bluuebunny/crossref_metadata_2025_split huggingface dataset:
AN EXPERIMENTAL ANALYSIS OF THE CURATIVE ACTION OF PENICILLIN IN ACUTE BACTERIAL INFECTIONS
Authors: Wood W. Barry , Smith Mary Ruth 
Published: June 2004

Three strains of pneumococcus (types I and III), equally sensitive to penicillin, have been shown to be killed by the antibiotic in vitro when grown either in enriched beef infusion broth or in a thin serous exudate. Killing of the bacteria resulted promptly when the penicillin was added during the logarithmic phase of growth but failed to occur if addition of the antibiotic was delayed until the later "stationary" growth phase. In analogous experiments with thick purulent exudates from established subcutaneous abscesses, the pneumococci failed to grow rapidly, and added penicillin exerted only a relatively slow bactericidal effect.
The relevance of these in vitro observations to the curative action of penicillin was demonstrated in a systematic histologic study of the antimicrobial effect of the drug in experimental (type I) pneumococcal pneumonia. Evidence was obtained that at least two distinct processes are involved. The first, the direct bactericidal effect of the penicillin itself, was shown to operate in the outer edema zone of the spreading pneumonic lesion where the micro-organisms multiply rapidly in the thin serous exudate. The second, which predominates in the older more central portions of the lesion, was demonstrated to depend upon destruction of the pneumococci by phagocytosis. Here the bacteria, having presumably reached a relatively stationary phase of growth in the alveolar exudate, are resistant to the bactericidal action of the penicillin but are readily destroyed by the phagocytes.
THE PROPERDIN SYSTEM AND IMMUNITY
Authors: Wardlaw Alastair C. , Pillemer Louis 
Published: June 2004

Methods for the preparation and standardization of reagents suitable for studies on the bactericidal action of the properdin system are described. The preparation and properties of serum free of properdin (RPb) are presented in detail because of the necessity for a suitable RPb in these studies.
The properdin system is responsible for the bactericidal action of normal human serum against a variety of microorganisms. The present work shows that the removal of properdin from serum also removes bactericidal activity. Addition of properdin to properdin-deficient serum restores bactericidal activity. A quantitative relationship exists between the final properdin concentration and bactericidal activity against sensitive organisms. The possibilities of a bactericidal assay for properdin are discussed.
It is demonstrated that, in addition to properdin, the four components of complement (present in RPb) are necessary for the destruction of properdinsensitive bacteria. If any component is missing, bactericidal activity is lost; when the component is replaced, bactericidal activity is restored. Magnesium is also necessary for the bactericidal activity of the properdin system. Maximal bactericidal activity is obtained with magnesium concentrations similar to that of normal human serum (10–3 to 10–4 M). The bactericidal activity of the properdin system occurs only at temperatures above 15°.
Resistant strains have been encountered in species of bacteria sensitive to the properdin system. Resistance or sensitivity is a characteristic of the individual strain and not of the species.
The widespread occurrence of the properdin system in normal mammalian serum and the variety of bacteria destroyed by it suggest that the properdin system is a factor in natural resistance.
PHAGOCYTIN: A BACTERICIDAL SUBSTANCE FROM POLYMORPHONUCLEAR LEUCOCYTES
Authors: Hirsch James G. 
Published: June 2004

A technique has been developed for collecting large numbers of polymorphonuclear leucocytes from peritoneal exudates in rabbits. These cells are obtained essentially free from other cell types and from debris.
When microphages so procured are disrupted by physical methods and extracted with aqueous salt solutions, the soluble fraction manifests striking bactericidal activity, especially on Gram-negative enteric bacilli. The susceptible microorganisms are not lysed.
This bactericidal substance, which has been called phagocytin, appears to be limited in distribution mainly to the polymorphonuclear leucocyte. No phagocytin is present in extracts of rabbit heart, kidney, or skeletal muscle, and rabbit liver and spleen contain much less than do packed leucocytes.
Extracts of human and of guinea pig microphages show less bactericidal activity than rabbit cell preparations. Similar extracts of rat and mouse polymorphonuclear leucocytes contain no demonstrable phagocytin.
As indicated by its behavior on dialysis, on exposure to proteolytic enzymes, and on salt fractionation, phagocytin appears to be a protein with general properties characteristic of a globulin. It is clearly different from lysozyme and from properdin.
Although phagocytin is reasonably stable at temperatures of 65°C. and lower for several hours, solutions of it gradually lose bactericidal activity on standing for prolonged periods at 4°C. This instability, and also the ease with which phagocytin is inactivated, presumably by adsorption, on exposure to a variety of materials, have thus far rendered fruitless efforts to isolate it.
EFFICIENCY OF GLUTAMYL PEPTIDE POLYMERS AS PLASMA VOLUME EXTENDERS
Authors: Rosenthal William S. , O'Connell Daniel J. , Axelrod D. Robert , Bovarnick Max 
Published: June 2004

