bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF NUTRITION ON THE PRODUCTION OF ACUTE DISSEMINATED ENCEPHALOMYELITIS IN MICE
Authors: Schneider Howard A. , Lee Johanna M. , Olitsky Peter K.
Published: June 2004

The susceptibility of homozygous BSVS mice to acute disseminated encephalomyelitis (ADE) has been found to be nutritionally dependent. On a laboratory stock regimen of commercial fox chow pellets, whole wheat bread, and milk this genotype is 100 per cent susceptible to the disease. On a "synthetic" diet, containing a minimal list of vitamins adequate for growth and maintenance, susceptibility was found to be reduced to 15 per cent. Supplementation of the "synthetic" diet with biotin, folic acid, and vitamin B12 restored susceptibility to a frequency of 70 per cent. Increasing the supplements tenfold had no further effect in restoring susceptibility frequencies to the 100 per cent level.

In the restoration of susceptibility, folic acid and vitamin B12 were equally effective as single supplements and equivalent to the triple vitamin supplement. The effect of single biotin supplementation was less.

An outbreak of fatal pasteurellosis among BSVS mice latently infected with Pasteurella and used in an ADE susceptibility test has been described. The fatal pasteurellosis has been ascribed to a constellation of determinants including (a) diet, (b) sex, (c) inoculation events, and (d) latent infection with Pasteurella. With males the susceptible sex it was possible to avert the fatal pasteurellosis and continue the nutritional experiments by using females exclusively.
THE LEECH AS A POTENTIAL VIRUS RESERVOIR
Authors: Shope Richard E.
Published: June 2004

Leeches, fed on swine infected with hog cholera, contained virus for as long as 87 days after their infective blood meals. In three instances, infected leeches apparently transmitted hog cholera virus to susceptible swine in the process of normal feeding.

Myxoma virus persisted in leeches for as long as 154 days after the ingestion of a blood meal from rabbits with myxomatosis.

Leeches fed consecutively, first on swine with hog cholera, and later on rabbits with myxomatosis, acquired both viruses. In such dually infected leeches, the hog cholera virus persisted for as long as 122 days and the myxoma virus for as long as 110 days, the longest periods tested.

Leeches fed consecutively, first on rabbits with myxomatosis, and later on swine with hog cholera, acquired only the myxoma virus. Hog cholera virus could not be demonstrated in such dually fed leeches.

Myxoma and hog cholera viruses appeared to be present in about equivalent amounts in the anterior and posterior thirds of the bodies of infected leeches.

Myxoma and hog cholera viruses were present in the bloody gut contents of infected leeches but were not demonstrable in the body tissues of these leeches.

It seems from the findings presented that leeches are not biological carriers of either myxoma or hog cholera virus but instead carry these two agents mechanically in their gastrointestinal tracts. In doing this, they appear to protect the viruses from various deleterious chemical and physical influences to which they would have been exposed in the open.

It is speculated that leeches could play a role in nature in perpetuating the blood-borne viruses of certain diseases in which close association with bodies of fresh water is of epidemiological importance.
THE LEUKOTOXIC ACTION OF STREPTOCOCCI
Authors: Wilson Armine T.
Published: June 2004

Following phagocytosis of certain streptococci human neutrophils undergo a rapid disintegration: the leukotoxic reaction. Monocytes and eosinophils are similarly injured, as are polymorphonuclear cells of rabbit and guinea pig blood.

The leukotoxic injury is not produced by culture filtrates of leukotoxic cocci nor does it follow phagocytosis of heat-killed cocci. The leukotoxic effect does not appear to be due to action of any presently known streptococcal product.

The distribution of leukotoxicity among streptococci is not random, for it was found in all strains tested of certain types of group A (6, 12), and was absent from almost all strains of other types (5, 14, 30). Still other types (3, 4) had both leukotoxic and non-leukotoxic representatives. The injury was also produced by some group C and G strains.

Often the streptococci that cause leukocyte death remain alive and proliferate in the cellular debris, but sometimes they are injured by the phagocyte before the latter disintegrates and are unable to proliferate on the slides. The capacity of a strain of streptococcus to injure leukocytes does not necessarily confer virulence on it. This is thought to be because a chain of streptococci, having survived its sojourn in a leukocyte it has killed, is still susceptible to phagocytosis by a fresh leukocyte, and serial phagocytoses may continue until the chain has been exposed sufficiently to the unfavorable intracellular environment to be, itself, killed.

Whether leukotoxicity plays a role in naturally occurring streptococcal disease is unknown. The high incidence of leukotoxicity in Type 12 strains suggested that it might be involved in acute hemorrhagic nephritis, but if so there must be other factors since leukotoxic strains are present in types and groups not now known to be associated with nephritis.
STUDIES ON RENAL JUXTAGLOMERULAR CELLS
Authors: Hartroft Phyllis M.
Published: June 2004

Hypertension in rats produced by constriction of one renal artery was associated with degranulation of juxtaglomerular cells in the contralateral, undamped, kidney. These findings are consistent with those of other investigators. Furthermore, the degree of granulation (JGI) in the unclamped kidney was inversely correlated with the level of blood pressure (r = –0.7).

Degranulation of JG cells also occurred in rats made hypertensive by application of a "figure-of-eight" ligature to one kidney and removal of the other one, except when the interference in blood supply was so severe that scarring resulted. In these damaged areas, granules persisted or increased in number even though they were decreased in adjacent relatively normal areas.

