bluuebunny/crossref_metadata_2025_split huggingface dataset:
AN ANTIVIRAL SUBSTANCE FROM PENICILLIUM FUNICULOSUM
Authors: Shope Richard E. 
Published: June 2004

A culture of P. funiculosum isolated on Guam proved capable of elaborating a substance which exerted a favorable therapeutic effect against swine influenza virus infections in white mice. The culture was extremely variable and irregular in its production of the antiviral substance, and during maintenance in the laboratory for several years gradually lost this property. Efforts to restore it were unsuccessful.
Subsequently it was found that the mold elaborated a substance, now designated helenine, which is therapeutically effective against Columbia SK encephalomyelitis virus infections in mice. Helenine appears to differ from the substance earlier procured from the mold, which was active against swine influenza virus infections in mice. It is frequently present in greater or lesser amount in the fluid portions of stationary cultures of P. funiculosum but is more regularly obtained and in larger amount, from the cellular components of the pellicles. When liberated from these latter by mechanical bruising and fracturing, it goes into solution in the culture fluids. It is precipitable from aqueous solution by 50 per cent acetone.
Infected mice injected with helenine in amounts less than the amount which produces a maximal therapeutic effect exhibit a dosage response. Increasing the dose above the optimum fails to increase the therapeutic effect.
Helenine exerts its maximum effect when given within the first 10 hours after viral infection but its influence is apparent even when treatment is delayed for up to 24 hours. It is not effective against massive amounts of virus and gives the best therapeutic results when used in the treatment of animals infected with from 10 to 1000 fatal doses of virus. Treatment of infected mice with helenine delays the entrance of virus into their brains for from 24 to 48 hours.
The mechanism by which helenine exerts its therapeutic effect against SK virus is not known but the findings presented suggest either that it causes an inhibition or interruption of multiplication of the virus, slowing down the whole process of infection and spread to the central nervous system, or that in some way it interferes temporarily with the neuroinvasiveness of the virus.
THE STAGES IN CALCIFICATION OF THE RAT KIDNEY AFTER THE ADMINISTRATION OF URANIUM NITRATE
Authors: Dahl Lewis K. 
Published: June 2004

The anatomical and histochemical alterations in rat kidneys after the parenteral administration of uranium nitrate [UO2(NO3)2·6H2O] have been studied. The histological effects produced by this agent over a wide range of dose levels were nearly identical in character and differed principally in their speed of evolution. The deposition of calcium always began at foci in the cytoplasm of the cells of the proximal convoluted tubules of the inner cortex. It remained intracellular until the cell boundaries were destroyed.
Deposits of calcium could be found before any other cellular damage could be demonstrated by histological examination. Later, when degeneration and necrosis were present, the foci of calcification were imperfectly related to them in location or degree. In contrast, the amount of calcification was correlated with the dose of uranium nitrate, being greatest in the kidneys of rats that received 20 mg./kg., next greatest in the 30 mg./kg. rats, less in the 10 mg./kg. rats, and slight in those that received 2 mg./kg.
Histochemical stains for ferric and ferrous iron, chondroitinsulfate, and polysaccharides gave results that were negative or unrelated to the deposits of calcium, thus making it unlikely that these substances held any appreciable amount of calcium in the tissue. Yet it is clear that some anion other than phosphate must be combined with part of the calcium; the results with the alizarin and von Kóssa stains confirmed an earlier result (1) in showing that the first deposits of calcium are formed without comparable accumulations of phosphate.
OBSERVATIONS ON A SUBMICROSCOPIC BASOPHILIC COMPONENT OF CYTOPLASM
Authors: Porter Keith R. 
Published: June 2004

