bluuebunny/crossref_metadata_2025 huggingface dataset:
Enthalpy arrays
Authors: Torres Francisco E. , Kuhn Peter , De Bruyker Dirk , Bell Alan G. , Wolkin Michal V. , Peeters Eric , Williamson James R. , Anderson Gregory B. , Schmitz Gregory P. , Recht Michael I. , Schweizer Sandra , Scott Lincoln G. , Ho Jackson H. , Elrod Scott A. , Schultz Peter G. , Lerner Richard A. , Bruce Richard H.
Published: June 2004

We report the fabrication of enthalpy arrays and their use to detect molecular interactions, including protein–ligand binding, enzymatic turnover, and mitochondrial respiration. Enthalpy arrays provide a universal assay methodology with no need for specific assay development such as fluorescent labeling or immobilization of reagents, which can adversely affect the interaction. Microscale technology enables the fabrication of 96-detector enthalpy arrays on large substrates. The reduction in scale results in large decreases in both the sample quantity and the measurement time compared with conventional microcalorimetry. We demonstrate the utility of the enthalpy arrays by showing measurements for two protein–ligand binding interactions (RNase A + cytidine 2′-monophosphate and streptavidin + biotin), phosphorylation of glucose by hexokinase, and respiration of mitochondria in the presence of 2,4-dinitrophenol uncoupler.
Global patterns of plant leaf N and P in relation to temperature and latitude
Authors: Reich Peter B. , Oleksyn Jacek
Published: June 2004

A global data set including 5,087 observations of leaf nitrogen (N) and phosphorus (P) for 1,280 plant species at 452 sites and of associated mean climate indices demonstrates broad biogeographic patterns. In general, leaf N and P decline and the N/P ratio increases toward the equator as average temperature and growing season length increase. These patterns are similar for five dominant plant groups, coniferous trees and four angiosperm groups (grasses, herbs, shrubs, and trees). These results support the hypotheses that (
i
) leaf N and P increase from the tropics to the cooler and drier midlatitudes because of temperature-related plant physiological stoichiometry and biogeographical gradients in soil substrate age and then plateau or decrease at high latitudes because of cold temperature effects on biogeochemistry and (
ii
) the N/P ratio increases with mean temperature and toward the equator, because P is a major limiting nutrient in older tropical soils and N is the major limiting nutrient in younger temperate and high-latitude soils.
Auditory capacities in Middle Pleistocene humans from the Sierra de Atapuerca in Spain
Authors: Martínez I. , Rosa M. , Arsuaga J.-L. , Jarabo P. , Quam R. , Lorenzo C. , Gracia A. , Carretero J.-M. , de Castro J.-M. Bermúdez , Carbonell E.
Published: June 2004

Human hearing differs from that of chimpanzees and most other anthropoids in maintaining a relatively high sensitivity from 2 kHz up to 4 kHz, a region that contains relevant acoustic information in spoken language. Knowledge of the auditory capacities in human fossil ancestors could greatly enhance the understanding of when this human pattern emerged during the course of our evolutionary history. Here we use a comprehensive physical model to analyze the influence of skeletal structures on the acoustic filtering of the outer and middle ears in five fossil human specimens from the Middle Pleistocene site of the Sima de los Huesos in the Sierra de Atapuerca of Spain. Our results show that the skeletal anatomy in these hominids is compatible with a human-like pattern of sound power transmission through the outer and middle ear at frequencies up to 5 kHz, suggesting that they already had auditory capacities similar to those of living humans in this frequency range.
Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia
Authors: Lee Jong-Min , Chan Kaimin , Kan Yuet Wai , Johnson Jeffrey A.
Published: June 2004

A basic leucine zipper transcription factor, NF-E2-related factor 2 (Nrf2), plays a critical role in the cellular defense mechanism by mediating a coordinate up-regulation of antioxidant responsive element-driven detoxification and antioxidant genes. Here, we report that targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia due to increased sequestration of damaged erythrocytes. Splenomegaly and spleen toxicity in Nrf2-/-mice raised a possibility of hemolytic anemia and splenic extramedullary hematopoiesis in Nrf2-/-mice. In support of this, hematology analysis revealed that Nrf2-/-mice suffer from anemia with abnormal red cell morphologies (i.e., Howell-Jolly bodies, acantocytes, and schistocytes). In addition, Nrf2-/-erythrocytes were more sensitive to H2O2-induced hemolysis, and erythrocyte-bound IgG levels were markedly increased in Nrf2-/-mice compared with Nrf2+/+mice. Because IgG bound to erythrocytes in the presence of oxidative damage in erythrocytes (regardless of Nrf2 genotype), these data support that Nrf2-/-erythrocytes have higher levels of damage compared with Nrf2+/+cells. Finally, Nrf2-/-mice showed increased levels of erythrocyte-bound IgG compared with Nrf2+/+mice after H2O2injectionin vivo, suggesting that the decreased glutathione and increased H2O2render the Nrf2-/-mice more susceptible to toxicity. Taken together, these observations indicate that a chronic increase in oxidative stress due to decreased antioxidant capacity sensitizes erythrocytes and causes hemolytic anemia in Nrf2-/-mice, suggesting a pivotal role of Nrf2-antioxidant responsive element pathway in the cellular antioxidant defense system.
Active oxygen species and antioxidants in seed biology
Authors: Bailly Christophe
Published: June 2004

