteria.

The use of mouse strains differing markedly in response to experimental infection with C. kutscheri is presented as a biologic model lending itself to further studies concerning factors which condition resistance to corynebacterial pseudotuberculosis, a disease of practical importance for investigators conducting experiments with murine species.
INVASION AND DESTRUCTION OF HOMOLOGOUS KIDNEY BY LOCALLY INOCULATED LYMPHOID CELLS
Authors: Elkins William L.
Published: June 2004

When lymphoid cell suspensions from the spleen, lymph nodes, blood, and thoracic duct of parental strain adult rats were injected beneath the renal capsule of F1 hybrid hosts, the transferred cells and/or their progeny invaded the underlying renal cortex and destroyed most of the tubules which they surrounded. The immunogenetic conditions under which this reaction was observed defined it as a graft vs. host reaction (GVHR). On the 7th day the GVHRs were histologically similar to primary renal homografts undergoing rejection. Lymphoid cells from donors tolerant to the other parental strain were inactive after transfer to the hybrid, whereas cells from either normal or sensitized donors consistently produced reactions of about equal severity. Lewis lymphoma cells displayed malignant, invasive activity but did not destroy either isologous or homologous tissue, showing that the presence of an infiltrate was not per se sufficient to damage the parenchyma. These observations indicate that the GVHRs were manifestations of the ability of the transferred lymphocytes to enter into a homograft reaction with consequent destruction of renal parenchyma, and support the hypothesis that at least some of the lymphocytes which are seen infiltrating primary homografts are the agents which effect their destruction.
EXPERIMENTAL RUNT DISEASE IN MICE CAUSED BY SALMONELLA TYPHIMURIUM, VAR. COPENHAGEN
Authors: Brooke Marcus S.
Published: June 2004

The strain of Salmonella typhimurium isolated from the subcutaneous abscess of a runted mouse and used in this study was somewhat unusual, but not unique, in that it had a high virulence for young mice, yet low infectivity. This strain could mimic many of the features, signs, and symptoms of immunological runting when injected into neonates, either in pure culture, or when mixed with spleen cells, or when present in infected isologous or F1 hybrid spleen cells. Thus, the incidence of Salmonella runting was dose-dependent and related to the age of the neonate. Runts failed to gain weight, were sickly, and usually died within 30 days. They had a marked splenomegaly and hepatomegaly associated with areas of necrosis. However, in marked contrast to immunological runts they did not have lymphoid atrophy.

The incidence of runting was diminished when frozen-thawed spleen cell suspensions were used, but not with sonicated or heated suspensions or spleen cells from lethally irradiated mice. Runting could be prevented by immunizing breeders with S. typhimurium, and serum from mice immunized against S. typhimurium protected neonates injected with this organism. Isologous adult spleen cells did not protect against Salmonella runting.

It is suggested that in studies on runting only the intravenous route be used and that heated cells serve as a control. More rigid criteria should be applied to runting than those frequently accepted and mice should be autopsied whenever possible.
THE ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES OF ARSENIC AZOPROTEINS
Authors: Broome J. D. , Kidd John G.
Published: June 2004

Experiments here given show that 4-arsonophenylazoproteins form complexes with fibrinogen which are resistant to the enzymic action of thrombin, coagulation being thus inhibited; also that arsenic azoproteins combine strongly with polymerizing fibrin, the reaction leading uniquely to acceleration of the process. Ordinary arsenicals have little or no effect on the proliferation of Lymphoma 6C3HED cells in vivo. 4-Arsonophenylazoproteins, by contrast, are strongly inhibitory, and they arrest the process of mitosis in metaphase, as does colchicine.

Considered together with the observations of the preceding paper, the findings suggest that 4-arsonophenylazoproteins may exert their anticoagulant and antilymphoma effects by similar or related means: in the former instance, by combining in vitro with fibrinogen and polymerizing fibrin, thus altering the clotting process as mentioned above; and in the latter instance by combining, perhaps in a similar way, with polymerizing proteins in the mitotic spindle of proliferating Lymphoma 6C3HED cells, thus arresting mitosis.

