bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE PATHOGENESIS OF HEMOPHILIA
Authors: Graham John B. , Barrow Emily M. 
Published: June 2004

It has been possible to duplicate in the hemophilic dog four of the major experiments which have suggested in humans an "anticephalin" hypothesis for the pathogenesis of hemophilia. The experiments in the dog have been considerably extended, as compared with the human experiments, by a variety of techniques.
I. Asbestos was placed in contact with hemophilic dog plasma, and the clotting time became shorter. When transfused, this plasma had no effect on the defective prothrombin utilization of hemophilic dogs, in contrast to untreated normal plasma.
II. The ionic strength of native dog plasma and dog plasma citrated (38 per cent sodium citrate) then recalcified (0.2 M CaCl2) were calculated. The ionic strength of the native plasma was approximately 0.15 while that of the citrated plasma was approximately 0.21.
Conductivity and freezing point determinations on the plasmas described above were consistent with the idea that the ionic strength of the citrated plasma was significantly higher.
The biphasic dilution curve, to which much significance has been attached in arriving at the "anticephalin" hypothesis, can be produced readily in the dog.
Diluting dog plasma with "iso-ionic" or "hyper-ionic" NaCl solution abolished the biphasic phenomenon. Dilution with distilled water exaggerated the biphasic curve. These experiments suggest that the biphasic curve is an artifact of uncontrolled ionic strength.
III. The prothrombin utilization rates of undiluted whole hemophilic dog blood and hemophilic dog blood diluted 1:2 with 0.85 per cent NaCl were found to be the same.
IV. Ether extraction of both normal and hemophilic dog plasma removed fibrinogen and reduced somewhat the concentration of prothrombin. In treated normal plasma AHF was reduced to the level of untreated hemophilic plasma, thus producing a quasi-hemophilic plasma.
Defibrination and ether extraction of both normal and hemophilic dog plasma "generated" clotting activity which shortened the clotting time of hemophilic plasma and was active in the thromboplastin generation test.
The activity "generated" by defibrination and ether extraction of dog plasma was adsorbed by a BaSO4 suspension and shown, therefore, not to be the anti-hemophilic factor (AHF).
Transfusion of ether-extracted normal or hemophilic dog plasma into hemophilic dogs had no effect on the prothrombin utilization rate, unlike untreated normal plasma which had a marked effect.
Thus, four of the main lines of evidence supporting the "anticephalin" hypothesis were duplicated in the dog. However, by extending the experiments it was found that all were explainable on bases other than the presence of "anticephalin." Such an hypothesis is not necessary, therefore, to explain the pathogenesis of canine hemophilia. The apparent identity of hemophilia in the two species suggests that the hypothesis is also not applicable to humans.
ACTION OF X-RAYS ON MAMMALIAN CELLS
Authors: Puck Theodore T. , Morkovin Dimitry , Marcus Philip I. , Cieciura Steven J. 
Published: June 2004

Survival curves of normal human cells from a variety of tissues exposed to varying doses of x-irradiation have been constructed, which permit definition of the intrinsic radiation sensitivity of the reproductive power of each cell type.
The mean lethal dose of x-irradiation for all the cells employed, including those from normal and cancerous organs, those exhibiting diploid and polyploid chromosome number; those from embryonic and adult tissues, including recently isolated cells and cultures which had been maintained in vitro for many years, and cells exhibiting either epithelioid or fibroblastic morphology, was found to be contained between the limits of 50 to 150 r.
Other similarities in the pattern of radiation effects, such as giant formation and abortive colonial growth, in these cells and that of the HeLa S3, previously studied, confirm the hypothesis that the pattern of reaction to x-irradiation previously elucidated, is representatative, at least in over-all outline, for a large variety of human cells.
While the radiation survival curves of various human cells are similar in the gross, small but important characterizing differences have been found. All epithelioid cells so far studied are approximately 2-hit, and more radioresistant than the fibroblast-like cells whose survival data correspond to a mean lethal dose of around 60 r, and which so far can be fitted by either 1-hit or 2-hit curves.
The earlier prediction that the major radiobiologic damage to mammalian cells is lodged in the genetic apparatus was confirmed by the demonstration of high frequency of mutants among the survivors of doses of 500 to 900 r.
All the data on the x-radiosensitivity of these cells can be explained on the basis of a defect resulting from primary damage localized in one or more chromosomes.
These considerations afford a convincing explanation of several aspects of the mammalian radiation syndrome.
CELLULAR SITES OF FORMATION OF GAMMA GLOBULIN
Authors: Ortega L. G. , Mellors R. C. 
Published: June 2004