Occlusion of one ureter in rats produced severe hydronephrosis in the homolateral kidney and an elevation in blood pressure. Juxtaglomerular cell granules persisted in the hydronephrotic kidney but were decreased in the contralateral one. This finding confirmed the results of the above experiments.

Unilateral nephrectomy in comparable rats had no effect on the degree of granulation of JG cells in the remaining kidney or on the level of blood pressure under the conditions of these experiments. The possibility that degranulation of JG cells in the contralateral kidney in the rats described above was due to compensatory hypertrophy was thereby excluded. An elevation in blood pressure was therefore implicated as an important factor in causing degranulation of juxtaglomerular cells.
BACTERICIDAL ACTIVITY OF RAT LEUCOCYTIC EXTRACTS
Authors: Fishman M. , Silverman M. S.
Published: June 2004

All extract of polymorphonuclear leucocytes of the rat, prepared by means of ultrasonic vibration, was found to be bactericidal against M. aureus. The bactericidal activity was primarily confined to the mitochondrial fraction of the leucocytes.

The rat leucocyte mitochondrial extract was bactericidal against both Gram-positive (M. aureus, ß-Streptococci, Diplococcus pneumoniae, Corynebacterium diphtheriae) and Gram-negative (Shigella dysenteriae, Salmonella enteritidis, Pasteurella pestis) bacteria. The Gram-positive organisms were more susceptible to the bactericidal activity of the mitochondrial extracts.
EXPERIMENTAL STUDY OF DIPHTHERITIC POLYNEURITIS IN THE RABBIT AND GUINEA PIG
Authors: Waksman Byron H. , Adams Raymond D. , Mansmann Herbert C.
Published: June 2004

Diphtheritic neuritis was produced in rabbits and guinea pigs by injection of underneutralized toxin-antitoxin mixtures. The disease is a progressive, ataxic paresis related in severity to the dose of injected toxin-antitoxin. Cerebrospinal fluids of rabbits with this disease showed "albuminocytologic dissociation" similar to that found in the same disease in man. Histologically the disease is a progressive demyelination of the peripheral nervous system, un-accompanied by axis cylinder damage or inflammation. It involves the spinal roots and sensory ganglia in the rabbit, the peripheral nerves in the guinea pig. Diphtheritic neuritis can be distinguished from experimental allergic neuritis in the rabbit and guinea pig on both clinical and histological grounds. The rabbit disease is however an excellent model of diphtheritic neuritis in man.

In the animals with diphtheritic neuritis, studied in the present work, there was vigorous production of circulating antitoxin and infrequently complement-fixing antibody to horse serum proteins. No antibody against rabbit spinal cord or sciatic nerve was demonstrated. Skin reactivity to both rabbit nerve suspension and diphtheria toxoid was present at 1 to 2 weeks following inoculation and reached a maximum well before the peak of antitoxin response. These reactions did not seem to be typical delayed reactions. No correlation existed between the development of diphtheritic polyneuritis and any of these immunologic events or the circulating complement level, either in time or in degree. Treatment of rabbits with 400 r whole body irradiation 48 hours before inoculation resulted in severe leukopenia lasting about 3 weeks, delay of antitoxin formation with considerable reduction of peak titers, and some decreased skin reactivity to toxoid. It had no effect on the disease process. It is concluded that diphtheritic polyneuritis is produced by a non-immunologic mechanism, e.g., direct toxicity.
THE ROLE OF A NATURAL ANTIBODY IN THE REJECTION OF MOUSE TUMOR CELLS BY THE CHICK EMBRYO
Authors: Green Howard , Lorincz Allan L.
Published: June 2004

Cells of the Krebs ascites tumor of mice grow well in the body of the chick embryo until about the 17th day of incubation, when degeneration of the tumor can be seen in tissue sections and viable tumor cells begin to disappear from the internal organs of the embryo.

This death of tumor cells follows the appearance in the chick embryo of serum gamma globulins. Among these are antibodies which can agglutinate the tumor cells in vitro, and destroy their viability. These antibodies occur in the blood without the introduction of any foreign antigen. Their possible origin is discussed.

Small numbers of mouse tumor cells growing in the chick embryo are completely eliminated shortly after the time when antibodies ordinarily become detectable. When the number of cells present is larger, viable cells persist longer, and at still higher cell numbers, the embryo or chick is unable to eliminate the tumor, and is itself killed by it.

Gamma globulins of older birds injected into young chick embryos bearing growing tumor clear the embryonic organs of viable tumor cells.
A STREPTOCOCCAL ENZYME THAT ACTS SPECIFICALLY UPON DIPHOSPHOPYRIDINE NUCLEOTIDE: CHARACTERIZATION OF THE ENZYME AND ITS SEPARATION FROM STREPTOLYSIN O
Authors: Carlson Arthur S. , Kellner Aaron , Bernheimer Alan W. , Freeman Elizabeth B.
Published: June 2004

All enzyme that destroys DPN has been found in fractionated and highly concentrated streptococcal preparations that also contain streptolysin O. The enzyme—streptococcal DPNase—was shown by electrophoretic separation and by other means to be distinct from streptolysin O. It is non-dialyzable, heat-labile, and has optimal activity in the pH range 7.2 to 7.8. The enzyme has a high degree of specificity for DPN, which it splits at the nicotinamide-ribose linkage.
DIPHOSPHOPYRIDINE NUCLEOTIDASE AS AN EXTRACELLULAR PRODUCT OF STREPTOCOCCAL GROWTH AND ITS POSSIBLE RELATIONSHIP TO LEUKOTOXICITY
Authors: Bernheimer Alan W. , Lazarides Penelope D. , Wilson Armine T.
Published: June 2004

Among 170 streptococcal strains, there were encountered 98 that yielded culture supernates which caused splitting of diphosphopyridine nucleotide (DPN). All of the latter belonged to Group A, C, or G. Release of DPNase accompanied the growth of diverse antigenic types of Group A streptococci, and data on the frequency of DPNase-producing strains for certain types are given. In contrast, cultures representing 3 species of yeasts and 42 species of bacteria other than streptococci of the Lancefield groups were examined for the presence of DPNase as an extracellular product of growth, but in none of these was the enzyme detected.

