bluuebunny/crossref_metadata_2025 huggingface dataset:
AN ENZYME IN MAST CELLS WITH PROPERTIES LIKE CHYMOTRYPSIN
Authors: Benditt Earl P. , Arase Margaret
Published: June 2004

Mast cells contain an enzyme which hydrolyzes 3-chloroacetoxy-2-naphthoic acid anilide. By using highly purified mast cells isolated by differential centrifugation in high density sucrose solutions we have been able to study this enzymatic activity in more detail.

The enzyme has properties similar to those of chymotrypsin: Chymotrypsin will hydrolyze the histochemical substrate, and the chymotrypsin and mast cell activities with this substrate are similarly inhibited by diisopropylfluorophosphate. The mast cell enzyme is capable of hydrolyzing the N-acetyl esters of tryptophan, tyrosine, and phenylalanine, the relative rates of hydrolysis being similar to those seen with chymotrypsin. A characteristic trypsin substrate, p-toluenesulfonyl arginine methyl ester, is not acted upon by the mast cell enzyme or chymotrypsin. The pH activity curve of the new cell enzyme is similar to that of chymotrypsin as determined with N-acetyl-L-tryptophan ethyl ester as substrate.
STUDIES ON THE RUNTING SYNDROME IN NEWBORN MICE
Authors: Siskind Gregory W. , Thomas Lewis
Published: June 2004

Runting was produced by homologous spleen or lymph node cell suspensions, but not by isologous spleen or homologous liver or kidney cell suspensions.

The incidence of runting (a) varied with the particular strain combination employed, (b) increased with increased dose of foreign cells, and (c) decreased as the time interval between birth and inoculation with foreign cells was increased.

A focal, coagulative necrotic, liver lesion was described in runted mice.

It was found that viable cells were required to produce the runting syndrome. Frozen-thawed cells, homogenized cells, and the cell-free supernatant of ground spleen suspensions failed to produce runting.

Runted mice were found to have an anemia of variable degree, and white blood cell counts ranging from marked leukopenia to severe leucocytosis. Mice receiving isologous spleen or homologous liver or kidney showed normal red and white blood cell counts.

Isologous spleen cells, given to newborn mice within 30 minutes following injection of homologous spleen cells, conferred significant protection against the runting syndrome. Isologous spleen injected 1 day after the injection of homologous spleen failed to protect. Newborn mice which had received homologous spleen cells were protected from becoming runted by treatment with "anti-cell donor strain" serum. The offspring of mothers which had been immunized against the spleen cell donor's strain failed to become runted when treated with homologous spleen cells.

The data are regarded as compatible with the concept, presented by previous workers, that runting is the result of an immunological reaction of foreign cells against a tolerant host.
SIMULTANEOUS PRODUCTION OF TWO CAPSULAR POLYSACCHARIDES BY PNEUMOCOCCUS
Authors: Austrian Robert , Bernheimer Harriet P. , Smith Evelyn E. B. , Mills George T.
Published: June 2004

Study of the capsular genome of pneumococcus has shown that it controls a multiplicity of biochemical reactions essential to the synthesis of capsular polysaccharide.

Mutation affecting any one of several biochemical reactions concerned with capsular synthesis may result in loss of capsulation without alteration of other biochemical functions similarly concerned.

Mutations affecting the synthesis of uronic acids are an important cause of loss of capsulation and of virulence by strains of pneumococcus Type I and Type III.

The capsular genome appears to have a specific location in the total genome of the cell, this locus being occupied by the capsular genome of whatever capsular type is expressed by the cell.

Transformation of capsulated or of non-capsulated pneumococci to heterologous capsular type results probably from a genetic exchange followed by the development of a new biosynthetic pathway in the transformed cell. The new capsular genome is transferred to the transformed cell as a single particle of DNA.

Binary capsulation results from the simultaneous presence within the pneumococcal cell of two capsular genomes, one mutated, the other normal. Interaction between the biochemical pathways controlled by the two capsular genomes leads to augmentation of the phenotypic expression of the product controlled by one and to partial suppression of the product determined by the other.

Knowledge of the biochemical basis of binary capsulation can be used to indicate the presence of uronic acid in the capsular polysaccharide of a pneurnococcal type the composition of the capsule of which is unknown.
DIFFERENTIATION OF CLOSELY RELATED CELLS BY A VARIANT OF POLIOVIRUS, TYPE 2, MEF1 STRAIN
Authors: Murphy William H. , Armstrong Raymond
Published: June 2004

By application of a variant of poliovirus, Type 2, MEF1 strain, as a selective agent it was possible to distinguish among stable parent strains of epithelial cells and their clonal derivatives by their differential morphologic response to infection. The variant of poliovirus grew in a number of cell strains without induction of observable cytopathogenic changes. Other strains of cells reacted to viral infection by manifesting partial or complete degeneration. Parent HeLa cells and virus underwent simultaneous serial propagation in the absence of homotypic antiserum to virus. The stability of the virus-cell relationship was established by results from replicate experiments conducted over a period of years. Some cell strains of common origin maintained in different laboratories did not react similarly to the cytopathogenic effect of virus. Representative experiments revealed that the morphologic response of HeLa cells to MEF virus infection was not influenced by the presence or absence of pleuropneumonia-like organisms. The differential morphologic response of cells to infection was confirmed by efficiency-of-plating experiments which revealed differences in the capacity of MEF virus to form plaques in the test cell strains. Serial passages of MEF virus in cell strains demonstrated differences in their selection for cytopathogenic "mutants" of virus.
AUTOANTIBODIES IN HUMAN ULCERATIVE COLITIS
Authors: Broberger Ove , Perlmann Peter
Published: June 2004

