bluuebunny/crossref_metadata_2025 huggingface dataset:
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 (<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.
HORMONAL INFLUENCES ON MAMMARY TUMORS OF THE RAT
Authors: Huggins Charles , Torralba Yolanda , Mainzer Klaus
Published: June 2004

A transplanted mammary fibroadenoma was found to grow in 95 per cent of intact adult female rats and the increment of tumor weights was progressive and logarithmic.

The growth of the tumor was retarded by ovariectomy and still more when this was combined with adrenalectomy. In ovariectomized rats the growth of the tumor was stimulated by phenolic estrogens, this increase being enhanced when progesterone was added.

In these responses to hormonal changes the mammary gland and the tumor resembled each other. Yet there are many differences between the growth of the fibroadenoma and that of the mammary gland. In contrast to the progressive growth which occurred in intact adult females there was a prolonged period of indolent growth of transplants in hypophysectomized rats; but after many weeks active growth began and the tumors eventually reached large size. During the period of quiescent growth the tumor was cytologically atrophic but after the growth spurt had started the microscopic appearance of the fibroadenoma resembled that of tumors growing in normal adult females. The mammary gland remained atrophic during both the slow and the accelerated phases of tumor growth, and so too with the other secondary sex expressions.

In hypophysectomized rats estrone and progesterone, when combined, stimulated the growth of the tumor, and this growth was accelerated by the additional administration of lactogenic or growth hormones. None of these hormones, separately, stimulated the growth of the tumor.

In ovariectomized rats other differences were demonstrated between the growth of the mammary gland and the fibroadenoma. Progesterone, injected alone, accelerated the growth of the tumor but not that of the mammary glands. The administration of phenolic estrogens exerted a biphasic effect on the growth of the tumor whilst that on the breast of its hosts was monophasic. With progressively increasing doses of these phenols there occurred primarily an augmentation of the rate of growth of the tumor until a peak was achieved; an increase of the dose above the optimal amount depressed the growth of the tumor. The stage of depression of growth was not observed in the mammary glands of these tumor-bearing rats.

Many steroids which induced gestational changes in the mammary gland accelerated the growth of the tumor. Among these were estrone and progesterone in combination and 17α-ethinyl-19-nor-testosterone administered alone. But gestational changes developed in the mammary gland of rats treated with 4-androstene-3α,17ß-diol, without growth of the tumor.

The evidence which we have presented proves that the mammary fibroadenoma tested had some of the functional properties of a normal mammary gland, and neoplastic traits as well. In its response to hormones it had characteristics which set it apart from all other endocrine targets of the rat.
THE PROPERDIN SYSTEM AND IMMUNITY
Authors: Wedgwood Ralph J. , Ginsberg Harold S. , Pillemer Louis
Published: June 2004

Detailed experiments are presented which indicate that the properdin system is an inhibitor of Newcastle disease virus. Viral inhibition required all known components of the properdin system: properdin, all four components of complement and magnesium; the removal of any one constituent resulted in a loss of inhibition; the replacement of the constituent restored antiviral effect. The inhibition of virus was temperature-dependent. The process of inhibition by serum resulted in a decrease in the amount of properdin available in the serum without any measurable effect on the components of complement. The prolonged incubation of inactive serum-virus mixtures with cation-exchange resin resulted in the restoration of some, but not all, of the hemagglutinating activity of the virus. The requirements of the properdin system and the implication of these findings were discussed.
IMMUNOHISTOCHEMICAL ANALYSIS OF AMYLOID BY THE FLUORESCENCE TECHNIQUE
Authors: Vazquez Jacinto J. , Dixon Frank J.
Published: June 2004