Further implications of the findings are discussed.
ACUTE AND CHRONIC ENTEROTOXIN ENTERITIS
Authors: Warren Sherwyn E. , Jacobson Myron , Mirany Jafar , Van Prohaska John
Published: June 2004

1. Dogs develop severe gastrointestinal symptoms in response to intraintestinal administration of staphylococcal enterotoxin. These symptoms are salivation, vomiting, and diarrhea.

2. Staphylococcal enterotoxin induces acute enteritis marked by edema, hyperemia, round cell infiltration, mucosal exudation, and destruction of intestinal villi.

3. Prolonged administration of enterotoxin into the lumen of the intestine produced thickening of the entire bowel wall, edema, dilatation of the lymphatics, and exaggeration of submucous lymphoid nodules. The hypertrophy of the lymphoid nodules is visible, in the gross, as enlarged longitudinal mucosal ridges. This abnormality is arranged in skip areas, not dissimilar to those observed in human regional enteritis.

4. Chronic enterotoxin enteritis is associated with mesenteric lymph node hypertrophy.

5. The intestinal mucosa shows minute ulcerations, loss of villi, submucous fibrosis, and evidence of chronic inflammation.
ANTIGENIC RELATIONSHIPS BETWEEN GROUPS B AND G STREPTOCOCCI
Authors: Curtis Stephen N. , Krause Richard M.
Published: June 2004

Trypsinized cell walls of Group B hemolytic streptococci are composed of a group-specific carbohydrate and mucopeptide. The carbohydrate extracted with hot formamide is composed of rhamnose, N-acetylglucosamine, and galactose. Quantitative precipitin inhibition studies have shown that L rhamose is the significant component of the antigenic determinant. The cross-reactivity between B and G carbohydrates is dependent upon the fact that Lrhamose is a determinant sugar in both antigens.
STRUCTURAL STUDIES OF HUMAN 7S γ-GLOBULIN (G IMMUNOGLOBULIN)
Authors: Franklin E. C.
Published: June 2004

1. Detailed physical, chemical, and immunologic studies of a protein closely related to the Fc fragment and heavy chain of G immunoglobulin (IgG), and elaborated by a subject with a lymphoproliferative disorder are presented.

2. The protein, which has a molecular weight of 51,000, was cleaved into two half molecules by reduction and alkylation.

3. The protein has few if any of the antigenic determinants of the antigen-binding (Fab) papain fragment of IgG, and has a striking similarity in its antigenic properties to the Fc fragment.

4. Fingerprint patterns resemble those of the crystallizable (Fc) fragment, and lack several peptides found in the heavy chain.

5. These findings suggest that the Fc fragment may be a real structural unit of IgG, and raise the possibility of the existence of three different types of polypeptide chains in G immunoglobulin.
EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM
Authors: Berry L. Joe , Smythe Dorothy S.
Published: June 2004

Cortisone acetate administered to mice at the same time as either the LD50 or 2 x LD50 of endotoxin significantly protected against lethality. Delaying the injection of cortisone to 1, 2, or 4 hours after that of endotoxin resulted in loss of protection with the possible exception of a 1 hour delay with the LD50 of endotoxin. Associated with this loss of protection was the failure of the hormone to induce liver tryptophan pyrrolase. Normal mice given only cortisone showed an increase in enzyme activity nearly three times that of control values when assays were carried out either 4 or 17 hours after the hormone was given. Endotoxin-poisoned mice showed normal levels of enzyme activity with concurrent injection of cortisone but depressed levels of enzyme when the cortisone injection was delayed for only 1 hour or more. Apparently, therefore, enzyme induction (or maintenance) is related to survival in endotoxin poisoning.

In line with this hypothesis was the observation that inhibitors of enzyme (protein) synthesis were found to potentiate the lethal action of endotoxin and to prevent the protective effect of cortisone. The inhibitors employed were actinomycin D, ethionine, 2-thiouracil, and 8-azaguanine. Activity of liver tryptophan pyrrolase was lowered by endotoxin and elevated by cortisone. When the two were given concurrently, normal enzyme activity was maintained. Chloramphenicol, an active inhibitor of protein synthesis in microorganisms but with limited effect in mammals, was without observable influence in these respects.