Sera from 30 children, suffering from ulcerative colitis, were examined for the presence of antibodies capable of reacting with antigens of normal human tissue. It was possible to demonstrate that most of the sera contained a precipitating and hemagglutinating factor, reacting with a constituent of human colonic tissue. This constituent was obtained, within 1 hour after death, from colonic tissue of newborn babies who had died without feeding. It could also be prepared from fetal tissue. The antigen can be extracted with phenol-water at 65°C. and seems to be a polysaccharide. The precipitating factor in the sera of the patients behaves electrophoretically as a γ-globulin.

Phenol-water extracts from liver and from kidney also reacted positively with the sera from certain patients. There are indications which suggest that the antigen obtained from these tissues is identical with that from colon.

Sera from 38 healthy children did not give any reactions with the extracts used. In additional controls, the sera of 32 children with various diseases, all of suspected autoimmune origin, were also tested. A few of these reacted positively with the phenol-water extracts from the organs mentioned above. Most likely, the antigen reacting in these cases is different from that reacting with the antibodies in the sera from patients with ulcerative colitis.

The possible role of the antibodies in the pathogenesis of ulcerative colitis and the mechanism of their formation are discussed.
THE ANTICOMPLEMENTARY EFFECT OF KIDNEY TISSUE
Authors: Beeson Paul B. , Rowley D.
Published: June 2004

In studying the problem of the peculiar susceptibility of the kidney to coliform bacterial infection it was found that kidney tissue, unlike that of other organs, interferes with the ability of normal serum to destroy these organisms.

The effect was attributable to strong anticomplementary activity, 5 to 15 times greater than that of other organs. Inactivation of complement by kidney tissue was found to have characteristics of a chemical reaction, the active principle being heat-labile, non-dialysable, and difficult to separate from tissue particles. Attempts to purify it or to obtain it in a soluble form usually resulted in great loss in activity.

The component of complement affected was the fourth; i.e., that which is characterized by susceptibility to injury by ammonia. Similarities were found to exist between the conditions of ammonia formation and complement inactivation by kidney homogenates, the most notable being enhancement by phosphate and glutamine.

The possibility is suggested that these findings may help to explain the vulnerability of the kidney to certain infections, especially those due to bacteria which are destroyed by the combined action of complement and antibody.
ALTERATIONS IN STATE OF MOLECULAR AGGREGATION OF COLLAGEN INDUCED IN CHICK EMBRYOS BY ß-AMINOPROPIONITRILE (LATHYRUS FACTOR)
Authors: Levene Charles I. , Gross Jerome
Published: June 2004

The lathyrogenic agents, ß-aminopropionitrile and semicarbizide, when applied to the chorio-allantoic membrane of the chick embryo produced a dramatic increase in fragility of the embryo.

This alteration was not associated with a change in the concentration of collagen, except in aorta, but was accompanied by a sharp increase in the amount of collagen extractible in cold 1 M NaCl from skin, bone, and aorta.

Increase in fragility and extractible collagen began within 3 hours after introduction of the agent and rose steadily for at least 72 hours. Essentially no collagen could be extracted from tissues of normal chick embryos. Both fragility and amount of extractible collagen were dosage- and time-dependent.

It is concluded that the extractible collagen in lathyrism consists of a large proportion of dissolved fibers previously insoluble and formed prior to administration of the agent. The data also suggest that the "lathyritic" collagen in vivo is not in molecular dispersion but in an aggregate or fibrillar form. It is dispersed by cooling.

The extracted collagen could be reconstituted to typical striated fibrils in vitro and the molecule appeared to be normal in the gross, with regard to asymmetry ratio and intramolecular helical structure.

The evidence at hand suggests that at least one of the defects induced by lathyrogenic agents is an interference with the normal intermolecular cross-linking within the collagen fibril.
THE PRESENCE OF PLASMA INHIBITORS DURING THE CRISIS PHENOMENON IN EXPERIMENTAL RELAPSING FEVER (BORRELIA NOVYI)
Authors: Calabi Ornella
Published: June 2004

The intensity and duration of Borrelia novyi infection in rats depends upon the dose of spirochetes administered. The spirochetemia in response to an inoculum of 1 x 108 spirochetes/kg. characteristically reaches a peak of 4 to 5 million organisms per c.mm. of blood at about 72 hours. Resolution of the primary infection occurs within 48 hours after the peak counts have been observed, with crisis ending at 100 to 120 hours after inoculation.

Treatment of the acute infection, so standardized, by 10 ml./kg. of crisis plasma intraperitoneally delays the onset of the spirochetemia 76 to 140 hours, and reduces the maximal spirochetal count 10–3 to 10–6 that of the unmodified controls. This is evidence that inhibitor is present in the plasma at the time of crisis and plays a role in limiting the primary infection and subsequent relapses. The activity of crisis plasma is not destroyed by freezing, or after storage at 4°C. for 4 days. Fractions I + II + III and IV + V+ VI from crisis plasma, obtained by method 10 of Cohn et al., were also effective in suppressing the acute spirochetemia, but differed in duration and effectiveness. The first of these was about as potent as the undiluted whole plasma, and the second about as potent as plasma diluted 1:4.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Collins Robert D. , Wood W. Barry
Published: June 2004

Study in vitro of the interaction of bacterial endotoxin with rabbit polymorphonuclear leucocytes has resulted in the following findings:

1. Incubation of endotoxin and leucocytes in saline results in: (a) the release of leucocytic pyrogen, and (b) the inactivation of endotoxin.

