bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF POLIOMYELITIS VIRUS ON HUMAN BRAIN CELLS IN TISSUE CULTURE
Authors: Hogue M. J. , McAllister R. , Greene A. E. , Coriell L. L.
Published: June 2004

Poliomyelitis virus I, Mahoney strain, affected human brain cells grown in tissue cultures usually causing death of the cells in 3 days. The neurons reacted in different ways to the virus, some died with their neurites extended, others contracted one or more of their neurites. Terminal bulbs were frequently formed at the tips of the neurites when they were being drawn into the cell body. The final contraction of the cell body and the change into a mass of granules were often very sudden. Vacuoles often developed in the neuron. There was no recovery.

Astrocytes, oligodendroglia, and macrophages were affected by the virus but not as quickly as the neurons.

The age of the tissue culture was not a factor when the cells were in good condition.

The age of the individual donor of the brain tissue was a factor; the fetal brain cells appeared to be more sensitive to the virus than the adult brain cells. The fetal neurons often reacted ½ hour after inoculation while the adult neurons reacted more slowly, 2 to 24 hours after inoculation.

All these changes seemed to be caused by virus infection because they were prevented by specific antiserum or by preheating the virus.
STUDIES ON ANTIBODY PRODUCTION
Authors: Coons Albert H. , Leduc Elizabeth H. , Connolly Jeanne M.
Published: June 2004

A method for the specific histochemical demonstration of antibody in cells and parts of cells is described. It consists of carrying out a two stage immunological reaction on frozen sections of tissues: (a) allowing reaction between antibody in the tissue and dilute antigen applied in vitro, and (b) the detection of those areas where this antigen has been specifically absorbed by means of a precipitin reaction carried out with fluorescein-labelled antibody. Examination under the fluorescence microscope reveals the yellow-green fluorescence of fluorescein over those areas where a precipitate has formed.

A study of the hyperimmune rabbit on the first few days after the last of a series of intravenous antigen injections reveals that antibody against human γ-globulin or ovalbumin is present in groups of plasma cells in the red pulp of the spleen, the medullary areas of lymph nodes, the submucosa of the ileum, and the portal connective tissue of the liver. Because of extensive non-specific reactions, the bone marrow could not be examined. Small amounts of antibody were occasionally visible in cells in the lymphoid follicles of the spleen and lymph nodes, so that a minor contribution by lymphocytes to antibody synthesis cannot be excluded.
THE ANTIGENIC SIMILARITY OF HUMAN LOW DENSITY LIPOPROTEINS
Authors: Levine Lawrence , Kauffman Dorothy L. , Brown Ray K.
Published: June 2004

The following human low density lipoproteins were prepared: ß-lipoproteins of densities greater than 1.040 (A, B,C) a ß-lipoprotein of –S1·063 = 5 (D), a lipoprotein of –S1·063 = 19 (E), and a lipoprotein of –S1·063 = 70 (F).

Data are presented which show the immunochemical homogeneity of the D lipoprotein rabbit-anti-D lipoprotein system.

Cross-reactions between antibody to A and D lipoproteins and the above lipoproteins have been demonstrated by quantitative precipitation, quanitative complement fixation, and single and double diffusion in agar.

The antigenic similarities appear to be associated with the protein portions of the molecule.

The antisera produced did not differentiate the low density lipoprotein classes.
ACTIVE ANAPHYLAXIS TO A FOREIGN PROTEIN INDUCED IN MICE BY THE TRANSFER OF TISSUE FROM ANIMALS PREVIOUSLY INJECTED WITH THE PROTEIN
Authors: McMaster Philip D. , Edwards Joshua L. , Sturm Ernest
Published: June 2004

Following single intravenous injections of a foreign protein antigen, bovine γ-globulin, into mice and rabbits, antigenic material persisting in the liver could be detected for several weeks. Ground liver tissue—taken from the mice and rabbits, just mentioned, either 4 or 6 weeks after injecting the antigen—when transferred repeatedly, at 2 or 3 day intervals, to the peritoneal cavities of normal, or unilaterally adrenalectomized, recipient mice, rendered the recipients sensitive to active anaphylaxis when they were challenged after a suitable interval by intravenous injections of the original antigen.