The immunohistochemical composition of amyloid deposits in secondary human amyloidosis and experimental amyloidosis in rabbits was studied by means of the "fluorescent antibody" technique of Coons et al. Quantitative studies of the relative amounts of gamma globulin present in the amyloid deposits by the use of radioiodinated fluorescent antibody are reported. It is concluded that amyloid deposits in several organs from cases of secondary human amyloidosis and experimental amyloidosis in rabbits contain considerable concentrations of gamma globulin. The presence of gamma globulin in amyloid might be interpreted as either a metabolic deposition of circulating globulin present in high concentrations in the plasma or as a result of an immunologic reaction involving antigen and antibody.
EFFECT OF THE LEVEL AND TYPE OF DIETARY FAT ON THE METABOLISM OF CHOLESTEROL AND BETA LIPOPROTEINS IN THE CEBUS MONKEY
Authors: Portman Oscar W. , Hegsted D. Mark , Stare Fredrick J. , Bruno Dorothy , Murphy Robert , Sinisterra Leonardo
Published: June 2004

A study was carried out to determine the effect of the level and type of dietary fat on the concentration of cholesterol and beta lipoproteins in the sera of Cebus monkeys. Three groups of monkeys were fed isocaloric diets containing a fixed ratio of alpha protein and cholesterol to calories but with different amounts of corn oil and sucrose. Corn oil provided 10, 32, and 45 per cent of the calories in the three diets, and the level of sucrose was varied inversely. After 8 weeks the serum cholesterol and Sf 12 to 100 beta lipoprotein concentrations were significantly greater in the medium and high fat groups. When corn oil was decreased from 45 to 10 per cent of dietary calories and sucrose was increased, the serum cholesterol fell in all cases, and when the reverse change was made, the concentration of serum cholesterol increased.

Variation in dietary sucrose had no specific effect. Substitution of starch for sucrose with diets otherwise constant did not cause significant change in the concentration of serum cholesterol.

When monkeys fed corn oil diets at any of three levels were changed to hydrogenated cottonseed oil diets at the same level, the serum cholesterol and Sf 12 to 100 beta lipoproteins rose. However, hydrogenated cottonseed oil had no greater hypercholesteremic effect than did corn oil in the absence of dietary cholesterol. Diets containing lard with cholesterol also produced strikingly greater serum lipide responses than did diets based on corn oil and cholesterol. Hydrogenated cottonseed oil had a greater hypercholesteremic effect than an unhydrogenated cottonseed oil from the same lot.

Preliminary studies indicated that the saturated fats (hydrogenated cottonseed oil) produced the most striking elevation of serum cholesterol values (above controls fed corn oil) when casein was the dietary protein.
ALTERATIONS IN SERUM GLOBULINS DURING THE FORMATION AND RESORPTION OF AMYLOID IN RABBITS
Authors: Richter Goetz W.
Published: June 2004

A marked increase of the serum beta globulins was found in rabbits developing amyloidosis as a result of prolonged treatment with ribonucleate administered by subcutaneous injections. Following cessation of treatment the beta globulin levels gradually returned to normal while the gamma globulin levels rose strikingly, the changes being accompanied by a resorption of amyloid from the spleen, and probably also from the kidneys. Electrophoretic studies provided some evidence that the increase in beta globulins which accompanied the development of amyloidosis resulted from the production of a globulin not normally present in rabbit serum. A protein or protein derivative that moved as a beta globulin when subjected to filter paper electrophoresis was excreted in substantial quantities in the urine of several amyloidotic rabbits, along with much smaller quantities of substances moving as albumin, alpha and gamma globulins.

Considered as a whole, the findings indicate a causal relationship between the abnormal production of circulating beta globulins and the deposition of amyloid in rabbits treated with ribonucleate. Hence it appears that a beta globulin may be directly involved in the formation of amyloid under the conditions of the experiments here reported.
DELAYED HYPERSENSITIVITY
Authors: Uhr Jonathan W. , Salvin S. B. , Pappenheimer A. M.
Published: June 2004

A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed.
SYNTHESIS OF SULFOMUCOPOLYSACCHARIDES IN THYROIDECTOMIZED RATS
Authors: Dziewiatkowski Dominic D.
Published: June 2004

The thyroid glands of rats were made non-functional by a single dose of iodine-131 on the 1st day after birth or by surgical removal on the 28th day. The incorporation of sulfate-sulfur into the sulfomucopolysaccharides of skeletons and pelts was found to be significantly depressed by thyroidectomy. Daily supplements of 5 or 10 γ of L-thyroxine, started on the 28th day, increased the uptake of sulfur-35, although it did not reach normal in the 2 weeks of treatment.