Active oxygen species (AOS) are involved in various aspects of seed physiology. Their generation, which occurs during seed desiccation, germination and ageing, may lead to oxidative stress and cellular damage, resulting in seed deterioration. However, cells are endowed with detoxifying enzymes and antioxidant compounds that scavenge AOS and participate in seed survival. The detoxifying mechanisms play a key role in acquisition of desiccation tolerance of developing seeds, completion of seed germination and seed storability. However, AOS must also be regarded as molecules intervening in cellular signalling. They are involved in growth processes occurring at early embryogenesis during seed development, and participate in the mechanisms underlying radicle protrusion during seed germination. AOS might also have a regulatory function in the changes in gene expression during seed development, dormancy and germination. Their interplay with other molecules, particularly with hormones such as abscisic acid, suggests that they should be considered as key components of an integrated signalling network involved in many aspects of seed physiology.
Phytic acid-phosphorus and other nutritionally important mineral nutrient elements in grains of wild-type and low phytic acid (lpa1–1) rice
Authors: Lott John N.A. , Liu Jessica C. , Ockenden Irene , Truax Michael , Lott John N.A.
Published: June 2004

Mineral nutrient stores in cereal grains are mainly phytate, a salt of the phosphorus-rich compound phytic acid. Quantitative measures of total phosphorus, phytic acid-phosphorus, potassium, magnesium, calcium, iron, manganese and zinc were obtained for whole grains, embryos and rest-of-grain portions of cv. Kaybonnet rice (wild type) (Oryza sativa L.) and a low phytic acid (lpa1–1) mutant strain with a 45% reduction in phytic acid. P, K and Mg were present in higher amounts than Ca, Mn, Fe and Zn in both grain types. Whole-grain amounts of total P, Ca, Mn and phytic acid-phosphorus were lower in whole lpa1–1 grains than in wild-type grains; K, Mg and Fe amounts were similar, and Zn was higher. Embryos, which comprise 3.5% or less of grain dry weight, were comparatively rich in all measured elements. The lpa1–1 mutation influenced the phytic acid content of the embryo more than that of the aleurone layer. Aleurone-layer cells of wild-type grains had many phosphorus-rich globoids 2μm or larger in diameter, whereas lpa1–1 grains contained more of the smaller globoids. The reduction in globoid size was consistent with the reduction in phytate. Energy-dispersive X-ray analysis of both aleurone-layer cells and sections of globoids in aleurone-layer cells revealed that P, K and Mg were the main mineral nutrient elements present in both grain types; traces of Ca, Mn, Fe or Zn were present. Starchy endosperm cells contained virtually no P, K or Mg, whereas scutellum cells were rich in these elements.
Seed-dormancy variation in natural populations of two tropical leguminous tree species: Senna multijuga (Caesalpinoideae) and Plathymenia reticulata (Mimosoideae)
Authors: Lacerda Daniela R. , Lemos Filho José Pires , Goulart Maíra F. , Ribeiro Renata A. , Lovato Maria Bernadete
Published: June 2004

Senna multijuga and Plathymenia reticulata are tropical tree species native to the Brazilian Atlantic Forest and the Brazilian Cerrado, respectively. Seed-coat dormancy variation was evaluated within and among natural populations of these two species. Scarified and non-scarified seeds from different plants within populations were germinated at 28°C, and the percentage of germinated seeds was estimated for both species. Mean germination percentages of non-scarified seeds tended to be higher for P. reticulata populations (40 and 62%) than for S. multijuga populations (9 and 35%). After scarification, germination percentages increased significantly in both species, with all populations showing mean values above 84%. The level of seed dormancy, evaluated through the experiment with non-scarified seeds, differed significantly within and among populations of both species (P < 0.05). The values of the coefficient of genotypic determination were high for populations of both species (b = 0.85). Although this coefficient is an overestimation, since it includes non-genetic maternal effects, its high values suggest that a considerable part of the phenotypic variation in seed dormancy in S. multijuga and P. reticulata is of genetic origin. Variation in seed dormancy can be an important factor for increasing genetic diversity in populations of these species, making them able to respond to environmental changes.
Desiccation sensitivity and cell cycle aspects in seeds of Inga vera subsp. affinis
Authors: Rocha Faria José Marcio , van Lammeren André A.M. , Hilhorst Henk W.M.
Published: June 2004

The desiccation sensitivity of seeds ofInga veraWilld. subsp.affinis, a recalcitrant-seeded tree from Brazil, was analysed, focusing on water relations and cell-cycle aspects, including DNA content and the microtubular cytoskeleton. Seeds were collected at four developmental stages, dried to different moisture contents (MCs), assessed regarding water activity and set to germinate. Samples of fresh (non-dried) developing and mature seeds were used for assessment of DNA content by flow cytometry. Immunohistochemical detection of microtubules (MTs) was done in mature seeds at different MCs. Slight desiccation of immature seeds increased germination, but further drying resulted in a quick decline of germinability. During seed development the desiccation sensitivity decreased slightly, but DNA content of the embryonic axis cells remained constant, suggesting no relation between those two parameters. Embryonic axis cells of mature seeds showed abundant cortical microtubule arrays, which were not affected by mild desiccation, but broken down by further drying. It appeared that, upon rehydration, damaged cells were not able to reconstitute the microtubular cytoskeleton. The failure of germination ofInga veraseeds after drying could not be attributed to cellular damage to DNA synthesis and mitosis, since the radicle protruded by means of cell elongation, without a need for cell division. However, the breakdown of MTs during desiccation, and their subsequent inability to reassemble upon rehydration, may be related to the decreased germination, since MTs are required for cell elongation.
VITAMIN A AND ENDOCHONDRAL OSSIFICATION IN THE RAT AS INDICATED BY THE USE OF SULFUR-35 AND PHOSPHORUS-32
Authors: Dziewiatkowski Dominic D.
Published: June 2004