Of the Group A streptococci examined, 41 strains had pedigrees suggesting that they were the etiologic agents of acute glomerulonephritis, and 39 of these were found to produce DPNase.

There is an association between capacity of streptococi to form DPNase and capacity to kill leukocytes. A possible mechanism of leukotoxicity is suggested.
ENZYMATIC VARIANTS OF INFLUENZA VIRUS
Authors: Padgett Billie L. , Walker Duard L.
Published: June 2004

Slowly reacting enzymatic variants of the Lee strain of influenza B virus were isolated by the serial application of a technique which concentrated the fraction of the virus population obtained by slow elution followed by passage of this fraction at high dilution in chicken embryos. The variants were stable upon serial passage in chicken embryos and did not differ significantly from the parent virus in any of the characteristics tested other than those relating to the virus enzyme.

Enzymatically, the variants had a much slower rate of activity on chicken mucoproteins than the parent virus. Their activity was greater at 25°C. than at 37°C. and was much enhanced by calcium ions and depressed by a calcium chelating agent. The enzyme of the variant virus was more labile to heat than that of the parent virus although their hemagglutinins were equally stable. It was estimated that the variants comprised less than 3 per cent of the original population of the Lee strain of influenza B virus particles.
THE PROPERDIN SYSTEM AND IMMUNITY
Authors: Pillemer Louis , Landy Maurice , Shear Murray J.
Published: June 2004

High molecular weight polysaccharide complexes derived from normal and neoplastic mammalian tissues were found to combine with properdin and to inactivate C'3 in vitro. These polysaccharide preparations were also found to alter properdin levels and non-specific resistance to Gram-negative infection in mice. In these manifestations, the tissue polysaccharides bore a marked resemblance to bacterial lipopolysaccharides.

Some implications of the interactions of tissue polysaccharides and properdin in certain disease states are considered.
IMPAIRMENT OF THE ANTIGENICITY OF A PROTEIN ANTIGEN FOLLOWING ITS INJECTION INTO RABBITS
Authors: McMaster Philip D. , Edwards Joshua L.
Published: June 2004

The findings presented in this paper indicate that 60 gm. of liver tissue, taken from adult donor rabbits 2 weeks after injecting them with large amounts of bovine γ-globulin, and transferred to the peritoneal cavities of recipient rabbits prepared for a secondary reaction, contain enough of the antigen to induce the formation of detectable amounts of precipitin in the recipient rabbits. On the other hand, liver taken from donors 21 and 28 days after injecting them with the same antigen fails to bring about a similar effect. The findings outlined in the paper suggest that the antigen is degraded after the 2nd week to such an extent that it fails to engender the formation of complete antibody in the recipient animals, although previous work has shown (2–4) that the transfer of liver tissue from similar donor rabbits to mice renders the recipient mice anaphylactically sensitive to the antigen, bovine γ-globulin.

The implications of the findings are discussed.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Petersdorf Robert G. , Bennett Ivan L.
Published: June 2004

Intravenous administration of bacterial endotoxins in dogs is followed within 2 hours by the appearance of a fever-producing substance in the blood. This endogenous pyrogen differs from the endotoxins originally administered by its ability to produce fever in tolerant recipients and failure to promote tolerance after repeated daily injections. Endogenous serum pyrogen is destroyed by heating at 90°C. for 30 minutes, and is also inactivated to some degree by incubation at 37°C. for 24 hours. Suppression of fever by aminopyrine does not affect appearance of the endogenous factor. Animals made febrile with dinitrophenol, kaolin, or lysergic acid do not elaborate a fever-promoting substance in the blood. Sterile abscesses, accompanied by elevations in body temperature of the host, are unassociated with detectable amounts of secondary pyrogen in the serum. The absence of endogenous pyrogen in the blood of febrile dogs made leukopenic with nitrogen mustard favors the idea that polymorphonuclear leukocytes injured by endotoxins release the endogenous factor. On the other hand, the finding that the granulocytopenic animals are febrile when no circulating endogenous pyrogen is present, casts doubt upon the essential role of this substance in endotoxin fever.
DISSIMILARITY IN OXYGEN CONSUMPTION BETWEEN THE THORACIC AND ABDOMINAL AORTA IN RATS
Authors: Christie R. W. , Dahl L. K.
Published: June 2004

Measurement of oxygen uptake by thoracic and abdominal segments of rat aorta showed significantly lower rates in the abdominal than in the thoracic aorta of adult animals. The evidence suggests that as a rat ages the respiratory rate of abdominal aorta falls more sharply than that of the thoracic segment. This result may provide an explanation for the relatively high incidence of atherosclerosis in abdominal aorta.
THE RELATIONSHIP BETWEEN THE VASCULAR MANIFESTATIONS OF SHOCK PRODUCED BY ENDOTOXIN, TRAUMA, AND HEMORRHAGE
Authors: Zweifach Benjamin W. , Benacerraf Baruj , Thomas Lewis ,   With the Technical Assistance of P. Viera
Published: June 2004

In studies designed to establish the interrelationship between bacterial endotoxins and the vascular sequelae of hemorrhagic and traumatic shock, the effect of factors known to influence the phagocytic behavior of the reticulo-endothelial system (RES) were investigated.