Autoradiograms of sections of tibiae and pelts confirmed the analytical data. The findings suggest that the synthesis of sulfomucopolysaccharides is depressed in thyroidectomized rats.
STUDIES ON A SUBSTANCE THAT PROMOTES TUMOR HOMOGRAFT SURVIVAL (THE "ENHANCING SUBSTANCE")
Authors: Kandutsch A. A. , Reinert-Wenck U.
Published: June 2004

Using the death of mice due to the growth of tumor homografts as an end point, the distribution and properties of a tumor homograft-promoting substance(s), the "enhancing substance," were studied.

Activity was most largely present in tumor and spleen tissues while that in the liver, kidney, and stomach was relatively slight.

Activity was widely distributed in fractions prepared from tumor. Although DNAP and crude RNAP fractions were active, activity could not be associated with either RNA or DNA. The fraction possessing the highest concentration of activity was a residue fraction which was insoluble in water or in dilute or strong saline solutions.

Extraction of lyophilized tumor with acetone or 3:1 alcohol:ether reduced, but did not eliminate, activity in the insoluble fraction. However, activity was completely lost after extraction with 80 per cent alcohol at room temperature.

Enhancing activity of a tumor fraction was irreversibly lost after exposure for 1 hour to a solution more acid than pH 5 or more alkaline than pH 9. Activity was completely lost after exposure to 50 per cent urea or 90 per cent phenol.

Activity was not altered by incubation with trypsin, hyaluronidase, DNAase or the receptor-destroying enzyme of V. cholerae, but it was decreased when trypsin or hyaluronidase was injected with the incubated tumor fraction.

Activity was rapidly destroyed by treatment with dilute solutions of sodium periodate at pH 7. Under similar conditions, treatment with KMnO4 resulted in less extensive destruction of activity while H2O2, K2Cr2O7, and NaIO4 previously inactivated by reaction with glucose had no apparent effect on activity.

These results are interpreted as indicating the presence of both carbohydrate and protein in the structure of the activity substance.
THE INFLUENCE OF ADRENOCORTICOTROPIC AND GROWTH HORMONES ON ANTIBODY FORMATION
Authors: Hayashida Tetsuo , Li Choh Hao
Published: June 2004

The influence of pituitary adrenocorticotropic hormone (ACTH) and growth hormone (somatotropin, STH), singly and in combination, has been studied in normal, young adult rats, with respect to antibody formation against Fraction IA of Pasteurella pestis.

When ACTH was administered during the period of immunization, in a daily dose just sufficient to prevent body weight increase relative to the non-treated, immunized controls, serum antibody levels against the specific antigen employed were significantly depressed.

The administration of STH alone resulted in a marked increase in body weight. The increase in antibody level was not significant at the 5 per cent level when compared with the control values.

The same dosage of STH given simultaneously with ACTH maintained body weight at a level slightly above that of the controls, and resulted in an effective counteraction of the antibody depression produced by the latter hormone.
STUDIES ON BACTERIEMIA
Authors: Rogers David E. , Melly Marian Ann
Published: June 2004

Intravenous injection of staphylococci produced a marked, transient granulocytopenia inrabbits. Leukopenia was rapidly followed by return of polymorphonuclear leukocytes to the peripheral blood, and normal circulating granulocyte levels were reestablished within 20 to 40 minutes.

