bluuebunny/crossref_metadata_2025 huggingface dataset:
THE RELATION OF THE KREBS CYCLE TO VIRAL SYNTHESIS
Authors: Ackermann W. W. ,   With the Technical Assistance of Elaine Kleinschmidt and Hilda Kurtz
Published: June 2004

A further study has been made of the relationship of reactions of the Krebs cycle to the propagation of influenza virus. By the administration of sublethal doses of sodium fluoroacetate which were found to increase the concentration of citrate in the mouse lung, it was possible to demonstrate a blocking of the citric acid cycle in that organ. Further, the intraperitoneal administration of these concentrations of fluoroacetate was found to inhibit markedly the propagation of influenza, Type A, virus in the lungs of mice.

The inhibition was observed when the fluoroacetate was administered 15 minutes, 6 hours, or 12 hours after the mice were inoculated with virus. This effect was also demonstrable when the concentration of the viral inoculum was varied over a range of virus titers from 103.5 to 106.5.

Sodium fluoroacetate was found to have no effect in vitro on the infectivity or hemagglutinating property of the virus.

The significance of these findings with regard to chemotherapy and to the mechanism of viral synthesis is described.
LOCALIZATION OF ADRENOCORTICOTROPIC HORMONE BY HISTOCHEMICAL AND IMMUNOCHEMICAL METHODS
Authors: Marshall John M.
Published: June 2004

The fluorescent antibody technique was adapted to the localization of native protein antigens in cells and tissues. This method was applied specifically to the localization of adrenocorticotropic hormone in the pituitary gland.

An antiserum to hog ACTH was produced in an adrenalectomized rabbit. The γ2-globulin fraction of the serum was conjugated with fluorescein. After purification, the fluorescent antibody solution stained selectively the cytoplasm of basophil cells of the hog pituitary. No cells of sheep or beef pituitary or of hog kidney were stained. A fluorescent globulin solution prepared from normal rabbit serum gave no selective staining in any of these tissues.

Immunochemical tests showed that the fluorescent antibody gave a precipitin reaction with a highly active ACTH preparation of low molecular weight. The supernatant solution from this reaction showed a loss of hormone activity.
INFLUENCE OF THE PHYSIOLOGICAL BLOOD CLOTTING PROCESS ON THE COAGULATION OF BLOOD BY STAPHYLOCOAGULASE
Authors: Tager Morris , Lodge Anne L.
Published: June 2004

The conversion of plasma to serum results in a variable loss of the coagulase-reacting factor (C.R.F.) of the plasma.

The C.R.F. loss is incurred during the process of prothrombin conversion: conditions which favor the most effective prothrombin conversion result in maximal C.R.F. loss, while factors which interfere with prothrombin conversion spare the C.R.F.

In a system containing an adequate concentration of calcium, thrombo-plastin, and prothrombin, the C.R.F. loss reflects the amount of prothrombin conversion-accelerating substances (factor V or AC globulin).

If fibrin clots are produced directly by thrombin, and prothrombin conversion is excluded, there is no significant C.R.F. loss.
A SPECIFIC COMPLEMENT-FIXATION TEST FOR INFECTION WITH POLIOMYELITIS VIRUS
Authors: Casals Jordi , Olitsky Peter K. , Anslow Ralph O.
Published: June 2004

A complement-fixing antigen has been developed, using as source of material CNS tissue from newborn mice infected with the newborn mouse-adapted strain of the Lansing type, MEF1 virus. With this antigen, specific reactions have been obtained with sera from mice, cotton rats, and monkeys immunized with the Lansing-type virus, and from monkeys and chimpanzees convalescent from infection with this virus.

Twenty-one of 35 human sera obtained from individuals convalescent from poliomyelitis were positive and 6 of 22 from apparently normal persons having Lansing-neutralizing antibody, while this held true for only 1 of 19 from those having no Lansing-neutralizing antibody.

The fact that positive results were found in sera from patients having an infection with poliomyelitis virus of the Brunhilde type and at the same time no Lansing-neutralizing antibody brings up the possibility of the existence of a cross-reaction in complement fixation between the two types.
MECHANISM OF PRODUCTION OF PULMONARY LESIONS IN MICE BY NEWCASTLE DISEASE VIRUS (NDV)
Authors: Ginsberg Harold S.
Published: June 2004

Infectious NDV particles produce extensive pulmonary consolidation in the mouse in the absence of demonstrable virus multiplication. The lesions are indistinguishable from those of influenza A virus infection. This effect of NDV was blocked by intranasal injection of RDE or immune serum before virus inoculation, but not by immune serum injected 5 minutes or more after NDV. Influenza A virus infection did not diminish fixation of NDV in excised lungs but did interfere with the injurious action of this agent in the living mouse. The analogy between these reactions and those which take place in a progressive virus infection is pointed out, and the mechanism of production of lesions in virus pneumonias discussed.
INHIBITION OF ESCHERICHIA COLI BY p-AMINOBENZOIC ACID AND ITS REVERSAL BY p-HYDROXYBENZOIC ACID
Authors: Davis Bernard D.
Published: June 2004

p-Aminobenzoic acid (PABA) exerts three metabolic effects on E. coli: it acts as a normal vitamin at low concentrations, as a source of another vitamin, p-hydroxybenzoic acid (POB), at moderate concentrations, and as a growth inhibitor at high concentrations (150 to 1600 µg./ml.). The inhibition is competitively reversed by POB in 1/100 the concentration of PABA. The inhibition is also reversed to a limited extent by shikimic acid and compound X, precursors of POB.

p-Nitrobenzoic acid is an inhibitory competitor of both POB and PABA.