2. Cell-free extracts of leucocytes also inactivate endotoxin.

3. Incubation of leucocytes in "physiological" saline causes rapid discharge of leucocytic pyrogen. In contrast, relatively little pyrogen is released by leucocytes incubated in fresh serum.

4. The release of leucocytic pyrogen in serum is markedly stimulated by the presence of endotoxin.

5. Leucocytes obtained from tolerant rabbits interact with endotoxin in essentially the same manner as leucocytes from normal rabbits.

The pertinence of these findings to the pathogenesis of fever and to related information concerning human leucocytes has been discussed.
CELLULAR ORIGIN OF RHEUMATOID FACTOR
Authors: Mellors Robert C. , Heimer Ralph , Corcos Josué , Korngold Leonhard
Published: June 2004

Fluorescein-labelled aggregated human γ-globulin was found to react in precipitin-type tests with serums of individuals with rheumatoid arthritis. This reagent was also highly reactive and specific for the localization of rheumatoid factor in frozen sections of synovial membranes, lymph nodes, and subcutaneous nodules.

In synovial membranes from patients with active rheumatoid arthritis, rheumatoid factor was present in the cytoplasm of plasma cells at various stages of development and maturity. The appearance of the cytoplasm and the occasional presence nearby of extracellular particles suggested the possibility of a secretory process. All other cells were devoid of rheumatoid factor. Some plasma cells contained 7S and/or 19S γ-globulin and many lacked detectable γ-globulin.

In lymph nodes from a patient with active rheumatoid arthritis, rheumatoid factor was present in approximately one in ten germinal centers as well as in internodular plasma cells. The rheumatoid factor was localized in the cytoplasm and the characteristic protoplasmic processes of the germinal-center cells. All other cells were devoid of rheumatoid factor. 7S and/or 19S γ-globulin was demonstrated in approximately eight in ten germinal centers in these lymph nodes.

Plasma cells with rheumatoid factor were also seen on occasion in rheumatoid subcutaneous nodules.

Tissue sections of comparable structure prepared from normal and pathological control material did not contain rheumatoid factor.

Staining for rheumatoid factor was blocked by pretreatment of sections either with unlabelled aggregated human γ-globulin or with rabbit antiserum against 19S human γ-globulin.
EFFECT OF NUTRITION ON THE RESISTANCE OF MICE TO ENDOTOXIN AND ON THE BACTERICIDAL POWER OF THEIR TISSUES
Authors: Dubos Rene J. , Schaedler Russell W.
Published: June 2004

Mice on inadequate nutritional regimens were found to be more susceptible to various bacterial diseases than mice fed a complete diet containing 15 to 20 per cent casein. The tests of susceptibility included: (a) infections with virulent bacteria; (b) injection of large doses of avirulent coagulase-negative staphylococci; and (c) lethal effects of bacterial endotoxins.

The infection-enhancing effect of nutritional deficiencies could be rendered even more striking by administering the infective inoculum simultaneously with a sublethal dose of endotoxin.

Despite their great susceptibility to infection, malnourished animals retained much of their ability to eliminate bacteria from the blood, liver, spleen, kidneys, and lungs, at least during the early phases of the infectious processes. This was true even when the animals had received endotoxin simultaneously with the infective dose.

The results suggest that under the conditions of the present study, the nutritional state influenced the outcome of infection not primarily by affecting the fate of the pathogens in vivo, but rather by modifying the ability of the host to resist their toxic effects.
COMPOSITION AND SYNTHESIS OF LIPIDS IN RESTING AND PHAGOCYTIZING LEUKOCYTES
Authors: Elsbach Peter
Published: June 2004

The lipid content of rabbit polymorphonuclear leukocytes, obtained from peritoneal exudates, constituted 8.7 ± 2.9 per cent of the dry weight of these cells; 60 per cent of all lipids were phospholipids, 20 per cent triglycerides, and the remainder cholesterol and cholesterol esters and a small amount of non-esterified fatty acids (2 to 4 per cent).

The composition of the fatty acids in leukocytes, as determined by gas-liquid chromatography, was slightly different from rabbit serum and red blood cells, but markedly different from the dietary fat.

The synthesis, turnover, and composition of lipids in rabbit leukocytes at rest and during phagocytosis in vitro were compared. Lipid content and composition were not affected by the phagocytic process. However, active phagocytosis resulted in an increase in the rate of turnover of lipids. This stimulation of lipid metabolism was more marked in triglycerides and cholesterol esters than in phospholipids. It is suggested that the increased turnover of lipid during phagocytosis may reflect a general metabolic stimulation accompanying this process, rather than a specific synthesis of phospholipid for the production of new cell membrane.
STUDIES ON FRACTIONS OF METHANOL EXTRACTS OF TUBERCLE BACILLI
Authors: Williams Curtis A. , Dubos Rene J.
Published: June 2004

Fractionation procedures yielding partially purified vaccine preparations from a 60°C. methanol extract of tubercle bacilli have been described. Some of the preparations have the characteristics of lipopolysaccharides. Certain ones have been found capable of increasing resistance to experimental tuberculosis in albino mice of the Rockefeller Swiss strain. The levels of resistance elicited by these preparations are equivalent to those following vaccination with BCG (Phipps) in this strain of mice as reported by other authors. The admixture of two of the crude fractions in amounts as small as 0.05 mg. each per dose per mouse affords an even greater increase in resistance. Neither of these substances alone in larger doses can approach this degree of efficacy in mouse protection experiments.