The administration of vitamin A to vitamin A-deficient rats resulted in a decreased concentration of inorganic sulfate-sulfur in the serum from a value of 2.5 mg. per cent to 1.8 mg. per cent, the latter being close to the value of 2.0 mg. per cent found in normal rats of the same age.

The uptake of sulfate and phosphate by femurs and tibiae of vitamin A-deficient rats was less than that in normal rats of the same age. An increased uptake followed the administration of vitamin A: radioautography indicated that in the case of sulfate, its uptake was particularly increased in the epiphyseal cartilage; an increased uptake of phosphate was particularly evident in the diaphysis immediately adjacent to the epiphyseal cartilage plate.

The specific activity of the sulfate-sulfur in the chondroitin sulfate samples isolated from the skeletons of vitamin A-deficient rats fell progressively as the deficiency continued. Following administration of vitamin A, the specific activity approached and exceeded the value given by the sample from the skeletons of normal rats of the same age.

A substantial increase was found in the value of the specific activity of the sulfate-sulfur of sulfomucopolysaccharides isolated from skins of vitamin A-deficient rats that had been given vitamin A.

Following administration of vitamin A to rats deficient in this vitamin, an increased accumulation of some sulfur-containing material was found in regions of active calcification.
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Henle Werner , Liu Oscar C. , Finter Norman B. ,   With the Technical Assistance of Mary I. Knickerbocker
Published: June 2004

The period and rate of liberation of influenza virus from entodermal cells of the allantois have been studied by deembryonating eggs within a few minutes after infection, exchanging the medium thereafter at hourly intervals and assaying the virus concentration in the harvests thus obtained (differential growth curves). If the inoculum was sufficiently large, presumably all available cells immediately became infected and only 1 infectious cycle was expected to occur. If the inoculum was small, so that only a fraction of the cells adsorbed virus, the infectious process was held to 1 cycle by continuous exposure of the remaining susceptible cells to RDE. In either case, the results obtained indicate that once cells have been infected they produce and liberate virus at nearly constant rates for periods of 30 hours or longer before the yields decrease rapidly. Evidence has been presented which strongly suggests that such prolonged periods of liberation are observed not only in deembryonated eggs but also in the intact chick embryo.

Attempts have been made in the discussion to reconcile these findings with previous estimates of the liberation period and to integrate them with histologic observations and electron micrographs of thin sections of infected allantoic membranes having a bearing on the mode of liberation.
ISOLATION OF B VIRUS (HERPES GROUP) FROM THE CENTRAL NERVOUS SYSTEM OF A RHESUS MONKEY
Authors: Melnick Joseph L. , Banker Dushyant D.
Published: June 2004

While passaging a recently isolated strain of poliomyelitis virus through a rhesus monkey, another virus was procured from its central nervous system. After intracerebral inoculation, the virus produced meningoencephalitis in monkeys, cotton rats, hamsters, guinea pigs, and rabbits; after intracutaneous inoculation a necrotic skin lesion was produced in the monkey and rabbit and this was often followed by myelitis. The virus could also be passed in newborn mice less than 48 hours old and in chick embryos by inoculation of the chorioallantoic membrane.

Immunological and host range studies revealed this virus to be related to the B virus originally described by Sabin and Wright in 1934 (1).

To our knowledge this is the first record of B virus having been isolated from a monkey, and lends support to the inclusion of this agent as the simian member of the herpes group.

The infection is not uncommon in monkey stocks, as revealed by the finding of antibodies to the virus in their sera. In the present series 9 of 44 monkeys gave positive antibody tests.

Gamma globulin prepared in the United States in 1945, 1951, and 1953, as well as a certain proportion of sera from normal individuals in Bombay, India, and elsewhere, showed neutralizing activity against the new strain of B virus, and also to herpes simplex virus. This may be the result of the partial crossing which exists between the two viruses.
CHEMICAL STRUCTURE OF STEROIDS IN RELATION TO PROMOTION OF GROWTH OF THE VAGINA AND UTERUS OF THE HYPOPHYSECTOMIZED RAT
Authors: Huggins Charles , Jensen Elwood V. , Cleveland Anne Stack
Published: June 2004

In the hypophysectomized albino rat which is protected from contact with steroids in the ration and environment the uterus and vagina are highly atrophic but are sensitive indicators of activity of substances which promote their growth. Both the pituitary growth hormone and certain steroids have the common property of inducing growth of these tissues.

The vaginal epithelium consists of 2 layers of cells which differ profoundly in their growth in response to steroids, depending on the molecular structure of these compounds. The differential response to modifications of chemical structures of steroids permits evaluation of the importance of the intramolecular components for the process of growth.