Differential arterio-venous leukocyte studies showed that polymorphonuclear leukocytes were trapped within the pulmonary vascular bed and, less constantly, in the splanchnic viscera during the initial 10 to 20 minutes following the injection of staphylococci. Granulocytes were subsequently found in larger numbers in blood leaving the lungs and splanchnic tissues, suggesting that entrapped polymorphonuclear leukocytes rapidly reentered the blood stream. This sequence of changes in circulating granulocytes was not significantly altered by splenectomy or the administration of cortisone.

It has previously been shown that virtually all staphylococci in the blood stream are found within circulating polymorphonuclear leukocytes 10 to 40 minutes after the injection of culture (9). It is during this period that granulocytes return to the blood stream in large numbers.

These observations suggest that staphylococci are phagocyted by polymorphonuclear leucocytes temporarily sequestered in the lungs and splanchnic viscera. It appears probable that some sequestered granulocytes containing living staphylococci subsequently return to the circulation. Such intraleukocytic staphylococci are believed to play a role in the maintenance of bacteriemia.
THE RETENTION OF S35-LABELLED BOVINE SERUM ALBUMIN IN NORMAL AND IMMUNIZED RABBIT LIVER TISSUE
Authors: Garvey Justine S. , Campbell Dan H.
Published: June 2004

The S35-label of S35-BSA was detected in the liver tissue of rabbits to the extent of 0.02 per cent (10 µg or ≃ 1014 molecules) of the injected material at 140 days after injection.

The rate of loss of antigen at the termination of the experiment was of such an order that significant amounts would be expected to persist for at least several years.

Data are reported which extend the retention data previously reported on S35-labelled hemocyanin. They indicate that amounts of the order of 0.05 per cent (25 µg.) of antigen material persist at 330 days after injection.

All of the radioactivity of material retained in the liver tissue 6 weeks after injection was immunologically related to the original S35-BSA antigen.

Preliminary studies are reported which indicate that the retained antigen is bound to ribonucleic acid.

A new method is described for the isolation of p-azophenylsulfonate bovine serum albumin from tissue extracts by means of a Dowex 2 adsorbent.
QUANTITATIVE STUDIES ON THE PROPERDIN-COMPLEMENT SYSTEM
Authors: Leon Myron A. ,   With the Technical Assistance of Edna Chapman and Arnold Ransby
Published: June 2004

The reaction of human, bovine, and pig properdin with excess zymosan exhibits an induction period followed by a rapidly accelerating formation of the properdin-zymosan (PZ) complex. Two methods for determining the quantity of PZ complex are given, one using human serum lacking properdin, the other using a fraction of pig serum containing complement components, C'1, C'3 and C'4.
AN UNUSUAL PROTEIN COMPONENT OF HIGH MOLECULAR WEIGHT IN THE SERUM OF CERTAIN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Franklin E. C. , Holman H. R. , Müller-Eberhard H. J. , Kunkel H. G.
Published: June 2004

In the sera of a number of patients with rheumatoid arthritis an unusual, high molecular weight protein component could be detected by direct ultracentrifuge analysis of whole serum. This material sedimented more rapidly than the normal 19 S component and reached concentrations up to 340 mg. per cent. Similar components were not observed in a limited control series.

The high molecular weight material was present in the γ-globulin fraction of serum and joint fluid. It had an S20,w of approximately 22 S and could be dissociated into 2 fractions, one of which had a sedimentation coefficient of approximately 19 S.

Evidence for a direct relationship between the 22 S component and the γ-globulin precipitation test was obtained. The latter reaction was found to occur in the presence of altered, aggregated γ globulin. Absorption of serum with altered γ globulin removed the 22 S component. There also appeared to be a connection with the sheep cell agglutination reaction and the latex fixation test. The 22 S fraction was always observed in sera giving the most positive tests. Procedures of density gradient and repeated preparative ultracentrifugation demonstrated that each of these reactions was caused by a high molecular weight fraction.