Measures which induced a so called "blockade" of the RES were uniformly associated with an exacerbation of the vascular effects of the endotoxin of E. coli. Such pretreatment also counteracted the cross-tolerance induced by endotoxins against the lethal effects of hemorrhage or drum trauma.

The vascular reactions characteristic of irreversible hemorrhagic shock could be simulated by a combination of pretreatment with carbon or proferrin and the infusion of small doses of E. coli endotoxin.

An increase in the phagocytic activity of the RES, induced by repeated injections of certain colloids, was associated with an enhanced tolerance of shock.

Measurement of carbon clearance values indicated that although an augmented phagocytic capacity was present in rats with induced tolerance to bacterial endotoxins, the development of resistance to trauma was not associated with a comparable change in the phagocytic function of the RES.
DESOXYCORTICOSTERONE-MIMETIC ACTION OF AMMONIATED GLYCYRRHIZIN IN RATS
Authors: Kraus Shirley D.
Published: June 2004

The desexycorticosterone-mimetic action of ammoniated glycyrrhizin on electrolyte and water metabolism and on pituitary-adrenal function, was demonstrated in rats. Retention of sodium and water was observed in both intact and adrenalectomized rats during 4 hour minerosteroid assays, the degree of retention being a function of log dose. In intact rats, the antidiuretic effect of glycyrrhizin was immediate and cumulative, while retention of sodium appeared only after a latent period and did not increase with time. Adrenalectomized rats, 3 days after the operation, showed a more marked antidiuretic effect than intact rats, but no greater retention of sodium.

Rats receiving glycyrrhizin prior to histamine stress showed a marked decrease in adrenal ascorbic acid depletion, suggesting that glycyrrhizin had suppressed the output of ACTH.

Whether glycyrrhizin acts on the same target organ as desoxycorticosterone in producing sodium and water retention is still an open question. However, the fact that it is capable of producing a pituitary-adrenal inhibition which resembles that of naturally occurring adrenal steroids is further evidence of the strong pharmacological resemblance between glycyrrhizin and desoxycorticosterone.
THE PREPARATION, PURIFICATION, AND AMINO ACID SEQUENCE OF A POLYPEPTIDE RENIN SUBSTRATE
Authors: Skeggs Leonard T. , Kahn Joseph R. , Lentz Kenneth , Shumway Norman P.
Published: June 2004

A purified preparation of a polypeptide renin substrate prepared by tryptic degradation of the protein renin substrate has been analyzed by the fluorodinitrobenzene method and after degradation with renin, carboxypeptidase, and phenylisothiocyanate, has been found to possess the amino acid sequence; asp-arg-val-tyr-ileu-his-pro-phe-his-leu-leu-val-tyr-ser. The first 10 of these amino acids constitutes hypertensin I which is released by cleavage of the leucyl-leucine bond by renin. The remaining 4 amino acids, leu, val, tyr, ser, apparently link hypertensin I to the protein renin substrate.
STUDIES ON PRIMARY ATYPICAL PNEUMONIA
Authors: Liu Chien
Published: June 2004

By means of fluorescein-labelled antibody, the primary atypical pneumonia virus was found to multiply exclusively in the cytoplasm of the epithelial cells lining the bronchioles and air sacs of developing chick embryos. When 13-day old embryos were inoculated intra-amniotically and incubated at 35°C. for 5 days or longer, over 90 per cent of the inoculated embryos became infected.

Between 1954 and 1956, seven strains of PAP virus were isolated from sputums or nasopharyngeal washings in patients during the acute stage of the PAP infection. One strain of virus was isolated from the frozen lung of a patient who died at Boston in 1943. All eight recently isolated strains and the Mac strain isolated by Eaton et al. in California in 1944 were antigenically closely related if not identical. PAP virus is not related antigenically to agents of psittacosis, Q fever, adenovirus (Types 1 to 6), influenza A or B, or PVM.
LEUKOPENIA WITH GRANULOCYTOPENIA IN EXPERIMENTAL MUCORMYCOSIS (RHIZOPUS ORYZAE INFECTION
Authors: Bauer Heinz , Sheldon Walter H.
Published: June 2004

Mucormycosis was produced in rabbits with sustained, severe leukopenia and granulocytopenia induced by repeated injections of nitrogen mustard. Initially, these animals developed extensive fungus lesions at the site of inoculation which later became granulomatous and tended to heal. Only the early phases of host resistance appeared impaired by the virtual elimination of the polymorphonuclear leukocyte as a factor in the host response. Despite the persistent leukopenia and granulocytopenia, the later phases of host resistance resembled those of the normal animal. Thus, the behavior of the infection in this experiment differs greatly from the unchecked progression of mucormycosis in the metabolically abnormal animal with acute alloxan diabetes. The differences in the course of the disease and in the morphologic appearance of the lesions indicate that metabolic alterations in the host affect all phases of host resistance and not only the polymorphonuclear leukocytic response.
FLUORESCENT ANTIBODY DETECTION OF THE ANTIGENS OF THE SHOPE PAPILLOMA VIRUS IN PAPILLOMAS OF THE WILD AND DOMESTIC RABBIT
Authors: Noyes Wilbur Fiske , Mellors Robert C.
Published: June 2004

The results obtained by a fluorescent antibody study of the Shope papilloma virus in papillomas of the wild and domestic rabbit are presented.