The number and site of functional groups, the geometry of the molecule and the state of oxidation are of high importance in determining physiologic activity of steroids in the androstane series; these features are less specific in the estrane series.

Side groups at positions C3 and C17 are of importance in the promotion of growth by steroids in the androstane series, but these active centers are not equivalent in their physiological influence. As a generalization, hydrogenation of the oxygen function at C17 (but not at C3) and dehydrogenation at critical areas of the ring structure increase the quantitative efficacy of steroids in promoting growth. The position of double bonds and the state of oxidation at both C3 and C17 determine the qualitative type of growth—cellular pattern, which a compound in the androstane series induces in the vaginal epithelium.
THE SELECTIVE LOCALIZATION OF MURINE PLEUROPNEUMONIA-LIKE ORGANISMS IN THE FEMALE GENITAL TRACT ON INTRAPERITONEAL INJECTION IN MICE
Authors: Nelson John B.
Published: June 2004

Acute oophoritis and salpingitis were commonly observed in weanling mice injected intraperitoneally with murine pleuropneumonia-like organisms of the catarrhal type (4 strains). Organisms of the injected strain were regularly recovered in cultures from the ovary or uterus during the 3rd to the 5th week but not after the 12th week. They were also obtained from the vagina through the 5th week and with varying results, depending on the strain, from the heart's blood through the 1st week.

PPLO injected into the vagina survived for some weeks but did not migrate inwardly nor were they transmitted outwardly to exposed mice. In male mice peritoneal abscesses were sometimes present but the genital organs were normal and free from PPLO. Otitis media, with positive exudate cultures, occurred more often in females and varied in rate with the strain of PPLO. PPLO of the conjunctival type failed to survive in the abdominal cavity of mice and produced no reaction in either the genital or the respiratory tract.
STUDIES ON A LIPOPROTEINASE OF GROUP A STREPTOCOCCI
Authors: Krumwiede Elma
Published: June 2004

The opalescence produced in serum by group A streptococci has been investigated.

The development of opalescence is shown to be initiated by an enzyme attached to the bacterial cell which acts upon the α1-lipoprotein fraction of serum liberating the lipids from the protein.

This enzyme has been termed a lipoproteinase.

Evidence is presented which suggests that the degree of opalescence which develops following lipoproteinase activity is influenced not only by factors attached to the bacterial cell but also by substances present in serum.

The lipoproteinase is antigenic and many human sera contain specific antibodies which inhibit the action of the enzyme.
SOME MUTANT PHAGES PRODUCED DIRECTLY BY BACILLUS MEGATHERIUM 899A WITH THEIR RATE OF OCCURRENCE
Authors: Murphy James S. ,   With the Technical Assistance of Robert L. Gosney, Jr.
Published: June 2004

The rate at which cultures of B. megatherium 899a produce certain mutants of its phage T (wild type) has been investigated in two media; one (peptone) in which reinfection of sensitive cells, if present, is virtually certain, and one (asparagine) in which reinfection is extremely unlikely. Little difference either in the number or types of mutants produced has been detected.

It is concluded that phage mutants are produced directly by B. megatherium 899a and that no intermediate passage through a sensitive cell is necessary for the mutation.

396 individual mutant plaques have been isolated and classified into at least 18 types of plaque-forming mutants of B. megatherium 899a.

The over-all mutant ratio found was in the order of 1:2000 while individual mutants appeared with rates between 1:7000 and less than 1:100,000.
VIRAL HEPATITIS ASSOCIATED WITH TRANSPLANTABLE MOUSE LEUKEMIA
Authors: Braunsteiner Herbert , Friend Charlotte
Published: June 2004

An hepatic disease caused by a filterable agent carried in leukemic mice is described. Ordinarily the virus remains latent and asymptomatic. If, however, the mice are treated with urethane or methylformamide before and after virus inoculation, the disease becomes manifest and is characterized by extremely marked liver necrosis.

Infant mice, a large percentage of weanlings, and adult Bagg albino mice are killed when injected with a filtrate from organs of diseased animals. Adult F1 and Swiss mice show signs of the disease but generally recover. They succumb, however, when simultaneously treated with urethane or methylformamide. By continuing the treatment of consecutive transfer generations an acute disease can be induced which finally kills all adult F1 mice without the treatment. At this stage the original leukemia may be lost.

Mice which have recovered from the subacute disease are resistant to the acute disease, and mice injected with the latent form of the agent are immune to the subacute disease. However, even immunized animals lose their resistance if they are treated with urethane. The acute or subacute disease can be reduced to the latent stage by passing the agent through several generations of immunized animals.

The relationship of this hepatitis virus of mice to viruses causing similar diseases is discussed, as is the possibility that these agents are closely related, if not identical.
TISSUE REACTIONS TO ANAPHYLACTIC AND ANAPHYLACTOID STIMULI; PROTEOLYSIS AND RELEASE OF HISTAMINE AND HEPARIN
Authors: Ungar Georges , Damgaard Evelyn
Published: June 2004

Addition of the specific antigen to slices of liver or lung taken from sensitized guinea pigs, or the addition of anaphylactoid agents (tween 20, octadecylamine, morphine, and 48/80) to tissue slices from normal animals, or the perfusion of lung with these agents, has been shown to cause protein breakdown and liberation of histamine and heparin. The dose correlation between these phenomena raises the question of which is the causal event. Suppression of histamine and heparin release by inhibition of proteolysis suggests that the latter is the more fundamental reaction, but the problem probably can not be decided on the basis of present knowledge.