The cellular sites of formation of γglobulin in lymphatic tissues of man and in a representative human lymphoid infiltrate have been studied by fluorescent antibody technique.
The findings indicate that γ-globulin is formed in the germinal centers of lymphatic nodules and in the cytoplasm of mature and immature plasma cells of two types—those with and those without Russell bodies.
The germinal center cells that synthesize γ-globulin have been designated "intrinsic" cells to distinguish them from the medium and large lymphocytes, and the primitive reticular cells that occur elsewhere and do not produce γ-globulin. Unlike the plasma cells, which function as individual units, the intrinsic cells apparently form γ-globulin only when they are arranged in discrete aggregations. The function, the blood supply, and the systematic cellular arrangement of germinal centers justifies the postulate that they are miniature organs of internal secretion of γ-globulin.
The release of γ-globulin from its sites of formation appears to be accomplished by holocrine and apocrine secretion. Presumably, these secretory mechanisms are adaptations required for the production of antibody since they have not been described in parenchymal cells that form the other serum proteins.
The cells found to form γ-globulin appear to be identical with those previously shown to form specific antibody in response to a variety of antigens in the experimental animal. This evidence indicates that normal γ-globulin, if it exists, originates in the same cells that produce antibody. It is suggested, also, that each of the 3 morphologically distinct categories of cells that synthesize γ-globulin represents a response to a particular form of antigenic stimulation.
Nuclear participation in the process of γ-globulin synthesis was not detected by the technique employed.
DIETARY FAT AND HYPERCHOLESTEREMIA IN THE CEBUS MONKEY
Authors: Portman Oscar W. , Sinisterra Leonardo 
Published: June 2004

A series of studies of cholesterol metabolism in the Cebus monkey were carried out in an attempt to understand the mechanisms responsible for the great differences in serum cholesterol levels when different dietary fats were used. Three groups of monkeys, one fed diets including 45 per cent of calories as corn oil, a second corn oil plus cholesterol (0.1 gm./100 calories), and a third lard plus cholesterol for 5 months (mean serum cholesterol values were 237, 268, and 601 mg. per cent, respectively) were injected with emulsions of cholesterol-4-C14. The mean biological half-lives for the disappearance of serum radiocholesterol were 8.8, 8.4, and 6.6 days respectively. Esterification of radiocholesterol as measured by equilibration of specific activities of serum-free cholesterol and total cholesterol was delayed in the monkeys fed lard plus cholesterol. When cholesterol-4-C-14-stearate was given intravenously to a series of monkeys, an erratic non-exponential biological decay curve resulted. Specific activity for free serum cholesterol was greater than that for total cholesterol within 1 hour after the injection.
After 7 months on experimental diets including corn oil with added cholesterol and lard with added cholesterol the levels of lipides in most tissues were not different for the two dietary groups, nor were they appreciably elevated above previous control figures for monkeys not fed cholesterol. Total lipide levels in the adrenals of monkeys fed corn oil were twice those of monkeys fed lard.
Monkeys were fasted before and after intragastric administration of cholesterol-4-C14 in small formula meals including various fats and fatty acids. The disappearance of total cholesterol from the serum consisted of a rapid followed by a slow exponential function. The type of fat and fatty acid appeared to influence the rate of disappearance of radiocholesterol. There was a broad range of apparent activity of the different fats and fatty acids in promoting cholesterol absorption.
A COMPARISON OF THE GROWTH OF SELECTED MYCOBACTERIA IN HELA, MONKEY KIDNEY, AND HUMAN AMNION CELLS IN TISSUE CULTURE
Authors: Shepard Charles C. 
Published: June 2004

