bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical and functional analysis of a 9-nt RNA sequence that affects translation efficiency in eukaryotic cells
Authors: Chappell Stephen A. , Edelman Gerald M. , Mauro Vincent P.
Published: June 2004

We previously identified an internal ribosome entry site (IRES) within the 5′ leader of the mRNA encoding the Gtx homeodomain protein and showed that shorter nonoverlapping segments of this 5′ leader could enhance the translation of a second cistron in a dicistronic mRNA. One of these segments was 9 nt in length, and when multiple copies of this IRES module were linked together, IRES activity was greatly enhanced. To further expand the potential uses of these synthetic constructs and facilitate analyses of the mechanism by which they affect translation, we show here that an IRES containing five linked copies of the 9-nt sequence can also enhance translation in the 5′ leader of a monocistronic mRNA. Moreover, a search for interactions of the IRES module with cellular factors revealed specific binding to 40S ribosomal subunits but not to other cellular components. Based on the results of earlier studies suggesting that this sequence could bind to a complementary segment of 18S rRNA, we tested various sequences for possible links between the length of the complementary match, their binding to ribosomes, and their influence on translational efficiency. We found that the length of the complementary match was directly correlated with the ability of RNA probes to bind to ribosomes. In addition, translation was maximally enhanced (≈8-fold) by a 7-nt segment of the 9-nt element; the enhancement declined progressively as the complementary stretches became progressively longer or shorter. The results suggest that the
Gtx
9-nt sequence affects translation efficiency by a mechanism that involves base pairing to 18S rRNA.
Painting of fourth in genus
Drosophila
suggests autosome-specific gene regulation
Authors: Larsson Jan , Svensson Malin J. , Stenberg Per , Mäkitalo Maria
Published: June 2004

Painting of fourth (POF) is a chromosome-specific protein in
Drosophila
and represents the first example of an autosome-specific protein. POF binds to chromosome 4 in
Drosophila melanogaster
, initiating at the proximal region, followed by a spreading dependent on chromosome 4-specific sequences or structures. Chromosome-specific gene regulation is known thus far only as a mechanism to equalize the transcriptional activity of the single male X chromosome with that of the two female X chromosomes. In
Drosophila
, a complex including the male-specific lethal proteins, “paints” the male X chromosome, mediating its hypertranscription, explained to some extent by the acetylation of lysine 16 on histone H4. Here, we show that
Pof
is essential for viability in both sexes and for female fertility. POF binding to an autosome, the F element, is conserved in genus
Drosophila
, indicating functional conservation of the autosome specificity. In three of nine studied species, POF binds to the male X chromosome. When bound to the male X, it also colocalizes with the dosage compensation protein male-specific lethal 3, suggesting a relationship to dosage compensation. The chromosome specificity is determined at the species level and not by the amino acid sequence. We argue that POF is involved in a chromosome-specific regulatory function.
Unexpected complexity in the haplotypes of commonly used inbred strains of laboratory mice
Authors: Yalcin B. , Fullerton J. , Miller S. , Keays D. A. , Brady S. , Bhomra A. , Jefferson A. , Volpi E. , Copley R. R. , Flint J. , Mott R.
Published: June 2004

Investigation of sequence variation in common inbred mouse strains has revealed a segmented pattern in which regions of high and low variant density are intermixed. Furthermore, it has been suggested that allelic strain distribution patterns also occur in well defined blocks and consequently could be used to map quantitative trait loci (QTL) in comparisons between inbred strains. We report a detailed analysis of polymorphism distribution in multiple inbred mouse strains over a 4.8-megabase region containing a QTL influencing anxiety. Our analysis indicates that it is only partly true that the genomes of inbred strains exist as a patchwork of segments of sequence identity and difference. We show that the definition of haplotype blocks is not robust and that methods for QTL mapping may fail if they assume a simple block-like structure.
Effects of cigarette smoke on the human airway epithelial cell transcriptome
Authors: Spira Avrum , Beane Jennifer , Shah Vishal , Liu Gang , Schembri Frank , Yang Xuemei , Palma John , Brody Jerome S.
Published: June 2004

Cigarette smoke is the major cause of lung cancer, the leading cause of cancer death, and of chronic obstructive pulmonary disease, the fourth leading cause of death in the United States. Using high-density gene expression arrays, we describe genes that are normally expressed in a subset of human airway epithelial cells obtained at bronchoscopy (the airway transcriptome), define how cigarette smoking alters the transcriptome, and detail the effects of variables, such as cumulative exposure, age, sex, and race, on cigarette smoke-induced changes in gene expression. We also determine which changes in gene expression are and are not reversible when smoking is discontinued. The persistent altered expression of a subset of genes in former smokers may explain the risk these individuals have for developing lung cancer long after they have discontinued smoking. The use of gene expression profiling to explore the normal biology of a specific subset of cells within a complex organ across a broad spectrum of healthy individuals and to define the reversible and irreversible genetic effects of cigarette smoke on human airway epithelial cells has not been previously reported.
Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry
Authors: Syka John E. P. , Coon Joshua J. , Schroeder Melanie J. , Shabanowitz Jeffrey , Hunt Donald F.
Published: June 2004