In the wild rabbit papillomas the viral antigens occurred exclusively in the nucleus and were present in the differentiating cells of the keratohyaline layers and in the keratinized layers. The antigens were not present in the deeper proliferating epithelial cells of the papillomas.

The Shope viral antigens were present in very minute amounts in papillomas of the domestic rabbit, as compared with papillomas of the wild rabbit, and were only detected in the superficial keratinized layers.

It is postulated that virus is present in the nuclei of the proliferating cells of the papillomas of the wild and domestic rabbit but exists there in an early stage of development, consisting mainly of nucleic acid and deficient in protein, therefore non-antigenic and not demonstrable by fluorescent antibody. The nucleic acid moiety of the virus may be infective, and the protein component may provide immunologic specificity and serve to preserve transmissibility. The protein-deficient virus can be referred to as masked virus.
AN ELECTRON MICROSCOPIC STUDY OF INCOMPLETE VIRUS FORMATION
Authors: Adams W. Robert , Prince Alfred M.
Published: June 2004

The morphologic changes occurring in Ehrlich ascites tumor cells infected with chick embryo-adapted Newcastle disease virus were studied with phase microscope, conventional light microscope, and electron microscope. Intracytoplasmic inclusions appeared 2 to 4 hours following infection and progressively increased in size and numbers until cytolysis occurred. No significant alterations in mitochondria or other cell organelles were detected during the initial period of inclusion development. The inclusions were composed of a multilaminated shell, probably derived from the agranular reticulum of the EAT cell, surrounding an inner core packed with dense particles, measuring 3 to 14 mµ in diameter. These particles were tentatively identified as the newly synthesized "incomplete virus" which had been previously demonstrated by fluorescent antibody techniques. The possible role of the inclusions is discussed.
FATE OF NON-VIRULENT GROUP A STREPTOCOCCI PHAGOCYTIZED BY HUMAN AND MOUSE NEUTROPHILS
Authors: Wilson Armine T. , Wiley Grove G. , Bruno Pauline
Published: June 2004

The fate of non-virulent group A streptococci phagocytized in vitro has been investigated by destroying the phagocyte with electric current and observing whether the liberated cocci multiply.

Human and mouse peripheral blood neutrophils quickly injure ingested cocci, the time required to produce 50 per cent non-survival of chains being 8 and 6¾ minutes, respectively.
THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION
Authors: Kilbourne Edwin D. ,   With the Technical Assistance of L. M. Daves Burch and Barbara Ann Pokorny
Published: June 2004

The administration of cortisone to chicken embryos infected with influenza B virus results in (a) an initial inhibition of viral synthesis and (b) an eventual increase in the final yield of virus attained. Increased yields of virus are attained regardless of the number of viral particles in the infecting inoculum or the proportion of particles which are infective.

Changes in the distribution ratios of allantoic fluid and intramembrane virus are effected by cortisone only as the secondary result of reduction in viral synthesis.

The manifest effect of cortisone on influenza A virus increase is inhibitory unless inocula containing relatively high proportions of inactive viral particles are used.
SURFACE PHAGOCYTOSIS
Authors: Smith Mary Ruth , Wood W. Barry
Published: June 2004

Experiments recently reported (18) have been interpreted to indicate that surface phagocytosis plays no significant part in natural antipneumococcal defense. A repetition of these experiments has revealed: (a) that the cellular content of the leucocytic suspensions used in the phagocytic tests was of a different order of magnitude from that of the exudates which usually exist in infected tissues, (b) that the suspensions were too dilute to allow surface phagocytosis of pneumococci to occur, and (c) that the ratio of bacteria to leucocytes. was such that, when a sufficiently concentrated exudate was employed, the pneumococci injured the leucocytes and thus prevented phagocytosis from taking place.

When conditions of the tests were suitably controlled, and conventional quantitative methods were employed to measure the end results of the phagocytic reaction, the essential observations relating to surface phagocytosis were fully confirmed. The significance of this non-antibody mechanism of defense in pneumococcal infections was thus further substantiated.
MELIOIDOSIS: PATHOGENESIS AND IMMUNITY IN MICE AND HAMSTERS
Authors: Dannenberg Arthur M. , Scott Eva M.
Published: June 2004

The pathogenesis of acute respiratory melioidosis mice and hamsters is described. Inhaled organisms giving rise to lesions seemed to be first engulfed by the mononuclear alveolar phagocytes, but in less than 1 day polymorphonuclear cells made their appearance. In spite of this defense reaction, the bacteria continued to multiply and their products caused focal necrosis. These foci enlarged and gave rise to septicemia, toxemia, and eventually death, which usually occurred in 3 to 10 days depending on the dose. Melioidosis, is, therefore, an acute septicotoxemic disease resembling plague and anthrax in this respect.

In hamsters the disease process developed more rapidly than in mice and death occurred sooner. The course of the disease in hamsters was sometimes complicated by intraglomerular deposits resembling "fibrinoid," which were similar to those of the generalized Shwartzman phenomenon. This phenomenon may have been an indirect cause of both the perifocal hemorrhage and the extremely large number of bacteria in some of the hamster lesions.

When low infecting doses of organisms were employed, mice, but not hamsters, developed a chronic type of disease, lasting 2 to 8 weeks. This was characterized by large abscesses in the spleen or lung, marked proliferation of mononuclear phagocytes and plasma cells, and increased immunity against reinfection (about 40-fold against respiratory challenge).