The relationship between the unusual protein complex and various 19 S γ-globulins and 19 S antibodies is discussed.
HOMOLOGOUS IMMUNOLOGICAL STUDIES OF OCULAR LENS
Authors: Halbert S. P. , Locatcher-Khorazo D. , Swick L. , Witmer R. , Seegal B. , Fitzgerald P.
Published: June 2004

Five lens antigens of rabbits can induce antibodies homologously as evidenced by agar precipitin technics.

Cross-reactions of lenses of other species (organ specificity) may be due to similarity of varying numbers of these antigens.

Newborn and 26-day embryo rabbit lenses seem to have decreased concentrations of, or lack, one antigen present in adult rabbit lens.

Streptolysin "O" concentrates appear to act as an adjuvant for homologous lens immunization in rabbits.
HORMONAL INFLUENCES ON MAMMARY TUMORS OF THE RAT
Authors: Huggins Charles , Mainzer Klaus
Published: June 2004

Many members of the androstane series profoundly retarded the growth of a transplanted benign mammary fibroadenoma of the rat; the restraint of tumor growth was in direct proportion to the amount of the administered compound until its maximal effect was achieved. Certain steroids closely related to the androstane inhibitors accelerated the growth of the tumor. These effects of divergent sort depend on the molecular structure of the steroid.

The molecular structure of androstane derivatives, which is of high significance in modifying the rate of growth of the benign mammary tumor, consists of multiple components. These include (a) the presence and number of ketone and hydroxyl groups in special orientation at specific sites, (b) the sites of dehydrogenation in the molecule, and (c) the presence, number, and state of hydrogenation of alkyl groups at designated molecular positions. These multiple factors determine whether androstane compounds will inhibit growth of the tumor, enhance it, or fail to influence its growth.

The androstane compounds which caused either the restraint or the promotion of tumor growth had the common property of inducing proliferation of the normal mammary epithelium.

Two mechanisms are involved in the restraint of growth of mammary fibroadenoma by androstane inhibitors. The primary effect is the abolition of action of phenolic estrogens and progesterone when dihydrotestosterone is administered concurrently, presumably through direct action at the tumor cell level A secondary contributory suppressive effect is the depression of ovarian activity, and consequently of the production of phenolic estrogens and progesterone, by these compounds.

Transplanted mammary fibroadenoma in the rat possesses neoplastic traits and also some growth properties of normal mammary epithelium; inhibition of these latter by hormonal methods commonly retarded the growth of the tumor. But in hypophysectomized rats dihydrotestosterone failed to inhibit the growth of a mammary fibroadenoma with unusually low hormonal dependence as determined by functional tests of its growth.
ON THE CONCENTRATION OF 5-HYDROXYTRYPTAMINE IN MAMMALIAN ENTEROCHROMAFFIN CELLS AND ITS RELEASE BY RESERPINE
Authors: Benditt Earl P. , Wong Ruth L.
Published: June 2004

The enterochromaffin cells of the guinea pig duodenum and 5-hydroxytryptamine incorporated into gelatin models gave, after formalin fixation, nearly identical reactions with methenamine silver, ferric-ferricyanide, and diazotized o-aminoazotoluene. Following formaldehyde fixation the indole reaction with p-dimethylaminobenzaldehyde was negative in tissue enterochromaffin cells; similarly the indole reaction was negative after formaldehyde fixation of gelatin models.

In the duodenum of the guinea pig 5-hydroxytryptamine appears to be largely, if not entirely, contained in the enterochromaffin cells. Its intracellular concentration estimated from relative cell volume and assay of concentration in the whole tissue, was not less than 5 mg./gm. of cells, and as judged by the intensity of staining reaction may have been as high as 10 to 20 mg./gm. of cells.

