bluuebunny/crossref_metadata_2025 huggingface dataset:
PHYSICAL PROPERTIES OF THE RED CELL AGGLUTININS IN ACQUIRED HEMOLYTIC ANEMIA
Authors: Fudenberg H. H. , Kunkel H. G.
Published: June 2004

The sera of 8 patients with acquired hemolytic anemia associated with elevated levels of cold agglutinins were studied by various procedures of zone electrophoresis. The agglutinating activity was found associated with proteins of variable mobility in the different cases. The majority represented "fast" γ-globulins. The 4 sera with the highest titers of cold agglutinins showed distinguishable abnormal electrophoretic components. The titers correlated with the height of the abnormal components.

Ultracentrifugal analysis of the electrophoretic fractions indicated that the cold agglutinins were associated with proteins having a sedimentation coefficient of approximately 19 S. The abnormal component from the serum with the highest biological activity showed almost no contamination with lower molecular weight proteins. The amount of 19 S material found correlated with the titer of agglutinating activity.

The high molecular weight character of the cold agglutinins was confirmed by procedures of density gradient zone centrifugation. The biological activity sedimented with proteins of the 19 S class in all the sera including those of relatively low titer with which no abnormal electrophoretic components were observed.

Dissociation of the abnormal high molecular weight components was possible by means of certain sulfhydryl compounds. This resulted in disappearance of cold agglutinin activity.

Some of the cases could be classified as macroglobulinemias because of the very large content of high molecular weight components. However, the same disease picture occurred without recognizable elevation of these components.

The sera of 3 patients with severe acquired hemolytic anemia of the warm type associated with warm incomplete antibodies failed to show similar abnormal electrophoretic components and the antibody activity sedimented with proteins of the 7 S class.
INFLUENCE OF DIETARY MAGNESIUM ON CARDIAC AND RENAL LESIONS OF YOUNG RATS FED AN ATHEROGENIC DIET
Authors: Hellerstein E. E. , Vitale J. J. , White P. L. , Hegsted D. M. , Zamcheck N. , Nakamura M. ,   With the Technical Assistance of T. Faherty
Published: June 2004

Young male rats fed an atherogenic diet for 24 to 26 days developed magnesium deficiency.

The renal lesions, calcium deposition in tubular lumens in the outer zona intermedia, are morphologically consistent with those seen in animals fed magnesium-free diets. It was necessary to feed 8 to 16 times the normal requirement of magnesium to prevent completely these lesions. The limitations in the pathogenesis of these renal lesions are discussed.

The addition of 2 mg. per cent of thyroxine to the diet markedly lowered or abolished deposition of calcium in the kidney; it also lowered atherogenesis to a minimum but did not abolish it.

Early lesions of atherosclerosis of the cardiac valves and of the aorta were observed. These were more prominent in animals on a 10 per cent than in those on a 20 per cent protein diet. The atherosclerosis was diminished but not abolished by exceedingly high dietary levels of magnesium in the 10 per cent protein group. Such a decrease was not noted in the 20 per cent protein group.

There did not appear to be significant variation in the morphology of the fatty livers in and between the various groups and subgroups as judged by staining with Sudan IV.
STUDIES ON THE MECHANISM OF HYPERSENSITIVITY PHENOMENA
Authors: Osler Abraham G. , Hawrisiak Mary M. , Ovary Zoltan , Siqueira Maria , Bier Otto G.
Published: June 2004

Experiments are described indicating that the magnitude and sensitivity of the passive cutaneous anaphylaxis (PCA) response in normal rats to a given level of immune reagents, may be enhanced by the addition of hemolytically active sera.

A similar enhancement in normal rats has been obtained with C' component reagents possessing properties associated with the third component of C'.

Parallelisms between in vitro fixation of C' and PCA induction by antigen and antibody are shown. The horse anti-pneumococcus system has low C'-fixing potencies and is also less efficient than the rabbit polysaccharide system in the induction of PCA.

Findings of a similar nature were observed in the reaction of rabbit anti-ribonuclease with ribonuclease, the acetylated and guanidinated derivatives of the enzyme.

The injection of hemolytically active serum into C'-deficient rats was accompanied by a partial restoration of PCA. Restorative effects were also noted with heated and ammonia-treated serum.

The return of hemolytic potency and responsiveness to PCA in C'-depleted rats, follow a similar time course.

The data presented indicate that the PCA reaction can be studied as a function of at least three variables, antigen, antibody, and a serum constituent resembling C'.
THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION
Authors: Kilbourne Edwin D. ,   With the Technical Assistance of Barbara Ann Pokorny
Published: June 2004

The interference with viral synthesis which is induced by large quantities of non-infective influenza B virus is inhibited or negated with small quantities of cortisone and other C-21 steroids. The specificity of this effect is attested by the inactivity of 11-alpha hydroxy epimers of highly active compounds. Maximal activity in negation of interference is associated with the presence of oxygen at the C-11 position of the steroid molecule.

In view of the demonstration that negation of interference can occur, it is concluded that the phenomenon of multiplicity reactivation of non-infective virus is not primarily influenced by cortisone. Rather, it is suggested that the reactivation phenomenon is unmasked by cortisone through its inhibiting effect on the autointerference intrinsic in multiplicity infection.