The cytoplasmic ground substance of animal tissue cells grown in vitro has been found by electron microscopy to contain, as a part of its submicroscopic structure, a complex reticulum of strands, to be referred to as the endoplasmic reticulum. It has been found in all types of cells extensively studied.
The components of this reticular system vary considerably in size and form, apparently in some relation to physiological changes in the cell. Thus in one cell of a culture colony it may be finely divided into strands or canaliculi, 50 to 100 mµ in diameter, whereas in an adjacent cell of the same type the components of the reticulum may be relatively coarse, 600 mµ in diameter, and vesiculated. The membrane, which can be shown to limit the system and separate it from the rest of the ground substance, is similar in thickness to the plasma membrane surrounding the cell.
Photomicrographs of living cells taken by phase contrast and dark field microscopy define a structure of similar form and indicate that the reticulum of the electron microscope image has its equivalent in the living unit. Where its component units are sufficiently large, a structure of identical form can be resolved by light microscopy in cells stained with hematoxylin or with toluidine blue. This indicated that the endoplasmic reticulum is to be identified with the basophilic or chromophilic component (the ergastoplasm) of the cytoplasm and that such properties of this component as have been determined by cytochemical methods, such as a high RNA content, may be assigned to this "submicroscopic" system.
NEUTRALIZATION OF VIRUSES BY HOMOLOGOUS IMMUNE SERUM
Authors: Tyrrell David A. J. , Horsfall Frank L. 
Published: June 2004

Neutralization experiments with Newcastle disease, influenza A, or bacterial virus, T3, reveal, under all conditions studied, a linear relationship between the logarithm of the serum dilution end point and that of the quantity of virus used. With Newcastle disease and influenza A, the slope of the neutralization line varies markedly with the host-cell system used and in the chick embryo is strikingly affected by the route of inoculation. The other variables examined have no definite effect upon the slope. Reactivation of neutralized influenza virus is demonstrable in the chick embryo on dilution of the mixture.
There appears to be an inverse relationship between the degree of susceptibility of a host to infection with influenza A virus and the neutralizing titer of a serum as measured in that host. With the T3-serum system, comparable results are obtained when the number of unneutralized virus particles chosen as the end point is varied widely.
STUDIES ON THE GENERALIZED SHWARTZMAN REACTION
Authors: Good Robert A. , Thomas Lewis 
Published: June 2004

In order to explore the hypothesis that the occurrence of thrombosis of small blood vessels is an essential stage in the development of the local and generalized Shwartzman reactions, the effect of heparin was studied.
Aqueous heparin, administered intravenously, and "depot" heparin, injected subcutaneously, prevented completely the occurrence of the local and generalized Shwartzman phenomena. The amounts of heparin required for protection were similar to the amounts required to produce sustained incoagulability of the blood of rabbits for a period of at least 4 hours.
The local and generalized Shwartzman reactions were prevented when heparin was given at the time of provocation, but not when heparin was administered during the period of preparation.
Heparin prevented the development of bilateral cortical necrosis of the kidneys following a single intravenous injection of meningococcal toxin in rabbits previously treated with cortisone or thorotrast.
Hemorrhagic necrosis of the skin which follows an intradermal injection of toxin in thorotrast-treated rabbits was also prevented by heparin.
Provocation of the dermal Shwartzman reaction with glycogen, saline suspension of rabbit liver, and human serum was prevented by treatment with heparin.
Heparin itself, in the preparations and dosages used, had no consistent effect on either white blood cell or platelet counts. Heparin had no effect on the occurrence of polymorphonuclear leukopenia which follows an intravenous injection of meningococcal toxin.
Treatment with heparin did not interfere with the lethal effect of single, large doses of meningococcus toxin.
In animals in which bilateral cortical necrosis of the kidneys was prevented by heparin, occlusion of the glomerular capillaries by "fibrinoid" material did not occur.
These observations support the concept that vascular occlusion plays an essential role in the development of the local and generalized Shwartzman reactions.
A HISTOLOGICAL STUDY OF INFECTIOUS CANINE HEPATITIS BY MEANS OF FLUORESCENT ANTIBODY
Authors: Coffin David L. , Coons Albert H. , Cabasso Victor J. 
Published: June 2004

A study of experimental infectious canine hepatitis in dogs by means of specific fluorescent antibody indicates that the intranuclear inclusions of this disease contain high concentrations of viral antigen.
The increase in virus in the nuclei, as indicated by the accumulation of specific antigenic material, begins on the nuclear membrane and spreads from there to the interior of the nucleus, with the gradual formation of larger granules. Subsequently there appear the homogeneous inclusion bodies characteristic of this infection.
OBSERVATIONS CONCERNING THE PRODUCTION AND EXCRETION OF CHOLESTEROL IN MAMMALS
Authors: Friedman Meyer , Byers Sanford O. , Shibata Eichi 
Published: June 2004