Mice 18 hours postinfection with Salmonella typhimurium, strain SR-11, given at a level that caused first deaths on the 3rd day, had a lower than normal activity of liver tryptophan pyrrolase and responded to cortisone induction with a smaller increase in enzyme level than that found in control mice. Each is characteristic of endotoxin poisoning. Animals 42 hours postinfection were free of these signs of endointoxication, an observation in agreement with earlier experiments where other measures of endotoxin were employed.
PRODUCTION OF INFLAMMATORY CHANGES IN THE MICROCIRCULATION BY CATIONIC PROTEINS EXTRACTED FROM LYSOSOMES
Authors: Janoff Aaron , Zweifach Benjamin W.
Published: June 2004

Lysosomal granules of rabbit exudate polymorphonuclear (PMN) leucocytes were isolated and then lysed by freezing-thawing. Topical application of this material to rat and rabbit mesentery produced sticking and emigration of leucocytes, stasis of blood flow, and petechial hemorrhage. The granule-free, supernatant fraction of the homogenized leucocytes failed to produce any of these reactions.

Cationic proteins extracted from these granules by weak acid and precipitated by ethanol at concentrations of 20 and 45 per cent, were also tested on heterologous, homologous, and autologous mesenteric vessels. The 20 per cent ethanol-precipitated fraction produced all of the aforementioned injury reactions, whereas the 45 per cent fraction was inactive. The intensity of inflammatory changes produced by the active cationic protein fraction was greater than that produced by lysed whole granules.

Both the 20 per cent and 45 per cent ethanol fractions of cationic protein induced clumping of rabbit platelets, in vitro.

The 20 per cent ethanol fraction also caused a slight acceleration in rate of swelling of isolated rabbit liver mitochondria.

The active material proved to be non-pyrogenic in rabbits.

This material exhibited no kinin-like effects when tested on isolated smooth muscle preparations (rabbit aorta and guinea pig ileum). In the rat, the protein produced a transient vasodepression which was inhibited by pretreatment of the animal with an antihistamine.

Ultraviolet absorption data and ribose assays showed that the 20 per cent ethanol fraction contained only 4 per cent or less of ribonucleic acid. Upon electrophoresis in starch gel, using acid buffer, this fraction separated into at least three major components which migrated towards the cathode.

Precipitation of one of the slowly migrating components by titration of the fraction to pH 10.5 greatly increased the inflammatory activity of the material.

The inflammatory basic protein fraction was essentially devoid of acid phosphatase, beta glucuronidase, acid ribonuclease, lysozyme, and catalase activity. The non-inflammatory basic protein fraction contained appreciable quantities of acid ribonuclease and lysozyme.

The foregoing data demonstrate that certain of the cationic proteins present in lysosomes of rabbit exudate PMN leucocytes can reproduce one of the cardinal features of the inflammatory response; namely, adhesion and emigration of leucocytes in the microcirculation. These findings offer fresh support for the role of lysosomes in the pathogenesis of tissue injury, and may help to account for the propagation of leucocyte emigration to peak numbers during inflammatory reactions.
STUDIES ON ANTIGENICITY
Authors: Levine Bernard B. , Benacerraf Baruj
Published: June 2004

The enzymatic degradation of fluorescein conjugates of poly-L-lysine, poly-D-lysine, and exhaustively succinylated poly-L-lysine by aqueous extracts of spleens from "responder" (guinea pigs which can develop immune responses to hapten-poly-L-lysine conjugates) and "non-responder" guinea pigs was investigated.

The in vivo degradation of H3-tagged dinitrophenyl conjugates of these synthetic polyamino acids was also studied by measuring urinary excretion of radioactive low molecular weight degradation products of these conjugates after their intraperitoneal injection.

It was found that both responder and non-responder guinea pigs can degrade succinylated and unsuccinylated poly-L-lysine conjugates into small molecular fragments, but they cannot degrade hapten-poly-D-lysine conjugates.

