bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
PHASE CONTRAST AND INTERFEROMETRIC MICROSCOPY OF THE L.E. CELL PHENOMENON
Authors: Rifkind Richard A. , Godman Gabriel C.
Published: June 2004

Alterations in the cellular morphology of polymorphonuclear leukocytes and lymphocytes under the influence of serum from patients having disseminated lupus erythematosus were observed under the phase contrast microscope. These changes appear to involve the cell nucleus without significant visible incorporation of cytoplasm. In the formation of the L.E. body, there is a loss of internal nuclear structure and a subsequent nuclear swelling and extrusion of the nuclear contents from the cell to form the free L.E. body. The possible incorporation of cytoplasmic substance cannot alone account for the large mass of the L.E. body as contrasted with the parent nucleus or nuclear lobe. Measurements of dry mass by means of the interference microscope show a two and one-half-fold increment in dry mass in L.E. bodies compared to parent lymphocyte nuclei. This confirms previous cytochemical studies, and establishes that an influx of protein into the leukocyte nucleus is an integral part of the L.E. phenomenon. That the accumulation of extraneous protein within the L.E. body is simultaneous with or subsequent to a disruption of the normal structure of the leukocyte nucleus is apparent from these studies, but the pathogenesis of this alteration is as yet unknown.
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.
PREDETERMINATION BY INFECTION AND BY VACCINATION OF ANTIBODY RESPONSE TO INFLUENZA VIRUS VACCINES
Authors: Davenport Fred M. , Hennessy Albert V. ,   With the Technical Assistance of Phyllis H. Fabisch
Published: June 2004

The antibody orienting effects of prior infections with antigenic variants of influenza viruses were confirmed by studies with monovalent adjuvant vaccines and with polyvalent aqueous and adjuvant preparations. In either case, the predominant antibody response was of a "booster" type, directed against the major antigens of strains of original infection. It was shown that vaccination with appropriate strains, selected as antigenic prototypes, could orient or predetermine subsequent antibody response upon revaccination. Moreover, the effects of exposure by vaccination were found to be durable and to constitute a foundation upon which future antibody dividends could be accumulated. As a result, it seems feasible to induce by vaccination a more lasting broad composite antibody protection against influenza if appropriate preparations and schedules are used.
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.
ALTERATIONS IN THE BLOOD COAGULATION SYSTEM INDUCED BY BACTERIAL ENDOTOXINS
Authors: McKay Donald G. , Shapiro Sandor S. , Shanberge Jacob N.
Published: June 2004

Bacterial endotoxins in vitro are capable of shortening the coagulation time of normal whole blood, native platelet-rich and platelet-poor plasma, and the blood of a hemophilic patient in silicone but not in glass. The point in the coagulation system at which the endotoxins act has not been found but the search has been narrowed by the demonstration that these materials act independently of leukocytes and red blood cells, and do not act as preformed thromboplastin or thrombin. The shortening of the coagulation time in vivo 4 hours after endotoxin injection is probably through a different mechanism than in vitro.
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.
IRREVERSIBLE HEMORRHAGIC SHOCK IN GERMFREE RATS
Authors: Zweifach B. W. , Gordon H. A. , Wagner M. , Reyniers J. A.
Published: June 2004

Evidence has been provided that a state of irreversible hemorrhagic shock can be induced in a bacteria-free environment in rats reared under germfree conditions. The response to bleeding, the duration of the hypotensive episode and the pathological changes were the same in the germfree and in normal stock rats. The findings are interpreted as evidence opposed to the concept that bacteria or bacterial products are implicated, as primary factors, in the pathogenicity of shock.
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.
THE FORMATION OF MYELOMA PROTEIN BY A MOUSE PLASMA CELL TUMOR
Authors: Nathans Daniel , Fahey John L. , Potter Michael
Published: June 2004

The origin of the myeloma protein found in mice bearing the plasma cell tumor X5563 has been investigated. Specific activity-time curves of the myeloma proteins isolated from the tumor and from the plasma of these animals were compared following intravenous injection of L-lysine-C14. The results indicate that myeloma protein is synthesized in the plasma cell tumor.
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.
GLYCYRRHIZIN-INDUCED INHIBITION OF THE PITUITARY-ADRENAL STRESS RESPONSE
Authors: Kraus Shirley D.
Published: June 2004

Glycyrrhizin decreased the resistance of intact male mice to prolonged exposure to cold (8 hours at 5°C.) and it decreased the ability of intact male rats to mobilize glucose when subjected to 48 hours of fasting. It is suggested that glycyrrhizin, like desoxycorticosterone, depresses the output of ACTH.
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.
KWASHIORKOR TYPE OF FATTY LIVER IN PRIMATES
Authors: Wilgram George F. , Lucas Colin C. , Best Charles H.
Published: June 2004