The absorption of oral cholesterol by rats was followed directly by analyses of the thoracic lymph and indirectly by calculating the deficit of fecal cholesterol under the amount fed. The two methods checked within about 20 per cent, with fecal analyses indicating the greater absorption. The absorbed cholesterol was found to be deposited in the liver, only very minor quantities being found in other organs or plasma.
Bile is necessary for normal absorption of cholesterol, although very small amounts are absorbed even in its absence. Excess oral cholic acid increases the absorption of cholesterol by otherwise normal animals. The rat absorbs about 47 per cent of a single 50 mg. dose of cholesterol and about 34 per cent of a 100 mg. dose.
VARIATION IN THE FUNCTIONAL POWER OF HUMAN SWEAT GLANDS
Authors: Dole Vincent P. , Thaysen Jørn Hess 
Published: June 2004

A method has been worked out for the measurement of the volume of sweat produced by individual glands. A special paper, impregnated with iodine, absorbs water in a uniform way and shows the area of wetting by a sharply defined blue dot. Indirect calibrations showed that 1 cm.3 of water would form a spot of 700 cm.2 area, and that this relation of volume to area was a constant one over a wide range. The actual volumes encountered in prints of the sweat glands were from 5 x 10–9 to 4 x 10–6 cm.3.
The relative activity of glands at any instant of time can be expressed by the statistical distribution of log diameter of the dots on the print. This distribution, which might at first sight seem rather artificial, has the advantage of being unaffected by a proportionate change in the output of water from each gland. Thus it is independent of the duration of contact between print paper and skin, and of changes in the average flow from the field as a whole. It is sensitive only to changes in the activity of glands relative to each other.
The methods of printing and statistical analysis were used to study the relative activity of glands in a field of 22 mm. diameter. Glands of the forearm and back were studied both under direct stimulation with mecholyl and under the reflex stimulation of environmental heat, similar results being obtained with the two kinds of stimuli. Glands of the abdomen and leg, stimulated with mecholyl, were studied in one experiment.
Detailed comparison of the dots in consecutive prints showed that the large dots remained large and the small dots continued to be small. These persistent differences in the outflow of water from adjacent glands were interpreted as being due to differences in the functional power of the glands.
Repeated prints of the glands during a period of 75 minutes, in which the sweat flow was declining, showed that the relative activity of the glands remained constant. This meant that the set of glands, although differing greatly in power, varied together as a functional unit.
Different regions of the body show not only the variation of glandular power within each small area, but also marked differences in the average power of glands belonging to the different regions. Glands of the back, for instance, show a much greater outflow than glands of the forearm when stimulated equally with a local injection of mecholyl. Equal rates of outflow, therefore, do not mean equal states of functional activity, unless the regions being compared are of equal functional power.
THE SUBMICROSCOPIC ORGANIZATION OF AXON MATERIAL ISOLATED FROM MYELIN NERVE FIBERS
Authors: De Robertis E. , Franchi C. M. 
Published: June 2004

A technique has been developed for the extrusion of axon material from myelinated nerve fibers. This material is then compressed and prepared for observation with the electron microscope. All the stages of preparation and purification of the axon material can be checked microscopically and in the present paper they are illustrated with phase contrast photomicrographs.
Observation with the electron microscope of the compressed axons showed the presence of the following components: granules, fibrils, and a membranous material. Only the larger granules could be seen with the ordinary microscope. A considerable number of dense granules were observed. Of these the largest resemble typical mitochondria of 250 mµ by 900 mµ. In addition rows or small clusters of dense granules ranging in diameter from 250 to 90 mµ were present. In several specimens fragments of a membrane 120 to 140 A thick and intimately connected with the axon were found. The entire axon appeared to be constituted of a large bundle of parallel tightly packed fibrils among which the granules are interspersed. The fibrils are of indefinite length and generally smooth. They are rather labile structures, less resistant in the rat than in the toad nerve. They varied between 100 and 400 A in diameter and in some cases disintegrated into very fine filaments (less than 100 A thick).
The significance is discussed of the submicroscopic structures revealed by electron microscopy of the material prepared in the way described.
STUDIES OF THE EFFECT OF BACTERIAL ENDOTOXINS ON RABBIT LEUCOCYTES
Authors: Cluff Leighton E. 
Published: June 2004