If it is accepted that influenza virus infections in ovo are self-limited in part by viral autointerference, present evidence is consistent with the view that negation of this autointerference is the mechanism by which cortisone induces definitively increased yields of virus.
OCCURRENCE OF DELAYED HYPERSENSITIVITY DURING THE DEVELOPMENT OF ARTHUS TYPE HYPERSENSITIVITY
Authors: Salvin S. B. ,   With the Technical Assistance of Jane Nishio
Published: June 2004

Guinea pigs were injected in the footpads with either purified diphtheria toxoid or recrystallized egg albumin in Freund adjuvant without mycobacteria. Each guinea pig was then skin-tested only once with the specific antigen and bled for antibody determination. After injection of the sensitizing antigen, a latent period occurred during which neither sensitivity nor circulating antibody could be detected. A period of delayed sensitivity followed wherein circulating antibody could not be discerned and which could be transferred by lymph node cells. Ultimately, the Arthus type sensitivity developed, accompanied by circulating antibody. The duration and severity of reactions to homologous antigens during the last 2 phases varied with the antigen and with the dose. An increase in the sensitizing dose decreased the duration of the delayed type of allergy, a decrease in the dose prolonged the delayed type. Inclusion of mycobacterium in the sensitizing inoculum tended to introduce delayed sensitivity earlier and delay the onset of Arthus type sensitivity. When specific precipitate in antibody excess was included with the toxoid in the sensitizing dose, the onset of the Arthus phase was hastened. When lymph nodes from a large number of sensitized donors were removed during the latter part of the latent period, recipients of the cells showed a delayed type sensitivity.
EFFECTS OF 3-METHYLCHOLANTHRENE ON THE ENDOCRINE SYSTEM AND METABOLISM OF THE RAT AND ITS INFLUENCE TO RETARD GROWTH OF MAMMARY TUMORS HITHERTO REFRACTORY
Authors: Huggins Charles , Pollice Lucio
Published: June 2004

The repeated administration of 3-methylcholanthrene to adolescent rats resulted in (a) a profound, incomplete, and selective depression of certain hypophyseal functions; (b) decreased growth of transplanted mammary tumors; and (c) a retardation of body growth. Only the last mentioned effect was reversed by forced feeding.

The retarded rate of body growth induced by 3-methylcholanthrene was prevented by the concurrent administration of dihydrotestosterone or progesterone, or by ovariectomy; rats so treated became overweight despite the injection of 3-methylcholanthrene. Phenolic estrogens intensified the retardation of body growth induced by 3-methylcholanthrene and emaciation resulted.

The administration of 3-methylcholanthrene resulted in decreased gonadotrophin production by the pituitary and the ovaries were more drastically affected by the depression of pituitary activity than the adrenals were. The compound exerted differential effects on the pituitary glands of males and females respectively. Hormonal functions of both ovary and testis were decreased in rats treated with 3-methylcholanthrene but, whilst ovarian weight was much reduced, the size of the testis was not decreased and the germinal epithelium of the male was little affected by the treatment in most instances. There was a considerable reduction of the content of alkaline phosphatase in the breast of intact rats treated with 3-methylcholanthrene but atrophy of the mammary epithelium did not occur and hyperplasia of the mammary tree was often observed.

The administration of 3-methylcholanthrene considerably slowed the growth of transplanted mammary tumors characterized by high dependence on hormones and the concurrent administration of gonadotrophin restored the growth rate of the tumors.

The administration of 3-methylcholanthrene or androstan-17ß-ol-3-one was only moderately effective in controlling the growth of transplanted mammary tumors characterized by low hormonal dependence; the combined administration of these compounds was highly efficacious in retarding the growth of these refractory tumors.

3-Methylcholanthrene partially retarded the growth of mammary fibroadenomas in hypophysectomized rats.
DEMONSTRATION IN VITRO OF ANAPHYLACTOID RESPONSE OF THE UTERUS AND ILEUM OF GUINEA PIGS INJECTED WITH TESTIS OR SPERM
Authors: Katsh Seymour
Published: June 2004

Female guinea pigs were injected with the following materials: homogenates of guinea pig testis in saline or in adjuvant; suspensions of washed guinea pig sperm in saline or in adjuvant; homogenates of rabbit testis in adjuvant; guinea pig sperm and rabbit sperm in adjuvant. Control animals were not injected or were injected with adjuvant alone.

At various times between 15 and 39 days after injection, the animals were sacrificed. Their ilea and uterine horns were removed and tested in vitro for reaction to washed epididymal sperm of the guinea pig, rabbit, or bull.

It was found that the animals which were injected with homologous testis or sperm in adjuvant possessed organs which responded strongly to the challenge with homologous sperm. The response was a contracture which began 10 to 30 seconds after the sperm were injected into the bath and lasted for 5 minutes to 4 hours, the longest period of observation. Responses which lasted for periods of 5 minutes to 30 minutes were obtained with the uteri of the animals injected with guinea pig testis in saline or with guinea pig sperm in saline. Animals which were injected with rabbit testis and adjuvant responded to rabbit sperm, and animals injected with guinea pig sperm and rabbit sperm in adjuvant reacted to both gametes.

A large proportion of the control animals possessed organs which reacted weakly to the challenge with homologous sperm. Retesting the organ which had contracted following exposure to sperm indicated that desensitization had occurred. Testing with heterologous sperm indicated a species selectivity.

The evidence is interpreted to mean that injections of sperm or testis induce a hypersensitivity which is similar in some respects but differs from true anaphylaxis.