The retardation of growth produced by PABA and other competitive analogues of POB (p-nitrobenzoic acid; 4,4'-dihydroxydiphenyl sulfone; phenosulfazole) is converted to complete bacteriostasis by the addition of L-aspartic acid in a remarkably low concentration (1 µg./ml.)) without change in the competitive ratio with POB. The mechanism underlying this synergism is not clear.

In contrast to wild type, mutants that require POB not only are inhibited by much lower concentrations of the above analogues, but also show inhibition by weaker competitors of POB such as p-hydroxybenzenesulfonamide, p-chlorobenzoic acid, and p-fluorobenzoic acid.
OBSERVATIONS WITH THE ELECTRON MICROSCOPE ON THE SOLVATION AND RECONSTITUTION OF COLLAGEN
Authors: Vanamee Parker , Porter Keith R.
Published: June 2004

The course of events in the solvation and reconstitution of collagen obtained from rat tail tendon is described as seen with the electron microscope. Under the influence of 0.01 per cent acetic acid the collagen fibers swell and dissociate into submicroscopic filaments, the smallest of which are probably beyond the resolution of the electron microscope. These filaments can be made to reconstitute into fibers either by the addition of neutral salts to the acid solution or by raising the pH. The structural form of the resulting fibers is influenced by the concentration of the salt and by the pH of the solution employed. Saline-concentrations around 1 per cent and pH's ranging from 4.8 to 6.8 lead to the formation of needle-shaped crystals, or tactoids, showing the striated structure characteristic of collagen. Saline concentrations outside of this range (0.5 per cent and 5.0 per cent) lead to the formation of long fibrils without evidence of striations. pH's on the alkaline side of 6.8 bring about the formation of long slender fibers. Some of the possible reasons for these different fiber forms are discussed.

Apparently fibers are formed in vitro by the lateral and longitudinal association of the filaments seen in the original solutions. Some of the fibers thus formed may in turn associate laterally and longitudinally to form the larger fibers.

The formation of the needle-shaped crystals appears to be an orderly process since it leads to the formation of a periodicity in the fibers. The striations in the smaller fibers are uniform and regularly spaced at around 210 A. With continued growth of these fibers there is a simultaneous development of a more obvious and precise banding. It is evident that two out of each group of three regularly spaced striae are more prominent. This produces the macroperiod of collagen measuring around 640 A in length.
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Liu Oscar C. , Henle Werner
Published: June 2004

The combined passage of influenza A and B viruses in series, as reported by Sugg and Magill, has been confirmed. When the mixed passage materials were not too highly diluted both agents could be traced through 10 transfers.

Growth curve experiments revealed that both agents developed independently, as measured by hemagglutination-inhibition tests in the presence of specific immune sera against one or the other type. However, the hemagglutinin titers of the 2 viruses in the mixed series were always substantially lower than those recorded when the strains were used individually as seed in the same concentrations as were employed in the mixed series.

Assay of the infectivity titers of the individual strains in the presence of appropriate immune sera led to the demonstration that the time required for the growth cycle of influenza B virus varied with the dose of seed virus. With undiluted infected allantoic fluid as seed only 4 to 5 hours elapsed before new generations of virus were liberated. With increasing 10-fold dilution of the seed the constant period became increasingly longer until it stabilized at 8 to 10 hours. This finding offers an explanation for the seeming discrepancy between the observations on interference between the 2 viruses and the difference reported previously in the extent of their growth periods, on the one hand, and the fact that the 2 agents could be carried simultaneously in series through numerous passages in the chick embryo.
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Henle Werner , Liu Oscar C.
Published: June 2004

Evidence has been presented that influenza viruses both of type A and B partially inactivated by ultraviolet irradiation may regain their capacity to propagate in the allantoic membrane of the chick embryo. In using such irradiated preparations as inocula for growth curve experiments it could be shown that the development of hemagglutinins as well as of infectivity preceded at rates resembling those noted with more than 10 times the amount of infective virus actually found in the irradiated seed. Partial inactivation of the inocula by heating to 56°C. gave similar results.

The phenomenon was observed only with seed irradiated for short periods of time so that the virus particles sustained only few hits of radiation. On prolonged exposure resulting in numerous hits per virus particle the capacity of reactivation was lost. Likewise, an irradiated preparation capable of reactivation in the allantoic membrane, could not be diluted more than about 30-fold and still clearly produce this phenomenon. This indicated that reactivation is obtained only when one host cell adsorbs more than one non-infective virus particle but not upon adsorption of a single particle.

These data are in striking agreement with the phenomenon of "multiplicity reactivation" observed in the bacteriophage-E. coli system by Luria and Dulbecco.
ABSENCE OF A PROSTHETIC GROUP IN A TYPE-SPECIFIC POLYSACCHARIDE OF PNEUMOCOCCUS
Authors: Heidelberger Michael , MacLeod Colin M. , Markowitz Harold , DiLapi Marie M.
Published: June 2004

The specific polysaccharide of Type III pneumococcus, with only 0.05 per cent of N and 0.01 per cent of P, still shows almost maximal precipitation of a Type III antipneumococcus rabbit serum and the expected antigenicity in man. There is therefore no evidence that a prosthetic group is involved in these characteristic activities.
AN ELECTROPHORETIC STUDY OF A STREPTOCOCCAL PROTEINASE AND ITS PRECURSOR
Authors: Shedlovsky Theodore , Elliott S. D.
Published: June 2004

An electrophoretic study of crystalline preparations of a streptococcal proteinase and its precursor established their isoelectric points at pH values of 8.42 and 7.35 respectively (ionic strength 0.10).