Tissue proteolysis induced by the agents investigated in this work results from the action of a protease present in normal tissues as an inactive precursor. Conversion of the proenzyme requires the intervention of a kinase. The tissue kinase seems to be different from the serum kinase which has been shown to be related to complement. Serum kinase, however, also acts on tissue proenzyme and probably plays an important role in tissue reactions as elicited in the intact animal.
ACCELERATION OF HEPATIC CHOLESTEROL SYNTHESIS BY TRITON WR-1339
Authors: Frantz Ivan D. , Hinkelman Beverly T.
Published: June 2004

Synthesis of cholesterol from acetate in the rat was studied after injection of triton WR-1339, both in the whole animal and by the liver slice technique. Synthesis appeared to be increased 3-fold 24 hours after the injection. It was depressed after 72 hours, concurrently with a rise in the cholesterol concentration in the liver and its fall towards normal in the blood. When triton was injected into cholesterol-fed animals, or when their bile ducts were ligated, cholesterol synthesis was faster than in the untreated, normally fed controls, despite, in some instances, an elevated concentration of cholesterol in the liver.
IMMUNOLOGIC UNRESPONSIVENESS INDUCED BY PROTEIN ANTIGENS
Authors: Dixon Frank J. , Maurer Paul H. ,   With the Technical Assistance of Maria P. Deichmiller
Published: June 2004

1. Repeated large infusions of heterologous plasma proteins can induce a state of specific immunologic unresponsiveness in rabbits. In normal adult rabbits this unresponsiveness in most instances lasts only about as long as the heterologous proteins are detectable in the host (3 to 4 months). In rabbits infused from the time of birth and perhaps x-radiated adult rabbits the induced immunologic unresponsiveness lasted throughout the period of observation (10 to 11 months), long after disappearance of all detectable foreign proteins.

2. This unresponsiveness appears to be specific for the antigens administered in excess and does not prevent antibody responses to even closely related antigens.

3. The unresponsiveness was not transmitted to first generation offspring.

4. The mechanism of the temporary unresponsiveness which occurs in normal adult rabbits may be dependent upon the actual presence of the antigen in the host. However, the unresponsiveness does not result from a simple neutralization of antibody, as it is formed, by the antigen, as has been suggested in the case of pneumococcal polysaccharide induced immunologic paralysis.

5. On the other hand, the mechanism of the lasting immunologic unresponsiveness developing in the "newborn" and perhaps the x-rayed rabbits may depend upon the acceptance of the foreign protein as essentially non-antigenic by the host. A similar situation is seen in the naturally occurring placental transfer of dissimilar red blood cell types between fraternal twins.
CORRELATIONS BETWEEN PLASMA PROTEIN FRACTIONS, ANTIBODY TITERS, AND THE PASSIVE TRANSFER OF DELAYED AND IMMEDIATE CUTANEOUS REACTIVITY TO TUBERCULIN PPD AND TUBERCULOPOLYSACCHARIDES
Authors: Cole Leon R. , Favour Cutting B.
Published: June 2004

Guinea pigs sensitized with tubercle bacilli demonstrate a dual allergic response mediated by two chemically distinct plasma fractions:

1. Antibody to tuberculopolysaccharide is located exclusively in fraction II (gamma globulin). This fraction will passively transfer systemic anaphylaxis and urticarial type skin reactivity to tuberculopolysaccharide, and contains the Middlebrook-Dubos antibody.

2. Antibody to tuberculoprotein is contained exclusively in a new plasma fraction called fraction IV-10. By Cohn's Method X, fraction IV-10 is a part of fraction IV (alpha globulin) and to a lesser extent V (albumin). This fraction will passively transfer to normal guinea pigs a delayed type skin sensitivity to tuberculin PPD which is maximal between 18 and 30 hours, and it contains the Boyden antibody.

When fractions II and IV-10 are combined, the antibody to tuberculopolysaccharide inhibits the passive transfer of delayed type reactivity. Combination of these two fractions does not alter their separate in vitro hemagglutinating properties. Adsorption of IV-10 with Boyden sensitized cells removes its ability to transfer delayed type tuberculin sensitivity. Adsorption of II with Middlebrook-Dubos-sensitized cells removes its capacity to effect passive transfer of immediate type reactivity to tuberculopolysaccharides.
REACTIVATION OF NON-INFECTIVE VIRUS IN A CORTISONE-INJECTED HOST
Authors: Kilbourne Edwin D. ,   With the Technical Assistance of L. M. Daves
Published: June 2004

The administration of cortisone to chick embryos inoculated with large quantities of inactive influenza B virus results in a rate of viral increase greater than is concommittantly observed with inocula of comparable infectivity which are devoid of inactive particles. Thus, more than a mere negation of autointerference is effected.

It is concluded that in the presence of cortisone reactivation has occurred of non-infective virus to a state in which it can participate in viral synthesis.

Cortisone-induced viral reactivation is dependent upon a high partide/cell ratio and is thus analogous to the previously described phenomenon of "multiplicity reactivation."

Cortisone does not influence either homologous or heterologous viral interference unless reactivation of the inactive interfering virus occurs.

Virus reactivable with cortisone possesses both interfering and enzymatic properties.