The findings are discussed from the point of view of the nature of the response and the implications regarding natural immunity to sperm.
THYROID FUNCTION IN EXPERIMENTAL STREPTOCOCCAL PNEUMONIA IN THE RAT
Authors: Reichlin Seymour , Glaser Robert J. ,   With the Technical Assistance Of Barbara B. Pesch And Christa Kinderman
Published: June 2004

In order to study the effects of a severe bacterial infection on thyroid function rats were subjected to group A streptococcal pneumonia, and thyroid activity determined by measurement of the rate of discharge of I131 from the thyroid gland.

Decreased thyroid activity of moderate to marked degree was observed in the majority of infected animals. Infected animals ate less than normal animals. Since fasting leads to decreased thyroid function, I131 release rates were measured in control animals pair-fed with infected animals and in control and infected animals force-fed a normal intake. The reduction in thyroid activity seen in acute infection was found to be partly but not entirely due to the associated voluntary food restriction.

Although the adrenal glands of rats dying of pneumonia were very large, the thyroid inhibition occurring during the course of experimental pneumonia was not secondary to increased adrenocortical function since infected, adrenalectomized animals, receiving injections of cortisone, showed thyroid inhibition comparable to that observed in intact infected animals.

The possible influence of the level of thyroid activity on resistance was evaluated. In two experiments a total of 80 rats in 3 groups was pretreated with propylthiouracil and injected daily with 3 dosage levels of 7-thyroxine for 3 weeks prior to inoculation. Under these conditions mortality rates in infected animals fell with decreasing levels of thyroid function. However, induced hypothyroidism was found to afford no protective effect in comparison with untreated infected animals.
STUDIES ON THE FORMATION OF COLLAGEN
Authors: Gross Jerome
Published: June 2004

Some properties of cold neutral salt extracts of fresh guinea pig dermis have been described in terms of viscosity, electrophoresis and sedimentation patterns, partial composition, the collagen content, conditions for extraction of collagen, and the effect of certain enzymes.

Viscosity of the extracts depended on the collagen in solution as demonstrated by removal of this protein by precipitation or enzymatic degradation. The intrinsic viscosity of the crude 0.45 M extract, as well as that of the isolated collagen was 14.5, identical with that for collagen dissolved by dilute acid, indicating the same high asymmetry ratio for both.

Electrophoresis of the skin extracts revealed a slow moving, high, sharp, poorly diffusing boundary in addition to a pattern superficially resembling that of serum. The ultracentrifuge pattern revealed a slowly sedimenting, hypersharp boundary following a large rapidly diffusing peak. The slow moving boundaries in both patterns were abolished by collagenase or heat precipitation of the collagen fraction. Hyaluronidase had no effect on either pattern.

Neutral sulfate, chloride, and phosphate extracted more collagen than did thiocyanate. Very little collagen was extracted at 37°C. as compared with that removed at 3°C.

A two stage fractionation procedure employing dilute trichloroacetic acid and ethanol is described for the isolation and purification of soluble collagen from crude extracts.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: King M. Kenton , Wood W. Barry
Published: June 2004

An endogenous pyrogen, which is indistinguishable from leucocytic pyrogen, has been demonstrated in the blood streams of rabbits with fevers caused by experimental pneumococcal and streptococcal infections. Like the endogenous pyrogen previously detected in the serum of animals with fever produced by the intravenous injection of typhoid vaccine, the newly discovered circulating factor acts directly upon the thermoregulatory centers of the brain. Its origin from polymorphonuclear leucocytes at the site of infection appears to have been established.

The possible relationship of this circulating endogenous pyrogen to the pathogenesis of other forms of fever is discussed.
STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES
Authors: Atkins Elisha , Huang Wei Cheng
Published: June 2004

Observations have been made on the fever-inducing properties of an endogenous pyrogen found in the circulation of rabbits after the intravenous inoculation of Newcastle disease virus (NDV).

When endogenous pyrogen was given to a normal recipient, a biphasic fever was produced which simulated that seen with bacterial endotoxins. With the use of a technique of serial passive transfer, it has been shown that the "double-humped" response results from two separate actions of the injected pyrogen. The first of these appears to be a direct stimulation of the thermoregulatory centers. The second involves the release of further endogenous pyrogen in the normal recipient to cause, in turn, the second fever peak. Since the injection of endogenous pyrogen did not produce a significant change in the number of circulating leukocytes, it is inferred that this substance is different from either bacterial or tissue polysaccharides.

In rabbits rendered tolerant by a previous injection of virus the second fever peak failed to appear and the response to endogenous pyrogen was monophasic. Evidence indicates that the absence of a second fever peak in the tolerant recipient was not due to rise in temperature on the preceding day of virus injection or to the development of either serum inhibitors or tolerance to virus itself.

It is postulated that prior mobilization of endogenous pyrogen by virus may have modified the ability of the tolerant recipient to liberate further amounts of this substance in response to an injection of endogenous pyrogen.
STUDIES ON ANTIBODY SYNTHESIS INITIATED IN VITRO
Authors: Stevens Kingsley M. , McKenna John M.
Published: June 2004

Ten µg. of the lipopolysaccharide endotoxin of Salmonella typhosa was given to rabbits intravenously to enhance the subsequent antibody response to an unrelated substance. The spleens were removed 24 hours later, diced, and incubated 1 hour with the antigen, bovine-γ-globulin (BGG), in a protein-free medium. After washing, the tissues either were extracted at once or planted and the fluids and tissues harvested 1 to 3 days later. Antibody was determined by a modification of the Boyden hemagglutination technique.