A series of polymers of polyglutamic acid have been tested as plasma volume expanders. The results indicate that those polymers prepared from backbones of 40,000 molecular weight or over and side chains of 3,000 molecular weight or over, will have plasma volume retention half-life of 15 hours or longer.
Measurements of the oncotic efficiency of these polymers in vivo indicated a blood stream fluid retention of approximately 51 ml./gm. of polymer. Similar measurements of polymer-serum albumin solutions in vitro showed a retention of 52 ml./gm. of polymer.
The clinical response to infusion of solutions of these polymers indicated no untoward pharmacological properties. Although the number of trials presented is too small for ultimate conclusion regarding either the physiological or clinical effects of these polymers, they do provide a strong indication of the desirability of further clinical testing of this polymer and a sound basis on which to plan the larger scale preparation of polymer. Both measures are currently under way.
ELEVATION OF PROPERDIN LEVELS IN MICE FOLLOWING ADMINISTRATION OF BACTERIAL LIPOPOLYSACCHARIDES
Authors: Landy Maurice , Pillemer Louis 
Published: June 2004

The administration of a single small dose of bacterial lipopolysaccharide produces in mice a considerable rise in properdin levels. This is accompanied by an early, transient, non-specific increase in resistance to certain bacterial infections. Bacterial lipopolysaccharides were shown to possess far greater activity than other substances previously studied in bringing about an elevation of properdin levels.
After the injection of bacterial lipopolysaccharides, high molecular weight substances appear in the circulation, which interfere with the combination of properdin with zymosan and thus affect the assay of properdin.
The administration of small amounts of bacterial lipopolysaccharides to mice at appropriate times before experimental infection "conditions" the mice so that they maintain normal or elevated properdin titers during the infectious process in contrast to control mice which show a progressive decline in properdin to low levels and death.
The significance of this observation and its relationship to natural resistance to Gram-negative pathogens are considered.
ANALYTICAL PATHOLOGY
Authors: Ortega Louis G. , Mellors Robert C. 
Published: June 2004

The principal objective of this investigation was to define the roles of injected and autogenous, kidney-localizing antibodies in the pathogenesis of rat nephrotoxic nephritis by relating data obtained with fluorescent antibody techniques to clinical and histologic observations.
Such an analysis of the nephritis that developed in 28 rats after injection with the crude γ-globulin fraction of nephrotoxic serum has led us to the following conclusions:—
The renal localization of nephrotoxic antibodies is primarily and, perhaps, exclusively in the membranes of the glomerular tufts. These antibodies are demonstrable, as antigens, in the glomeruli for up to 3 months after injection.
In the acute stage of the nephritis, non-antibody, autogenous globulins are present in the glomerular tufts, probably as components of edema fluid. From 6 and 9 days to 3 months after injection, autogenous antibodies are localized in the glomerular tufts in a pattern that corresponds closely to that of the nephrotoxins.
The essential requirements for the operation of the mechanism postulated by Kay are fulfilled in rat nephrotoxic nephritis.
NATURE OF FLUIDS WHICH FUNCTIONALLY DISTEND THE KIDNEY
Authors: Swann H. G. , Valdivia Luis , Ormsby A. A. , Witt W. T. 
Published: June 2004