Reactivation of virus with cortisone cannot be effected in vitro but is mediated by the host cell.

Two hypotheses concerning the action of cortisone are presented.
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Paucker Kurt , Henle Werner
Published: June 2004

The role of inactivated influenza virus in the von Magnus phenomenon has been studied by exposing standard virus preparations in vitro to 37°C. for periods up to 6 or more days. The rate of inactivation of the infectious property of the line of PR8 virus employed was found to be approximately 1.1 log10 unit per day, denoting a half-life of 6½ hours. The rate of inactivation was similar in the allantoic cavity of chick embryos.

On allantoic passage of such heated seeds without dilution it was seen that with a decrease in the infectivity of the inocula proportionately less infectious virus was found in the harvests. The yields of hemagglutinins were much less affected, and thus ID50/HA ratios of as low as 101.0 were observed in the 24 hour harvests. The ratios of the yields always equalled or were higher than those of the inocula. On 100- or 1000-fold dilution of the heated seeds standard virus was obtained.

Growth curves in intact chick embryos or in deembryonated eggs (differential yields) revealed that non-infectious hemagglutinins appeared in the tissues or were liberated therefrom as soon as any virus activity became detectable. Furthermore, once maximal liberation had been established, infectious virus and non-infectious hemagglutinins were released for extended periods of time at nearly constant rates and in unchanging proportions, the latter depending upon the seed employed.

Heated standard virus and undiluted passage seeds (von Magnus), selected on the basis of similar ID50 and HA concentrations, failed to yield similar results in differential growth curves in deembryonated eggs. Although the hemagglutinin titers in the 2-hourly harvests were nearly identical, the undiluted passage seeds produced as little as 1 per cent of the infectious virus which was derived from the heated inocula. Thus considerable differences exist between the 2 types of seeds.
FORMATION OF AMINES BY INTESTINAL MICROORGANISMS AND THE INFLUENCE OF CHLORTETRACYCLINE
Authors: Melnykowycz J. , Johansson K. R.
Published: June 2004

Although gastric and intestinal contents from rats failed to show amino acid decarboxylase activity when tested against five different amino acids (glutamic acid, arginine, lysine, tyrosine, and histidine), the feces contained at least seven different amines, some known to be pharmacologically active. Putrescine, histamine, and tyramine were identified by means of paper chromatography in both intestinal material and mixed fecal cultures; four other spots were found, three of which had Rf values similar to agmatine, ethanolamine, and ephedrine. The formation of lysine and glutamic acid decarboxylases was not enhanced by an increased acidity during growth while increased oxygen tension was inhibitory to amino acid decarboxylase synthesis in these fecal cultures. The feeding of chlortetracycline to rats, or its presence at a very low concentration in media in which the mixed cultures were grown, reduced the capacity of intestinal microorganisms to produce amines. Cells from mixed fecal cultures grown in the presence of chlortetracycline lacked or contained but weak amino acid decarboxylase activities. The action of the enzymes themselves was unaffected by the presence of the antibiotic in the Warburg cup during assay. The results suggest that amines formed within the intestinal tract might be toxic to the rat, and that chlortetracycline accelerates animal growth by suppressing their production.
ELECTRON MICROSCOPY OF EARLY CYTOPLASMIC CHANGES DUE TO INFLUENZA VIRUS
Authors: Harford Carl G. , Hamlin Alice , Parker Esther
Published: June 2004

Recently improved methods for visualization of thin tissue sections by electron microscopy have been applied to the study of early changes in the bronchial epithelium of mice infected by inhalation of aerosols of influenza virus.

In confirmation of previous findings by the authors, inclusion bodies have been demonstrated in ciliated and non-ciliated cells of infected bronchial epithelium. In addition to 3 strains of mouse-adapted Type A virus, 2 unadapted strains gave qualitatively the same results. The inclusion bodies were found to be composed largely of particles of a size estimated to correspond to the known size of influenza virus. The viral lesion of the cytoplasm was also associated with linear formations which were thought to be abnormal forms of endoplasmic reticulum. Well developed microvilli were found on the ciliated borders of ciliated cells, but no evidence was found of viral growth in this region.
THE ACCELERATION AND INHIBITION OF MIGRATION OF HUMAN LEUCOCYTES IN VITRO BY PLASMA PROTEIN FRACTIONS
Authors: Ketchel Melvin M. , Favour Cutting B. ,   With the Technical Assistance Of Katherine Krause and Frances Mao
Published: June 2004

A new method is described for the quantitative study of leucocyte migration. Blood drawn into a capillary tube is centrifuged, forming a buffy coat. The migration of the leucocytes from the buffy coat into the plasma is measured by means of an ocular micrometer.

While there is a great deal of variation from one normal individual to another in the migration rates of leucocytes those of each individual show relatively little variation in migration from day to day (Table I).

In all cases of illness studied, the average migration rates fall within the normal range, but there was a wider variation in the day to day migration rate than obtains in normal healthy individuals (Tables II and III).

From experiments in which the cells with typically "slow" and "fast" migration rates were tested in both the "slow" and "fast" plasmas, it could be concluded that while the cells invariably have some influence on the migration rate, the major factors influencing leucocyte migration reside in the plasma (Table V).