The protective activity appears to involve the stimulation of two supplementary mechanisms, one providing a peak resistance between 1 and 3 weeks post vaccination but falling off to a lower level thereafter, the other not responding fully until approximately 6 weeks but continuing undiminished through a 12 week post-vaccination period. The first of these peaks corresponds to an increase in resistance against staphylococci as well as tubercle bacilli. The possibility that the term "broad specificity," rather than "non-specificity," might best describe this phenomenon permits the implication of classical immune mechanisms.
A METHOD FOR TITRATING ENDOTOXIC ACTIVITY IN THE SKIN OF RABBITS
Authors: Larson Carl L. , Ribi Edgar , Milner Kelsey C. , Lieberman Jacob E.
Published: June 2004

The primary inflammatory response of rabbits to intradermal injection of bacterial products has been used as the basis of a sensitive assay for endotoxins. Injection of materials into the skin of the lateral surfaces, rather than the ventral surface of the abdomen, was essential. The method was evaluated by comparison with the mouse toxicity test. Statistical examination revealed an excellent correlation between the mean threshold dose for producing skin lesions in rabbits (SLD50) and the median lethal dose for mice (LD50). For potent endotoxins (LD50 = 0.2–0.3 mg.) the skin test dose was about one-thousandth of the lethal dose for mice. Thereafter the LD50 increased in the proportion of about 0.3 mg. per 1 µg. increase in SLD50. The method of testing was devised for endotoxins prepared in various ways from Salmonella enteritidis and S. typhosa but was directly applicable to endotoxins from several other species of enteric Gram-negative bacteria.
THE ROLE OF OPSONINS IN NON-SPECIFIC IMMUNITY
Authors: Rowley Derrick
Published: June 2004

A study of the recoveries of radioactivity, and of viable bacteria following injection of P32-labelled E. coli into the mouse peritoneum, has indicated that the rapid decrease in viable bacteria which occurs is largely due to peritoneal events, and not to the transport of bacteria elsewhere.

The serum from mice given lipopolysaccharides 48 hours previously, when used to pretreat bacteria before intraperitoneal injection, was found to stimulate phagocytosis to a greater extent than did pretreatment with normal serum. In addition, macrophages themselves were found to be affected by contact with lipopolysaccharides, either in vivo or in vitro in such a way as to promote their phagocytic abilities. It is suggested that the provocation of non-specific immunity by bacterial lipopolysaccharides involves two facets at least; firstly, an increase in the opsonic capacity of the serum, and secondly an increase in the inherent capacity of phagocytic cells to perform this function.
ANTIGENIC ANALYSIS OF CERTAIN GROUP B ARTHROPOD-BORNE VIRUSES BY ANTIBODY ABSORPTION
Authors: Clarke D. H.
Published: June 2004

A method for carrying out antibody absorption studies for antigenic analysis of group B arthropod-borne (arbor) viruses is described and examples of homologous and heterologous absorption curves are presented. Evidence that antigenic structure can be a stable property was obtained with three strains of West Nile virus isolated from different hosts in different countries over a period of years. Comparative studies with viruses of the Japanese B-St. Louis-West Nile subgroup indicate that each virus contains a completely specific antigen as well as one or more cross-reactive components. Strains of yellow fever virus isolated in America were shown to lack an antigen present in strains of African origin although no differences were found between isolates from the same geographical area. The attenuated 17 D vaccine strain of yellow fever was found to have acquired an additional antigen not present in the unadapted parent or in other strains tested. However, alteration in pathogenicity for man was not found to be necessarily attended by any antigenic modification, as shown by the antigenic identity of the French neurotropic vaccine strain with its pantropic parent.
THE PATHOLOGIC EFFECTS OF INTRAVENOUSLY ADMINISTERED SOLUBLE ANTIGEN-ANTIBODY COMPLEXES
Authors: McCluskey Robert T. , Benacerraf Baruj , Potter Jacobus L. , Miller Frederick
Published: June 2004

The intravenous administration to mice of soluble antigen-antibody complexes in antigen excess resulted in a high incidence of glomerulonephritis and less frequently in endocarditis or arteritis. These lesions are present within 48 hours of the first of 3 injections and disappear within 2 weeks.

The same pathological changes were produced with complexes prepared from either rabbit or chicken antibody. In the case of rabbit antibody, the severity of the glomerulonephritis was greater with the ovalbumin antiovalbumin system than with the BSA system.

Anaphylaxis regularly occurred in mice given complexes prepared from rabbit antibody, but was not seen following administration of complexes prepared from chicken antibody.

Pretreatment with cortisone diminished the severity of the glomerulo-nephritis and resulted in accumulation of amorphous, eosinophilic material within glomerular capillaries in mice injected with antigen-antibody complexes.