Bacterial endotoxin injected intravenously into rabbits inhibited the migration of leucocytes from the buffy coat of centrifuged blood (4). Repeated daily injections of endotoxin resulted in the rabbits becoming resistant to the fever-inducing action of the toxin, and migration of leucocytes from centrifuged blood was no longer inhibited by injection of the toxin. Leucocyte migration from the buffy coat of centrifuged blood after injection of toxin into the rabbits appeared gradually over the first few days of repeated injections, and disappeared during the 10 to 15 days after cessation of daily injections of toxin. The resistance to endotoxin, demonstrated by leucocyte migration and pyrogen tolerance, could not be passively transferred with serum from resistant animals, and was non-specific, in that resistance to one endotoxin conferred some resistance to toxin from an organism of a different species. No relationship could be demonstrated between precipitin titer and resistance. Thorotrast abolished resistance to the fever-inducing activity of endotoxin, but its effect on leucocyte resistance was not clear, since when injected alone it inhibited migration of leucocytes from the buffy coat of centrifuged blood.
The suggestion is made that the failure of toxin to inhibit the migration of leucocytes from resistant rabbits is due either to the presence of leucocytes which have become adapted to the toxin by repeated exposure, or to rapid removal of the toxin by the reticulo-endothelial system. It is unlikely that leucocyte resistance participates in the development of tolerance to the fever-inducing action of endotoxin. However, in view of the participation of the leucocyte in the pathogenesis of the Shwartzman reaction, the presence of leucocytes resistant to endotoxin may be responsible in part for the development of resistance to the Shwartzman phenomenon.
THE INACTIVATION OF HERPES SIMPLEX VIRUS BY PHOSPHATASE ENZYMES
Authors: Amos Harold 
Published: June 2004

Tissue phosphatases which are present in virus suspensions were found to contribute in considerable measure to the inactivation of herpes simplex virus.
Phosphatase inhibitors and phosphatase substrates have been found to prolong the survival of the virus.
Exogenous phosphatases, both acid and alkaline, have been demonstrated to bring about the loss of infectivity of suspensions of this virus.
STUDIES ON THE CHEMISTRY OF THE TRANSFORMING ACTIVITY
Authors: Zamenhof Stephen , Alexander Hattie E. , Leidy Grace 
Published: June 2004

The transforming principles of Hemophilus influenzae have been purified by a new method including fractional extraction. The active molecule behaves in these extractions like the bulk of the DNA preparation. The minimal amount of DNA necessary for transformation appeared to be of the same order of magnitude as the amount of DNA in a single cell.
Quantitative study has been made of the resistance of transforming activity to various agents. When subjected to heat, the temperature at which the activity starts to decrease corresponds rather closely to the temperature at which the viscosity of the bulk of the DNA preparations starts to decrease. Similar correspondence was found when the transforming principle was subjected to pH changes. This is further evidence that the behavior of the active molecules is similar to the behavior of the average DNA molecule of the preparation. The activity is reduced by exposure to low ionic strength and by dehydration. Desoxyribonuclease in concentrations less than 10–4 γ/cc. is able to destroy the activity; a lag period during which the activity but not the viscosity decreases has been observed. NaNO2 at pH 5.3, HCHO and 10–5 M Fe++ reduce or destroy the activity; the importance of intact amino groups in the DNA molecule for the activity is discussed. Several protein-denaturing, sterilizing, and mutagenic agents have been found to have no effect on the transforming activity.
AN ABSOLUTE METHOD FOR ASSAY OF VIRUS HEMAGGLUTININS
Authors: Levine Seymour , Puck Theodore T. , Sagik Bernard P. 
Published: June 2004