Experiments in which the plasma proteins were fractionated according to the method of Lever et al. indicated the presence of a system of proteins which regulate leucocyte migration. A heat-labile (56°C. for 30 minutes) component of fraction II was able to accelerate leucocyte migration, while fraction III acted as an inhibitor (Tables IX and X).
STUDIES ON INFLUENZA INFECTION IN FERRETS BY MEANS OF FLUORESCEIN-LABELLED ANTIBODY
Authors: Liu Ch'ien
Published: June 2004

Yellow-green fluorescence representing viral antigens was detected in both the nucleus and cytoplasm of epithelial cells of the respiratory tract in ferrets infected with influenza virus. This nuclear fluorescence was the chief manifestation of cross-fluorescent staining reactions among three strains of influenza A virus studied, PR8, Farrington, and Fm1. Absorption experiments with influenza viral V and soluble S antigens showed that S antigen was responsible for the presence of fluorescence in the nucleus and for the cross-staining reactions among these strains.
STUDIES ON ANTIBODY PRODUCTION
Authors: Leduc Elizabeth H. , Coons Albert H. , Connolly Jeanne M.
Published: June 2004

After an antigenic stimulus, antibody is first demonstrable in the cytoplasm, and often in a spot in the nucleus, of large, immature cells in the medullary areas of the lymph node draining the site of injection. Morphologically, these cells have basophilic cytoplasm and a large nucleus, and are typical hematogenous stem cells. As these cells multiply and differentiate, the concentration of antibody in their cytoplasm increases, until colonies of typical mature plasma cells containing antibody have developed.

There is a marked difference between the primary and the secondary responses, the former characterized by the development of very few antibody-containing cells while in the latter there are hundreds in a similar area. The morphology of the cells involved in both responses is identical.

Occasionally, antibody was also found in low concentration in association with the lymphoid follicles.

The implications of these findings for an understanding of antibody synthesis are discussed.
STUDIES ON ANTIBODY PRODUCTION
Authors: White Robert G. , Coons Albert H. , Connolly Jeanne M.
Published: June 2004

After subcutaneous injection of hen's ovalbumin or diphtheria toxoid precipitated with aluminum phosphate, the production of antibody, as judged by the presence in the tissues of antibody-containing cells, proceeds partly within the regional lymphatic glands and partly in the granulation tissue surrounding the nodule which develops at the site of injection. The first production of antibody takes place in the regional lymphatic gland and antibody production in the local granuloma becomes apparent only from 14 days onwards (rabbit).

Antibody-containing plasma cells were demonstrated in the local granuloma up to 7 weeks. Antibody-containing cells in the regional lymphatic glands reach maximum numbers at 2 weeks following injection and decrease thereafter to few cells at 5 weeks.

The adjuvant effect of the aluminum phosphate is interpreted as due partly to the delay in absorption of antigen from the local site of its injection which results in prolongation of stimulation of cells within the regional lymphatic glands, and partly to the production of a local granuloma which contains antibody-producing plasma cells.
A COMPLEMENT FIXATION TEST FOR POLIOMYELITIS
Authors: Schmidt Nathalie J. , Lennette Edwin H. ,   With the Technical Assistance of Jessie Doleman and Anna Wiener
Published: June 2004

A macroscopic (tube) complement fixation test for poliomyelitis, using infected tissue culture fluids, is described.

The test was applied to 27 individuals with a clinical diagnosis of poliomyelitis. In 18 patients it was possible to make a laboratory diagnosis of poliomyelitis on the basis of a rise in complement-fixing antibody titer and in 4 others on the basis of a high stationary antibody titer. One individual gave a high and equal antibody response to two virus types, 3 others had no detectable antibody, and 1 appeared not to have poliomyelitis.

Heterotypic reactions were encountered, but gave little difficulty in interpreting homologous responses. In those patients from whom a virus had been recovered, the serologic findings corresponded to the virus type recovered.

The possible occurrence of dual infections with the viruses of poliomyelitis and Western equine and St. Louis encephalitis is discussed.
STUDIES WITH THE ELECTRON MICROSCOPE OF VIRUS-HOST RELATIONSHIPS IN EHRLICH ASCITES TUMOR CELLS
Authors: Friedlaender Marlene , Moore Dan H. , Koprowski Hilary
Published: June 2004

Evidence is presented suggesting that anopheles A virus in the Ehrlich ascites tumor cell is harbored and propagated within the endoplasmic reticulum which in this system consists of an extensive canalicular network.

The organization and differentiation of endoplasmic reticulum within the cell are described and the significance of such a location of virus is discussed.
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: Nelson John B.
Published: June 2004

Observations on the behavior of MHV (Pr) in the cerebral tissue of Princeton and Swiss weanling mice indicated a limited neurotropism. The virus migrated to the brain on intraperitoneal injection and was established there by cranial passage, though with difficulty in Swiss mice. Intracerebral multiplication was rarely followed by outward signs of nervous disorder. A slight pathologic reaction occurred in the brains of intracerebrally injected Princeton mice, but it was negligible compared with that of the ensuing hepatitis. In Swiss mice, injected intracerebrally with a mixture of MHV (Pr) and Eperythrozoon coccoides, a related virus with restricted pathogenicity and host range, possibly a mutant, was isolated from the liver and brain.