Peptide sequence analysis using a combination of gas-phase ion/ion chemistry and tandem mass spectrometry (MS/MS) is demonstrated. Singly charged anthracene anions transfer an electron to multiply protonated peptides in a radio frequency quadrupole linear ion trap (QLT) and induce fragmentation of the peptide backbone along pathways that are analogous to those observed in electron capture dissociation. Modifications to the QLT that enable this ion/ion chemistry are presented, and automated acquisition of high-quality, single-scan electron transfer dissociation MS/MS spectra of phosphopeptides separated by nanoflow HPLC is described.
Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases
Authors: Cortez David , Glick Gloria , Elledge Stephen J.
Published: June 2004

The minichromosome maintenance (MCM) 2-7 helicase complex functions to initiate and elongate replication forks. Cell cycle checkpoint signaling pathways regulate DNA replication to maintain genomic stability. We describe four lines of evidence that ATM/ATR-dependent (ataxia-telangiectasia-mutated/ATM- and Rad3-related) checkpoint pathways are directly linked to three members of the MCM complex. First, ATM phosphorylates MCM3 on S535 in response to ionizing radiation. Second, ATR phosphorylates MCM2 on S108 in response to multiple forms of DNA damage and stalling of replication forks. Third, ATR-interacting protein (ATRIP)-ATR interacts with MCM7. Fourth, reducing the amount of MCM7 in cells disrupts checkpoint signaling and causes an intra-S-phase checkpoint defect. Thus, the MCM complex is a platform for multiple DNA damage-dependent regulatory signals that control DNA replication.
Environment, agriculture, and settlement patterns in a marginal Polynesian landscape
Authors: Kirch P. V. , Hartshorn A. S. , Chadwick O. A. , Vitousek P. M. , Sherrod D. R. , Coil J. , Holm L. , Sharp W. D.
Published: June 2004

Beginning
ca.
A.D. 1400, Polynesian farmers established permanent settlements along the arid southern flank of Haleakala Volcano, Maui, Hawaiian Islands; peak population density (43-57 persons per km
2
) was achieved by A.D. 1700-1800, and it was followed by the devastating effects of European contact. This settlement, based on dryland agriculture with sweet potato as a main crop, is represented by >3,000 archaeological features investigated to date. Geological and environmental factors are the most important influence on Polynesian farming and settlement practices in an agriculturally marginal landscape. Interactions between lava flows, whose ages range from 3,000 to 226,000 years, and differences in rainfall create an environmental mosaic that constrained precontact Polynesian farming practices to a zone defined by aridity at low elevation and depleted soil nutrients at high elevation. Within this productive zone, however, large-scale agriculture was concentrated on older, tephra-blanketed lava flows; younger flows were reserved for residential sites, small ritual gardens, and agricultural temples.
Repetition suppression of faces is modulated by emotion
Authors: Ishai Alumit , Pessoa Luiz , Bikle Philip C. , Ungerleider Leslie G.
Published: June 2004

Single-unit recordings and functional brain imaging studies have shown reduced neural responses to repeated stimuli in the visual cortex. By using event-related functional MRI, we compared the activation evoked by repetitions of neutral and fearful faces, which were either task relevant (targets) or irrelevant (distracters). We found that within the inferior occipital gyri, lateral fusiform gyri, superior temporal sulci, amygdala, and the inferior frontal gyri/insula, targets evoked stronger responses than distracters and their repetition was associated with significantly reduced responses. Repetition suppression, as manifested by the difference in response amplitude between the first and third repetitions of a target, was stronger for fearful than neutral faces. Distracter faces, regardless of their repetition or valence, evoked negligible activation, indicating top-down attenuation of behaviorally irrelevant stimuli. Our findings demonstrate a three-way interaction between emotional valence, repetition, and task relevance and suggest that repetition suppression is influenced by high-level cognitive processes in the human brain.
Cold-induced imbibition damage of lettuce embryos: a study using cryo-scanning electron microscopy
Authors: Nijsse Jaap , Walther Paul , Hoekstra Folkert A.
Published: June 2004

The impact of rehydration on a multicellular organism was studied in lettuce (Lactuca sativaL.) embryos, using cryo-scanning electron microscopy (cryo-SEM). Naked embryos were sensitive to imbibitional stress, whereas embryos with an intact, thick-walled endosperm were not. Imbibitional injury to naked embryos was mainly confined to the outer 2–3 cell layers of the axis. These cells failed to swell and appeared poorly hydrated. Deeper layers were not affected even after extended periods of cold rehydration. The proportion of damaged cells (6–7% of total) roughly corresponded with the additional K+that gradually leached from the embryos. Damaged embryos were able to survive the loss of their surface layers and form adventitious roots. The swelling of inner tissues caused the dead surface layers to rupture into patches. Plasma membranes in dried embryos showed normal bilayer structure with a homogeneous distribution of intra-membrane particles (IMPs), also after non-injurious rehydration. Imbibitionally damaged plasma membranes showed many irregularities, such as globular insertions, that probably resulted from malfusions in the ruptured membrane, but the IMPs were still randomly distributed.
An experimental assessment of seed adhesivity on animal furs
Authors: Couvreur Martine , Couvreur Martine , Vandenberghe Bart , Verheyen Kris , Hermy Martin
Published: June 2004