A rapid and precise method is described for determination of absolute numbers of hemagglutinating particles present in virus suspensions. The method involves spectrophotometric measurement of the number of red cells dimerized by the virus under conditions in which formation of larger aggregates is precluded.
Results of this procedure are compared with those of titrations based on egg infectivity and the polystyrene microsphere electron micrography for influenza virus; and with plaque count titrations on chick embryo cell monolayers in the case of the virus of Newcastle disease. The agreement is well within the limits expected in view of the different quantities which the various procedures measure.
The conversion factor for transforming titre in hemagglutinating units based on the pattern procedure into absolute number of agglutinating particles is the same for influenza and Newcastle disease virus.
The precipitation of red blood cells by Newcastle disease virus at 23°C. is optimal at pH's between 6.2 and 5.8.
THE EFFECT OF TUBERCULIN AND CORTISONE SINGLY AND IN COMBINATION ON EXPLANTED TISSUES OF GUINEA PIGS, MICE, AND RABBITS
Authors: Holden Margaret , Seegal Beatrice Carrier , Adams Lillian B. 
Published: June 2004

Tuberculin (P.P.D.) and cortisone acetate, singly and in combination, were added to explanted splenic tissue derived from guinea pigs, mice, and rabbits, and buffy coats obtained from rabbits. These tissues came from normal animals or from animals which had been infected with the tubercle bacillus or immunized with killed tubercle bacilli.
5 µg./ml. of tuberculin or 0.5 µg./ml. of cortisone was the largest concentration of the respective reagents which was tolerated by cultured cells from normal animals.
From the results with all tissues studied it would appear that P.P.D. selectively damaged only the growing cells of splenic tissues from sensitive guinea pigs and to a lesser degree the migrating cells of buffy coats obtained from sensitive rabbits.
Cortisone appeared to have increased toxicity for only explanted splenic cells from tuberculin-sensitive guinea pigs.
The specific effect of P.P.D. on tissues from tuberculin-sensitive animals was not modified by cortisone under the conditions of these experiments. Thus these data furnished no evidence that cortisone had any direct effect on the response of the sensitive cells to P.P.D.
THE ANTIMYCOBACTERIAL ACTIVITY OF A PEPTIDE PREPARATION DERIVED FROM CALF THYMUS
Authors: Dubos René J. , Hirsch James G. 
Published: June 2004

A stable, water-soluble substance which possesses potent antimycobacterial activity under certain conditions in vitro has been prepared from calf thymus. This substance has been tentatively named thymus peptide. In final concentrations of 1 to 10 µg. per ml. of an albumin medium it inhibits the growth of various strains of mammalian mycobacteria, but manifests only little or no inhibitory activity against a variety of other microbial species.
The ability of thymus peptide to inhibit the multiplication of tubercle bacilli diminishes when the inoculum is large, or when the medium is acidic. It is also markedly antagonized by addition of enzymatic hydrolysate of casein or beef heart infusion broth to the culture medium.
Thymus peptide does not exert a rapid bactericidal action on tubercle bacilli, but organisms exposed to this compound for longer than 2 weeks could not be made to multiply in ordinary culture media.
Substances similar or identical to the thymus peptide preparation could be extracted from calf spleen, sheep thymus, beef lymph nodes, and calf pancreas, but not from calf lung or calf liver.
CHEMICAL STUDIES ON A BASIC PEPTIDE PREPARATION DERIVED FROM CALF THYMUS
Authors: Hirsch James G. , Dubos René J. 
Published: June 2004

A substance possessing antimycobacterial activity under certain conditions in vitro has been prepared from aqueous extracts of calf thymus. Chemical studies have demonstrated that the activity of this substance is due to a basic peptide or a mixture of basic peptides. Although this thymus fraction has been shown to be essentially free of compounds other than peptides, it has not been obtained in a homogeneous state.
The thymus peptide preparation is soluble in water and in the lower alcohols. Its solubility is minimal between pH 10 and 11, suggesting that its isoelectric point may be in this vicinity. The microbiological activity of thymus peptide is destroyed by acid or alkaline hydrolysis and also by trypsin digestion, but is unaffected by pepsin digestion. Cellulose membranes are permeable to thymus peptide.
The most noteworthy finding concerning the amino acid composition of thymus peptide is the preponderance of the basic amino acids lysine and arginine, which together account for about 40 per cent of the weight of this substance. No cystine, and only trace amounts of other amino acids containing sulfur, are present in the thymus peptide preparation.