Preparations of the proteinase appeared to be electrophoretically homogeneous over a pH range of 5 to 8.5. Precursor preparations contained a relatively low concentration of the active enzyme visible as a separate peak in electrophoretic patterns of sufficiently concentrated solutions.

Autocatalytic conversion of precursor to active enzyme was complete and resulted in a corresponding change in the electrophoretic pattern.

Treatment of precursor preparations with trypsin produced incomplete conversion to the active enzyme and resulted in the formation of a modified precursor protein. This differed from the parent substance in electrophoretic mobility and in susceptibility to trypsin, but resembled it in immunological specificity and, as previously shown, in susceptibility to conversion to active enzyme by autocatalysis.

Serological reactions of precursor and active enzyme components withdrawn from the cell after electrophoresis are described. It appears that the precursor protein may have two antigenic groups, one specific, the other shared by the active enzyme which behaves as a single antigen.
THE EFFECT OF CHEMICAL AND PHYSICAL AGENTS ON THE PHAGE RECEPTOR OF PHASE II SHIGELLA SONNEI
Authors: Barry Guy T. , Goebel Walther F.
Published: June 2004

A study has been made of the effect of bactericidal agents on the phage adsorption properties of Phase II. Sh. sonnei. The ability of this microorganism to adsorb T3, T4, and T7 phages can be altered by treating the bacteria with chemical and physical agents.
THE EFFECT OF ADRENOCORTICOTROPIC HORMONE ON INFLAMMATION DUE TO TUBERCULIN HYPERSENSITIVITY AND TURPENTINE AND ON CIRCULATING ANTIBODY LEVELS
Authors: Osgood Charles K. , Favour Cutting B.
Published: June 2004

The treatment with adrenocorticotropic hormone of guinea pigs sensitized with heat-killed tubercle bacilli caused suppression of their skin reactivity to tuberculin. Similar animals treated with saline did not show this change.

Normal guinea pigs treated with adrenocorticotropic hormone showed suppression of inflammation, but not necrosis, produced by intracutaneous oil of turpentine. There was slight, but probably not significant, diminution of inflammation during saline administration.

Tuberculin complement-fixing antibody titers were not altered by either adrenocorticotropic hormone or saline administration.

Adrenocorticotropic hormone produced marked eosinopenia and lymphopenia in guinea pigs.
THE DOMINANT ROLE OF THE LIVER IN PLASMA PROTEIN SYNTHESIS
Authors: Miller L. L. , Bly C. G. , Watson M. L. , Bale W. F.
Published: June 2004

A direct study of the isolated rat liver perfused with oxygenated blood containing amino acids and lysine-ϵ-C14 has yielded facts indicating that the liver synthesizes practically all the plasma fibrinogen, the albumin fraction, and probably more than 80 per cent of the plasma globulin fraction.

The response of the isolated perfused liver in protein synthesis is qualitatively and quantitatively analogous to that of the intact animal, notably in (a) the ability to discriminate between natural L-lysine and D-lysine, (b) the per cent of isotopic amino acid converted to CO2, (c) the per cent utilized in liver and plasma protein synthesis.

The results obtained with the perfused liver are compared and contrasted with those reported for tissue homogenates, minces, and slices.
STUDIES ON ENTRY AND EGRESS OF POLIOMYELITIC INFECTION
Authors: Faber Harold K. , Silverberg Rosalie J. , Dong Luther
Published: June 2004

Within 48 hours after simple oropharyngeal exposures of cynomolgus monkeys to poliomyelitis virus, histological signs of infection were found in ganglia supplying the exposed mucous membranes. At 3 days, virus was found in the Gasserian, petrosal-nodose, and superior cervical sympathetic ganglia. Lesions were most extensive and severe in the Gasserian. Virus continued to be detected daily from the 3rd to the 8th day, inclusive, in the Gasserian but not on the 9th; from the 3rd to the 6th day, inclusive, in the petrosal-nodose but not on the 7th, 8th, or 9th; on the 3rd and 6th days only, in the superior cervical sympathetic; and on the 5th day only, in the celiac.

In all the ganglia examined, the histological signs of infection increased to a maximum on the 5th day, and thereafter declined. In the sympathetic ganglia, a secondary late increase was observed on the 7th day.

During the first 7 days, no signs of infection were found in the CNS in 84 per cent of the animals examined, and in the remainder such lesions as were found were probably not significant. In control animals permitted to survive, the median period before the onset of symptoms of poliomyelitis, when these occurred, was 9 days (range 7 to 16 days), and in the animals with symptoms typical extensive lesions were found in the CNS. In two control animals failing to show symptoms and sacrificed at 26 and 30 days respectively, histological signs of infection were present in the Gasserian and other ganglia but none in the CNS.
THE GROWTH CURVE OF THE LANSING STRAIN OF POLIOMYELITIS VIRUS IN THE CENTRAL NERVOUS SYSTEM OF THE MOUSE
Authors: Ainslie John D.
Published: June 2004

After intracerebral inoculation of mice with a 10 per cent suspension (approximately 2000 LD50) of the Lansing strain of poliomyelitis virus, the infectivity titer in the brain decreased for approximately 6 hours. It then rose rapidly for 12 to 18 hours to reach titers of over 10–4. The rise in titer in the spinal cord closely paralleled that in the brain for 18 hours, after which the titer surpassed that in the brain by as much as one log. The infectivity titers in the central nervous system of unparalyzed mice remained between 10–3.5 and 10–4.2 for at least 7 days. With the onset of paralysis it was found that the titer was consistently and significantly higher in the spinal cords of paralyzed mice than in their brains or in the brains or cords of unparalyzed mice.