Epizoochory is widely recognized as an effective long-distance seed dispersal mechanism. Nevertheless, few studies have focused on the investigation of its influencing factors. One of the key aspects of epizoochory is the adhesive interaction between seeds and furs. We describe a new method to quantify experimentally and standardize the adhesivity of seeds to animal fur, as a measure of epizoochorous dispersal potential. The method excludes the impact of animal behaviour and environmental factors, and allows the ranking of species according to their adhesivity score. We measured adhesivity scores for 66 species on the furs of seven mammals. Deep furs with long, rough, undulated hairs implanted at a large angle were most suited for seed adhesion, while seeds adhered less well to shallow furs with short, smooth, straight hairs implanted at small angles. Seeds with specialized adhesive appendages had higher adhesivity scores than seeds with unspecialized appendages and seeds without appendages. However, an interaction effect between certain seed and fur types exists. Although seed morphology is a good predictor for seed adhesivity on fur, less well-adhering seed types often still have relatively high adhesivity scores. Therefore, it is likely that nearly all species are, to some extent, able to disperse epizoochorously.
Seed mass variation potentially masks a single critical water content in recalcitrant seeds
Authors: Daws Matthew I. , Gaméné Christiane S. , Glidewell Sheila M. , Pritchard Hugh W.
Published: June 2004

For recalcitrant seeds, mortality curves of germination versus water content typically imply a wide range of desiccation sensitivities within a seed population. However, seed to seed differences in water content, during desiccation, may confound our interpretation of these mortality plots. Here, we illustrate this problem for two batches ofVitellaria paradoxa(Sapotaceae) seeds collected in 1996 and 2002. Whole seeds were desiccated to various target water contents (TWCs) using silica gel. During desiccation, smaller seeds in the population dried most rapidly. Consequently, there was a significant linear relationship between whole-seed water content and seed mass during the drying process. In addition, following desiccation to low TWCs, only the largest seeds in the population retained viability. Taken together, this suggests that the larger seeds survived, not as a consequence of great relative desiccation tolerance, but as a result of taking longer to desiccate. Subsequently, the critical water content (CWC) for viability loss was calculated, based on the assumptions that in the seed population whole-seed water content during desiccation was normally distributed and the smallest, and hence driest, seeds were killed first. Using this approach, the driest seeds in the population that were killed, at each TWC, were always below a single CWC (c. 20% and 26% in 1996 and 2002, respectively). In subsequent experiments the effect of seed size variation on the response to desiccation was confirmed by conducting desiccation screens on seeds sorted into two discrete size classes, i.e. the seed-lot heterogeneity in mass was reduced. Using this approach, the mortality curves had a steeper slope. Furthermore, data for 24 tropical tree species from the Database of Tropical Tree Seed Research (DABATTS) revealed that seed lots with less variability in mass had steeper mortality curves. Thus, taken together, the data suggest that, at least for whole seeds, the wide range of desiccation sensitivities typically inferred is an artefact of seed to seed variation in mass, and hence water contents, during drying.
INTERFERENCE BETWEEN POLIOMYELITIS VIRUSES IN TISSUE CULTURE
Authors: Ledinko Nada , Melnick Joseph L.
Published: June 2004

The inhibition of multiplication of one poliomyelitis virus by a poliomyelitis virus of another immunologic type has been established by using tissue cultures of monkey testes. The degree of interference varied from none, to partial, to complete, depending upon the time between inoculation of the interfering and the challenge viruses, and the amount of each virus inoculated. Reciprocal interference was demonstrated between Types 1, 2, and 3 poliomyelitis viruses.

Under conditions which resulted in complete suppression of the growth of one poliomyelitis virus by another, interference by poliomyelitis virus with the multiplication of four antigenically distinct "orphan" viruses and of three antigenically related strains of Coxsackie virus could not be demonstrated.

Poliomyelitis virus rendered non-infective by formalin or by irradiation with high energy electrons or with ultraviolet light, or treated so that only traces of residual active virus remained, failed to interfere with the propagation of active homologous virus.
STUDIES ON THE TRANSFER OF LYMPH NODE CELLS
Authors: Harris Susanna , Harris T. N.
Published: June 2004

At various intervals, from 10 minutes to 21 days, after the injection of dysentery bacilli into the hind foot pads of rabbits the popliteal lymph nodes were excised. The cells of the lymph nodes were teased free, washed, and injected intravenously into normal rabbits. In each case aliquots of the same cell suspension were either incubated at 37°C. for 24 hours or heated at 52°C. for 20 minutes and then injected into other normal rabbits, as controls.

In the case of lymph node cells obtained 4 or 3 days after the injection of antigen, antibody was found in the serum of recipients on the 1st day after the transfer of untreated cells. The titer increased until the 3rd day and then began to decline after the 5th or 7th day. In the sera of recipients of incubated cells antibody was not found, except on occasion after the 4th day and in low titer. This late appearance of antibody was attributed to the presence of small amounts of antigen in the original cell suspension.

As the interval between injection of antigen and collection of cells was increased beyond 4 days the effectiveness of the transfer decreased progressively until at 14 days no transfer effect was obtained.

When cells which were obtained 2 days after the injection of antigen were transferred, antibody appeared on the 2nd day after transfer and then followed the characteristic curve, whereas in the case of incubated cells antibody did not appear until the 3rd day after transfer. After the transfer of untreated 1 day cells antibody did not appear in the recipient until the 3rd day, and then followed the type of curve seen with 2, 3, and 4 day cells. Following transfer of incubated 1 day cells antibody also appeared on the 3rd day.