HeLa, monkey kidney, and human amnion cells in tissue cultures were compared as sites for the multiplication of strains of tubercle bacilli or original and reduced pathogenicity, and for several other species of mycobacteria capable of causing disease in humans.
The arrangement of the pathogenic species inorder of their growth rates in HeLa cells was Mycobacterium fortuitum, Mycobacterium balnei, and the "yellow bacillus," followed closely by the tubercle bacillus. This order was also correct for these species in monkey kidney and human amnion cells, and is the same as that seen in bacteriological media.
The arrangement of the strains of tubercle bacilli in order of their growth rates in all three types of cells was: H37Rv, then R1Rv, and lastly H37Ra, which multiplied about as slowly as BCG. An INH-resistant strain grew about as rapidly as H37Rv.
Growth of the pathogenic species occurred at about the same rates in HeLa and monkey kidney cells, but was distinctly slower in human amnion cells, which are less active metabolically.
Irradiation of the cells in doses up to 5000 r did not affect the subsequent growth of mycobacteria in them.
Preliminary experiments with human leprosy bacilli indicate that they can be introduced into these cells in high numbers and that the bacilli then persist for the life of the cells.
LOCALIZATION OF STREPTOCOCCAL ANTIGENS IN TISSUES
Authors: Kaplan Melvin H. ,   With the Technical Assistance of Mary Meyeserian and Audrey Swift
Published: June 2004

A method has been described for the detection of streptococcal antigens in tissues using the indirect immunofluorescent technique. This method has been applied to the histologic distribution in the mouse of M protein of types 1, 5, 12, and 19. Histologic localization of these M proteins was similar, and their rates of disappearance from the tissues were comparable.
The major sites of deposition were the endocardium and adjacent subendocardium of the heart, alveolar walls of the lung, glomerular tufts of the kidney, and reticulo-endothelial cells of liver, spleen, lymph nodes, and adrenal gland. M protein was distributed in considerably lesser concentration in capillary endothelium and connective tissue sites in myocardium, kidney, skin, and gastrointestinal tract. Traces were also present in adrenal cortical cells. It was observed only rarely in cell nuclei.
After injection of 0.5 mg. M protein fraction, the concentration of antigen diminished to undetectable levels in all organ sites by 4 days, except in the renal glomerulus, where traces were visible at 8 days. In mice injected with streptococcal culture intraperitoneally, M protein was detected at sites of focal abscesses in liver and spleen, and on the serous surfaces of these organs.
The histologic distribution of M protein is compared with that described previously for pneumococcal polysaccharide and animal protein. Differences in the extent of distribution and in the characteristics of antigen deposition are pointed out.
THE PREVENTION OF THE GENERALIZED SHWARTZMAN REACTION WITH SODIUM WARFARIN
Authors: Shapiro Sandor S. , McKay Donald G. 
Published: June 2004

Using intravenous sodium warfarin, rabbits were rendered hypoprothrombinemic and subjected to two intravenous injections of Shear's polysaccharide. None of the 9 animals surviving the required period of time developed bilateral renal cortical necrosis or histologic thrombi in the kidney, liver, spleen, or lungs. In a control group of 7 animals treated only with endotoxin, 6 developed bilateral renal cortical necrosis.
It is concluded that the prothrombin complex is necessary for the production of the generalized Shwartzman reaction by bacterial endotoxins and that this phenomenon is essentially a process of disseminated intravascular coagulation.
ELECTRON MICROSCOPY OF SALIVARY GLAND VIRUSES
Authors: Luse Sarah A. , Smith Margaret G. 
Published: June 2004

A human and a mouse strain of the salivary gland virus have been examined by electron microscopy. The human strain was transmitted, prior to examination, to tissue cultures derived from human myometrial cells, while the mouse strain was examined in mice inoculated intraperitoneally.
The nuclear forms associated with both strains of virus were morphologically similar. Nuclear inclusions, composed of particles interspersed with dense clumped chromatin, were a striking feature of infected cells. The cytoplasmic forms were of 2 types—one a 300 to 500 mµ homogeneous dense spherical form, and the other a target-like form composed of a central dense dot in a pale zone surrounded by a dense shell—the entire configuration measuring 100 to 180 mµ. The target-like particle appeared to be identical in both strains. The spherical cytoplasmic forms in cells infected with the human strain appeared to be solid, while in cells infected with the mouse strain there was evidence of formation of target-like forms within the spheres.
Possible mechanisms by which infection of the cell may occur, as well as possible mechanisms and sites of multiplication of virus, are discussed.
INTERACTION OF THE RHEUMATOID FACTOR WITH ANTIGEN-ANTIBODY COMPLEXES AND AGGREGATED GAMMA GLOBULIN
Authors: Edelman G. M. , Kunkel H. G. , Franklin E. C. 
Published: June 2004