After inoculation of 1 per cent virus suspension the increase in titer occurred about 9 hours later than after the inoculation of 10 per cent virus suspension, and the onset of clinical signs of illness was also delayed. Once the titers began to rise, the rate was the same after the inoculation of either concentration of virus, and the maximal levels reached were the same. With both concentrations of virus, maximal infectivity titers in non-paralyzed mice were reached about 9 hours before the onset of signs of poliomyelitis.

The significance of these findings is discussed.
GROUP A STREPTOCOCCUS POLYSACCHARIDE: STUDIES ON ITS PREPARATION, CHEMICAL COMPOSITION, AND CELLULAR LOCALIZATION AFTER INTRAVENOUS INJECTION INTO MICE
Authors: Schmidt Willard C.
Published: June 2004

A method was developed for the extraction of the group A streptococcus polysaccharide employing pepsin digestion of ground streptococcal cells. This method did not result in the isolation of polysaccharide with chemical and physical chemical properties different from those exhibited by preparations extracted with hot formamide.

Studies of the chemical composition of this polysaccharide demonstrated it to be composed chiefly of rhamnose and glucosamine monosaccharide units in the approximate ratio of five moles of rhamnose to two moles of glucosamine.

The fate of the polysaccharide after intravenous injection into mice was studied using the fluorescent antibody technique. It was found to be rapidly eliminated by the kidney. The presence of the polysaccharide in the renal tubular epithelial cells during the excretory phase was the only evidence of its cellular localization that could be detected under the conditions of these experiments.
OBSERVATIONS CONCERNING THE PRODUCTION AND EXCRETION OF CHOLESTEROL IN MAMMALS
Authors: Byers Sanford O. , Friedman Meyer
Published: June 2004

Plasma cholesterol was observed to fall after release of biliary obstruction without any concurrent change in biliary excretion of cholesterol.

Excision of the nerve trunks accompanying the hepatic artery did not change the degree of hypercholesteremia following biliary obstruction.

No significant change in the cholesterol content of hepatic tissue occurred following biliary obstruction.

Animals with gastro-intestinal systems removed exhibited no significant change in plasma cholesterol, whereas those subjected to gastro-intestinal removal plus biliary obstruction exhibited a marked hypercholesteremia.

Anastomosis of the bile duct to the inferior vena cava resulted in a hypercholesteremia similar to that occurring after obstruction of the bile duct.
THE ANTISTREPTOCOCCAL PROPERTY OF MILK
Authors: Wilson Armine T. , Rosenblum Herman
Published: June 2004

Lactenin is reversibly inactivated by the exclusion of atmospheric oxygen. It is also inactivated by the sulfur-containing reducing agents cysteine, glutathione, thioglycollic acid, and BAL.

Group A streptococci which have been acted upon by lactenin have been killed, and not merely prevented from multiplying, since they cannot be revived by inactivating lactenin through the addition of a reducing agent.

Thiamine in great excess inactivates lactenin. The mechanism by which it accomplishes this has not been discovered, but it suggests that the mode of action of lactenin may be to deny thiamine to the lactenin-sensitive cell. Lactenin sensitivity is not, however, related to a requirement for exogenous thiamine, nor does lactenin appear to function by binding environmental thiamine in a form unavailable to the sensitive cell.
AN ELECTROPHORETIC EXAMINATION OF A URINARY MUCOPROTEIN WHICH REACTS WITH VARIOUS VIRUSES
Authors: Perlmann Gertrude E. , Tamm Igor , Horsfall Frank L.
Published: June 2004

A mucoprotein isolated from human urine and possessing the capacity to react with a number of viruses is electrophoretically homogeneous at pH 6.8 and 8.6. After treatment with influenza virus and elimination of its biological activity, the substance remains homogeneous and its electrophoretic mobility is decreased by approximately 20 per cent.
ON THE RESPONSE OF GENETICALLY RESISTANT AND SUSCEPTIBLE RABBITS TO THE QUANTITATIVE INHALATION OF HUMAN TYPE TUBERCLE BACILLI AND THE NATURE OF RESISTANCE TO TUBERCULOSIS
Authors: Lurie Max B. , Abramson Samuel , Heppleston A. G.
Published: June 2004

If genetically resistant and susceptible rabbits inhale a certain number of human type tubercle bacilli, no tuberculosis in the lungs of the resistant animals is seen, as a rule several months after infection, while there is a variable and often extensive disease in the susceptible rabbits. The analogy to the presence or absence of active tuberculosis in man infected with the tubercle bacillus is evident.

The inhaled tubercle bacilli multiply for but a short time in the resistant rabbits and are usually rapidly and completely destroyed. In the susceptible rabbits, the bacilli multiply profusely for a much longer time and persist in large numbers even months after inhalation.

Whatever be the cause of the more rapid destruction of tubercle bacilli in the resistant animal, the resulting more rapid release of the contained antigens enhances the development of allergic sensitivity and antibodies in these animals.

The development of an acquired resistance against tubercle bacilli of the human type is sufficiently rapid to affect the genesis of the initial gross primary pulmonary foci that result from the inhalation of a given number of bacilli. The greater the genetic resistance, the fewer the initial primary foci.

Variations in genetic resistance are essentially variations in the rate of development of acquired resistance.