These studies demonstrate that in addition to the known requirements for antigenicity of macromolecules, i.e. the presence of antigenic determinants, and their capacity to be degraded by immunological tissues, the resulting degradation products must undergo certain additional, as yet unidentified, specific metabolic steps in order to induce an immune response.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Collier R. J. , Pappenheimer A. M.
Published: June 2004

Intracellular levels of ATP, GTP, and hexose phosphates have been determined in HeLa cells at intervals after exposure to saturating doses of diphtheria toxin. Toxin causes no significant change in the level of any of these phosphorylated intermediates either in the presence or absence of glucose over a period of at least 5 to 6 hours. It is concluded that the inhibition of protein synthesis which occurs in HeLa cells at about 2 hours after the addition of saturating doses of toxin, does not result from an effect of toxin on energy metabolism.
STUDIES ON ANTIBODY PRODUCTION
Authors: Butler William T. , Coons Albert H.
Published: June 2004

The effect of drugs upon the primary and the secondary antibody response to diphtheria toxoid in mice was studied using an experimental system previously described.

Triethylenethiophosphoramide (thio-TEPA), chloramphenicol, 6-mercaptopurine, 8-azaguanine, and versenate were found to inhibit, partially or completely,"priming" for the secondary response.

Thio-TEPA, chloramphenicol, and 6-mercaptopurine, in doses exceeding those effective in inhibiting priming, did not cause alteration of the secondary response when given only during the secondary response. However, when chloramphenicol and amethopterin were given for 5 days prior to and at least 5 days after the second antigen injection, slight suppression of peak secondary titers occurred.

Therefore, drug dosages effective in suppressing priming had less effect on the secondary response. It thus appears that there is a real difference between "priming" and the induction of antibody synthesis.
STUDIES ON ANTIBODY PRODUCTION
Authors: Cruchaud Andre , Coons Albert H.
Published: June 2004

Young adult mice were primed with 20 Lf (56 µg) of diphtheria toxoid and given a second injection of the same size 40 days later. This procedure produces a reproducible secondary response which can be used as a standard. Chloramphenicol in maximum dosage prevents the unknown process by which the animal is primed for the second response. To be fully inhibitory, the drug must be given from the hour of the first antigen injection in maximum dosage for 2 weeks. A delay of 48 hours in starting the drug allows completion of the priming process, and shorter delays produce partial inhibition. Hence the initiation of priming is a rapid process sensitive to chloramphenicol. Subsequent changes in the cell population necessary for the full development of priming are not sensitive to chloramphenicol.

The secondary antibody response is not inhibited in mice by chloramphenicol at the doses employed.
ANTIGENS IN IMMUNITY
Authors: Miller J. J. , Nossal G. J. V.
Published: June 2004

The localization of antigen in primary follicles and germinal centers of rat popliteal lymph nodes described previously using I125- and I125-labeled antigen has been confirmed by direct staining with fluorescent antibodies. A fine web of phagocytic reticulum in primary follicles was found to be responsible for antigen localization in this area. The nature of this web was confirmed by studies of the localization of colloidal carbon. This unique feature of primary follicles is discussed in relation to its importance in the induction of immune responses, our belief being that the great surface area of antigen retaining cytoplasm in primary follicles is responsible for the appearance of germinal centers in these particular parts of the node.
THE INHERITANCE OF THE PROTEIN AND NUCLEIC ACID CHARACTERISTICS OF T2 AND T6 BACTERIOPHAGE
Authors: Jesaitis Margeris A.
Published: June 2004

A study of the immunological properties of phage strains derived from T2 x T6 crosses revealed that the majority of the progeny differ serologically from the parental viruses. Some hybrids were found to contain head membranes having the serological specificity of both T2 and T6 phages, while others contained tail sheaths of the former and the tail fibers of the latter. Since the immunological properties of all hybrids were heritable, it has been concluded that the serological specificity of the head proteins of T2 and T6 is controlled by at least two genetic determinants, and that the specificities of the fiber and sheath proteins may be governed by single genes.