The effect of highly purified rheumatoid factor on the precipitin reactions of various antigen-antibody systems was determined. The amount of nitrogen precipitated was increased over a broad range when the factor was added to ovalbumin, human albumin, or human gamma globulin, and the corresponding rabbit antibodies. In the zone of antigen excess, soluble antigen-antibody complexes were precipitated by rheumatoid factor.
Soluble aggregates of human and rabbit gamma globulin, produced by heating at 63°C., treatment with urea plus mercaptoethanol or treatment with guanidine, also precipitated with rheumatoid factor. Ultracentrifugal analysis of dissolved specific precipitates showed the presence of aggregated gamma globulin. The sedimentation rate of reactive aggregates was greater than 20 S, and concentrated preparations free of the non-reactive 7 S gamma globulin could be prepared by various procedures of zone centrifugation. These aggregates showed a high inhibitory capacity in the sensitized sheep cell agglutination reaction.
Solid gamma globulin, prepared by heat denaturation, also selectively adsorbed the rheumatoid factor, and removed or decreased the activity in the various precipitation and agglutination reactions. Elution of highly purified active preparations from the solid gamma globulin could be carried out with urea or acid buffers.
Evidence for interaction between rheumatoid factor and low molecular weight gamma globulin without precipitation, was also obtained. This interaction appears to occur in the circulation of patients with rheumatoid arthritis.
The question of whether the rheumatoid factor represents an antibody to gamma globulin was discussed. Points of similarity to the behavior of complement also were cited.
IMMUNOLOGICAL UNRESPONSIVENESS IN RABBITS PRODUCED BY NEONATAL INJECTION OF DEFINED ANTIGENS
Authors: Smith Richard T. , Bridges Robert A. ,   With the Technical Assistance of Enid Thomson
Published: June 2004

The phenomenon of immunological unresponsiveness induced in the neonatal rabbit by a single injection of a defined protein antigen, has been characterized semiquantitatively, and studies bearing upon the mechanism of such unresponsiveness have been presented.
A single intraperitoneal injection at birth of 10 to 100 mg. BSA, HGG, ovalbumin, or a human macroglobulin, or an oral feeding of 100 mg. BSA, induced a state of unresponsiveness lasting at least 90 to 120 days. 100 mg. BSA given from birth to 17 days of age, but not later, produced unresponsiveness of 90 to 120 days' duration.
Data are presented which show that the duration of unresponsiveness is finite and related to the amount of antigen given at birth, and that it may be indefinitely prolonged by repeated injections of antigen.
Disappearance of injected antigen in the unresponsive animal was exponential with time, with no accelerated or immune phase. Administration of the antigen in adjuvants resulted in significant shortening of the duration of unresponsiveness. The transfer of immune cells to the unresponsive host while resulting in vicarious antibody formation, did not affect the underlying unresponsive state.
Negative results of attempts to produce unresponsiveness to a variety of bacterial antigens are presented. The implications of the data are discussed, particularly in reference to the other experimental models of immunological tolerance, and to the various theories of acquired immunity. It is clear that any satisfactory theoretical explanation of acquired immunity will have to account simultaneously for the phenomena of immune tolerance.
GAMMA GLOBULINS IN GERM-FREE RATS
Authors: Gustafsson Bengt E. , Laurell Carl-Bertil 
Published: June 2004

The electrophoretic fractions of serum proteins were studied up to the 5th generation in a colony of germ-free rats. The germ-free animals had significantly lower concentrations of beta and the gamma globulins, while the other fractions were within normal limits.
Assuming that the gamma globulins survive equally long in the circulation in germ-free animals as in controls, the production of gamma globulins in normal rats is three times as rapid as in germ-free rats. This suggests that the normal flora of microorganisms is an important stimulant for the gamma globulin-producing cells.
OCCURRENCE OF R ANTIGEN SPECIFIC FOR GROUP A TYPE 3 STREPTOCOCCI
Authors: Lancefield Rebecca C. ,   With the Technical Assistance of William N. Everly
Published: June 2004