The work throws some light on the state of the antigenic material that persists for 4 to 6 weeks in the livers of the donor animals. Obviously it is sufficiently unchanged, at least in its reactive groups, to engender in the recipient mice antibodies capable of reacting with the original antigen.
STUDIES ON THE IMMUNOLOGICAL RESPONSE TO FOREIGN TUMOR TRANSPLANTS IN THE MOUSE
Authors: Mitchison N. A.
Published: June 2004

The transfer of transplantation immunity by lymph node cells has been the subject of investigation. Transplantable tumors have been used to provoke and to measure transplantation immunity. Cells from the lymph nodes draining a tumor homograft were transferred as mince or in suspension into the peritoneum of a secondary host to confer immunity. These cells could confer immunity while the immunizing graft was undergoing breakdown during the primary, and also during the more rapid secondary, response. Cells from other nodes and from the spleen, and also whole blood or serum failed in these experiments to transfer immunity. In one combination of tumor and host, serum from immunized donors enhanced tumor growth.

Evidence has been presented favoring the hypothesis that the lymph node cells were immunologically activated before transfer, and that they conferred immunity by continuing to function in their host. Immunization by tumor cells transferred along with the cells of the nodes could not account for the failure of lymph node transferred into susceptible animals to give rise to tumors; nor for the failure of tumor cells to give rise to immunity as rapidly as transferred lymph node cells. Freezing and thawing of the transferred cells prevented transfer of immunity. Cells from donors immunized against an isoantigen failed to confer immunity on hosts which carried that isoantigen, offering evidence of absorption of antibody. The duration of immunity transferred within an inbred strain was shorter than actively induced immunity, but longer than could have been expected of passively transferred immunity. After transfer of cells into foreign hosts, immunity declined more rapidly, as if the transferred cells were destroyed by the homograft reaction of the host.

The possibility that cells of the host were activated has also been discussed. A brief review showed that similar problems are raised in other systems of transfer of immunity by cells.
STUDIES ON THE GENERALIZED SHWARTZMAN REACTION
Authors: Thomas Lewis , Brunson Joel , Smith Richard T.
Published: June 2004

Lesions indistinguishable from those of the generalized Shwartzman reaction occured in rabbits when a single intravenous injection of Gram-negative bacterial endotoxin was accompanied, or followed, by an injection of one of the following synthetic, heparin-like, acidic polymers-sodium polyanethol sulfonate, dextran sulfate, or sodium polyvinyl alcohol sulfonate.

These reactions were produced by doses of polymer or of endotoxin which were without demonstrable effect when given singly.

Heparin, in those similar to those previously shown to protect rabbits against the lesions of the generalized Shwartzman reaction, prevented the reaction to the combined injection of endotoxin and acidic polymers.

Nitrogen mustard, which was previously shown to prevent the lesions of the generalized Shwartzman reaction from occurring after two intravenous injections of endotoxin, had no protective action against the lesions produced by the combined injection of endotoxin and polymer.

Cortisone did not affect the reaction to endotoxin and polymer.

The role of fibrinogen in the reaction under study is discussed in the paper which follows.
PROPAGATION OF INFLUENZA VIRUS IN "IMMUNE" ENVIRONMENTS
Authors: Magill Thomas P.
Published: June 2004

Influenza virus can survive, and can be propagated in immunological environments induced in mice by vaccination with the homologous strain of virus: survival was associated with the emergence of variants which differed from the parent strain in antigenic characteristics.

The data concerning hemagglutinating activity of the variants, on the one hand, and of the antigenicity, on the other, are compatible with the concept that the structure of the influenza virus includes a surface arrangement which is distinct from the inner virus bulk.

The points (a) that propagation was accomplished with difficulty whenever the immunological environment was altered, and (b) that once established, passage was continued without difficulty, are interpreted to indicate that the mechanism of variation may involve a rearrangement of the basic hereditary mechanism.
THE REQUIREMENT OF OVALBUMIN FOR THE GROWTH OF GROUP A HEMOLYTIC STREPTOCOCCUS IN A SYNTHETIC MEDIUM
Authors: Slade Hutton D. , Slamp William C.
Published: June 2004

Crystalline ovalbumin, when heated under controlled conditions, promoted growth of Streptococcus hemolyticus in a synthetic medium. A similar activation of albumin also was produced by ultraviolet irradiation or by shaking under nitrogen. Untreated albumin failed to permit growth under the same conditions. The activity of treated albumin was destroyed by aeration or by reaction with iodoacetate.

The data suggest that the activity of ovalbumin for the streptococcus depends on the presence of "exposed" SH groups. However, other sulfhydryl-containing compounds (thioglycolate, glutathione, cysteine) could not replace ovalbumin.