It is suggested that variations in genetic resistance to inhaled human type tubercle bacilli may affect the prevalence of alveolar phagocytes capable of acquiring adequate resistance to the growth of the bacilli in their cytoplasm. The prevalence of such cells is subject to hormonal and immunological influences.
THE ISOLATION AND ASSAY OF HYPERTENSIN FROM BLOOD
Authors: Skeggs Leonard T. , Kahn Joseph R. , Shumway Norman P.
Published: June 2004

A method has been described for isolation and assay of hypertensin from the blood of dogs. An ethanol filtrate of blood drawn from the femoral artery is prepared and concentrated by evaporation. The hypertensin is extracted into n-butanol from which it is adsorbed into alumina, and subsequently eluted with dilute ethanol. The eluate is then evaporated to dryness, dissolved in water, and assayed by intravenous injection into rats.
FACTORS RELATED TO THE GROWTH OF PSITTACOSIS VIRUS (STRAIN 6BC)
Authors: Morgan Herbert R.
Published: June 2004

The inhibitory action of sodium sulfadiazine on the growth of psittacosis virus (6BC) in embryonated eggs is readily reversed by citrovorum factor but not by small amounts of vitamin B12.

In embryonated eggs, the pteroylglutamic acid analogues, 9-methylpteroylglutamic acid and 4-aminopteroylaspartic acid, produced some suppression of the growth of psittacosis virus (6BC). 4-Aminopteroylglutamic add, 4-amino-N10-methylpteroylglutamic acid, and 4-aminopteroylaspartic acid inhibited the growth of this virus in tissue cultures at concentrations which were not toxic for the host tissue. The inhibitory action of 4-amino-N10-methylpteroylglutamic acid and 4-aminopteroylaspartic acid was readily overcome by addition of citrovorum factor.

Growth of meningopneumonitis virus in embryonated eggs or tissue culture is suppressed by 4-aminopteroylaspartic acid.

The advantages of the tissue culture technic for studies on the growth of viruses are discussed.
FACTORS RELATED TO THE GROWTH OF PSITTACOSIS VIRUS (STRAIN 6BC)
Authors: Morgan Herbert R.
Published: June 2004

In various amounts and mixtures, adenine, guanine, xanthine, hypoxanthine, thymine, thymidine, cytidylic acid, and an enzymatic digest of desoxyribonucleic acid all failed to influence the inhibition by sulfadiazine of the growth of psittacosis virus (6BC) in embryonated eggs.

A number of purine analogues, including benzimidazole, 2,6-diaminopurine, and 8-azaguanine, inhibited the growth of psittacosis virus (6BC) in tissue cultures at concentrations which had no obvious toxic effects on the host tissues. The virus inhibitory action of 2,6-diaminopurine was reversed by addition of adenine and that of 8-azaguanine by guanine.

The growth of psittacosis virus (6BC) was inhibited by the pteridine compounds 2-ammo-4-hydroxy-6-formylpteridine and xanthopterin, while other related substances had little or no inhibitory activity. Xanthine reversed the inhibitory effects of 2-amino-4-hydroxy-6-formylpteridine. There was no correlation between the inhibitory activity of the pteridines on xanthine oxidase and multiplication of the virus.
EVIDENCE THAT ASCHOFF BODIES OF RHEUMATIC MYOCARDITIS DEVELOP FROM INJURED MYOFIBERS
Authors: Murphy George E.
Published: June 2004

Comparative studies on the histopathogenesis of experimentally induced lesions of myocardial Aschoff body type in rabbits and of many myocardial Aschoff bodies from several active rheumatic fever patients have revealed the following:

Almost invariably these experimental lesions and very frequently the myocardial Aschoff bodies studied in their early stages have been shown to originate in and evolve from lesions of heart muscle fibers.

The mono-, multi-, and non-nuciested cell masses, most characteristic of myocardial disease of the rheumatic type, appear to be damaged muscle fibers their fragments, and syncytial cell masses of probable muscular origin that proliferate from beneath the sarcolemma and in the tracks of damaged muscle fibers in reaction to that damage.

In addition to destructive changes in cardiac muscle fibers an attempt at myofiber regeneration may occur in some myocardial Aschoff bodies.

The most distinguishing histologic feature of the myocardial Aschoff bodies in rheumatic heart disease are the peculiar lesions of muscle fibers. Therefore, it is proposed that they be designated as myofiber Aschoff bodies in order to indicate their origin more accurately.

The results of these investigations contrast with the widely accepted theory that all myocardial Aschoff bodies originate as injured interstitial collagen, and that, as they evolve, they consist of damaged interstitial collagen intermingled with cells of non-myogenic derivation that proliferated in response to that collagen injury.

These studies, furthermore, provide evidence that experimental homologues of rheumatic myocardial Aschoff bodies have been induced in a very few among many rabbits subjected to reposted focal infections with group A streptococci of different serological types. Hence, they support the concept that the myocardial Aschoff bodies of rheumatic fever are induced by repeated infections with group A streptococci of several different serological types; even though only a certain few among the many patients so infected develop these lesions.
QUANTITATIVE IMMUNOCHEMICAL STUDIES WITH THE PURIFIED FACTOR IN MOUSE MILK CONNECTED WITH MAMMARY CARCINOMA
Authors: Heidelberger Michael , Graff Samuel , Haagensen C. D. ,   With the Technical Assistance of Arnold Powell and Anton Samuel
Published: June 2004

Antisera to the mouse milk factor (F), containing up to 0.5 mg. of antibody nitrogen per ml. are readily obtainable in rabbits, especially when adjuvants are added to the antigen.

Quantitative data on the anti-F content of the sera are given, also on the total nitrogen precipitated by the non-casein fraction of C57 mouse milk which does not contain F.

The antisera were also absorbed with casein fractions but the difficulties in the way of quantitative analysis were not overcome.