Fatty livers resembling those seen in the early stages of kwashiorkor have been produced in primates. Monkeys were fed, for about 1 year, purified diets free from choline and betaine and low in methionine. Supplementation with choline slightly improved food consumption and gain in weight. Choline prevented the appearance of any stainable lipide in the liver of the control animals. The extent to which the slightly greater intake of protein, including methionine, in the choline-supplemented animals contributed to the prevention of the periportal accumulation of fat in the liver is being determined.
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.
ALTERED REACTIVITY TO EPINEPHRINE IN THE HYPERSENSITIVE RABBIT
Authors: Gatling Robert R.
Published: June 2004

A series of experiments are reported which illustrate and characterize an altered state of reactivity of the skin of the hypersensitive rabbit to epinephrine (and norepinephrine). The requirements for the production of the lesion are: a state of hypersensitivity, circulating antigen and antibody and focal deposition of epinephrine or norepinephrine. The size and intensity of the reaction appear to be directly related to the amount of epinephrine injected (within certain limits) and to the degree of hypersensitivity as measured by the Arthus reaction. Although circulating antigen is required, the precise quantity does not seem to be as critical as does the amount of circulating antibody; a certain minimum amount is necessary, however. Experimental evidence is given which indicates the utilization of antigen in the production of the lesion. Data tending to identify this lesion with the Arthus reaction are given. The possibility of an analogous relationship between the mechanism of this experimental lesion and the necrotizing arteritis of the collagen diseases is postulated.
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.
STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES
Authors: Deinhardt Friedrich , Bergs Victor V. , Henle Gertrude , Henle Werner
Published: June 2004

Efforts were made to obtain information on some of the quantitative aspects of host cell-virus interactions in MCN cultures persistently infected with Newcastle disease, mumps, and 6-6 viruses, and to elicit the mechanism which permits simultaneous maintenance of virus and cells for indefinite periods of time.

It was shown by 4 different technics that only between 10 and less than 1 per cent of the cells yield infectious virus, depending upon the agent employed and, possibly, variations in the conditions of the cultures. No evidence was found to indicate production of non-infectious virus materials.

Only the cells carrying infectious virus are capable upon transfer to uninfected cultures to transmit the infection. Cells from persistently infected cultures, which are free of infectious virus at the time of transfer, failed to liberate virus at a later time during incubation periods of up to 4 weeks.

The virus-producing cells contain at any given moment not more than 1 infectious unit of virus, suggesting a linear mode of production; i.e., as soon as a virus particle is completed, it is released.

Upon inoculation of MCN test tube cultures with chick embryo-adapted NDV persistent infection and interference with vesicular stomatitis virus (VSV) is established with considerable delay. In contrast, following transfer of MCN-adapted NDV, in form of MCNNDV cells or first allantoic passage seeds derived therefrom, the number of virus-producing cells increases logarithmically, doubling every 6 to 8 hours until a total of about 104 is reached. Thereafter their numbers rise in proportion to the increase in total cell population; i.e., doubling approximately every 48 hours.

At the time when 104 virus-producing cells are present in the culture interference with VSV is solidly established. In order to obtain this result about 106 cells must have adsorbed virus particles, or, in other words, at least 106 virus units must have totally been produced instead of the 104 measured by infectivity assay.

The implications of these and previously reported data have been discussed in detail and a scheme of the course of events in persistently infected cultures has been presented.
THE "DELAYED HYPERSENSITIVITY" INDUCED BY ANTIGEN-ANTIBODY COMPLEXES
Authors: Raffel Sidney , Newel J. Michael
Published: June 2004

The "delayed hypersensitive" reactivity induced by antigen-antibody complexes has been studied from the standpoints of the role of such complexes in establishing this state, and the relationship of this state to classical delayed hypersensitivity.

It has been shown that the reactivity established by antigen-antibody complexes appears early after injection, disappears within a few days, and is characterized by several properties which make it appear similar to true delayed hypersensitivity, including its appearance, its relative persistence for 48 hours, and its occurrence in the absence of antibodies. By the same tokens, it may be distinguished from hypersensitive reactions of the immediate type. It is referred to here as reactivity of the Jones-Mote type.

Antigen alone stimulates exactly the same kind of early reactive state, but with larger doses of antigen this is later replaced by other immunologic responses including circulating antibodies and Arthus reactivity. If sufficiently small doses of antigen are employed, however, the "monophasic" reaction which follows antigen-antibody complexes consisting of the Jones-Mote type of skin responsiveness may be seen.