When mice and hamsters inhaled high infecting doses of organisms, a peracute disease resulted with death in 1 to 3 days. Increased numbers of bacteria were observed in the lesions, and the histological changes in the spleen resembled those following the intravenous injection of Malleomyces pseudomallei toxin or the intramuscular injection of large doses of cortisone. These changes were characterized by a swelling of the phagocytes of the white pulp with nuclear debris.

The peracute, the acute, and the chronic forms of melioidosis in mice are similar to analogous clinical forms found in man.
STUDIES ON THE EFFECT OF TRITON (WR-1339) ON GUINEA PIG TISSUES
Authors: Hudgins Paul C. , Patnode Robert A.
Published: June 2004

Guinea pig red cells exposed to triton WR-1339 either in vitro or in vivo demonstrate an increased sensitivity to hemolysis by thermal shock. Although the sensitivity of guinea pig leucocytes to thermal shock remains unchanged after a single injection of triton, their resistance to disruption by acetone and by sonic vibration is increased significantly. Resistance to sonic vibration appears to be maximum within a few hours after injection and then it gradually wanes. Paraffin oil-induced peritoneal exudate cells (monocytes) and leucocytes from whole blood are rendered more resistant to disruption by sonic vibration when exposed to triton in vitro.

These findings are discussed briefly in relation to the therapeutic effect of triton in experimental tuberculosis.
STUDIES ON THE EFFECT OF TRITON (WR-1339) ON GUINEA PIG TISSUES
Authors: Patnode Robert A. , Hudgins Paul C.
Published: June 2004

The administration of triton WR-1339 (300 mg./kg. subcutaneously) to tuberculin-sensitive guinea pigs 2 hours before the intradermal injection of PPD depresses slightly their skin sensitivity to tuberculin and essentially obliterates the lytic effect of tuberculin on their circulating leucocytes. When leucocytes from tuberculin-sensitive guinea pigs are exposed to triton in vitro at a concentration level attainable in vivo the cells are partially protected against lysis by PPD.
STUDIES OF THE HEMOLYSIS OF RED BLOOD CELLS BY MUMPS VIRUS
Authors: Moberly Merle L. , Marinetti Guido V. , Witter Robert F. , Morgan Herbert R.
Published: June 2004

Evidence from microscopic studies indicates that hemolysis caused by the mumps virus hemolysin is a chemical type of hemolysis. Chromatographic analyses of the reaction mixture of erythrocytes and mumps virus following hemolysis indicate that hemolysis is not due to the action of a lecithinase A and that lysolecithin does not play a part in this process. The alteration of a component of the erythrocyte similar to sphingomyelin suggests that some of the phosphatides other than lecithin may be either directly or indirectly affected in the process of hemolysis of red blood cells by the mumps virus.
THE ANTIBACTERIAL ACTIVITY OF HEMOGLOBIN
Authors: Hobson Derek , Hirsch James G.
Published: June 2004

Low concentrations of hemoglobin (0.1 µg./ml. or less) exert a lethal action on some Gram-negative bacteria under certain conditions in vitro. Hemoglobins from various mammals and the distinct genetic types of human hemoglobin all manifest similar bactericidal activity.

The bactericidal effect is a function of the globin moiety of the molecule; native and acid or acid-alcohol denatured globins have the same degree of activity.

Hemoglobins kill enterobacteriaceae only under precisely controlled conditions. The test medium must be low in ionic concentration and acid in reaction. Various strains of Escherichia and Salmonella are susceptible to the lethal effect of hemoglobin, while the few strains of Shigella, Klebsiella, and Proteus examined were resistant.

Certain acid polysaccharides and basic amines or proteins block the bactericidal effect when incorporated in the test in low concentration. Present evidence also suggests that exposure of the microorganisms to certain cations such as magnesium renders them resistant to the lethal action of globin. Hemoglobin loses its bactericidal power when complexed with haptoglobin, and serum fractions rich in free haptoglobin protect otherwise susceptible bacteria from killing by hemoglobin.

The reaction appears to be a bactericidal rather than a bacteriostatic one. At 38°C. maximal killing requires approximately 30 minutes; at temperatures of 28°C. or 0°C. the bactericidal action does not take place. The minimal concentration of hemoglobin required to kill 50 per cent of the microorganisms in the test is unrelated to the size of the bacterial inoculum.

Under conditions suitable for bactericidal action, hemoglobin is adsorbed onto heat-killed susceptible strains of coliform bacteria; material possessing bactericidal activity can be eluted with dilute mineral acid.
COLICINE K
Authors: Goebel Walther F. , Barry Guy T.
Published: June 2004

By chemical fractionation a substance having colicine K activity has been obtained from the culture medium of E. coli K235 L+O.

Colicine K activity was found associated with the O antigen of this microorganism.

When the O antigen was dissociated, colicine K activity remained with the protein component of the antigen.
STUDIES ON THE FORMATION OF COLLAGEN
Authors: Gross Jerome
Published: June 2004

The total amount of neutral salt-extractible collagen in the skin of growing, suckling guinea pigs amounted to about 10 per cent of the total collagen of the dennis. This is roughly equivalent to a 1 to 2 day increment in dermal collagen incident to growth.

Fourteen days of static weight maintained by limited caloric intake reduced the neutral salt-extractible collagen to very low levels. Following this period, 5 to 7 days of steady weight gain induced by ad lib. feeding was required to produce significant increases in this collagen fraction. Return to control levels occurred within 12 days of continuous growth.