Antisera to fractions of C57 mouse milk were also obtained and the reactions of F and the C57 proteins with these sera were studied.

The results, as far as they go, are in accord with the earlier belief that the milk factor possesses an immunological specificity not present in normal mouse tissues.
RADIOAUTOGRAPHIC STUDIES OF SULFATE-SULFUR (S35) METABOLISM IN THE ARTICULAR CARTILAGE AND BONE OF SUCKLING RATS
Authors: Dziewiatkowski Dominic D.
Published: June 2004

Fifteen minutes after intraperitoneal injection of sulfur-35 as sodium sulfate to 7-day-old rats the concentration of the isotope was highest in the cartilage at the epiphyseal-diaphyseal junction of long bones but was demonstrable throughout the entire epiphysis. Up to the 24th hour the pattern of deposition did not change as the concentration continued to increase.

As centers of secondary ossification developed, there occurred in them an increased concentration of some form of sulfur, insoluble as the barium salt. This sulfur was probably derived from the cartilage which the center of secondary ossification replaced.

Up to about the 30th minute after injection the sulfur-35 was deposited transitorily in a high concentration in discrete loci of the bone marrow. Excluding this transitory deposition, the highest concentration of the radioisotope in the bone marrow was seen in the specimens removed 24 hours after administration.

In the bone shaft the sulfur-35, in a form which was insoluble in an alkaline solution of barium ions, was deposited diffusely up to the 24th hour after its administration. Thereafter, the radioisotope decreased in concentration in the middle portion of the bone shaft. However, the concentration of a similarly characterized sulfur-35-bearing component in the ends of the diaphysis continued to increase up to at least the 96th hour after injection.
SERUM AND URINARY FIBRINOLYTIC ACTIVITY RELATED TO THE HEMORRHAGIC DIATHESIS IN IRRADIATED DOGS
Authors: Colgan J. , Gates E. , Miller L. L.
Published: June 2004

The urine and serum fibrinolytic activity were measured in dogs following whole body radiation ranging from 450 to 800 r generated by 1,000 kv. and 250 kv. machines.

The fibrinolytic activity of the urine showed a precipitate rise 4 to 5 days before death in all dogs with pulmonary hemorrhage as the main cause of death.

The fibrinolytic activity of the serum showed a similar rise, which was most pronounced in the case of those animals which did not survive.

The fibrinolytic activities of the urine and serum approached control levels at about the 24th day after irradiation in all the surviving dogs.

The possible mode of activation of the fibrinolytic enzyme in vivo is discussed and approaches to prevention of the hemorrhagic syndrome are suggested.
SERIAL TRANSPLANTATION OF RABBIT PAPILLOMAS CAUSED BY THE SHOPE VIRUS
Authors: Rogers Stanfield
Published: June 2004

Two cutaneous papillomas produced with the Shope virus in adult domestic rabbits were transferred to their leg muscles and thence to those of several successive groups of rabbits of various ages. The growths failed to establish themselves in some newborn animals, but in many formed huge masses, immobilizing the legs with result in early death. Not infrequently they did well for months after their hosts had matured, yet nevertheless they failed regularly on further transfer in adults. They were eventually lost because left long prior to passage on the supposition that they might gain the ability to succeed in mature hosts.

The papillomas when growing actively sometimes penetrated the reactive tissue encapsulating them and replaced the adjacent muscle. They often entered lymph and blood vessels but never metastasized, nor did they undergo carcinomatous change though their total period of proliferation was as considerable as that elapsing in many instances before cancer appeared in papillomas produced by the same virus material and left on the skin.
STUDIES ON THE INHIBITION OF PROTEOLYTIC ENZYMES BY SERUM
Authors: Shulman N. Raphael
Published: June 2004

The mechanism of the inhibition of trypsin, plasmin, and chymotrypsin by serum was studied using fibrin tagged with radioactive iodine as a substrate.

Enzyme-inhibitor relationships were studied by: (a) varying the concentration of serum; (b) varying the concentration of enzyme; and (c) by diluting the enzyme-serum mixture. The results indicate that the inhibition of trypsin, plasmin, and chymotrypsin is a stoichiometric and irreversible reaction.

By using the Lineweaver-Burk graphical method of analysis it was demonstrated that the inhibition of trypsin and chymotrypsin is a non-competitive reaction. This finding supports the conclusion that inhibition by serum is an irreversible type of reaction.

The substrate was found to exert a retarding effect on the activity of plasmin. The possibility of a plasmin inhibitor in fibrinogen was suggested.

The suitability of the various procedures used in evaluating serum proteolytic inhibition was discussed.
STUDIES ON THE INHIBITION OF PROTEOLYTIC ENZYMES BY SERUM
Authors: Shulman N. Raphael
Published: June 2004

Variation in the inhibition of trypsin, chymotrypsin, and plasmin by serum was studied in 65 normal individuals and in 117 patients with a variety of diseases.

It was shown that elevated inhibition for trypsin and chymotrypsin is associated with disease processes that bring about cellular destruction.

Changes in the inhibition of trypsin and chymotrypsin were closely correlated with changes in the erythrocyte sedimentation rate and fibrinogen concentration that occur in association with disease.

Intravenous typhoid vaccine was found to produce parallel changes in the inhibition of trypsin and chymotrypsin and in the fibrinogen concentration in human beings.

It was concluded that the diagnostic significance of increased trypsin or chymotrypsin inhibition is the same as that of increased fibrinogen concentration; it is a common, non-specific response to a variety of pathological conditions and has no value as a specific diagnostic test.