The dermal reactivity under discussion is unlike classical delayed hypersensitivity chiefly in its evanescent character; it is present only during a few days early after antigen administration.

It is suggested that this kind of reactivity, which may perhaps require a category of its own, may be related to the "tissue immunity" to tumor transplants which has been observed in mice.
THE ETIOLOGIC AGENTS OF VARICELLA AND HERPES ZOSTER
Authors: Weller Thomas H. , Witton Helen M.
Published: June 2004

The preparation of antigenic materials capable of specific fixation of complement in the presence of convalescent phase sera from patients with varicella and herpes zoster is described. Satisfactory antigens were obtained by the repetitive harvest and subsequent concentration of the pooled nutrient fluids from bottle cultures of human embryonic skin-muscle tissue or of monkey kidney tissue infected with varicella or herpes zoster viruses. Specific fixation of complement was also demonstrated with antigens prepared from extracts of the infected cell sheets harvested from bottle cultures.

In individuals with varicella, complement-fixing antibody usually appeared in the serum 4 or 5 days after the development of the exanthem and further significant increases in titer were characteristically observed during the 2nd week of illness.

The complement-fixing antibody response in herpes zoster tended to follow the same pattern as in varicella, with the exception that in sera from some individuals relatively high titers were present in the acute phase specimen.

Complement-fixing antigens prepared from varicella strains or from a zoster strain reacted to essentially the same degree with convalescent sera from the homologous and the heterologous clinical entities. The varicella-zoster antigens did not fix complement in the presence of paired sera obtained from a limited number of individuals with primary infections due to herpes simplex virus or from individuals with generalized vaccinia infection.

Specific inhibition in vitro of the focal cytopathic process produced by the varicella-zoster viruses was demonstrated. This was accomplished by the incorporation of the sera under test as constituents of nutrient media of the cultures, either prior to or at the time of their inoculation with virus. The neutralization of focal cytopathogenicity thus obtained was relative in degree and never absolute; it was therefore assayed by repetitive counts of the number of focal lesions per culture in the various test groups.

Inhibition of varicella-zoster viral cytopathogenicity occurred in the presence of convalescent serum from either clinical entity.

The results of the immunologic studies with the viruses of herpes zoster and varicella as propagated in vitro are considered as providing further evidence in support of the concept of the close relationship and probable identity of the two agents.
DELAYED HYPERSENSITIVITY
Authors: Uhr Jonathan W. , Brandriss M. W.
Published: June 2004

Guinea pigs with delayed hypersensitivity to protein antigens show a specific febrile response accompanied by a lymphopenia following injection of a desensitizing dose of specific antigen. No signs of shock are observed in highly sensitive animals following this injection. The response is not prevented in sensitive guinea pigs by inducing endotoxin tolerance or by pretreating with cortisone before specific challenge. Using a suitable antigen in sufficiently sensitive animals as little as 100 µg. can elicit a pronounced febrile response. Injection of a desensitizing dose of antigen specifically abolishes systemic as well as skin reactivity for several days. Normal or hypersensitive (delayed-type) animals passively sensitized with sufficient amounts of serum antibody show hypothermia after specific challenge and may show a delayed type of fatal shock. Differences were noted between their systemic reactivities, however, and the reactivity seen in specifically challenged tuberculous animals.
THE MAMMALIAN CELL-VIRUS RELATIONSHIP
Authors: Holland John J. , McLaren Leroy C.
Published: June 2004

Phases of attachment, reception or penetration, and eclipse of Type 1 poliovirus infecting HeLa cells in monolayer were studied. Firm attachment was not completely dependent on salt concentration, and was sensitive to temperature change. Like attachment, progressive resistance of adsorbed virus to inactivation by externally applied antibody was temperature-sensitive. Penetration was shown to be independent of physiologic integrity of cells. Virus in process of penetration was not affected by ribonuclease. Eclipse of adsorbed virus was not dependent on metabolic activity or physical integrity of HeLa cells. Debris from poliovirus-susceptible cells inactivated the virus in a manner similar to the kinetic course of virus adsorption by intact cells, and released cell-associated infective virus in similar amounts. All cells insusceptible to poliovirus infection failed to yield active debris. Virus inactivation by debris, like virus reception by intact cells, was temperature-sensitive. Debris could not inactivate virus adsorbed to cells, or alter the progressive incapacity of antibody to neutralize penetrating virus. The active debris factor was insoluble, was not associated with cell nuclei, was inactivated by fat solvents and trypsin treatment, and was destroyed by beat inactivation or sonic disruption. Anti-HeLa serum applied to cells before exposure to virus reduced the rate of virus adsorption, while antiserum treatment immediately following virus adsorption was ineffective. These findings suggested that the capacity of HeLa and other susceptible cells to adsorb, receive, and eclipse poliovirus was associated with organized cytoplasmic lipoprotein structures not possessed by insusceptible cells. The reaction of virus with receptor substance contained in debris was not readily reversed by treatment shown not to affect virus and to destroy activity of uncombined debris. Sensitivity of poliovirus adsorption by HeLa cells to change in environmental salt concentration or temperature was dependent on the method of measurement.
THE EFFECT OF HIGH DOSES OF X-IRRADIATION ON THE PHAGOCYTIC, PROLIFERATIVE, AND METABOLIC PROPERTIES OF THE RETICULO-ENDOTHELIAL SYSTEM
Authors: Benacerraf B. , Kivy-Rosenberg Evelyn , Sebestyen Martha M. , Zweifach Benjamin W.
Published: June 2004