Reserpine administered parenterally caused release of the chromogenic material of duodenal enterochromaffin cells and a parallel reduction in the amount of extractable 5-hydroxytryptamine.
A DENSIMETRIC METHOD FOR ASSAY OF SMALL AMOUNTS OF ANTIDIURETIC HORMONE
Authors: Thorn Niels A.
Published: June 2004

A sensitive and reproducible method for assay of antidiuretic activity, described in this paper, yielded accurate measurements in the range 60 to 540 micropressor units of pitressin, corresponding to about 15 to 130 micropressor units of arginine-vasopressin. The method differs from previous techniques mainly in using urine density, rather than urinary flow rates, as the index of response.
USE OF DIFFERENT I181-LABELLED ANTIBODY ELUATES IN THE CHARACTERIZATION OF SHIGELLA AND VIBRIO ANTISERA
Authors: Freter Rolf
Published: June 2004

The results presented indicate that blocking curves of decreased slope are obtained with the Talmage test when the labelled antibody eluate contains a portion of antibody which is not represented in the unknown serum. The blocking curves of late antisera had steeper slopes than those of early antisera when tested against labelled antibody eluates prepared from late antisera. This situation was reversed when labelled eluates from early antisera were used in the Talmage test. The findings were interpreted to indicate that early antisera did not have a full complement of antibodies, directed against all surface antigens of the bacterial cell.
THE ROLE OF VASOCONSTRICTION IN THE LOCAL SHWARTZMAN REACTION
Authors: Rall David P. , Kelly Margaret G.
Published: June 2004

The local Shwartzman reaction was provoked in the skin of the ear, hind leg, and costovertebral angle of the rabbit, as well as in the ventral abdominal skin.

Certain adrenergic blocking drugs reduced the incidence of positive reactions when given prior to the provocative dose of bacterial polysaccharide.

Epinephrine and other vasoconstrictor drugs administered intradermally into the prepared skin site produced typical hemorrhagic-necrotic lesions when the usual intravenous injection of polysaccharide was omitted. This reaction could be blocked by adrenergic blocking drugs, but appeared to be augmented by heparin or nitrogen mustard.

A hypothesis has been developed to help explain the mechanism of the local Shwartzman reaction. Following the preparatory dose, tissue metabolic changes occur which lead to increased lactic acid production and render the area particularly susceptible to anoxia. Following the provocative dose, adrenergic vasoconstriction occurs. It is suggested that this vasoconstriction may be intensified at the prepared site by small residual amounts of the preparatory dose of polysaccharide which might potentiate the action of the epinephrine.

The anoxia initiated by the vasoconstriction is prolonged and intensified by the formation of intravascular thrombi around clumps of leucocytes and platelets. This anoxia, superimposed on the local metabolic changes, leads to the characteristic lesion of hemorrhage and necrosis. Thus a combination of factors, all of causal importance and largely due to known pharmacologic properties of bacterial lipopolysaccharide, occur in specific sequence to lead to the classic local Shwartzman reaction.
STUDIES OF DELAYED HYPERSENSITIVITY IN VITRO
Authors: Glasgow Lowell A. , Morgan Herbert R.
Published: June 2004

Guinea pigs experimentally infected with mumps virus develop a delayed, hypersensitive skin reaction following the intradermal injection of heat-inactivated mumps virus. This in vivo hypersensitivity is accompanied by a state of cellular hypersensitivity which can be demonstrated in vitro by the addition of mumps viral antigen to cultures of splenic macrophages, following which they become less motile and undergo lysis. These observations support the hypothesis that the state of hypersensitivity which develops early in mumps virus infections may have a role in the pathogenesis of the disease.
THE ENHANCING EFFECT OF MURINE HEPATITIS VIRUS ON THE CEREBRAL ACTIVITY OF PLEUROPNEUMONIA-LIKE ORGANISMS IN MICE
Authors: Nelson John B.
Published: June 2004

Pleuropneumoma-like organisms (PPLO) of the catarrhal type were isolated from the brain of a Swiss mouse during the cranial passage of mouse hepatitis virus-MHV(C). Cranial injection of the PPLO alone in Swiss and Princeton weanlings was attended by a meagre growth of the organisms in the brain, with no pathologic change.