Furthermore it was found that nucleic acids of hybrids had similar proportions of unsubstituted, mono- and diglucosylated hydroxymethylcytosine nucleotides to the nucleic acid of either T2 or T6 phage. Since the parental and hybrid viruses having chemically similar nucleic acids contained in some instances serologically different proteins, it has also been concluded that the extent of glucosylation of the hydroxymethylcytosine component of viral nucleic acids and the immunological properties of viral proteins are independently heritable traits of T2 and T6 bacteriophages.
A STUDY OF THE CROSS-REACTIVITY OF ANTIPURIN-6-OYL SERUM WITH DEOXYRIBONUCLEIC ACID (DNA)
Authors: Butler Vincent P. , Tanenbaum Stuart W. , Beiser Sam M.
Published: June 2004

The specificity of the reaction of antipurin-6-oyl sera with thermally denatured DNA has been studied by means of hapten inhibition techniques. The relative order of effectiveness of various haptens as inhibitors of the complement fixation reaction between DNA and antipurin-6-oyl serum was found to be comparable to their relative order of effectiveness as inhibitors of the precipitin reaction between purin-6-oyl-protein conjugates and antipurin-6-oyl serum. Antipurin-6-oyl antibody has been purified and has been shown to be capable of reacting with thermally denatured DNA. It is concluded that the reactivity of these purine-specific antisera with DNA is a property of antibody with specificity for the purin-6-oyl moiety.

In addition, the reaction between antipurinoyl sera and DNA has been demonstrated by the techniques of radioimmunoelectrophoresis and passive cutaneous anaphylaxis.
THE STIMULATION OF DNA SYNTHESIS IN CULTURES OF RABBIT LYMPH NODE AND SPLEEN CELL SUSPENSIONS BY HOMOLOGOUS CELLS
Authors: Chapman Niles D. , Dutton Richard W.
Published: June 2004

An early proliferative response follows the mixing of homologous spleen or lymph node suspensions obtained from two unrelated rabbits. The rate of incorporation of radioactive thymidine has been used as a quantitative measure of this response. Thymus cells do not respond to homologous cell suspensions but may on occasion serve to stimulate the response in homologous spleen or lymph node cells. Homologous erythrocytes or autologous tissues do not stimulate a response.

No response occurs if the two cell populations are separated by a Millipore membrane.

Autoradiographic studies have established that 1 to 2 per cent of the intial cell population is involved in the response and they are large undifferentiated cells by the time they can first be identified as responders. There was no morphological evidence of any cellular interaction and the viability of mixed suspensions was not measurably different from that observed in separate suspension.

Simultaneous additive responses could be obtained to homologous cells and to antigen when cell suspensions from immunized rabbits were used. The interaction of the cell populations from the two rabbits did not appear to suppress the response of each to antigen.

The speed and magnitude of the response were in everyway comparable with the secondary response of cell suspensions from immunized rabbits exposed to the immunizing antigen. No evidence was obtained of any enhancement of the response to homologous cells by prior immunization with homologous tissues, but the possibility that it had occurred was not rigidly excluded.
MUCUS IN INTESTINAL CONTENTS OF GERMFREE RATS
Authors: Lindstedt Göran , Lindstedt Sven , Gustafsson Bengt E.
Published: June 2004

The fecal excretion of total nitrogen and of total hexosamines has been determined in germfree and conventional rats. Germfree rats excreted more hexosamines than the conventional rats, while no difference in the nitrogen excretion was found. Infection of the germfree rats with a normal flora resulted in a temporarily increased excretion of hexosamines and nitrogen over a period of 2 to 3 days after which they reached the level of the conventional animals.

The contents of the germfree cecum contained 65 to 137 mg of hexosamines and 57 to 127 mg of nitrogen as compared to 1.2 to 5.3 and 7.4 to 23 mg in conventional animals. The high figures for hexosamines were due to an increase in the total amount of contents in the cecum and to a fivefold increase in the concentration of hexosamine-containing material.