The amount of collagen extracted from the dermis of young guinea pigs with cold neutral salt solutions varied directly with growth rate (weight gain) and was greatly diminished after short periods of restricted caloric intake. Two days of fasting diminished the total extracted collagen by one-half.

Three consecutive extractions with citrate buffer pH, 3.5, of the residues remaining after exhaustive saline extraction removed 40 per cent more collagen from the skins of actively growing animals than from those of animals fasted for 2 days. However, subsequent extraction of residues with dilute acetic acid equalized the total amount of collagen extracted at acid pH from the two groups.

The viscosity of cold neutral extracts was unrelated to the concentrations of non-collagenous proteins and carbohydrates but varied directly with the collagen content.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: King M. Kenton , Wood W. Barry
Published: June 2004

The evolution of an acute inflammatory exudate produced in rabbits by the intraperitoneal injection of saline has been described. Evidence has been presented that polymorphonuclear leucocytes release endogenous pyrogen into the cell-free fluid of the exudate. Leucocytes from such exudates have also been shown to release pyrogen into the surrounding medium during incubation in vitro at 37°C. The results of parallel cytological studies have provided evidence which suggests that the leucocytes give up their pyrogen while functionally intact.

These observations add further support to the hypothesis that polymorphonuclear leucocytes play a significant role in the pathogenesis of fever.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: King M. Kenton , Wood W. Barry
Published: June 2004

By means of a method designed to compare the febrile responses produced by intracarotid and intravenous injections, the endogenous pyrogen, which is contained in leucocytic exudates and is present in the serum of rabbits 2 hours after intravenous injections of typhoid vaccine, has been shown to act directly upon the thermoregulatory centers of the brain. In contrast, the exogenous bacterial pyrogen present in serum obtained 5 minutes after vaccine injections was found to act by a different and less direct mechanism. These observations add strong support to the original hypothesis that endogenous pyrogen, presumably derived from polymorphonuclear leucocytes, is an essential factor in the pathogenesis of endotoxin fever.
STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES
Authors: Atkins Elisha , Huang Wei Cheng
Published: June 2004

Tolerance to the pyrogenic action of intravenously injected virus has been studied in rabbits given either PR8 strain of influenza A virus or Newcastle disease virus (NDV). The following findings suggest that the capacity of the animal to release an endogenous pyrogen is a critical factor.

(a) Viruses produce fever by the release of endogenous pyrogen.

(b) Tolerance to the pyrogenic effect of reinjected virus is associated with a decrease or absence of endogenous pyrogen production.

(c) Tolerance to virus fever may be induced by the prior injection of endogenous pyrogen.

(d) Cross-tolerance has been demonstrated between virus and bacterial endotoxin (typhoid vaccine), both of which cause the release of endogenous pyrogen.

A difference has been noted in the mechanism of tolerance to successive injections of virus and of bacterial endotoxin. Repeated injections of endotoxins bring about an accelerated clearance of these substances from the blood stream with the result that there is a diminished stimulus to endogenous pyrogen production. Tolerance to virus, on the other hand, is unaccompanied by changes in the rate at which virus disappears from the circulation. It is postulated that circulating endogenous pyrogen, induced by the injection of a number of pyrogenic agents including viruses, temporarily suppresses the further release of endogenous pyrogen and thereby contributes to virus tolerance.
EFFECT OF SECONDARY INJECTIONS OF ANTIGEN UPON THE RETENTION IN LIVER OF A PRIMARY INJECTION
Authors: Garvey Justine S. , Campbell Dan H.
Published: June 2004

The retention of antigen in rabbit liver tissue, resulting from a primary intravenous injection, is influenced by immunization brought about by subsequent intravenous injections of the same antigen. In rabbits given a single primary intravenous injection of radioactive antigen, the retention of radioactivity in liver tissue, after a period of 21 days, was greater than when the primary injection was followed by secondary injections of the same, but non-radioactive antigen. The results were similar for both S35-azohemocyanin and S35-azo-bovine-serum-albumin, except the hemocyanin was retained to a greater extent than the albumin.

There was very little if any correlation between the number of secondary injections and retention of the initial injection. Quantitative antibody nitrogen data, obtained for the serum of each rabbit showed, in general, an inverse relationship between circulating antibody and radioactivity retained, i.e. the higher the circulating antibody titer, the lower the retention of radioactivity in liver tissue.

Passively administered homologous antibody did not produce a change in the retention of the primary injection of antigen nor did secondary injections of a heterologous native protein injected according to the same immunization schedule as the homologous azoprotein. From these results it may be concluded that an intracellular antibody-forming activity influences the loss (or retention) of antigen deposited in liver tissue and that the mechanism is immunologically specific.
THE EFFECT OF BACTERIAL CONSTITUENTS ON THE RESISTANCE OF MICE TO HETEROLOGOUS INFECTION AND ON THE ACTIVITY OF THEIR RETICULO-ENDOTHELIAL SYSTEM
Authors: Boehme Diethelm , Dubos René J.
Published: June 2004

Administration of small amounts of salmonella endotoxin (20 µg.) or of acetone-extracted BCG cells (100 µg.) increases the resistance of mice to infection with Myco. fortuitum as well as their ability to clear carbon particles from their blood stream. Whereas the increased resistance to infection persists for many weeks, the clearing power returns to a normal level within a few days.

When normal mice are infected with Myco. fortuitum, there occurs during the first phase of the infectious process a rise in clearing power for carbon particles followed by a fall during the terminal phase of the disease. The rise occurs more rapidly and is more pronounced in animals previously treated with salmonella endotoxin or with killed BCG cells. This acceleration and intensification of the phagocytic response to infection can be detected even in animals which exhibit a normal phagocytic index when tested several weeks after administration of endotoxin or of BCG.