The effect of moderately high doses of x-irradiation upon the reticulo-endothelial system of mice and rats was investigated.

A dosage of 600 r to mice and 850 r to rats did not interfere with the ability of the RES to clear colloidal particles from the blood. However the 850 r x-ray dose to rats prevented recovery of normal phagocytic function after "blockade."

In mice, 600 r interfered with the ability of the RES to respond to the usual stimulating effect of zymosan.

The ability of the RES of mice which have received 600 r of x-rays to clear P32-labelled E. coli from the blood was not significantly altered. These mice responded poorly to immunization, as demonstrated by the slow rate of clearance of the bacteria from the blood of immunized, irradiated individuals as compared with that of immunized controls. This reflected the lowered antibody production and not deficiency of phagocytic mechanism.

There was no evidence of a changed capacity of the Kupffer cells of mice which had received 600 r of x-rays to break down denatured protein enzymatically.
THE RENAL LESIONS OF ELECTROLYTE IMBALANCE
Authors: Holliday M. A. , Winters R. W. , Welt L. G. , MacDowell Muriel , Oliver Jean
Published: June 2004

Potassium depletion in rats augments the specific renal lesions of phosphate loading.

Since it has been shown that phosphate loading increases the specific cardiac lesions of potassium deficiency (12), it is concluded that the similar types of electrolyte imbalance (potassium depletion-phosphate load) act conversely in the two organs.
A STUDY OF THE DISTRIBUTION OF 2,4-DINITROBENZENE SENSITIZERS BETWEEN ISOLATED LYMPH NODE CELLS AND EXTRACELLULAR MEDIUM IN RELATION TO INDUCTION OF CONTACT SKIN SENSITIVITY
Authors: Eisen Herman N. , Kern Milton , Newton William T. , Helmreich Ernst
Published: June 2004

Although induction of contact skin sensitivity by low molecular weight 2,4-dinitrobenzenes requires the formation in vivo of 2,4-dinitrophenyl-proteins, analogous protein conjugates prepared in vitro are unable to induce this hypersensitive state. Low molecular weight 2,4-dinitrobenzenes are concentrated by isolated lymph node cells, but a representative 2,4-dinitrophenyl-protein conjugate (2,4-dinitrophenyl-bovine serum albumin) was not taken up to a detectable extent by these cells. It is inferred that there exist large quantitative differences in the extent to which dinitrophenyl-proteins are localized within cells following the administration to an intact animal of (a) those simple dinitrobenzenes which are both concentrated by lymph node cells and have the capacity to form protein conjugates in vivo, and (b) 2,4-dinitrophenyl-protein conjugates prepared in vitro. It is suggested that this difference could account for the fact that a varietyof 2,4-dinitrophenyl-proteins prepared in vitro are unable to induce contact skin sensitivity.
ORIGIN OF ANTI-HUMAN BLOOD GROUP B AGGLUTININS IN WHITE LEGHORN CHICKS
Authors: Springer Georg F. , Horton Richard E. , Forbes Martin
Published: June 2004

While anti-human blood group B agglutinins are present in the majority of ordinary White Leghorn chicks by the age of 30 days, none could be demonstrated in germfree chicks up to the age of 60 days. Anti-B agglutinins in trace amounts were first found in germfree chicks 66 days old and increased to an average titer of about 1:2 by 91 days of age. This titer amounts to about 10 per cent of that found in ordinary chicks. The appearance of antibody in low titer is attributed to trace amounts of non-living antigenic contaminants penetrating the germfree barrier.