The rabbit antibody used in these experiments failed to sensitize guinea pig skin to passive cutaneous anaphylaxis when injected in the form of soluble complexes. This indicates that these complexes do not dissociate to a detectable extent in vivo and thus favors the interpretation that complexes localize as such in the sites where tissue damage occurs.

Chicken anti-mouse erythrocyte antibody produced hemolysis of mouse red cells in the presence of mouse complement. In contrast to a similar rabbit anti-serum, the hemolytic activity of the chicken antibody with mouse complement was very slight. This suggests that complement does not play an important role in the pathogenesis of these experimental lesions.
ON THE ROLE OF RIBONUCLEIC ACID IN ANIMAL VIRUS SYNTHESIS
Authors: Tamm Igor , Bablanian Rostom
Published: June 2004

Ribonuclease is a highly active inhibitor of vaccinia virus multiplication in vitro in the chorioallantoic membrane removed from embryonated chicken eggs. It is also a highly active inhibitor of pock formation by vaccinia and herpes simplex viruses on the chorioallantoic membrane in vivo. Marked inhibitory effects were obtained with 12.5 µg. of RNase. However, complete inhibition was not obtained with several hundred micrograms of the enzyme.

RNase caused no inactivation of the infectivity of vaccinia virus particles but it had a marked inhibitory effect on multiplication of this virus when administered many hours after infection of host cells had occurred. RNase also failed to inactivate the infectivity of herpes simplex virus particles.

The results obtained indicate that ribonucleic acid is necessary for the multiplication of two DNA-containing viruses; i.e., vaccinia and herpes simplex.
IMMUNOLOGIC PRODUCTION OF ANTIANGIOTENSIN
Authors: Deodhar Sharad D.
Published: June 2004

The parenteral administration of benzoylangiotensin II-azo-BGG to rabbits produced an antiserum with antiangiotensin activity.

Antiangiotensin inhibited the biological action of p-aminobenzoylangiotensin II, valine5-angiotensin II (free acid form), isoleucine5-angiotensin II and valine5-angiotensin II (amide form), but it was totally inert towards angiotensin 1.

Antiangiotensin activity was distinguished from that of serum angiotensinase by the following observations: (a) an angiotensinase-free γ-globulin fraction contained antiangiotensin, (b) angiotensinase inactivated angiotensin II (both the amide and free acid forms) and angiotensin I in contrast to the remarkable specificity for angiotensin II exhibited by antiangiotensin.

Serological demonstration of antiangiotensin included: (a) a comparison of its precipitin reaction with the angiotensin BGG complex with the reaction with BGG alone, (b) the partial inhibition of the precipitin reaction with the angiotensin BGG complex by angiotensin II, (c) a precipitin reaction with a different angiotensin II protein complex (cat serum).

Angiotensin II administered parenterally as the free polypeptide was not antigenic.
PASSIVE TRANSFER OF TOLERANCE TO PYROGENICITY OF BACTERIAL ENDOTOXIN
Authors: Freedman Henry H.
Published: June 2004

The typical febrile response of normal rabbits given bacterial endotoxin intravenously may be modified by prior administration of plasma or, less effectively, serum of endotoxin-tolerant donors. This altered response is characterized by disappearance of the second rise in fever and by a striking reduction in fever index. It thus resembles the course of fever shown by rabbits made tolerant to endotoxin by one or more previous daily doses. This transfer of tolerance by plasma or serum depends critically upon the manner in which tolerance is induced in the donors.

The plasma of donor rabbits made tolerant, then given an RES-blocking dose of carbon, still confers tolerance upon normal recipient rabbits. Such donors have lost their tolerance and are highly sensitive to endotoxin at the time their blood is taken.

The implications of these findings for endotoxin tolerance and for transfer of this phenomenon are discussed. The evidence is consistent with the hypothesis that both tolerance and its transfer are based upon RES function and are independent of antibody.
HEREDITARY PREMATURE SENESCENCE OF THE RABBIT
Authors: Pearce Louise , Brown Wade H.
Published: June 2004

The occurrence of hereditary premature senescence in a family of pure bred Belgian hares belonging to a rabbit-breeding colony organized for the investigation of constitutional problems, has been described. Representatives of 20 generations of the complex have been studied. The condition was a degeneration of variable degrees of severity and two principal forms were recognized, the acute and the chronic, the chronic being the more frequent. The chronic form has now been described in terms of the principal local or external manifestations; that is, degeneration of the coat and skin, lesions of the eyes and feet, and reproductive abnormalities, and of the general deterioration which in severe cases pursued a progressive course characterized by muscle wasting, fat reduction, emaciation, weakness, and death. The acute form will be described in the next paper (2).
FURTHER OBSERVATIONS ON THE BEHAVIOR OF STAPHYLOCOCCI WITHIN HUMAN LEUKOCYTES
Authors: Rogers David E. , Melly Marian Ann
Published: June 2004

A specific serum factor was required for rapid phagocytosis of pathogenic staphylococci by human polymorphonuclear leukocytes when the ingestion process was studied in siliconed glass systems and the concentrations of staphylococci were maintained at low levels. In contrast to certain other microbes, the resistance to phagocytosis which characterized pathogenic staphylococci was relative, and phagocytosis was readily accomplished when large populations of staphylococci were present in the test system.