Approximately 50 per cent of Group A, Type 3 streptococci contain a hitherto undescribed antigen found only in Group A, Type 3 organisms. It is serologically distinct from Type 3 M antigen and is designated as 3 R antigen.
Strains containing 3 R antigen but no Type 3 M antigen are "glossy," avirulent Type 3 variants. These strains can be obtained by repeated transfers of virulent M-containing streptococci in artificial media under unfavorable conditions of growth. These degraded streptococci recover Type 3 M antigen during serial passage through mice. The amount of 3 R antigen in a strain is not affected by a decrease or increase in M antigen.
The 3 R antigen is unrelated to virulence. Antibodies to this antigen do not protect mice against infection or promote phagocytosis in bactericidal tests. The 3 R antigen-antibody system can give rise to confusion in M-precipitin reactions. In all these properties 3 R antigen is similar to 28 R antigen, although in certain other properties the two R antigens are not identical. They are serologically distinct.
Virulence and ability to grow in normal human blood under the conditions of the bactericidal test are correlated with the presence of M antigen of Group A, Type 3 streptococci. Mouse protection and specific inhibition of growth of Type 3 streptococci by phagocytosis in bactericidal tests are associated with the presence of Type 3 anti-M antibodies.
STUDIES ON THE TRANSFER OF LYMPH NODE CELLS
Authors: Harris Susanna , Harris T. N. , Farber Miriam B. 
Published: June 2004

In earlier studies it was shown that if rabbit lymph node cells were incubated with Shigella-trypsin filtrate and transferred to other, recipient, rabbits, agglutinins to Shigella appeared subsequently in the sera of the recipients. However, if leucocytes from the donor rabbits were injected into the recipients at a suitable interval prior to lymph node cell transfer, agglutinins to Shigella did not appear after cell transfer. In the present study, a number of experiments were done which bear on the immunologic character of this suppressive effect on the transferred cells, the "pre-injection effect."
X-irradiation of the recipients before the injection of donor leucocytes led to a decrease in the extent of the pre-injection effect, i.e. to the appearance of higher agglutinin liters, in the recipient animals.
It was found possible to transfer the pre-injection effect by cells of rabbit lymph nodes draining sites of injection of rabbit leucocytes. No such effect was obtained with heated aliquots of these cell suspensions or with lymph node cells from sheep-erythrocyte-injected donors.
It was also possible to transfer the pre-injection effect passively by serum. Suppression of transferred lymph node cells was observed regularly after injection of serum pooled from groups of rabbits which had been injected with leucocytes pooled from the blood of 60 to 70 rabbits. The active material in anti-leucocyte serum could be precipitated in the globulin fraction of the serum and could be removed by absorption with rabbit lymph node cells.
In the course of experiments on the passive transfer of the pre-injection effect by antisera of individual rabbits to leucocytes of individual donor rabbits, evidence was obtained of the existence in the sera of some normal rabbits of antibodies to some of the rabbit leucocyte antigens.
STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES
Authors: Bergs Victor V. , Henle Gertrude , Deinhardt Friedrich , Henle Werner 
Published: June 2004

Efforts were made to elucidate the nature of the resistance to vesicular stomatitis virus (VSV) observed in MCN cultures persistently infected with Newcastle disease, mumps, or 6-6 viruses (MCNNDV, MCNMps and MCN6-6, respectively).
Cells derived from persistently infected cultures adsorbed VSV to the same extent as their uninfected counterparts. Only a fraction of the adsorbed virus could be recovered from the cells indicating that it enters into an eclipse in all of the cell types.
While propagation of VSV in MCN cells is largely inhibited at low pH levels, the resistance of persistently infected cultures could not be ascribed to their increased lactic acid formation.
Resistance was not absolute in that a few cells in persistently infected cultures apparently supported VSV reproduction. Furthermore resistance of the cultures was found to be transitory in that the VSV infection gradually gained the upper hand after 2 to 4 weeks of incubation.
Addition of ultraviolet-inactivated NDV to MCN cultures induced resistance to VSV as long as the equivalent of at least one ID50 (for chick embryos) of inactivated virus was provided per cell. Establishment of resistance required some time and its duration depended upon whether or not the free inactivated NDV was removed or neutralized after given adsorption periods.
The transitory nature of resistance in persistently infected cultures, or in MCN cells following adsorption of inactivated NDV, is most likely explained by the fact that the cells continue to divide and that the daughter cells are, at least in part, susceptible to VSV.
The results are compatible with the conclusion that the resistance observed represents another example of interference between 2 viruses.