The growth of both catarrhal and conjunctival strains of PPLO in the brains of Swiss mice was greatly enhanced by the simultaneous injection of MHV(C). Rolling was not a characteristic sign prior to autopsy. Brain sections regularly showed a vigorous leukocytic response, commonly accompanied by the destruction of nerve cells in the anterior horns of the cerebrum. Injected in Princeton mice together with the virus, the organisms barely survived and were inactive. MHV(Pr) enhanced the growth and pathogenicity of PPLO in the brains of Princeton mice but failed to do so in Swiss.

The behavior of PPLO in the brain was likewise affected by the presence of agar, as earlier observed by Findlay et al. In comparison with the effect of MHV, the enhancement was reduced in rate in both strains of mice and was not accompanied by outward signs of nervous disorder. Hydrocephalus which often followed injection of the PPLO-agar mixture was also produced by agar-bouillon alone.
STUDIES ON THE CX-REACTIVE PROTEIN
Authors: Wood Harrison F. , Montella Sigfrido
Published: June 2004

It has been found that normal rabbits respond to the intravenous administration of Cx-reactive protein by producing this acute phase substance. When Cx-reactive protein incorporated in adjuvant is injected intracutaneously, in addition to producing Cx-reactive protein, the recipient animals develop a characteristic inflammatory reaction about the site of injection. This inflammatory reaction can be inhibited by the prior intravenous injection of thorotrast.
SOME PROPERTIES OF AN ESTERASE DERIVED FROM PREPARATIONS OF THE FIRST COMPONENT OF COMPLEMENT
Authors: Ratnoff Oscar D. , Lepow Irwin H.
Published: June 2004

Studies on an esterase derived from partially purified preparations of the first component of complement are described. The esterase hydrolyzed certain synthetic amino acid esters, among which N-acetyl-L-tyrosine ethyl ester was most susceptible. This was hydrolyzed maximally between pH 7.5 and 8.2, and at 41°C. The esterase could not be identified with other previously described hydrolytic enzymes. An esterase with similar properties could also be eluted from antigen-antibody aggregates which had been treated with serum.

Human serum contained a heat-labile inhibitor of the esterase which could not be identified with any of the known components of complement. The esterase was also inhibited by certain reducing agents.

The experiments described support the early hypothesis that complement exerts its action enzymatically, but the physiological role of the esterase derived from preparations of complement is not yet clear.
TURNOVER OF S35-SULFATE IN EPIPHYSES AND DIAPHYSES OF SUCKLING RATS
Authors: Dziewiatkowski Dominic D. , Di Ferrante N. , Bronner F. , Okinaka Gladys
Published: June 2004

S35-sulfate was injected intraperitoneally- into 7-day-old rats and their long bones were removed after intervals of time. The epiphyses were separated from the diaphyses for analysis.

From the diaphyses freed of bone marrow about 82 per cent of the S35 which they contained was extracted with a 2.5 N solution of sodium hydroxide. More, about 91 per cent of the S35, was thus extracted from the epiphyses.

Dialysis of the extracts against water showed that the fraction of S35 which was dialyzable decreased rapidly with time. After 1 hour about 80 per cent and 50 per cent of the S35 in the extracts of diaphyses and epiphyses, respectively were found in the dialysates, after 24 hours about 20 per cent and 4 per cent, and after 120 hours 12 per cent and 1 per cent. Similar values for the S35 in inorganic sulfate were found when the extracts were chromatographed on an anion exchange resin, dowex-2.

The S35, other than inorganic sulfate, was in the form of bound sulfate, which was released by acid hydrolysis. Uronic acid and hexosamines, primarily galactosamine, were associated with the S35. Indeed, on paper electrophoretograms and paper chromatograms the major S35-labelled component which was seen resembled chondroitin sulfate in its mobility. On the paper chromatograms, also a second S35-labelled component with a mobility lower than that of chondroitin sulfate was found. It is unlikely that the latter is a breakdown product of chondroitin sulfate, produced in the course of extraction with the sodium hydroxide solution. In fact, both components were also found in sodium versenate homogenates which had been dialyzed extensively against water.