Small amounts of antibody were synthesized as early as 1 hour after the addition of antigen. The antibody formed could be specifically inhibited with BGG, was not dialyzable, and did not sediment at 105,000 g for 2 hours.

Dose-response studies revealed no antibody formation when the BGG concentration was 0.005 or 0.05 mg./ml. The best responses were obtained at concentrations of 0.5 to 5.0 mg./ml. These results were found irrespective of whether the animal had previously received BGG in vivo.

Forty per cent autologous serum increased antibody formation about 9-fold over that secured with protein-free medium or with 40 per cent homologous serum. Antibody formed with this system could be detected by 50 per cent complement fixation test, although at much lower titer than found by hemagglutination.

While spleens from rabbits previously given BGG did not produce more antibody than spleens from normal rabbits, they differed in that they produced antibody without the involvement of endotoxin.

Under appropriate circumstances, endotoxin was effective in vitro in enabling spleen fragments to produce antibody to BGG.

Cortisone acetate administered to rabbits prior to the removal of the spleen severely inhibited antibody production in vitro. Sodium prednisolone phosphate added in vitro showed a similar irreversible effect at concentrations as low as 2 x 10–5 M. Nitrogen mustard inhibited antibody formation at concentrations as low as 10–4 M.
THE AMINO ACID REQUIREMENTS OF MONKEY KIDNEY CELLS IN FIRST CULTURE PASSAGE
Authors: Eagle Harry , Freeman A. E. , Levy M.
Published: June 2004

Monkey kidney cells tested in their first culture passage, 24 hours after their isolation from the animal host, required the same 13 amino acids for survival and growth as cell lines serially propagated in culture for years. Under the conditions of the present experiments, arginine, cystine, glutamine, histidine, and tyrosine proved necessary, over and above the 8 amino acids required for nitrogen balance in man.

With the serially propagated lines, glutamic acid substituted for glutamine only at extremely high and non-physiological levels. In the monkey kidney cell cultures, however, glutamic acid and glutamine were interchangeable, mole for mole; and aspartic acid and asparagine were also effective as glutamine substitutes.

Glycine was growth-stimulatory for monkey kidney cells in primary culture, and the cells grown in a glycine-deficient medium usually failed to survive subculture.
IMMUNOREACTIONS INVOLVING PLATELETS
Authors: Hill Terrell L.
Published: June 2004

Theoretical equations have been derived, using the methods of statistical mechanics, for associations between platelets, antibody, quinidine, and complement, based on a model of an immunoreaction described in the preceding paper of this series. The two cases considered (i.e. the possibilities that quinidine can attach first to antibody or platelets) lead to the same final equations. The comparison of the theoretical results with experimental results is contained in the preceding paper.
ANTIGENIC VARIANTS OF INFLUENZA A VIRUS (PR8 STRAIN)
Authors: Hamre Dorothy , Loosli Clayton G. , Gerber Paul
Published: June 2004

Seven variant strains of influenza A PR8-S virus, each derived from the previous one by serial passage in the lungs of mice immunized with the homologous agent have been produced. With the H.I. and neutralization procedures these variants showed a progressive serological deviation from the parent PR8-S virus. The seven variants provoked antibodies in varying titers to the preceding variants and the parent virus but not in relation to their position in the series. Thus, the seventh variant provoked significantly more antibody to the PR8-S virus than did the fifth variant. A possible explanation for this is presented. The first four variant viruses showed progressively less ability to react with antisera of the preceding variants and the PR8-S virus, and the three most recently derived variants showed essentially no ability to react with PR8-S and first variant antisera. The variant viruses remained antigenically stable through numerous lung passages in normal mice. Cross absorption tests revealed common antigenic components among the variant viruses and also individual characteristics which classify them as being different from one another. The implications of these findings in relation to studies by others have been discussed.
ANTIGENIC VARIANTS OF INFLUENZA A VIRUS (PR8 STRAIN)
Authors: Hamre Dorothy , Loosli Clayton G. , Gerber Paul
Published: June 2004

A second series of four variants of PR8-S virus has been produced by passage of the variants in the lungs of mice immunized with the PR8-S virus as well as the homologous strain. The PR8-S virus was added as a constant component of the vaccine so that a high antibody titer to it would suppress selectively the development of variants with PR8-S characteristics. Comparative H.I. and in ovo neutralization tests with the first and second series of variants revealed that the three variants, Fd/s, Gf/s, and Hg/s, of the second series, failed to react with PR8-S antisera and produced significantly smaller amounts of antibody which reacted with PR8-S, the variants of the first series, and the first variant (D/s) of the second series. Although these three variants reacted quite similarly in the H.I. and neutralization tests cross-absorption of these sera with the PR8-S virus and themselves revealed individual antigenic characteristics. While these studies emphasize the importance of the immune state of the host the precise mechanism in the selection of a new antigenic component in the emerging variant must yet be determined.
VITAMIN B12Co60 DISTRIBUTION IN DOG TISSUES DURING MANY MONTHS
Authors: Woods W. D. , Hawkins W. B. , Whipple G. H.
Published: June 2004

Experiments dealing with the distribution of B12Co60 in the dog indicate that with time (9 months after administration) there is a shift in the distribution of the vitamin as compared to the short term experiments, as well as prolonged retention of the vitamin within various dog tissues.

The heart, gastric mucosa, liver, spleen, and brain show high concentrations of the isotope in long term experiments.