The nature of the fluid draining from the kidney, after its artery was occluded, was investigated. Samples of systemic arterial blood, renal venous blood and urine were also analyzed. It was found that the fluid draining from the kidney after occlusion is a mixture of vascular blood and another fluid designated as "diluting fluid," each contributing half to the composite mixture. In volume the mixture is 26 per cent of the functionally distended kidney. With the assumption that the renal extracellular fluid can be considered a simple mixture of blood plasma and a cell-free fluid, the composition of the "diluting fluid" was deduced from the known compositions of vascular blood and total fluid draining. The ratios of its content in a given substance to that in systemic (or renal venous) plasma are: for Na and Ca, 1.0; K, 1.5; Cl, 1.2; PO4, 2.0; urea, 1.8; plasma protein, 0.3; albumin, 0.4; glucose, 0.4, and osmolarity, 1.2. The fluid bears little or no relation to urine, especially since the urine varied considerably between individual dogs whereas the "diluting fluid" was relatively constant in composition. It was also found that the hematocrit of the fluid draining after arterial occlusion progressively decreased as it flowed out, until the last portion contained only 5 per cent red cells.
It is concluded that since renal lymph has approximately the same composition in protein, urea, glucose, and inulin as does "diluting fluid," the latter is, in all probability, renal interstitial fluid. Under the conditions of the experiment, it drains out of the kidney slowly relative to blood drainage. It is large in volume, particularly when compared with the capillaries that nourish it. Its high protein content explains the observation that the kidney is apparently naturally distended with a fluid disproportionately rich in plasma protein.
REVERSIBLE CHANGES IN THE SUSCEPTIBILITY OF MICE TO BACTERIAL INFECTIONS
Authors: Schaedler Russell W. , Dubos René J. 
Published: June 2004

A study has been made of the time variations in the susceptibility of albino mice to experimental infections with Klebsiella pneumoniae, Staphylococcus aureus, and Mycobacterium tuberculosis.
Susceptibility to infection was determined by two criteria: (a) mortality rates following intravenous injection of a known infective dose; (b) numbers of bacterial colonies that could be recovered from the tissues of the infected animals at various times after infection. When measured in terms of either one of these two criteria, susceptibility was consistently modified by temporary deprivation of food, and by various changes in the composition of the diet.
Increase in susceptibility to infection could be detected within a few hours to a few days depending upon the nature and intensity of the nutritional disturbance imposed upon the animal. Under the proper conditions, return to a normal state of resistance could also occur within a very short time. There was commonly observed an explosive bacterial multiplication in mice receiving the infective dose shortly after being subjected to nutritional disturbances. In the case of infection with Klebsiella pneumoniae, however, this phase of increased susceptibility was often followed a few hours later by one during which the numbers of living bacteria that could be recovered from the various organs fell to a very low level. Many of the animals which had exhibited severe but transient bacteriemia recovered rapidly and survived the infection.
Mice rendered more susceptible to infection by being fed deficient diets progressively recovered their normal resistance while being kept on the same inadequate regimens. This adaptation occurred even though the weight of the animals on these regimens remained much lower than the weight of the animals fed a complete diet ad lib.
The weight of the animal at the time of infection appeared to have little bearing on susceptibility. However, susceptibility consistently increased during the periods while the animals were losing weight—whatever the cause of the weight loss.
The facts disclosed in the present study, as well as findings reported by other investigators, make clear that profound changes in susceptibility to infection can be brought about by varied non-specific procedures. These changes can occur within very short periods of time and are often rapidly reversible.
MODIFICATION OF THE HOMOTYPIC SPECIFICITY OF POLIOMYELITIS COMPLEMENT-FIXING ANTIGENS BY HEAT
Authors: Schmidt Nathalie J. , Lennette Edwin H. ,   With the Technical Assistance of Jessie H. Doleman and Shirley Hagens
Published: June 2004