Studies on the distribution of hexosamine-containing cecal contents between sediment and supernatant after centrifugation at 20,000 g for 2 hours demonstrated that 5 to 10 per cent of the hexosamines occurred in the sediment in the germfree rats, while 75 to 85 per cent was found in this fraction in the conventional rats. The soluble part of the cecal contents in germfree as well as in the conventional rats contained 70 per cent of hexosamines in molecules with a molecular weight above approximatively 100,000 as found by gel filtration experiments on sephadex gels.

The higher weight of the germfree cecal wall was reflected in a high total amount of nitrogen and hexosamines.

Isolated strains of bacteria capable of reducing the cecal size in vivo did not show any capacity to degrade the mucus in vitro in a test system, where a full intestinal flora was highly active.
THE INDUCTION OF AUTOIMMUNITY IN RABBITS FOLLOWING INJECTION OF HETEROLOGOUS OR ALTERED HOMOLOGOUS THYROGLOBULIN
Authors: Weigle William O.
Published: June 2004

Experimental autoimmunity was produced in rabbits following injection of altered homologous thyroglobulin. The thyroglobulin was altered by coupling to chemically defined haptens and by heating. With some preparations antibody to native thyroglobulin as well as thyroid lesions were produced. Injections of thyroglobulin coupled to the diazonium derivatives of arsanilic acid and sulfanilic acid were effective when given in either soluble form or incorporated into incomplete Freund's adjuvant) while injections of the same preparations precipitated by alum had relatively little effect on production of antibody or induction of lesions. The injection of native thyroglobulin in soluble form, incorporated into incomplete adjuvant or precipitated by alum usually resulted in production of little or no antibody and only rarely in the formation of lesions. The injection of a heterologous thyroglobulin into rabbits resulted in the production of antibody reacting with both the heterologous and rabbit thyroglobulin, but no thyroid lesions were observed.
CORROBORATION OF RECENT MODELS OF THE γG IMMUNOGLOBULIN MOLECULE
Authors: Fougereau M. , Edelman G. M.
Published: June 2004

The relationships between the polypeptide chains of γG immunoglobulin and fragments of the molecule produced by papain and pepsin have been investigated. Specific procedures were employed including peptide mapping of tryptic hydrolysates and analysis of molecules reconstituted from chains labeled with different iodine isotopes. By these means, the Fab fragment was shown unequivocally to consist of the light chain and a portion of the heavy chain, the Fd fragment. The Fc fragment was found to be comprised of the residual portions of the heavy chain. These findings support the gross arrangement of chains embodied in recent models of the γG immunoglobulin molecule.

The present studies have also provided additional information on the susceptibility of γG immunoglobulin to proteolytic cleavage. It was found that the portion of heavy chains corresponding to the Fd fragment was extensively cleaved by papain.
THE EFFECT OF HYPERGLYCEMIA ON HYPOTHALAMIC GOLD UPTAKE AND HYPERPHAGIA IN GOLDTHIOGLUCOSE-TREATED MICE
Authors: Edelman P. Michael , Schwartz Irving L. , Cronkite Eugene P. , Brecher George , Livingston Linda
Published: June 2004

The accumulation of gold in the hypothalamus and the development of hyperphagia and obesity were studied in mice given a single intravenous injection of goldthioglucose at various levels of blood glucose concentration. It was found that the glucose concentration prevailing at the time of goldthioglucose injection was correlated directly with the level of free and bound goldthioglucose in the blood 3 minutes later, with the hypothalamic uptake of gold, with the extent of the hypothalamic lesion, and with the severity of the subsequent hyperphagia and obesity.

Hyperglycemia was associated with an increased gold deposition throughout the brain.

A gold content of 88 ± 12 µg/mg wet tissue in the hypothalamus of fasted animals was associated with clearcut lesions in all animals studied, whereas a similar gold content in the control brain lobes of hyperglycemic animals was not associated with lesions in any animal. This finding indicates that some regions in the brain (e.g. the ventral hypothalamus) are more susceptible than others to damage by goldthioglucose.