This distribution, in the heart for example, does not fit with an hypothetical breakdown of B12Co60 complex and storage of a physiologically inactive fraction.

Repeated periods of anemia produced by phenylhydrazine make it possible to demonstrate radioactive material in red cell stroma of dogs that have previously received vitamin B12Co60. This radioactive material must have come from other body stores, such as liver and stomach.

The high concentration of B12Co60 in the gastric mucosa suggests a relationship between it and the intrinsic factor as described by Castle.
HOST-HOMOGRAFT TISSUE INTERACTIONS FOLLOWING EXCHANGE BLOOD TRANSFUSIONS IN RABBITS
Authors: Andresen Richard H. , Monroe Clarence W. , Hass George M. , Madden Dorothy A.
Published: June 2004

Under ordinary conditions musculofascial cross-grafts made between pairs of rabbits of the same strain and species elicited classical host-homograft tissue interactions. When the cross-grafting was done 7 to 10 days after exchange transfusions leading to introduction of about 40 per cent of foreign blood, the classical host-homograft reaction failed to develop. In its stead there was an harmonious interaction characterized by abundant vascularization of each graft, with minimal stromal replacement and without a trace of inflammation. This reaction resembled a common type previously described in cross-grafts made between postparabiotic twins but lacked some conspicuous features of the reaction of an animal to grafts of its own tissues.
STUDIES ON THE ANTIGENICITY OF ß- AND α1-LIPOPROTEINS OF HUMAN SERUM
Authors: Scanu Angelo , Lewis Lena A. , Page Irvine H.
Published: June 2004

The techniques of agar immunoelectrophoresis and agar double diffusion were applied to the study of the antigenicity of ß- and α1-lipoproteins separated by ultracentrifugation from normal human sera. The effects of delipidation were also investigated.

It was shown that ß- and α1-lipoproteins are antigenically distinct. For each class of lipoprotein studied, a single antigenic component was demonstrated. In some, but not all, preparations of α1-lipoprotein a second, small antigenic component was detected, and identified as albumin. Absorption with lipoprotein-free serum or albumin removed this component without changing the lipoprotein band.

Delipidation did not affect the antigenicity of either ß- or α1-lipoproteins. Immunoelectrophoresis, because of its high sensitivity and specificity, provides an additional criterion of purity for antigenic proteins in addition to the data that can be obtained from ultracentrifugal and free electrophoretic analysis.
A BIOCHEMICAL AND MORPHOLOGIC STUDY OF MYELINATION AND DEMYELINATION
Authors: Majno Guido , Karnovsky Manfred L.
Published: June 2004

Bilateral transection was performed on rat sciatics. At varying intervals after the operation, samples of nerve were taken both distal and proximal to the level of transection, as well as from the tissue which bridged the gap between the stumps. These samples were incubated in Warburg flasks, with glucose and a labelled lipide precursor (acetate or phosphate). The total lipides were then extracted and their radioactivity was measured. Normal rat sciatics served as controls, and the biochemical and histological findings were correlated.

In the distal portion undergoing Wallerian degeneration, the lipide content began to fall before any removal of myelin could be detected histologically. It is suggested that there is a period of "non-cellular removal" prior to the physical breakdown of the myelin. Changes in respiration and in lipogenesis from acetate followed a triphasic course, and agreed with the histological findings in that after a period of predominantly passive changes (approximately 1 to 3 days) there follows a period of cellular reaction (4 to 50 days) and a period of atrophy (from 50 days onward). The incorporation of phosphate into the lipides was increased at all stages examined, even as early as 22 hours after section. This increased P32 incorporation could not be reproduced in nerves allowed to degenerate in vitro. It is suggested that the hypertrophying Schwann cells synthesize some lipide moieties at a considerably faster rate than others.

Proximal to the level of transection, lipogenesis from acetate was depressed, for as long as 32 days postoperatively. It appears, therefore, that the maintenance of the myelin sheath is impaired also above the level of transection.

In the "union tissue" which developed between the stumps, prior to the appearance of histologically visible myelin, lipogenesis was low; later it rose above levels for normal nerve. This pattern of lipogenesis in regenerating nerve is similar to that found in growing nerves.
NEUTRALIZING ANTIBODIES TO STREPTOCOCCAL DIPHOSPHOPYRIDINE NUCLEOTIDASE IN THE SERUM OF EXPERIMENTAL ANIMALS AND HUMAN BEINGS
Authors: Kellner Aaron , Freeman Elizabeth B. , Carlson Arthur S.
Published: June 2004

Specific neutralizing antibodies directed against streptococcal DPNase were induced experimentally in rabbits and guinea pigs by the injection of partially purified preparations of the enzyme. Similar antibodies capable of inhibiting the biological activity of the enzyme were found to occur naturally in the serum of a very high percentage of human beings, and the titer of these antibodies often rose sharply following streptococcal infections. The antibody response to streptococcal DPNase in general paralleled that to streptolysin O, though in some instances antibodies to one increased when those to the other did not.
FURTHER STUDIES ON THE CHEMICAL BASIS FOR SEROLOGICAL SPECIFICITY OF GROUP A STREPTOCOCCAL CARBOHYDRATE
Authors: McCarty Maclyn
Published: June 2004

Azoproteins prepared with p-aminophenyl-ß-N-acetyl-glucosaminide react in precipitin tests with Group A streptococcal antisera. The reaction is nonreciprocal, and antisera to the azoprotein do not react with Group A carbohydrate.