A factor promoting phagocytosis was present in eight of eight normal adult sera. In contrast, the sera of twenty-eight of thirty normal rabbits did not promote phagocytosis. Serum obtained from 2 rabbits maintained in the rabbit colony for several months acquired the ability to opsonize pathogenic staphylococci.

The phagocytosis-promoting factor was almost completely removed by prior absorption of test sera with the homologous strain. The factor was incompletely removed by absorption with heterologous strains of pathogenic staphylococci and was not significantly reduced by absorption with coagulase-negative staphylococci or unrelated microorganisms.

Present evidence suggests that the factor promoting phagocytosis is a thermostable opsonin. While the activity of heated serum could not be restored by the addition of small amounts of fresh serum or complement, the addition of large amounts of complement partially restored opsonic activity. Incubation of staphylococci in fresh serum prior to heat inactivation did not reduce subsequent phagocytosis, further suggesting the heat stability of the phagocytosis-promoting factor.

Preliminary studies correlating the presence of antistaphylococcal hemagglutinins and phagocytosis-promoting factor in certain sera suggest that the two factors were not necessarily related.

The phagocytosis of staphylococci in fresh human serum was inhibited by the addition of fresh or inactivated rabbit serum. Further studies on the nature of such inhibition are in progress.

Once ingestion was accomplished, coagulase-positive staphylococci consistently survived in significant numbers within the cytoplasm of human granulocytes. Coagulase-negative staphylococci appeared to be destroyed within the leukocyte and could not be recultured from the cytoplasm following 3 to 4 hours of intracellular residence.
STUDIES ON ANTIBODY FORMATION BY PERITONEAL EXUDATE CELLS IN VITRO
Authors: McKenna John M. , Stevens Kingsley M.
Published: June 2004

Cells from peritoneal exudates of rabbits sacrificed 3 days after an intraperitoneal injection of sterile mineral oil were grown in tissue cultures in medium 199 (75 per cent); normal rabbit serum (25 per cent). Antibody produced by the cells was assayed by an hemagglutination technique in which the antigens used were adsorbed to formalinized tanned sheep erythrocytes. These sensitized cells agglutinate in the presence of antibody specific to the adsorbed antigen. It has been demonstrated that:

Peritoneal exudate cells produced hemagglutinating antibody to bovine gamma globulin (BGG) in a replicating tissue culture system for approximately 3 weeks when taken from animals given either primary or secondary injections of BGG. The mean hemagglutinating titer was 30 for the primary and 32 for the secondary systems. Since the other cell types did not persist, it is felt that monocytes were responsible for these results.

Monocytes taken from normal rabbits and exposed to either BGG or egg albumen (EA) in vitro produced titers of 28 for about 2 weeks.

Monocytes taken from rabbits given hyperimmunizing injections of BGG produced titers of 147 for about 1 week.

Endotoxin from Salmonella typhosa caused the monocytes to form antibody as if they had been taken from hyperimmunized rabbits. This was true both when the antigen was given in vivo together with the endotoxin as well as when the cells were exposed to antigen in vitro. The titers were 223 and 97, respectively.

Neither freshly harvested nor cultured monocytes were phagocytic for carbon particles or bacteria in vitro. Monocytes in tissue culture appeared to assume the morphology of fibroblasts, but did not stain with the characteristics of fibroblasts. The morphologic changes and staining characteristics of monocytes in tissue culture have been described.

The implications of these findings have been discussed and an attempt made to integrate them into general biological theory.
ON THE SIZE OF THE TOXIC PARTICLE PASSING THE INTESTINAL BARRIER IN BOTULISM
Authors: Heckly Robert J. , Hildebrand G. J. , Lamanna Carl
Published: June 2004

On the basis of toxicity assays using partition centrifugation cells it was established that the sedimentation coefficient of type A botulinum toxin appearing in the lymph of orally poisoned rats was 7.9 x 10–18 cm. per dyne sec. with 95 per cent confidence limits of 4.4 to 11.4 x 10–13 cm. per dyne sec. This is a significantly lower value than that obtained for crystalline toxin but is well within the range of size for proteins.

Exposure of crystalline toxin for 2 hours to digestive processes in a section of the duodenum of living rats did not significantly reduce the sedimentation coefficient of the toxin. The S20 of crystalline toxin employed in the present study ranged between 12 and 21 with a mean value of 17.9.

While it was observed that both botulinum toxin and albumin sedimented from lymph in glycerol gradient tubes to essentially the same level no evidence was developed to indicate association between toxin in lymph and serum albumin. The electrophoretic mobility of toxin in lymph is like that of crystalline toxin and not albumin. Dialysis of toxic lymph against serum albumin does not result in the appearance of toxin in the dialysate.
INHIBITION OF LIPOPROTEIN LIPASE ACTIVITY FOLLOWING INJECTION OF PITUITARY EXTRACTS INTO RABBITS
Authors: Kellner Aaron , Hirsch Robert L. , Freeman Elizabeth B.
Published: June 2004

Rabbits given a single subcutaneous injection of an alkaline extract of hog, bovine, or human anterior pituitary glands developed marked hyperlipemia within 12 to 24 hours. The injections in some instances were followed by sickening and death of the animal, though no anatomical changes responsible for these consequences could be determined. No such sequelae were observed in animals given much larger injections of comparable extracts made from other tissues.