Increased plasmin inhibition occurred too infrequently to permit detailed study.
DEVELOPMENT, PERSISTENCE, AND SIGNIFICANCE OF TYPE 2, POLIOMYELITIS COMPLEMENT-FIXING ANTIBODY IN MAN
Authors: Casals Jordi , Olitsky Peter K. , Sabin Albert B.
Published: June 2004

Sera from 81 patients with a diagnosis of paralytic or non-paralytic poliomyelitis, and from 159 individuals of similar age groups giving no history of the disease, were tested with a high titered, complement-fixing poliomyelitis antigen of Type 2 (Lansing-like). The antigen consisted of brain tissue from newborn mice injected with the MEF1 strain of virus as previously adapted to these animals. The presence or absence of Type 2 neutralizing antibody in the sera under test was found not to affect the complement fixation.

Positive reactions were obtained with 57 per cent of the sera deriving from non-paralytic patients and in 70 per cent from paralytics, when the specimens were tested at a dilution of 1:16. The complement-fixing antibody was often present in highest titer as early as 24 hours after the onset of poliomyelitis, and in almost all instances within 7 days. In about half of the patients a 4-fold or greater drop in titer occurred within 3 months, with little or no change in the others.

The incidence of titers of 1:16 or higher with the control sera varied with the season of the year at which they were procured, 3 per cent of the winter samples proving positive and 13 per cent of the summer.

The tests of sera from the group of patients from whom poliomyelitis virus was recovered, disclosed no significant differences between those having the paralytic and those having the non-paralytic disease.

Type 1 (Brunhilde-like) strains of virus were recovered from many of the patients yielding positive tests, although they presented no evidence of previous or concurrent infection with Type 2 virus. This finding shows that Type 1 virus can give rise in patients to Type 2 complement-fixing antibody.

The application of these data to the serologic diagnosis of poliomyelitis infection in man will of necessity be limited until information is obtained on the development, persistence, and significance of complement-fixation reactions with antigens deriving from Type 1 and Type 3 poliomyelitis strains.
HOMOTYPIC COMPLEMENT-FIXING ANTIBODY IN MONKEYS INFECTED WITH TYPE 2 POLIOMYELITIS VIRUS BY THE ORAL ROUTE
Authors: Casals Jordi , Olitsky Peter K. , Sabin Albert B.
Published: June 2004

CF tests with Type 2 poliomyelitis antigen (MEF1) were performed on the pre- and postinfection sera of 20 cynomolgus monkeys which developed paralytic, non-paralytic, or inapparent infection following oral administration of a Type 2 strain of virus (Y-SK). All the monkeys developed neutralizing antibody, and 17 developed CF antibody in an original serum dilution titer of 1:4 or greater. The 3 monkeys which did not develop this level of CF antibody were in a group of 7 which died within 8 days after onset of paralysis. The CF titers were as high at 2 to 6 days after onset of paralysis in the other 4 moribund or dead monkeys as in the surviving animals tested 4 weeks after the first dose of virus and the CF titers were of the same order of magnitude in the groups with paralytic, non-paralytic, or inapparent infection. The Type 2 poliomyelitis CF titers developed in monkeys as a result of infection with homotypic virus were not greater than those found in human beings infected with heterotypic Type 1 poliomyelitis strains.
THE PATHOGENESIS OF EXPERIMENTAL DYSENTERY INTOXICATION
Authors: Penner Abraham , Klein Samuel H.
Published: June 2004

All analysis of the mechanisms involved in the pathogenesis of the visceral lesions produced by Shiga toxin in the dog has indicated that the structural changes are produced by a vascular mechanism which is under control of the sympathetic nervous system. Paralysis of the latter at the myoneural junction or in the ganglia by means of drugs served to prevent the tissue changes as well as the hyperglycemia and hemoconcentration characteristic of the sympathomimetic response. The observations indicated that the toxin acted via a mechanism located in the central nervous system.

Further studies of the action of Shiga toxin by means of cerebral cross-circulation are reported here. In these the cerebral blood flow of one dog derived from the circulation of the trunk and limbs of another. Injection of the toxin into the femoral vein of this latter dog resulted in the appearance of visceral lesions, hemoconcentration, and hyperglycemia in the former whose brain only received blood containing the toxin. The resulting visceral changes were identical with those observed in the intact unanesthetized dog which had received the toxin directly. The observations indicate that, in dogs, Shiga toxin produces its characteristic visceral lesions via the central nervous system. Possible mechanisms are discussed.
EXPERIMENTS ON THE CAUSE OF THE RABBIT CARCINOMAS DERIVED FROM VIRUS-INDUCED PAPILLOMAS
Authors: Rous Peyton , Kidd John G. , Smith William E.
Published: June 2004

Tests were made to learn whether an anaplastic, epidermal carcinoma, the Vx2, which had originated more than 8 years previously from a virus papilloma in a domestic rabbit, still rendered its hosts immune to the virus. It had done so in the first 22 successive groups of animals to which it was transferred during a period of 3½ years, its growth regularly eliciting a blood antibody that neutralized the Shope virus and fixed complement in mixture with it; and on the assumption that this would continue to be the case no further observations were made for nearly 4½ years more. Then direct inoculation of animals carrying the tumor in its 46th Generation showed them to be as susceptible to the virus as normal rabbits; and sera procured from hosts of the 46th, 47th, 48th, and 50th Generations failed to neutralize the virus or fix complement with it. Tests of this last sort, repeated at intervals since,—most recently with sera from animals carrying the tumor in its 73rd Generation,—have yielded consistently negative findings.

Loss of the power to immunize against the papilloma virus was not attended by any perceptible change in the Vx2 carcinoma. Manifestly the antigen responsible for the immunity cannot, as such, have been the actuating cause of the tumor.