The necessity of appropriate absorption in order to obtain well defined specificities was pointed out. Several means commonly used to differentiate between normal and immune antibodies were employed in this investigation. None showed a difference between anti-B agglutinins from ordinary chicks and from germfree chicks intentionally immunized with blood group B active E. coli O86 or with B active preparations from human meconium. The implications of these findings on the origin of natural agglutinins are discussed. It is concluded, that measurable anti-human blood group B agglutinins in White Leghorn chicks are acquired early in life and are not inherited.

The possibilities as well as limitations of present day germfree technique for this kind of immunological research have been considered.
PERSISTENCE OF TYPE-SPECIFIC ANTIBODIES IN MAN FOLLOWING INFECTION WITH GROUP A STREPTOCOCCI
Authors: Lancefield Rebecca C.
Published: June 2004

Whole blood or sera were collected from individuals who had had infections with Group A streptococci of known serological type as long ago as 10 to 32 years. Most of these patients had not been treated with chemotherapeutic drugs. By means of bactericidal tests with all these sera, and mouse protection tests with some, type-specific antibodies could be demonstrated in at least half of them after a lapse of many years, the longest interval being 32 years.

Two biological methods for estimating the amount of M antigen produced by Group A streptococci are described. By selecting strains for use by these methods, optimal proportions of M antigen and antibody could be employed in the tests and small amounts of antibody were, therefore, demonstrable.

The assay methods for M antigen are also of value for other experimental purposes.
THE ROLE OF POLYMORPHONUCLEAR LEUKOCYTES IN THE INITIATION AND CESSATION OF THE ARTHUS VASCULITIS
Authors: Cochrane Charles G. , Weigle William O. , Dixon Frank J.
Published: June 2004

The role of polymorphs in the Arthus type hypersensitivity vasculitis has been studied. Polymorphs were found to play an essential role in not only producing the inflammatory vasculitis, but also were instrumental in ridding the damaged vessel of the antigen, probably by means of proteolytic catabolism at the inflammatory site.

A temporal relationship between the disappearance of antigen from the damaged vessels and a decrease in inflammatory reaction was found.

The earliest localization of antigen and its associated rabbit globulin in the Arthus vasculitis was found to be beneath the endothelium of small vessels.

Since submitting this article for publication, Sorkin and Boyden (J. Immunol., 1959, 82, 332) have reported the catabolism of antigen in the presence of antibody by mononuclear cells obtained from the peritoneal cavities of guinea pigs. Evidence was presented indicating that the antigen molecule was actually broken down by the mononuclear cells. Techniques similar to those reported here were used.
STUDIES ON BLOOD FACTORS RhA, RhB, AND RhC
Authors: Unger Lester J. , Wiener Alexander S. , Katz L.
Published: June 2004

Observations are described of the incidence among Caucasians and Negroes of the blood factors RhA, RhB and RhC which occur associated with the Rh0 factor in typical Rh-positive blood. The antiserums used for the tests were derived from Rh-positive patients who had had hemolytic transfusion reactions or erythroblastotic babies. Among a large series of individuals, it was found that only rarely is any of the blood factors RhA, RhB, or RhC lacking from "standard" Rh0-positive blood. On the other hand, about half of the specimens of Rh0 variant blood lack one or more of the factors RhA, RhB, and RhC, which, when present in such blood, are also almost always variants. Judging from the incidence of specimens lacking one or more of these factors, RhA, RhB, and RhB appear to be relatively independent of one another despite their association with blood factor Rh0. Tests for factors RhA, RhB, and RhC distinguish new rare varieties of Rh and ℜh agglutinogens, each genetically determined by corresponding allelic genes.

There is no doubt that more clinical cases will be found in which sensitized Rh-positive individuals have antibodies resembling anti-Rh0 in specificity. Four such cases have already been studied by the present authors, and in each case the antibodies were shown to be different from anti-Rh0 in specificity. Since they were also different from one another, they have been assigned the symbols anti-RhA, anti-RhB, anti-RhC, and anti-RhD, respectively, the first three being the antiserums used in the present study. Obviously, in order to avoid confusion of nomenclature, the specificity of antiserums from other similar cases will have to be compared with anti-RhA, anti-RhB, anti-RhC, and anti-RhD and shown to be different from all four, as well as anti-Rh0, before a distinctive symbol is assigned to them.
SIMULTANEOUS PRODUCTION OF TWO CAPSULAR POLYSACCHARIDES BY PNEUMOCOCCUS
Authors: Austrian Robert , Bernheimer Harriet P.
Published: June 2004

Pneumococci manifesting binary capsulation have been produced through the agency of transformation reactions. Such cells produce two capsular polysaccharides which are closely similar if not identical with those produced by corresponding singly capsulated strains.

Binary capsulation in pneumococcus provides a new basis for serologic cross-reactivity in this species.