Fluid obtained from HeLa cell cultures infected with poliomyelitis viruses served as a complement-fixing antigen. When used in the native state, i.e. untreated in any way, the fluids acted as homotypically specific antigens. When heated, however, the antigenicity was broadened and a high degree of heterotypic reactivity was encountered.
Data are presented indicating that the observed group reactivity was apparently based on common antigens shared by the three immunologic types of poliomyelitis virus. This reactivity appeared to be specific for the poliomyelitis viruses. No evidence was obtained in preliminary experiments that heating of the antigens releases a "soluble" antigen responsible for the group reactivity.
PHAGOCYTOSIS OF BACTERIA IN THE ABSENCE OF ANTIBODY AND THE EFFECT OF PHYSICAL SURFACE
Authors: Lerner Edwin M. 
Published: June 2004

The present experiments have shown that phagocytosis occurs in the absence of specific antibody and in the absence of a "suitable physical surface", as further that the presence of a rough surface does not increase the in vitro phagocytosis of pneumococci by polymorphonuclear leukocytes. This held true during repetition of Wood's experiments, as well as when more controlled quantitative techniques were employed, when conditions were made optimal for phagocytosis by increasing bacterial concentrations, and when blood leukocytes were substituted for exudate leukocytes.
Evidence has been presented previously that the stimulation of phagocytosis of E. coli, B. abortus, and Type IV Pneumococcus, after contact with filter paper or an active compound present in filter paper, is a chemical effect rather than a physical effect. This type of stimulation did not occur with the Type I A5 Pneumococcus.
The leukocyte of the circulating blood was found to be definitely superior to the exudate leukocyte in phagocytic capacity, under all the experimental conditions tested.
ON THE SPECIFICITY OF THE DESOXYRIBONUCLEIC ACID WHICH INDUCES STREPTOMYCIN RESISTANCE IN HEMOPHILUS
Authors: Leidy Grace , Hahn Eros , Alexander Hattie E. 
Published: June 2004

Streptomycin resistance of a high degree has been induced in sensitive populations of Hemophilus influenzae and Hemophilus parainfluenzae by desoxyribonucleic acids (DNA's) derived from streptomycin (SM)-resistant cells of at least one heterologous species of Hemophilus.
The specificity of the DNA which controls SM resistance has been studied within and among species of Hemophilus by comparing, in a given population, the proportion of cells transformed to SM-resistant by DNA's derived from highly resistant cells of heterologous type or species with the proportion changed by the DNA derived from SM-resistant cells of the homologous type or species. The ratio resulting from this comparison correlates in general with the degree of kinship between recipient and donor cells suggested by accepted methods of bacteriologic classification. The numerical value of the ratio is much lower when the species of the recipient population and donor of the DNA differ than when they are of the same species. The data suggest that this ratio is of value as an index of degree of kinship of recipient and donor cells.
Comparison of the activity of heterologous and homologous DNA's shows differences within species and degrees of differences among species not brought out by other available methods. The data suggest that H. influenzae is more closely related to H. parainfluenzae than to H. suis and that the relationship between H. parainfluenzae and H. suis is remote.
Within the species H. influenzae and H. parainfluenzae the ratio of hetero-specific transformants to homospecific transformants appears to be relatively constant for a given recipient population. This ratio also appears to be independent of the type or group source of the heterologous species SM resistance DNA.
The low proportion of cells in H. influenzae populations which are transformed to SM-resistant by DNA's derived from SM-resistant H. parainfluenzae and vice versa has been increased 4- to 15-fold by the replication of the heterologous species SM resistance DNA in the heterologous species. An alteration of the heterologous DNA by the host is suggested.
TRANSFER OF DELAYED HYPERSENSITIVITY TO DIPHTHERIA TOXIN IN MAN
Authors: Lawrence H. S. , Pappenheimer A. M. 
Published: June 2004

Simultaneous transfer of delayed hypersensitivity to diphtheria toxin and to tuberculin has been accomplished in eight consecutive instances in man using extracts from washed leucocytes taken from the peripheral blood of tuberculin-positive, Schick-negative donors who were highly sensitive (i.e., pseudoreactors) to purified diphtheria toxin and toxoid. The leucocyte extracts used for transfer contained no detectable antitoxin. The recipient subjects were Schick-positive (&lt;0.001 unit antitoxin per ml. serum) and tuberculin-negative at the time of transfer. All the recipients remained Schick-positive for at least 2 weeks following transfer and in every case their serum contained less than 0.001 units antitoxin at the time when they exhibited maximal skin reactivity to toxoid.
Evidence is presented which indicates that the transfer factor may be released from leucocyte suspensions under mild conditions in which most of the cells appear to remain morphologically intact.
Four adult Schick-positive subjects have been sensitized to diphtheria toxoid by intradermal injection of a few micrograms of purified toxoid in the form of a washed toxoid-antitoxin precipitate. Two of these sensitized individuals showed severe delayed skin reactions specifically directed against diphtheria toxin (or toxoid) at a time when their serum antitoxin level was less than 0.001 units/ml.
GENETICS OF SOMATIC MAMMALIAN CELLS
Authors: Puck T. T. , Fisher H. W. 
Published: June 2004