To establish the possibility of eliciting the cell transfer effect as early as 1 day after the injection of dysentery bacilli, recipient rabbits were x-irradiated 24 hours prior to the injection of cells. It was found that in the sera of such recipients of untreated cells antibody appeared on the 3rd day following transfer, while irradiated recipients of incubated cells did not develop any measurable amounts of agglutinin for the first 10 days.

It was concluded that a total of 3 days was required between the injection of antigen into the donor and the appearance of measurable antibody in the serum of the recipient, regardless of the fraction of that time spent by the cells in each of the animals involved, donor or recipient.

Following the transfer of untreated cells removed from lymph node as early as 10 minutes after the injection of antigen distal to them, antibody could be found in the sera of x-irradiated recipients 4 days later, whereas antibody did not appear following the transfer of heated cells to such recipients.
GROWTH CHARACTERISTICS OF INFLUENZA VIRUS
Authors: Ackermann W. Wilbur , Maassab Hunein F.
Published: June 2004

An analysis of the growth curve obtained in vitro for influenza virus in chorioallantoic membrane has been made using two known viral inhibitors, methoxinine and α-amino-α p-methoxyphenylmethanesulfonic acid. The action of these compounds has been shown to be specific for particular phases of viral development. Further, this action is sequential indicating that the inhibited phases do not occur concurrently.

The sulfonic acid interferes with the initiation of infection and with the release of newly formed virus from the host-cell. The former effect is dependent upon the relative concentrations of viral inoculum and sulfonic acid. The latter effect is prevented by the action of the receptor-destroying enzyme obtained from cholera vibrio extracts. It is proposed that a function of the viral enzyme is to facilitate the release of virus from the host-cell. The intracellular concentration of virus necessary to initiate this release is increased in the presence of α-amino-α p-methoxyphenylmethanesulfonic acid.

It was found that infection can be initiated in the presence of methoxinine under which condition viral increase is disallowed. The function in viral development of one biochemical process which is inhibited by methoxinine was found to be completed at an interval after initiation of infection and before the appearance of the infectious form of the virus. It is possible to define four stages of viral development in terms of sensitivity to methoxinine and α-amino-α-p-methoxyphenylmethanesulfonic acid.
THE INFLUENCE OF ANTICOAGULANTS ON THE FORMATION AND REGRESSION OF EXPERIMENTAL ATHEROSCLEROSIS
Authors: Horita Akira , Loomis T. A.
Published: June 2004

The prolonged administration of either heparin or dicoumerol has been demonstrated to be effective in retarding the formation of atheromata in the cholesterol-fed chick. This beneficial action is possibly produced as a result of a demonstrated antihypercholesteremic action exerted by these anticoagulants.

Heparin is ineffective in preventing the marked turbidity of sera from cholesterol-fed chickens.

After the formation of atherosclerosis in the chick neither heparin nor dicoumerol is effective in hastening the regression of this condition. The serum lipid picture as well as the degree of atheroma of the various groups in the regression experiments is unaffected by the anticoagulants.
THE MECHANISMS BY WHICH MACROPHAGES PHAGOCYTE ENCAPSULATED BACTERIA IN THE ABSENCE OF ANTIBODY
Authors: Sawyer William D. , Smith Mary Ruth , Wood W. Barry
Published: June 2004

Evidence has been presented: (1) that macrophages from experimentally produced inflammatory exudates are capable of phagocyting fully encapsulated Type I pneumococci and group A Friedländer's bacilli in the absence of antibody, (2) that the principal mechanisms involved are those of surface phagocytosis, and (3) that the majority of pneumococci ingested by macrophages in antibody-free preparations are ultimately destroyed.

The relationship of these phenomena to the mechanism of recovery in pneumococcal and Friedländer's bacillus infections has been briefly discussed.
INTRACELLULAR FORMS OF MENINGOPNEUMONITIS VIRUS
Authors: Gaylord William H.
Published: June 2004

Electron micrographs of intracellular memngopneumonitis virus have shown several types of particles which are presumably representative of different stages of a life cycle. They are: (a) Elementary bodies—dense particles 250 to 300 mµ in diameter with very dense central granules. (b) Intermediate forms—less dense than elementary bodies and larger. They are 300 to 400 mµ in diameter, contain a very dense central granule, and often have two or three limiting zones, (c) Circles 400 to 500 mµ in diameter—homogeneous structures with single membranes and no internal granules. They are often elongated and constricted at the center in the manner of budding yeast cells, (d) Circles 500 to 600 mµ in diameter with single membranes.mdash;One, two, and three dense granules may be present in some of these structures, (e) "Larger" structures, circular to elliptical, often with discontinuities or ruptures in their membranes. They sometimes seem to have internal septa.