Phenyl-N-acetyl-glucosaminides inhibit the reaction of Group A carbohydrate with homologous antisera and with antisera to the azoprotein. The ß-anomer is more effective as an inhibitor than the α-anomer.

Formation by a soil bacillus of the enzyme which removes N-acetyl-glucosamine from Group A carbohydrate is induced by phenyl-ß-N-acetyl-glucosaminide but not by the α-compound. The enzyme, like the glucosaminidase of emulsin, appears to be specific for ß-glucosaminides.

Neither the induced enzyme nor emulsin effectively remove all of the N-acetyl-glucosamine from the azoprotein antigens.

The findings support the view that ß-N-acetyl-glucosaminide side chains represent the major antigenic determinant of Group A streptococcal carbohydrate.
THE USE OF PRECIPITIN ANALYSIS IN AGAR FOR THE STUDY OF HUMAN STREPTOCOCCAL INFECTIONS
Authors: Halbert Seymour P.
Published: June 2004

As evidenced by precipitin analysis with pooled human gamma globulin, at least 12 distinct antigens were produced in cultures by one strain of Group A streptococcus (C203S). It was suggested on this basis, that these antigens were produced in vivo during human infections.

By the combined use of continuous flow electrophoresis on paper curtains, and column chromatography with calcium phosphate gels, five of these have been isolated in a probable high state of purity. One of the components was obtained from culture filtrates of a Group C streptococcal strain.

Three of the purified antigens have been tentatively identified as streptolysin "O", diphosphopyridinenucleotidase, and proteinase precursor. The latter could be very readily crystallized, and appears "identical" with that described by Elliott. The DPNase was of extremely high potency, 1 mg. being capable of destroying 12.6 gm. of DPN in 7½ minutes at 37°C.

The identity of the other two components is uncertain as yet. They are distinct from each other and the above products immunologically, and are not related to the "C" carbohydrate.

The applicability of these methods for the analysis of infectious diseases generally was discussed.
LATENT VIRAL INFECTION OF CELLS IN TISSUE CULTURE
Authors: Bader John P. , Morgan Herbert R.
Published: June 2004

Mouse fibroblasts (L cells) fail to support the growth of psittacosis virus (6BC strain) if they are maintained on a medium containing only inorganic salts and glucose for 2 days prior to infection. Virus propagation can be stimulated by the addition of a synthetic medium containing amino acids, water-soluble vitamins, glutamine, glucose, and inorganic salts. By omitting single amino acids from the complete synthetic medium, tyrosine, threonine, methionine, isoleucine, phenylalanine, tryptophan, leucine, valine, and cysteine or cystine were found to be essential for stimulation, while lysine, arginine, histidine, hydroxyproline, proline, glutamic acid, aspartic acid, serine, alanine, and glycine were not essential. The cells on deficient media showed varying degrees of degenerative changes, but there was little correlation between ability to support psittacosis virus growth and morphologic condition of the cells.

Glucose is also an essential component of the medium for viral growth, but the absence of glutamine had no effect on stimulation of virus propagation. L cell cultures maintained on media deficient in phenylalanine or tryptophan for 2 days before infection were also found to be incapable of supporting virus growth. The implications of this study in latent viral infections are discussed.
STUDIES OF THE PLASMIN SYSTEM
Authors: Norman Philip S. , Hill Betsy M.
Published: June 2004

There are two inhibitors of plasmin in the plasma proteins of the human. α1-antiplasmin is heat-labile and migrates as an α1-globulin on electrophoresis. It combines non-dissociably with plasmin at a rate that depends on temperature.

α2-antiplasmin is relatively more heat-stable and migrates as an α2-globulin on electrophoresis. It combines dissociably with plasmin independently of temperature.
STUDIES ON THE BACTERIOPHAGES OF HEMOLYTIC STREPTOCOCCI
Authors: Krause Richard M.
Published: June 2004

The lysis of cell walls of hemolytic streptococci by a phage-associated lysin has been described. A method is presented for preparing the lysin from Group C streptococcal phage lysates.

Following lysis almost all of the cell wall carbohydrate is recovered in solution. This material has the serological reactivity, physical-chemical properties, and values for nitrogen, rhamnose, and glucosamine similar to those of the carbohydrate isolated from the cell walls by the Streptomyces albus enzyme. Group C carbohydrate isolated by either enzyme inactivates Group C bacteriophage.

The protein liberated by the lysin from Group A Type 6 cell walls gives a type-specific precipitin reaction with homologous rabbit antiserum. Preliminary data are presented on the ammonium sulfate fractionation and the electrophoretic separation of a protein fraction with the serological reactivity of M protein.
DELAYED HYPERSENSITIVITY
Authors: Uhr Jonathan W. , Pappenheimer A. M. ,   With the Technical Assistance of Karen Baechle
Published: June 2004

Guinea pigs rendered hypersensitive (delayed-type) to protein antigen can be completely and specifically desensitized by a single injection containing a sufficient amount of the corresponding antigen. Although 1 to 2 mg. of specific antigen are required for complete desensitization, as little as 20 µg. suffices to decrease the size of specific skin reactions in sensitized animals. The duration of non-reactivity lengthens as the amount of antigen in the desensitizing injection is increased, but skin reactivity eventually returns and is accompanied by the appearance of excess circulating antibody. Desensitization can be accomplished with the antigen-antibody complex as well as by "free" antigen. The appearance of delayed skin reactions can be prevented in fully sensitized animals by intravenous desensitization 2 or more hours after intradermal challenge or by simply skin testing with a desensitizing dose of specific antigen. Injection of a desensitizing dose of antigen into specifically sensitized animals also results in a transient anergic state, the implications of which are discussed.
GENETICS OF SOMATIC MAMMALIAN CELLS
Authors: Puck Theodore T. , Cieciura Steven J. , Robinson Arthur
Published: June 2004

A methodology designed to eliminate mitotic inhibitor action and involving use of pretested fetal calf serum and careful pH and temperature control has been described by which cells from normal human and animal tissue can be maintained in active growth for long periods in vitro without development of aneuploidy.