The parental HeLa cell population, a morphologically uniform, human cancer cell strain, grown for several years in tissue culture by procedures always involving massive inocula, has been shown to contain different mutant cell types.
Two clonal lines have been isolated and established as reliable stock cultures. Both strains exhibit 100 per cent plating efficiency in high or low serum concentrations in the presence of a feeder system. In the absence of a feeder system and in low serum concentrations, the two strains are quantitatively differentiable: S3 still exhibits 100 per cent plating efficiency, while that of S1 lies in the neighborhood of zero.
These differences have remained stable throughout 100 successive generations of growth of each strain including 2 single cell isolations.
Application of these techniques to studies in the genetics of mammalian somatic cells and to specific cell-cell interactions has been indicated.
ELECTRON MICROSCOPY OF HELA CELLS INFECTED WITH ADENOVIRUSES
Authors: Harford Carl G. , Hamlin Alice , Parker Esther , van Ravenswaay Theodore 
Published: June 2004

HeLa cells were infected with adenoviruses (types 1–4) and sectioned for electron microscopy after intervals of 20 to 48 hours. Clusters of virus-like particles were found within the nuclei of infected cultures but not in those of uninfected controls. The particles were often arranged in rows as if in crystalline formation. Maximal diameter of particles was approximately 65 mµ, and internal bodies were demonstrated.
Lesions of infected cells included target-like structures of the nuclear membrane, large nuclear vacuoles (type 2), and increased numbers of large irregular electron-dense granules in the cytoplasm 48 hours after infection. Examination of infected cultures by light microscopy, using the Feulgen reaction, showed intranuclear inclusion bodies and a cytopathogenic effect consisting of clumping of cells without pyknosis of nuclei. A lipide stain showed numerous cytoplasmic granules that were not identical with the large, irregular, electron-dense granules of the cytoplasm.
Practically all the cells showed the viral cytopathogenic effect, but only a minority of cells were found to contain virus-like particles or intranuclear inclusion bodies.
NEPHROTOXIC SERUM NEPHRITIS IN RATS
Authors: Baxter James H. , Goodman Howard C. 
Published: June 2004

Studies have been carried out to determine the distribution of antigen capable of inducing the formation in rabbits of antibodies nephrotoxic for the rat. The results indicate that the antigen is present both in cortex and medulla of rat kidney. It can be extracted to a limited extent with saline. It is non-dialyzable and destroyed by boiling.
The nephrotoxic serum antigen is also present in rat lung and placenta, in amounts roughly comparable to that in kidney, and in a number of other rat organs in smaller amounts. These various tissues not only are capable of stimulating the production of nephrotoxic antibodies, but each tissue is also able to absorb the nephrotoxic antibodies induced by injections of other rat tissues. These studies indicate that the nephrotoxic serum antigen in various rat tissues is the same or closely related.
The nephrotoxic serum antigen of the rat is distinct from that of the dog and the rabbit, but there appears to be a cross-reaction between the nephrotoxic serum antigens of the rat and mouse.
It is concluded that the nephrotoxic serum antigen is not a specific component of kidney; it is neither limited to kidney in its distribution within the rat, nor is the rat antigen present in kidney tissue of 2 other species examined. Rather, it is probable that the antigen is to a large extent specific for tissue of a given species. The preponderance of renal injury following injections of the anti-organ sera presumably is due to the occurrence in the kidney of large amounts of the antigen in positions of physiological importance in which it is exposed directly to the circulating antibodies.