It has been inferred from these observations that the virus can multiply by binary fission or by multiple endosporulation and that elementary bodies are a spore-like stage.
THE EFFECT OF ALCOHOL ON THE CHOLINE REQUIREMENT
Authors: Klatskin Gerald , Krehl Willard A. , Conn Harold O.
Published: June 2004

Rats maintained for a period of 7 months on a fluid intake of 15 per cent alcohol and a diet marginal in lipotropic activity developed fatty infiltration and mild fibrosis of the liver. Similar changes were observed in pair-fed controls given an isocaloric equivalent of sucrose instead of alcohol, but not in pair-fed controls receiving neither alcohol nor sucrose supplements. To exclude the possibility that the alcohol effect was related to an augmentation of the caloric intake, a third group of controls was given the same amount of alcohol, but a limited number of calories. This was accomplished by subtracting from the basal diet an amount of sucrose equivalent in calories to the alcohol consumed. Under these conditions the hepatic changes following alcohol ingestion appeared to be enhanced. Choline or methionine, on the other hand, abolished the effects of both alcohol and sucrose supplements. There was no increase in fecal nitrogen excretion following alcohol ingestion, and no histological changes were observed in the pancreas.

These results are consistent with the hypothesis that alcohol increases the choline requirement of the rat, but do not support the contention that this effect is the consequence of an augmented caloric intake. Further studies are needed to establish conclusively the relationship between alcohol ingestion and the choline requirement, and to elucidate the mechanisms involved.
THE EFFECTS OF DRUGS UPON A GRADED COUGH RESPONSE OBTAINED IN SENSITIZED GUINEA PIGS EXPOSED TO AEROSOL OF SPECIFIC ANTIGEN
Authors: Winter Charles A. , Flataker Lars
Published: June 2004

A technique is described for measuring objectively and quantitatively the reaction of sensitized guinea pigs when exposed to an aerosol of specific antigen. The principle involves registration by semi-automatic means of the number of coughs produced in animals passively sensitized with known amounts of antibody. The number of coughs is shown to be linearly related to log dose of antibody within a limited range and a dose-response curve is presented.

The cough produced by this procedure is not inhibited by the antitussive drugs, codeine and propadrine, but can be inhibited by anti-allergic agents, such as cortisone and an antihistaminic drug. It is also inhibited by narcotine. The last is the only compound so far tested which suppresses both the cough produced by this procedure and that produced by a simple irritant.

The action of cortisone and the antihistaminic drug, pyrilamine, is shown to be synergistic. A small dose of pyrilamine in animals pretreated with cortisone gives a degree of inhibition which cannot be obtained by increasing the dose of pyrilamine in animals not treated with cortisone.
RESISTANCE TO FIBROMA VIRUS INFECTION. THE ROLE OF IMMUNE LEUKOCYTES AND IMMUNE MACROPHAGES
Authors: Ginder David R.
Published: June 2004

Leukocytes and macrophages, obtained from fibroma-immune rabbits and added to immune serum-fibroma virus mixtures, significantly increased the neutralization of fibroma virus as compared with immune serum alone. Immune cell suspensions from peritoneal exudates, regional lymph nodes, buffy coats, spleen, and liver were all effective in inhibiting fibroma virus. Approximately 2000 to 4000 immune cells/mm.3 were necessary to cause an effect but no particular cell type could be implicated as responsible for the inhibition of fibroma virus. Normal cells did not consistently and significantly inhibit fibroma virus and cells from rabbits immunized with other viruses did not inhibit fibroma virus.

Studies of the mechanism of action of the immune cells revealed: (a) that living cells were essential; (b) that normal cells, sensitized with immune serum, did not simulate the effects of immune cells; (c) that immune cells contained less preformed neutralizing antibody than an equivalent volume of immune serum, and (d) that inhibition of fibroma lesions was not the result of viral interference.

It is suggested that the fibroma-neutralizing effect of immune cells is related to intracellularly placed antibody or to cellular transfer of an ability to form specific antibody in recipient animals.
EFFECT OF METABOLIC FACTORS ON THE SUSCEPTIBILITY OF ALBINO MICE TO EXPERIMENTAL TUBERCULOSIS
Authors: Dubos René J.
Published: June 2004

Mice maintained on various types of diets were found to become more susceptible to tuberculosis when deprived of food for periods of 30 hours shortly after infection. In contrast, the susceptibility of the animals to the disease was unaffected by undernutrition resulting from limitation of food intake to a low but constant daily level.

The resistance of mice to tuberculosis appeared to be independent—within wide limits—of the protein content of the diet. It is true that mice fed a diet very low in protein and high in carbohydrate proved highly susceptible, but resistance was normal if part of the carbohydrate was replaced by fat (peanut oil)—without any change in the protein content of the food.

Resistance to tuberculosis could be consistently and markedly decreased by adding sodium citrate (or glutarate) to a variety of diets.

The survival time following infection was greatly shortened if dinitrophenol or thyroxine were administered per os in amounts sufficient to limit the weight gains of non-infected controls. There was usually a lag period of several days before the infection-enhancing effect of these metabolic stimulants became manifest.

The procedures which increased the susceptibility of mice to infection with virulent tubercle bacilli also made it possible to establish in these animals a fatal infection with BCG.

There was no constant relation between weight gains of uninfected mice on the various regimens, and the effect of the latter on susceptibility to tuberculosis.