Although increase in resistance to infection is correlated with activation of the so called reticulo-endothelial system, there is no evidence of any direct causal relationship between the two phenomena.
STUDIES ON BACTERIEMIA
Authors: Rogers David E. , Melly Marian Ann
Published: June 2004

Rabbits given an intravenous injection of an 18 to 24 hour broth culture of E. coli commonly died within 28 hours. The injection of a 4 hour broth culture of the same strain of E. coli containing equal numbers of living bacilli produced only an occasional death.

Initial clearance rates and subsequent bacteriemias were similar in animals receiving either culture. Study of changes in circulating leukocytes or the temperature response to washed bacterial cells or culture filtrates failed to reveal obvious differences in host response to young or old cultures.

It was found that both living bacterial cells and some substance or substances present in culture filtrates were required to produce subsequent death. The injection of whole old cultures containing both these factors produced hypothermia instead of the endotoxin type fever response which followed the injection of whole young cultures.

Subsequent experiments revealed that this hypothermia appeared to be secondary to a period of transient but profound shock which occurred soon after the injection in rabbits receiving old cultures. No significant alterations in arterial pressure accompanied injections of young cultures.

Evidence is presented which suggests that this period of hypotension rendered animals more likely to die with a persisting bacteriemia tolerated without event by non-shocked animals. The mechanisms which operate to increase mortality during the post shock period are as yet unclarified.
THE SWINE LUNGWORM AS A RESERVOIR AND INTERMEDIATE HOST FOR HOG CHOLERA VIRUS
Authors: Shope Richard E.
Published: June 2004

Evidence that the swine lungworm can serve as reservoir and intermediate host for the hog cholera virus has been presented. The virus, however, is ordinarily carried in a masked form and must be provoked to pathogenicity by some stress before it can cause apparent disease. In the present experiments, ascaris larvae supplied the provocation needed to induce hog cholera in swine carrying lungworms infected with masked hog cholera virus. Provocation of the masked virus by ascaris larvae was seasonal in that it was effective only during a period embracing the first 5 months of the year.
ADSORPTION AND MATURATION OF POLIOVIRUS IN SINGLY AND MULTIPLY INFECTED HELA CELLS
Authors: Darnell James E.
Published: June 2004

Studies with polio-infected HeLa cells using cell disruption techniques during the early stages of infection have shown that:

The inoculum of poliovirus adsorbed on HeLa cells is largely inactivated. Infective virus accumulates in a monolayer sheet of cells in advance of release into the medium.

The eclipse period is shorter in multiply infected cells than in those infected with a single particle.
THE NATURE OF ANTIGEN-ANTIBODY COMPLEXES FORMED IN RABBITS DURING AN IMMUNE RESPONSE TO BOVINE SERUM ALBUMIN
Authors: Weigle William O.
Published: June 2004

The immune elimination of soluble BSA, following an intravenous injection, is accompanied by the appearance of circulating antigen-antibody complexes. The pattern of the appearance of circulating antigen-antibody complexes and the immune elimination of antigen probably depends on the amount of antigen injected, the rate of antibody synthesis, and perhaps, the quality of antibody produced.

There is no relationship between the I* antigen-antibody complexes detected during the immune response in rabbits by ammonium sulfate precipitation and the material precipitated from immune sera as a result of treatment with alkali. Alkali-precipitable material present in the serum of rabbits at a time when I* antigen is also present contain at most only traces of the antigen.
THE DEVELOPMENT IN VITRO OF PARTICLES FROM CYTOPLASM
Authors: Nelson Eric L.
Published: June 2004

A system is described in which microscopically visible particles develop from cytoplasmic proteins incubated in vitro. The conditions required for the development of particles are those usually associated with enzymic reactions. The particles are believed to develop as a result of enzyme action on cytoplasmic proteins in the presence of compounds having certain specific chemical configurations. The relation of the particles to various "microorganisms," described in the literature as etiologic agents of disease, and to the problem of seemingly positive blood cultures is discussed.
THE DEVELOPMENT IN VITRO OF PARTICLES FROM CYTOPLASM
Authors: Nelson Eric L.
Published: June 2004

Spherical particles, 1 to 10 microns in diameter, resulted from the incubation at 37°C. of distilled water lysates of erythrocytes with deoxyribonucleic acid (DNA). The particles consisted of 88 per cent hemoglobin and 12 per cent DNA (dry weight basis).

An unknown factor, presumably an enzyme, present only in fresh red cell lysates, was required for particle development. Particle size was a function of the pH of the reaction mixture. The pH range was 4.8–5.8.

It was possible to trap extraneous proteins and polysaccharides in pockets within the hemoglobin particles during their development to the exclusion of some of the hemoglobin. The amount of any one substance so trapped was proportional to its concentration in the reaction mixture.

Some practical applications of the particles, as a means for making particulate various soluble substances (enzymes, antigens, antibiotics), are suggested.
THE DIFFERENTIATION OF THREE DISTINCT DESOXYRIBONUCLEASES OF GROUP A STREPTOCOCCI
Authors: Wannamaker Lewis W.
Published: June 2004

Group A streptococci were found to produce three different desoxyribonucleases, designated here as A, B, and C. These enzymes migrated separately on analysis with starch zone electrophoresis, were immunologically distinct, and showed certain differences in inhibition by citrate and in optimal pH of activity. The relative amount of each enzyme produced was a function of strain variation.