On the basis of these results it is suggested that the greatest part of the S35-labelled materials previously demonstrated by autoradiography to be progressively deposited in the metaphyses after 24 hours,—as the concentration of S35-sulfate concurrently decreased in the epiphyseal cartilage plates,—are akin to the chondroitin sulfate of the epiphyseal cartilage plates and are derived from the latter.
DIFFERENTIATION OF GROUP A STREPTOCOCCI WITH A COMMON R ANTIGEN INTO THREE SEROLOGICAL TYPES, WITH SPECIAL REFERENCE TO THE BACTERICIDAL TEST
Authors: Lancefield Rebecca C. ,   With the Technical Assistance of William N. Everly
Published: June 2004

In further study of streptococci having the R antigen, the bactericidal test has been used instead of the mouse protection test in investigating the type-specific M antigens of these organisms. The results have been confirmed by M anti-M precipitin tests, and a correlation between the M and T antigens of the strains has been shown.

On the basis of a specific M antigen, type 28 has been shown to comprise Griffith's strain Small and four other R-containing strains.

A number of other strains previously thought to belong to type 28 on the basis of R antigen reactions have now been identified as belonging either to type 2 or to a new type, designated 48, which shows a one-way cross-relationship to type 13.

The bactericidal test is suggested as a useful method for assessing M antigen in group A streptococci and for establishing type-specificity by means of a biological test which is more widely applicable than the standard mouse protection test.
CROSS-IMMUNITY BETWEEN BRUCELLA MELITENSIS AND MYCOBACTERIUM TUBERCULOSIS
Authors: Elberg Sanford S. , Schneider Patricia , Fong Jacob ,   With the Technical Assistance of James Akiyama
Published: June 2004

A non-specific element has been demonstrated in the resistance of monocytes derived from immunized rabbits. Vaccination by BCG or by an effective anti-brucellosis reagent induces protection in either case against both Mycobacterium tuberculosis and Brucella melitensis when studied by the monocyte culture method.

The activity of the antiserum required to demonstrate the resistance of the monocyte is not affected when the agglutinating action of the anti-Brucella rabbit serum is removed by absorption.

The ability of the monocytes from specifically immunized rabbits to retard the growth of virulent Brucella was demonstrated, not as an all-or-none phenomenon, but in the light of the unrestricted bacterial multiplication which occurs in monocytes from normal animals.
A CYTOCHEMICAL STUDY OF THE L.E. BODIES OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Godman Gabriel C. , Deitch Arline D.
Published: June 2004

The composition, with respect to nucleic acids, of the L.E. bodies resulting from the action of the plasma of patients with systemic lupus erythematosus on substrate leukocyte nuclei in different kinds of preparations was compared microspectrophotometrically with that of control lymphocyte nuclei. Binding of the basic dye methyl green to DNA was uniformly found to be depressed in L.E. bodies as compared with control nuclei. Since Feulgen-revealed DNA, which served as a standard of reference, was relatively unchanged in amount, the Feulgen:methyl green ratios of L.E. bodies were higher than those of lymphocyte nuclei. Acetylation, which covers basic groups of proteins, was found to increase methyl green uptake by DNA of L.E. bodies to values approximating those of control nuclei, with consequent revision, after acetylation of the Feulgen: methyl green ratios of L.E. bodies to values similar to those of lymphocyte nuclei. Ribonuclease was found to reduce methyl green staining; extraction with dilute acid had little effect. These data have been interpreted to indicate (a) the presence in L.E. bodies of DNA-associated proteins whose basic groups compete with the cationic dye for binding sites of DNA and so inhibit methyl green staining, and (b) the DNA itself is not detectibly altered in state or degree of polymerization. Photometric comparison of the mean Feulgen-stainable DNA content per L.E. body with that of control nuclei showed that DNA is not lost in the L.E. transformation of nuclei.