An inhibitor to lipoprotein lipase appeared regularly in the serum of the injected animals in association with the hyperlipemia. The injection of heparin into such animals failed to result in the elaboration of clearing factor, and serum from these animals inhibited in vitro the hydrolysis of lipid emulsions by active lipoprotein lipase obtained from normal rabbits or human beings. The inhibitor was produced only in vitro by the pituitary extracts. It did not antagonize the anticoagulant action of heparin, and is probably a lipoprotein.
ALLOTYPY OF RABBIT SERUM PROTEINS
Authors: Oudin Jacques
Published: June 2004

The relationships between six of the seven allotypes or families of allotypes (a, b, c, d, f, g) described in the preceding paper, have been studied from the standpoints of (1) their antigenic specificities, (2) their mutual influence on the limitation of their respective frequencies, and (3) their genetic control.

Although the six different allotypes (or families) react quite differently with the rabbit antisera, at least five of them react identically with a guinea pig antiserum. Therefore, a large portion of the antigenic specificity of these allotypes, distinct from their allotypic specificity, is uniform in all the individuals of the rabbit species and is termed for this reason "isotypic specificity."

In the early period of the rabbit's life, allotypes may be found in the serum, which are not determined by the genotype of the individual, but are directly transmitted by the mother. The allotypes of the antigenic species of globulin studied in this paper, which were synthesized by the young animal, did not appear in its serum before a certain period of time.

Allelic relationships between the genes which control allotypes were indicated by, (1) the absence of certain kinds of groupings of the allotypes, which limits the number of allotypic formulas in the population sample studied, (2) dosage effects, the concentration of certain allotypes (drawn from the penetration of the zones in gel tubes) being smaller in supposed heterozygotes than in supposed homozygotes, (3) the results of the analysis of the sera of a number of rabbits and of their parents.

Eight of the different antigenic substances studied in this paper (allotype e excluded) appear to be allotypic forms of what would have been considered to be a uniform protein antigen. They may be classified as follows: a first group which contains two allotypes b and d and a family of two allotypes c and c' apparently controlled by three allelic genes b c d, c and c' being controlled by the same gene; a second group which contains two allotypes a and f and a family g, g' apparently controlled by three allelic genes a f g. There are reasons to believe that this list is not complete, especially in the b c d group.
STUDIES ON INFECTION AND IMMUNITY IN EXPERIMENTAL TYPHOID FEVER
Authors: Edsall Geoffrey , Gaines Sidney , Landy Maurice , Tigertt W. D. , Sprinz Helmuth , Trapani R.-J. , Mandel Adrian D. , Benenson A. S.
Published: June 2004

A disease resembling human typhoid fever has been induced by feeding live cultures of Salmonella typhosa to young chimpanzees, thus confirming the classical reports of Grünbaum and of Metchnikoff and Besredka.

Detailed clinical observations, results of stool and blood cultures, and serological studies have confirmed the impression that the disease produced in chimpanzees closely resembles the mild form of human typhoid fever frequently seen in childhood.

Gross and histologic examination of intestines, mesenteric lymph nodes, liver, spleen, and other organs of orally infected chimpanzees has demonstrated that the pathological findings are essentially indistinguishable from those seen in mild typhoid fever in man.

The clinical spectrum of disease seen in chimpanzees ranged from moderately severe illness, through transitory illness, to afebrile infection with or without bacteriemia (but invariably with an antibody response), occasionally leading to the development of persisting biliary infection and the carrier state. Thus the range of illness observed in chimpanzees resembled that seen in man, except that the severe and complicated forms of typhoid fever were not observed in the chimpanzee. A reason for this difference is proposed and discussed.

In contrast to the limitations imposed upon the interpretation of human epidemiologic observations, it has been possible to demonstrate in the chimpanzee that clinical variation in disease pattern from animal to animal may occur despite the administration of the same dose of the same bacterial strain simultaneously to an entire group of animals under study; in other words, variation in clinical pattern is dependent on inherent, non-specific host factors as well as on dose, strain or preceding state of immunity.

Variation in dose and in challenge strain of S. typhosa employed also appeared to have an effect upon the likelihood of producing febrile as against afebrile infection in chimpanzees. The dose required to produce clinical disease, even with the more virulent strain, was excessively large compared to what is believed to be the dose required to produce illness in man; the limitations of this assumption, and suggested explanations for the findings, are discussed.

The production of the spectrum of typhoid fever in the chimpanzee has made possible the study of basic problems in this disease which are not amenable to definitive study through the use of prevailing laboratory techniques.
THE PHAGOCYTOSIS AND INACTIVATION OF STAPHYLOCOCCI BY MACROPHAGES OF NORMAL RABBITS
Authors: Mackaness G. B.
Published: June 2004

The phagocytosis and survival of staphylococci in the presence of rabbit macrophages has been studied quantitatively. The method permitted an independent measurement to be made of intracellular and extracellular bacteria during the course of phagocytosis. It was found that S. aureus was relatively resistant to phagocytosis. In the presence of specific immune serum, however, it was ingested at a rate comparable with that of S. albus in normal serum; under these conditions more than 90 per cent of bacteria of either strain were inactivated within 60 minutes. Since immune serum did not alter the susceptibility of S. aureus to inactivation within macrophages, it is concluded that S. aureus and S. albus are similar in respect to their ability to survive within macrophages.