These findings appear compatible with, but do not prove, the hypothesis that a decrease in resistance to infection can be brought about by metabolic disturbances which cause either a depletion of the glycogen reserves of the body, or a reduction in the glycolytic activity of inflammatory cells, or an increase in the concentration of certain polycarboxylic acids and ketones in the tissues.
JAUNDICE IN MICE DUE TO ANOMALIES OF THE BILIARY TRACT
Authors: Pappenheimer Alwin M. , Cheever F. S. , Salk Herman
Published: June 2004

There has been described a previously unrecognized disease of mice, characterized by progressive jaundice, first appearing during the nursing period. This has been shown to be due to congenital absence of the terminal segment of the common bile duct, or to the absence of intrahepatic ducts. In the former case, there is distension of the cystic and hepatic ducts, and of the gall bladder, with mucoid material. Biliary cirrhosis and infarct-like areas of necrosis are commonly found in the liver. The cause of the necroses has not been positively determined, but it is suggested that they result from defective arteriolization of the hepatic parenchyma. Inflammatory lesions of the biliary passages, when present, are attributed to secondary bacterial infection. Protozoan-like parasites were present in the gastric epithelium of all mice examined. Their relationship to the biliary and hepatic lesions is as yet undetermined.
PROTEIN METABOLISM IN THE MAMMALIAN KIDNEY
Authors: Eliasch Harald , Sellers Alvin L. , Rosenfeld Sheldon , Marmorston Jessie
Published: June 2004

The concentrations of amino acid and polypeptide nitrogen in plasma samples from the aorta, renal vein, and inferior vena cava of the rabbit have been determined. It was demonstrated that there were significantly higher concentrations of amino acids and polypeptides in the renal vein than in either aorta or inferior vena cava. The possible implications of these findings in relation to the role of the kidney in protein metabolism has been discussed.
COMPARATIVE HISTOLOGIC AND IMMUNOLOGIC STUDIES IN RABBITS OF INDUCED HYPERSENSITIVITY OF THE SERUM SICKNESS TYPE
Authors: Germuth Frederick G. , Pace Mary Geraldine , Tippett Jack C.
Published: June 2004

Sensitization of rabbits with bovine albumin and the cross-reactive antigen, egg albumin, increased the rate of bovine albumin elimination following its intravenous administration. Elimination of this antigen was complete in 7 and 10 days respectively instead of approximately 2 weeks as in unsensitized normal animals. The peak incidence of allergic tissue alteration was proportionately accelerated. Certain qualitative and quantitative differences between the histologic responses of the sensitized and unsensitized rabbits were noted. These differences were probably due to the shorter period of antigen-antibody interaction in the sensitized animals in which the antigen was quickly eliminated. The temporal relationship between the histologic and immunologic responses in sensitized animals adds further support to the hypothesis that the lesions which occur after the injection of foreign protein are the result of antigen-antibody combination.
THE ANTIBODY MECHANISMS OF RAGWEED ALLERGY. ELECTROPHORETIC AND CHEMICAL STUDIES
Authors: Cooke Robert A. , Menzel Arthur E. O. , Kessler Walter R. , Myers Phyllis A.
Published: June 2004

Three human serums containing artificially produced blocking antibody against low ragweed allergen were studied for the possibility of relating blocking antibody to electrophoretically definable components.

An adaptation of the qualitative passive transfer test to quantitative interpretation is described, methods and procedures are given and uncertainties and possible errors due to lack of precision and accuracy are presented and discussed.

At least 65 per cent, but probably more, if not all of the blocking antibody is attributable to gamma globulin. However, no rise of gamma globulin, either its absolute amount or its relative percentage value, paralleled the appearance of blocking antibody.

Blocking antibody is not contained in albumin or in alpha-1 globulin.

Blocking effect could not be ascertained unequivocally as being connected with alpha-2 or with beta globulin and sizable participation of these two latter electrophoretic components appears improbable.

Blocking antibody and sensitizing antibody appear to be chemically different entities.
THE EFFECT OF IONIZING RADIATION ON PHAGOCYTOSIS AND THE BACTERICIDAL POWER OF THE BLOOD
Authors: Shechmeister I. L. , Fishman M.
Published: June 2004

Exposure of rats to 600 r total body radiation did not influence either the rate or the extent of migration of their leucocytes 1 day after irradiation, but did decrease their migration on the 2nd and the 5th postirradiation day. Migration of rat leucocytes was not altered by infection of the animal with M. aureus.

Leucocytes of rabbits irradiated with 100 r showed a normal rate and extent of migration. However rabbits exposed to 500 r or 800 r showed depression of leucocyte migration at two postirradiation intervals, on the 3rd to 5th and the 10th to 13th days after irradiation, with normal activity intervening. By the 21st postirradiation day the ability of leucocytes to migrate returned to normal. The effect of radiation on total and differential W.B.C. counts and the relationship of this effect to migration is discussed.

The decrease in leucocyte migration could not be ascribed either to leucopenia or to plasma factors.
THE ANTIGENIC POTENCY OF NON-INFECTIOUS POLIOMYELITIS VIRUS AS DETERMINED BY ITS LIBERATING EFFECT ON ACTIVE VIRUS NEUTRALIZED BY IMMUNE SERUM
Authors: Krech Ulrich
Published: June 2004

The activation of poliomyelitis virus from a "neutral" virus-antibody mixture by the addition of non-infectious virus is described. The phenomenon was demonstrated in tissue cultures using both Petri dishes and roller tubes. The reaction was found to be type-specific and a relationship between antigen dilution and number of plaques counted was established.