Attempts were made to infect the cells providing 48th Generation cancers, by mixing them with a suspension of the papilloma virus at time of implantation, or by injecting this agent into the blood stream of rabbits in which the tumog had already begun to proliferate. Its morphology and rate of growth remained unaltered; but tests of the animals to which transfers were next made yielded what appeared to be evidence of some slight immunity to the virus.
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: Nelson John B.
Published: June 2004

The etiological agent of the acute hepatitis encountered in weanling mice of the Princeton strain is a virus found in the liver, spleen, kidneys, heart's blood, urine, and intestinal contents of experimentally infected animals. Older Princeton mice and weanlings from four other strains (Swiss, Webster's BSVS, C albino) and Bagg) proved to be less susceptible than Princeton weanlings.

The virus was demonstrable in Berkefeld V filtrates of liver suspensions and in supernatants after centrifugation at 10,000 G. In whole liver suspensions it was detectable in decreasing amounts through a dilution of 10–7.

Aureomycin and terramycin had no detectable effect on the activity of the virus in weanlings.
STUDIES ON A PROTEOLYTIC ENZYME IN HUMAN PLASMA
Authors: Ratnoff Oscar D. ,   With the Technical Assistance of Velma H. Axelrod and Rosemary K. Ashe
Published: June 2004

Calcium ions accelerated the activation of the proteolytic enzyme of plasma from its precursor in the globulin fraction. Calcium did not appear to potentiate fibrinolysis by active bovine or human plasma proteolytic enzyme, nor did it accelerate the activation of the precursor of this enzyme by chloroform or by streptokinase. Experiments with partially purified plasma proteolytic enzyme suggested that the acceleratory effect of calcium was mediated indirectly. Since the concentration of calcium which was effective was comparable to that present in plasma, it is possible that the phenomena reported are of biological significance.
PROTECTION AGAINST FATAL RENAL INJURY DUE TO CHOLINE DEFICIENCY BY RENAL DECAPSULATION
Authors: Baxter James H.
Published: June 2004

Decapsulation of the left kidney through a lumbar incision immediately prior to placing young rats on a choline-deficient diet afforded a significant degree of protection against animal mortality, compared with that which occurred as a result of the deficiency in the control groups. Decapsulation also was effective in reducing greatly the renal injury which developed in the decapsulated kidneys, as judged by a comparison of the decapsulated kidneys with the contralateral undecapsulated kidneys of the same animals. Decapsulation through an abdominal incision also was efficacious.

Decapsulation after 4 or 5 days on the deficient diet, at which time relatively early renal lesions were present in most of the animals, afforded little if any protection.

Experiments in which the usual adhesions between the decapsulated kidneys and surrounding tissues were prevented by covering the decapsulated kidneys with artificial capsules demonstrated that protection due to decapsulation could occur in the absence of adhesions.

Renal denervation without removal of the renal capsule was not associated with a decrease in renal damage or animal mortality.

Possible mechanisms of the protective effect of renal decapsulation in choline deficiency are discussed.
THE SOMATIC ANTIGEN OF A PHAGE-RESISTANT VARIANT OF PHASE II SHIGELLA SONNEI
Authors: Goebel Walther F. , Jesaitis Margeris A.
Published: June 2004

1. A phage-resistant variant of Phase II Shigella sonnei has been isolated and the type-specific antigen from it has been obtained.

2. The antigen of the variant microorganism, II/3, 4, 7, differs from that of the parent Phase II bacillus in serological specificity and in chemical make-up.

3. Although the antigen of Phase II Sh. sonnei inhibits all T phages to which the bacillus is susceptible, that of the variant fails to inhibit T3, T4, and T7.
THE USE OF PHOSPHORUS 32 IN STUDIES ON PLASMODIUM GALLINACEUM
Authors: Clarke Delphine H.
Published: June 2004

The measurement of the degree of incorporation of P32 into nucleic acids has been used as a quantitative means of studying parasite growth and development in vitro under various conditions.

An extract of normal chicken erythrocytes was found to be of unique importance as a constituent of the medium, both for intact parasitized cells and for lysates of such cells. Heated normal chicken serum possessed some favorable effect upon intact cells.

The major portion of the beneficial effect of the erythrocyte extract was found to be associated with the non-dialyzable portion, although the dialysate was shown to possess slight growth-promoting activity. Further attempts to characterize the extract in terms of its favorable effects upon parasite growth were unsuccessful.

A medium and conditions were developed which permitted the growth of a limited parasite population in lysates of parasitized red cells. The most important constituents of the medium were concentrated, freshly prepared erythrocyte extract and malate.

Comparative studies carried out with intact parasitized cells and with lysates showed that substances and conditions exerting quite marked effects upon the intact cell system were without effect or exerted a less marked effect upon parasite growth in lysates. The possible implications of these observations are discussed and the further exploitation of this comparative approach suggested as a means of furthering our knowledge of parasite-host cell relationships.
STUDIES ON THE EXTRACELLULAR CULTIVATION OF AN INTRACELLULAR PARASITE (AVIAN MALARIA)
Authors: Trager William
Published: June 2004

The extracellular survival and development in vitro of the erythrocytic stages of Plasmodium lophurae were favored by the addition to the culture medium of l-malic acid and concentrates rich in coenzyme A. In a concentrated extract of duck erythrocytes supplemented with these two substances in addition to adenosinetriphosphate, sodium pyruvate, and certain other materials of like nature, only 5 to 10 per cent of the extracellular parasites had become abnormal after 3 days of cultivation.