The inactivation of staphylococci occurred more slowly, and a greater percentage survived incubation for 180 minutes, in macrophages than in polymorphonuclear leucocytes. Moreover, they retained their morphology for many hours within the former cell, but disappeared rapidly from the cytoplasm of granulocytes. It is suggested that the antibacterial mechanisms of the two cell types are fundamentally different.

When studied over a prolonged period the staphylococci which survived early inactivation within macrophages were observed to die slowly over many hours. When they were recovered from cells and exposed to fresh macrophages, however, they were ingested and inactivated as readily as bacteria of the original population. It is suggested, therefore, that the prolonged survival in vitro of some staphylococci is due to variation in the efficiency of the antibacterial mechanism of exudative mononuclear phagocytes.
DELAYED HYPERSENSITIVITY
Authors: Uhr Jonathan W. , Scharff Matthew
Published: June 2004

The capacity to develop the delayed type of hypersensitivity to diphtheria toxoid and ovalbumin may persist in guinea pigs and rabbits that have received doses of x-ray sufficient to eliminate a detectable antibody response. Larger doses of x-irradiation can prevent development of delayed-type hypersensitivity in rabbits.
A MECHANISM OF THE GLYCOGENOLYTIC ACTION OF BACTERIAL ENDOTOXIN
Authors: Sanford Jay P. , Barnett Jack A. , Gott Cora
Published: June 2004

These experiments have demonstrated that liver glycogen may rise or fall after endotoxin administration, depending upon the antecedent diet and that total adrenalectomy followed by corticosteroid replacement abolishes the glycogenolytic effect of sublethal doses of endotoxin.

It is concluded that the derangements of carbohydrate metabolism observed following the administration of sublethal quantities of bacterial endotoxin represent, not a direct hepatotoxic effect of endotoxin, but rather the passive consequence of epinephrine release.
THE EFFECT OF DIPHTHERIA TOXIN ON THE METABOLISM OF HELA CELLS
Authors: Strauss Norman
Published: June 2004

The effect of toxin on the incorporation of uridine and thymidine into nucleic acids was investigated. P32 orthophosphate incorporation into the nucleoside phosphate fraction was also investigated. No early effect of toxin on nucleic acid synthesis was evident and only a slight effect of toxin on nucleoside phosphate formation was found prior to 1.5 hours after toxin addition. Both these processes, however, were found to be sensitive to dinitrophenol. These results are interpreted as indicating that toxin does not act by a general uncoupling of oxidation from phosphorylation. Other possible mechanisms of toxin action are proposed.
A CORRELATIVE STUDY BY ELECTRON AND LIGHT MICROSCOPY OF THE DEVELOPMENT OF TYPE 5 ADENOVIRUS
Authors: Morgan Councilman , Godman Gabriel C. , Breitenfeld Peter M. , Rose Harry M.
Published: June 2004

Stages in the nuclear changes consequent to infection with type 5 adenovirus are shown and described. Viral development seems to be confined to the nucleus where characteristic particles are found. The shape of the intracellular virus depends upon the method of preservation employed, appearing spherical after osmium tetroxide or freezing-substitution, occasionally exhibiting angulated faces after formalin and often assuming an hexagonal profile after potassium permanganate. The non-viral crystals are encountered in zones of low density, and it is suggested that crystallization results from the accumulation of protein in these areas. An hypothesis is presented to explain why these crystals, in contrast to the insect polyhedra, contain few viral particles.
A CORRELATIVE STUDY BY ELECTRON AND LIGHT MICROSCOPY OF THE DEVELOPMENT OF TYPE 5 ADENOVIRUS
Authors: Godman Gabriel C. , Morgan Councilman , Breitenfeld Peter M. , Rose Harry M.
Published: June 2004

The evolution of the intranuclear lesion produced by type 5 adenovirus in HEp-2 and HeLa cells is described as seen in the light microscope and the bodies formed in the course of the infection characterized histochemically. Some 12 hours after infection acidophilic protein bodies, without appreciable nucleic acid, first appear in the nucleus and coalesce into a network. Within or in association with this material, DNA-containing masses (viral aggregates) are formed which rapidly increase in amount and then coalesce. At the same time, a protein is produced, histochemically different from that of the acidophilic or basophilic structures mentioned, within the infected nucleus, which constitutes a matrix within which regular cytstals of a protein, (presumably non-viral) materialize. These structural and histochemical features are correlated with details which have been observed in parallel studies with the electron microscope.
CHANGES IN THE TITRE OF SERUM OPSONINS AND PHAGOCYTIC PROPERTIES OF MOUSE PERITONEAL MACROPHAGES FOLLOWING INJECTION OF ENDOTOXIN
Authors: Jenkin Charles , Palmer D. L.
Published: June 2004

A study has been made of the changes in the opsonic properties of mouse serum and bactericidal activity of mouse peritoneal macrophages at different times following the injection of various doses of lipopolysaccharide. It has been found that changes in the percentage of bacteria phagocytosed and killed within the mouse peritoneal cavity in a given time could be correlated with changes in the opsonic titre of the serum. Macrophages harvested from the peritoneal cavities of mice injected with endotoxin appear to be more efficient in phagocytosing bacteria in the presence of serum opsonins than macrophages obtained from normal mice. The relative importance of these changes in determining an animal's resistance to infection is discussed.