The relative potency of vaccine preparations determined in this system was found to be comparable to their relative potency in respect to protection-inducing activity in mice.
THE CELLULAR CHANGES PRODUCED IN TISSUE CULTURES BY HERPES B VIRUS CORRELATED WITH THE CONCURRENT MULTIPLICATION OF THE VIRUS
Authors: Reissig Magdalena , Melnick Joseph L.
Published: June 2004

A sequential study is reported of the morphological changes occurring after herpes B virus infection of cells as revealed in ultrathin sections under the electron microscope. Monolayer cultures of renal epithelial cells prepared from the natural host of the virus, the monkey, were infected, and the cellular alterations were correlated with the appearance of infective virus in the culture fluids.

The morphological changes consisted in swelling of the cells and disappearance of the nucleolus, followed by margination and gradual decrease of the nuclear chromatin. The inclusion material corresponded to the clear central areas of the nucleus, where the chromatin had disappeared. In the late stages of infection this inclusion material filled the nucleus and formed a classical type A inclusion body.

Characteristic particles appeared in the nucleus and cytoplasm of the infected cells a few hours after inoculation. They had a dense center surrounded by one or two membranes. Those with one membrane ranged in size from 60 to 100 mµ and those with two from 120 to 180 mµ. Particles showing the same wide variation in size and structure were seen both in the nucleus and in the cytoplasm. They were first visible on the external surface of the swollen but intact cells at about the same time new infective virus became detectable in the culture fluid.

A small number of the extracellular, and cytoplasmic, virus particles appeared "binucleated," containing two central bodies, each having its own membrane, both being surrounded by a single external coat. About 180 mµ in diameter, they were randomly distributed among the "mononucleated" particles.
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Paucker Kurt , Henle Werner
Published: June 2004

An experimental analysis is here presented of the conditions that lead to the appearance of non-infectious hemagglutinins (NIHA) in the allantoic fluid of chick embryos injected with standard influenza virus (PR8 strain) which had been exposed to 37°C. in vitro for various periods of time.

On progressive reduction of the infectivity of the undiluted inocula from about 109 to 103 ID50 (103.2 HA units) the yields of infectious virus in 24 hours decreased in straight correspondence 1 millionfold, but those of hemagglutinins only by a factor of 10. Thus the proportions of NIHA in the yields increased sharply but the total quantity obtained decreased gradually.

The quantities of infectious virus produced per ID50 injected were the same throughout this range; i.e., between 50 and 100 ID50, regardless of increasing proportions of heat-inactivated virus in the seeds. This value agrees with previous estimates of yields under other conditions. Thus, initiation and completion of first cycles by the infectious virus remaining in the inocula were not, or at most, slightly inhibited. The inactivated virus, therefore, failed to establish immediate interference. It was capable, however, of holding the infectious process to one cycle. Upon 10-fold dilution of the seeds essentially similar results were obtained except that a slight loss in interfering activity could now be detected with an increase in exposure to 37°C. With further dilutions little or no interference was noted.

The capacity to yield NIHA decreased slowly during exposure of the seeds to 37°C. over a period of 5 days, thereafter more rapidly. It could not be restored by addition of infectious virus. Furthermore, since NIHA was obtained when the seeds contained as little as 102 or 103 ID50, it is unlikely that it was derived from those cells which had adsorbed both infectious and inactivated seed virus. It is suggestive that multiple adsorption of inactivated virus particles per se will yield NIHA. The available information, as discussed, favors the view that the NIHA does not represent seed virus in some form but is newly produced.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Atkins Elisha , Wood W. Barry
Published: June 2004

The rate of clearance of intravenously injected typhoid vaccine was studied in unsensitized, sensitized, and pyrogen-tolerant rabbits by means of a passive transfer technique.

The blood of unsensitized rabbits which had not been previously exposed to bacterial pyrogen remained pyrogenic for normal recipients throughout a period of 2 hours following the injection.

In contrast, rabbits sensitized by having received either one or two injections of the vaccine at least 3 weeks prior to the experiment cleared their blood of the test vaccine within 30 minutes despite the fact that they exhibit the same febrile response as unsensitized rabbits. After 1 hour, however, a transferable pyrogenic substance was again demonstrable in the sera of this group. Reasons are discussed for believing that this newly appearing substance may be of endogenous origin and may be the factor which directly affects the thermoregulatory centers of the brain.

Rabbits which are made tolerant by repeated daily injections of vaccine have a characteristically depressed febrile response. Not only were the blood streams of such animals cleared of the injected vaccine within less than 5 minutes, but samples of their sera obtained 1 and 2 hours after the injection also failed to contain demonstrable quantities of the secondary pyrogen observed in sensitized animals. The latter observation is in keeping with the suggestion that the secondary pyrogen may play a critical role in the production of fever.
THE USE OF PRECIPITIN ANALYSIS IN AGAR FOR THE STUDY OF HUMAN STREPTOCOCCAL INFECTIONS
Authors: Halbert Seymour P. , Swick Lois , Sonn Constance
Published: June 2004

It has been shown by agar precipitin tests (Ouchterlony and Oakley) that human sera may contain from 0 to 5 antibodies against antigens present in a partially purified streptolysin O preparation, and from 0 to 7 antibodies against antigens in a crude ammonium sulfate concentrate of the streptococcal culture supernate used. These antigens were prepared from a Group A hemolytic streptococcus (strain C203S).