MHV (C), an actively hepatotropic virus recovered from leukemic Balb C mice, was much more neurotropic than MHV (Pr). Intracerebral injection of Balb C and Swiss weanling mice was attended by marked leptomeningeal and encephalitic lesions. Paralysis of the extremities occurred in some of the animals. The virus was essentially inactive in Princeton mice. During the intracerebral passage of MHV (C) in Swiss mice a pleuropneumonia-like organism was isolated from the brain. In conjunction with the virus this organism produced a vigorous leukocytic reaction.
THE MINIMUM VITAMIN REQUIREMENTS OF THE L AND HELA CELLS IN TISSUE CULTURE, THE PRODUCTION OF SPECIFIC VITAMIN DEFICIENCIES, AND THEIR CURE
Authors: Eagle Harry
Published: June 2004

Seven vitamins have to date proved essential for the survival and multiplication of a mouse fibroblast (strain L) and a human carcinoma cell (strain HeLa) in tissue culture: choline, folic acid, nicotinamide, pantothenic acid, pyridoxal, riboflavin, and thiamin. It was necessary to cultivate the cells for 5 to 15 days in a medium lacking the specific vitamin before the deficiency became apparent in the cessation of multiplication and the development of specific cytopathogenic effects. In their early stages these changes could be reversed by the addition of the missing vitamin, an in vitro, "cure" of a vitamin deficiency. The maximally effective concentrations were in the range 107 to 108 gm. per ml.

The probability that additional vitamins not demonstrably essential under the conditions of the present experiments are nevertheless required for survival and growth is discussed in the text.
AN INFECTIOUS HEPATITIS OF UNDETERMINED ORIGIN IN MICE
Authors: Jordan Janet , Mirick George S. ,   With the Technical Assistance of Marjorie G. Huck
Published: June 2004

Serial intraperitoneal passage in mice of a saline extract of the pooled livers, spleens, and kidneys of such animals has led to the demonstration after three or more passages of a transmissible agent causing hepatitis. The mice developed an illness after 3 to 4 weeks characterized by hepatosplenomegaly, and serous ascites. Spontaneous diuresis and recovery usually occurred during the subsequent 2 to 4 weeks.

Histological studies of the livers showed diffuse mononuclear infiltrations, focal accumulations of mononuclear cells, perivascular mononuclear cuffing, dilated sinusoids, and occasionally focal areas of necrosis.

Mice which have recovered from the disease showed no noteworthy resistance to it, and their sera failed to protect against the infectious agent. Attempts to infect rabbits, guinea pigs, monkeys, and embryonated hens' eggs yielded negative results, but young hamsters developed the disease in mild form.
A METHOD FOR COUPLING PROTEIN ANTIGENS TO ERYTHROCYTES
Authors: Cole Leon R. , Farrell Virginia R.
Published: June 2004

A technique has been described whereby tuberculin PPD is coupled, via tetrazotized benzidne, onto the surfaces of formalinized red blood cells. A stable antigen preparation is thereby obtained, which may be stored at –40°C. The purpose of the present method is to facilitate the study of antibody to tuberculoprotein.
A METHOD FOR COUPLING PROTEIN ANTIGENS TO ERYTHROCYTES
Authors: Cole Leon R. , Matloff J. Jay , Farrell Virginia R.
Published: June 2004

A serological technique, using formalinized red cells coupled to tuberculin PPD as antigen, has been assayed in a trial series of 124 tuberculous and 139 non-tuberculous patients. The stability of the antigen preparation, and the omission of an adsorption procedure for the removal of isoagglutinins facilitated the performance of the test. The results indicate that the technique warrants further trial as a diagnostic criterion of infection tuberculosis.
RED CELL STROMA PROTEIN RICH IN VITAMIN B12 DURING ACTIVE REGENERATION
Authors: Whipple G. H. , Robscheit-Robbins F. S. , Bale W. F.
Published: June 2004

During active blood regeneration in anemia in dogs an increase occurs in the stroma protein of the red cells.

When vitamin B12 with radioactive cobalt is given at the start of this blood regeneration one finds concentration of labeled B12 in the stroma protein but not in the hemoglobin.

After the acute phase of red cell regeneration is ended the concentration of B12 in stroma protein falls rapidly to very low levels within 2 weeks. Subsequent episodes of red blood cell regeneration seems not to cause remobilization of radioactive cobalt into red cells from other body stores.

It appears that the vitamin B12 is a factor of importance in the first steps of stroma protein formation in the first few days of the life of the red cell in the dog.

This response in dogs and the response in pernicious anemia to vitamin B12 may have some points in common.

Distribution of the B12-radioactive cobalt in the organs and tissues at autopsy has been recorded. Some very suggestive localizations were noted and some variation 1 week and 7 weeks after B12 injections.

Radioactive cobalt escapes in the urine during the weeks following B12 injections.
THE ROLE OF THE GOLGI COMPLEX IN FAT ABSORPTION AS STUDIED WITH THE ELECTRON MICROSCOPE WITH OBSERVATIONS ON THE CYTOLOGY OF DUODENAL ABSORPTIVE CELLS
Authors: Weiss Jules M. ,   With the Technical Assistance of Doris Fleisch
Published: June 2004

An electron microscopic study of the morphology of fat absorption in the duodenum of normal and fat-fed mice supports the view that all absorbed fat passes through the cytoplasm of absorptive cells. The Golgi complex plays an important role in the transport of fat across these cells.