By means of this procedure, it is possible reliably to establish cell cultures from minute skin biopsies which can be taken from any individual.

Clones of mammalian cells with chromosomal markers have been isolated by this means from x-irradiated non-irradiated cell cultures.

Application of these techniques to chromosome delineation in large numbers of human subjects; determination of chromosomal sex in patients; spontaneuos and induced genetic changes in somatic mammalian cells in vivo and in vitro; comparison of metabolic differences between normal and cancerous cells and other problems have been indicated.
THE EFFECT OF DIPHTHERIA TOXIN ON THE METABOLISM OF HELA CELLS
Authors: Strauss Norman , Hendee Edelmira D.
Published: June 2004

The effect of diphtheria toxin on certain metabolic processes in growing HeLa cells has been described. It was found that both aerobic respiration and glycolysis are insensitive to toxin action. The incorporation of S35-methionine was found to be completely inhibited by toxin prior to the appearance of any visible cell damage. It was also observed that toxin levels above 0.3 Lf per ml. had no further effect on the kinetics of inhibition of methionine uptake. The kinetics of intoxication were studied by adding diphtheria antitoxin to a partially intoxicated culture at various times and measuring the resulting rate of methionine uptake.

Low temperatures were found to block intoxication. Using this information, data were obtained suggesting that the initial step in the process of intoxication consists of a rapid adsorption of toxin by the cell.

The kinetics of toxin action on protein synthesis were compared with those of cyanide and 2,4-DNP. Diphtheria toxin eliminates completely any methionine uptake remaining after exposure of the cell to either of these respiratory inhibitors.

The significance of these results is discussed.
PARTICIPATION OF BICARBONATE IN RNA AND PROTEIN SYNTHESES AS INDICATED BY VIRUS PROPAGATION IN HUMAN CELLS
Authors: Chang R. Shihman ,   With the Technical Assistance of Helen Liepins
Published: June 2004

The propagation of a strain of Coxsackie virus, group B type 1, in human cell cultures depleted of bicarbonate has been studied. Under the described experimental conditions, bicarbonate depletion suppresses the propagation of this virus. This suppressive effect may be reversed by the addition of the following compounds to the bicarbonate-depleted cultures: (a) bicarbonate; (b) adenosine, guanosine, cytidine, and uridine; (c) adenylic, guanylic, cytidylic, and uridylic acids; (d) enzymatically degraded RNA prepared from yeasts or human embryo, or (e) RNA. The following compounds are unable to reverse the suppressive effect of bicarbonate depletion: (a) adenine, guanine, cytosine, and uracil, with or without ribose; (b) adenine, guanine, cytosine, and thymine; (c) deoxyadenosine, deoxyguanosine, deoxycytidine, and thymidine; (d) deoxyadenylic, deoxyguanylic, deoxycytidylic, and thymidylic acids; (e) enzymatically degraded DNA, or (f) DNA.

The same general results as with the Coxsackie virus have been obtained with a strain of poliovirus and vaccinia virus. The failure of bicarbonate depletion to suppress completely the propagation of the poliovirus under the described condition constitutes a major difference.

The significance of these findings is discussed.
STUDY ON GROWTH OF RICKETTSIAE
Authors: Cohn Zanvil A. , Bozeman F. Marilyn , Campbell Janis M. , Humphries James W. , Sawyer Thomas K.
Published: June 2004

A system has been described in which the penetration of Rickettsia tsutsugamushi (Karp strain) into tissue culture cells can be quantitated, and the factors affecting this process studied. The results indicated that rickettsial penetration in vitro depended largely on the viability of the organisms. Certain components of the fluid environment such as the divalent cations and protein were found to be of importance. The temperature dependence of the penetration process was found to vary with the nature of the suspending medium. A number of compounds related to L-glutamic acid enhanced penetration, whereas metabolic inhibitors depressed this process. Aureomycin at concentrations between 50 and 250 µg./ml. inhibited the penetration of rickettsiae while chloramphenicol at similar concentrations was ineffective. The results are discussed in terms of the biological and biochemical properties of this group of agents.
A HISTOLOGIC STUDY OF THE AUTO-ALLERGIC TESTIS LESION IN THE GUINEA PIG
Authors: Waksman Byron H.
Published: June 2004

The auto-allergic lesion in guinea pigs inoculated with homologous testis plus the Freund adjuvant was investigated histologically. The lesion was found to consist of disseminated foci of perivenous inflammation, lymphocytes and histiocytes predominating in the cellular infiltrate, with invasion of epididymal, rete, and seminiferous tubules and destruction of tubular contents. Guinea pigs up to 800 gm. showed a rapidly progressing diffuse hypo- or aspermatogenesis, which appeared to be secondary to the inflammatory disease. In these animals, the process resolved leaving an atrophic testis with few or no indications of the preceding inflammation and fibrotic scarring only in the rare instances in which actual necrosis of connective tissue elements had occurred. In 1200 gm. animals there was no general hypospermatogenesis and the late findings were limited to foci of aspermatogenesis. This disease then is an experimental auto-allergic orchitis followed by testicular atrophy without scarring. Its morphologic similarity to mumps orchitis and to sterility with "germinal cell aplasia" in man is commented on.
DELAYED HYPERSENSITIVITY IN THE DEVELOPMENT OF CIRCULATING ANTIBODY. THE EFFECT OF X-IRRADIATION
Authors: Salvin S. B. , Smith Robert F. ,   With the Technical Assistance of Jane Nishio
Published: June 2004