Strong evidence was presented suggesting that some of the bands seen with streptolysin O concentrate represented antibody reponses to streptococcal antigens heretofore undescribed.

Tests were also carried out with other streptococcal antigens, including streptokinase-desoxyribonuclease mixture from Group C streptococci (varidase-Lederle), crystalline proteinase, proteinase precursor, C carbohydrate, and sonic vibrated streptococcal cell extracts (group A, C203S). Fewer bands were seen with these preparations, and with some they were quite uncommon. The observations indicated that the predominating antibody responses in human streptococcal infections were to extracellular products of the micro-organisms, and only very slightly and infrequently to intracellular antigens.

The human sera studied included sera from patients with active or convalescent rheumatic fever, and non-rheumatic subjects suffering from a variety of illnesses. As was expected, the rheumatic subjects showed antibody responses to many more of the antigens present in these preparations than did the nonrheumatic group.

Pooled normal human gamma globulin was found to contain many of the antibodies found in potent human sera. This finding confirmed the antigen-antibody nature of the bands seen with individual sera. The epidemiological significance of these findings with gamma, globulin was briefly discussed.

It was found that rabbit, guinea pig, and human antibody precipitin bands join quite readily in the Ouchterlony tests. This finding adds another tool for the identification of the precipitin bands found with human sera.

Evidence was obtained which indicated differing immunological specificities of two samples of streptococcal desoxyribonuclease, one from Group A, the other from a Group C streptococcus.

The value of these technics as representing a new approach to the study of human infectious disease was discussed.
ASPERMATOGENESIS, ANAPHYLAXIS, AND CUTANEOUS SENSITIZATION INDUCED IN THE GUINEA PIG BY HOMOLOGOUS TESTICULAR EXTRACT
Authors: Freund Jules , Thompson George E. , Lipton Murray M.
Published: June 2004

Guinea pig testicles were extracted with acetic acid; the extract was purified by removing material in consecutive precipitations with 30 per cent saturated ammonium-sulfate, trichloracetic acid, and chloroform. The solution so purified, when administered with complete adjuvants, was highly active in inducing impairment of spermatogenesis in guinea pigs. The activity resisted autoclaving at 15 pounds' pressure for 20 minutes, proteolytic enzymes, and formamide.

Anaphylactic shock and cutaneous reaction to the purified homologous extract occurred in guinea pigs sensitized by the extract combined with adjuvants.

For the production of aspermatogenesis it was essential to incorporate killed mycobacteria into the water-in-oil emulsion containing the antigen; but anaphylactic sensitization did not require the presence of mycobacteria.
THE PLACENTA AND PROTEIN METABOLISM
Authors: Whipple G. H. , Hill R. B. , Terry R. , Lucas F. V. , Yuile C. L.
Published: June 2004

Plasma proteins tagged in vivo by feeding D-L-lysine-ϵ-C14 to donor dogs have been administered to pregnant dogs by both oral and intravenous routes.

A relatively small percentage of the C14 activity originally incorporated in these proteins is found to pass from mother to fetus after intravenous injection. The amount transferred tends to increase with the length of gestation period and total number of fetuses.

Plasma protein labeled with I131 does not cross the placenta in the dog, but does in the rabbit.

Evans blue dye does not cross the placenta of the dog.

After oral administration of labeled plasma protein or lysine, C14 is transferred promptly and in considerable quantity to the fetus.

Labeled plasma proteins disappear more rapidly from the circulation of pregnant than of normal dogs. This increased metabolic turnover occurs without excretion of any excess waste metabolites.

The chorionic epithelium, gram for gram, is probably 2 to 3 times as active as the hepatic epithelium in protein metabolism.

These findings indicate an important placental function related to maternal and fetal protein metabolism. While the placenta utilizes maternal plasma proteins and amino acids, in a quantitative sense the latter appear to supply the major nitrogen needs of the growing fetus.
A TISSUE FACTOR INFLUENCING SUCCINIC DEHYDROGENASE ACTIVITY IN TUBERCULOUS GUINEA PIGS
Authors: Martin S. P. , Cooper C. D. , Chaudhuri S. N. , Green R.
Published: June 2004

The alterations in succinic dehydrogenase activity during the course of infection with Mycobacterium tuberculosis strains H37Rv and BCG, as well as with dead bacilli, has been described. A tissue factor has been described which is prepared from normal bovine kidney and will restore enzyme activity in vitro. This factor is prepared by chromatographic analysis and contains a nucleotide with an ultraviolet absorption maxima at 250 mµ (pH 3) and a free sulfhydryl group. The role of this factor in the response to tuberculosis is discussed.
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: Straus Werner , Oliver Jean
Published: June 2004

Immunological analysis with a specific antiserum showed an increasing concentration of egg white proteins in the cortex of the kidney of the rat up to 18 hours after their intraperitoneal injection, and a fall in the following 40 hours.

Homogenates of the cortical tissue prepared at 18 hours, the period of maximum droplet development, showed a large amount of the egg white proteins in the supernatant, considerable amounts in the fraction which contained the mitochondria, but the highest concentration, 6 times that of any other cell fraction, in the highly purified preparation of droplets.

The relation of these findings to the morphological and histochemical evidence concerning the constitution of the droplets is discussed and the conclusion drawn that absorbed egg white proteins and mitochondrial substances are important elements in their formation.