The induction of delayed type of hypersensitivity to diphtheria toxoid in the guinea pig was not inhibited by total body irradiation up to 300 r in intensity. X-ray doses of 200 to 300 r administered about 18 hours before sensitization caused the period of delayed hypersensitivity to be extended to the 19th to 21st day postsensitization in. the absence of circulating antibody. X-ray doses of 50 to 100 r caused a decrease in the titer of circulating antibody, although delayed hypersensitivity lasted for a normal time. When 300 r irradiation was administered 18 hours after sensitization, delayed hypersensitivity lasted for the usual period and circulating antibody first appeared at the usual 13 to 14 days after sensitization. Introduction of normal serum or leucocytes into irradiated animals apparently did not reduce damage to the mechanism regulating the rate of antibody synthesis.
THE OCCURRENCE OF POLYGLYCEROPHOSPHATE AS AN ANTIGENIC COMPONENT OF VARIOUS GRAM-POSITIVE BACTERIAL SPECIES
Authors: McCarty Maclyn
Published: June 2004

A bacterial substance has been described which gives a precipitin reaction with certain antisera to Group A streptococci. The precipitating antigen is present in various Gram-positive bacteria, including most hemolytic streptococci, staphylococci, and aerobic sporulating bacilli. It is not present in any of the Gram-negative species examined or in pneumococci, clostridia, or corynebacteria.

Analysis of purified preparations obtained from Group A streptococci indicates that the antigen is a simple polymer of glycerophosphate. The identification has been confirmed by immunochemical studies, including precipitin tests and specific inhibition with synthetic polyglycerophosphates. In addition, the infrared spectra of bacterial and synthetic polyglycerophosphate are shown to be closely similar. Immunochemical analysis suggests that the amount of polyglycerophosphate present in Group A streptococci and staphylococci is approximately 1 per cent of the dry weight of the cells. The cellular localization and function of the polyglycerophosphate have not been established.
DOUBLE INFECTIONS OF SINGLE CELLS WITH ECHO 7 AND COXSACKIE A9 VIRUSES
Authors: Itoh Heihachi , Melnick Joseph L.
Published: June 2004

Virus particles derived from single cells infected with two enteroviruses have been studied. Evidence was obtained to indicate that phenotypic, but not genotypic, mixing occurs between Coxsackie A9 (CAP) and ECHO 7 (E7) viruses.

Monkey kidney cultures in monolayer were doubly infected with high multiplicities of CA9 and E7 viruses. During the latent period, the infected cells were suspended, diluted, and distributed under oil into droplets each containing a single cell, as checked by microscopic observation.

The virus particles released by individual cells into the microdrop were characterized in differential plaque neutralization tests. Fifteen per cent of the microdrops contained doubly neutralizable particles, 53 per cent yielded either CA9 or E7 particles, and 34 yielded particles of an intermediate character (deficits between 37 and 75 per cent).

On passage, the doubly neutralizable particles yielded progeny of both parental types. All passage strains behaved like the corresponding parent strain as regards pathogenicity for newborn mice, which is to say that this property was limited to virus particles with CA9 antigenicity.

Coxsackie A9 has a more rapid growth cycle than ECHO 7 in rhesus monkey kidney cell cultures, and a slower one in patas cultures. In rhesus, when E7 virus was added first, CA9 could be added up to 2 hours later, and still a significant number of cells yielded either CA9 or doubly neutralizable virus. The converse was observed in patas cells.
DEOXYRIBONUCLEIC ACID (DNA) AND PROTEIN ALTERATIONS IN HELA CELLS INFECTED WITH TYPE 4 ADENOVIRUS
Authors: Ginsberg Harold S. , Dixon Mary K.
Published: June 2004

During a single cycle of multiplication of type 4 adenovirus in HeLa cells an average 2-fold increase in total DNA occurred over that measured in uninfected cells. Of the total DNA from infected cells about 23 per cent was extractable into 0.15 M NaCl, a quantity approximately four and a half times greater than that of the DNA obtained from normal cells in 0.15 M NaCl. Ninety to 99 per cent of infectious virus was also extracted into the 0.15 M NaCl fraction. Concurrently with the accumulation of DNA in virus-infected cells there occurred a 2-fold increase in total protein. The proportionate increases in protein were approximately equal in 0.15 M NaCl and water extracts of infected cells. High speed centrifugation indicated that the bulk of the DNA and protein was not directly associated with infectious viral particles. Although in virus-infected cells a markedly increased synthesis occurred of a DNA which had solubility properties different from the major portion of normal host DNA, nucleotide analysis did not reveal any other qualitative differences. However, a marked change in nucleotide molar ratios was observed in the 0.15 M NaCl-soluble DNA from virus-infected cells.

It seems apparent from the findings that the biochemical alterations found in HeLa cells infected with type 4 adenovirus are intimately related to the infectious process.