A number of crude and crystalline proteins, and di- and tripeptides were inactive. Strepogenin and crystalline bovine serum albumin produced a weak growth response on extended incubation.

Approximately 50 per cent of the original protein in the culture disappeared during growth. Ovalbumin labelled with C14 was added to the synthetic medium. After growth of the culture the isotope was found associated with the cells and in the culture fluid in both dialyzable and non-dialyzable forms.

Under the conditions described, luxuriant growth of 15 strains (10 serological types) of Group A streptococci was obtained in 10 hours from small inocula. The growth was capable of repeated subcultivation.
PRESSOR SUBSTANCES IN ARTERIAL HYPERTENSION
Authors: Schroeder Henry A. , Perry H. Mitchell , Dennis Evie G. , Mahoney Laura E.
Published: June 2004

Some pharmacological and chemical qualities of pherentasin, a vasoconstrictor substance procured from human hypertensive blood, were studied by a new assay method using the spirally cut rabbit aorta. Of a number of drugs tested, six metal-binding agents including hydralazine inactivated the active principle. The material was stable in acid but not in alkali. It was destroyed by drying. Chemical analysis and inactivation procedures suggested the presence of primary amine and considerable sulfur; a peptide linkage was suspected because of inactivation by manganous ion and papain. The material was remarkably resistant to most pharmacological agents and appeared to act directly on smooth muscle.
THE TRANSFER OF LYMPH NODE CELLS IN THE STUDY OF THE IMMUNE RESPONSE TO FOREIGN PROTEINS
Authors: Roberts James C. , Dixon Frank J.
Published: June 2004

A secondary immune response to the soluble foreign protein antigens I*BSA and I*BGG has been demonstrated when lymph node cells, largely lymphocytes with a few reticulo-endothelial and plasma cells, from previously immunized rabbits were transferred to x-radiated recipient rabbits, and the recipients then challenged with antigen.

The total specific antibody synthesized by the transferred cells during the first 8 days of the secondary response amounted to approximately ⅔ of the wet weight of the transferred cells.

In an attempt to elicit a primary response, lymph node cells were obtained from normal, non-immunized donors, and transferred to x-radiated recipients. No immune response was observed upon antigenic stimulation.

When normal or previously immunized lymph node cells were incubated with antigen for periods up to 1 hour, washed and injected into recipients, no antibody production was observed.
GROWTH CHARACTERISTICS OF INFLUENZA VIRUS
Authors: Ackermann W. Wilbur , Maassab Hunein F.
Published: June 2004

A further analysis of the growth curve obtained in vitro for influenza virus in chorioallantoic membrane has been made using the viral inhibitor p-fluorophenylalanine. It has been found that p-fluorophenylalanine is phase-specific, does not interfere with the initiation of infection but rather acts during the productive period of the infectious sequence. The site of action of this fluoroderivative has been described relative to the site of action of methoxinine. By the use of this inhibitor in combination with methoxinine, it has been possible to recognize two stages of development which were not discernible from the usual growth curve. In a multicellular culture these two reactions, A and B, occur for the most part simultaneously, during the latent and productive periods. Reaction A is inhibited by methoxinine, but not by fluorophenylalanine. It begins early in the latent period and can proceed independent of reaction B. Reaction B is inhibited by fluorophenylalanine, but not by methoxinine, and it cannot proceed unless reaction A is proceeding or has operated for some prior interval.
ARE CARCINOGENS RESPONSIBLE FOR THE SUPERIMPOSED NEOPLASTIC CHANGES OCCURRING IN MOUSE TUMOR CELLS?
Authors: Dumbell Keith , Rous Peyton
Published: June 2004

Three spontaneous pulmonary adenomas of C mice, morphologically resembling those induced by methylcholanthrene or urethane, were propagated in host after host under conditions such that the neoplastic cells were directly exposed, while proliferating, to one or the other of these agents. The successive periods of test lasted for more than a year in some instances, the total exposure to the carcinogens far exceeding that required to change normal pulmonary cells into adenoma cells. One of the adenomas remained unaltered, and the others underwent cancerous changes; but these took place with equal frequency in the control growths, and their occurrence was neither hastened nor delayed by the carcinogens.

Two polymorphous mammary carcinomas of "milk-factor" type, with the characteristic tendency to form acini and tubules, were exposed to methylcholanthrene in the same way as the pulmonary adenomas and for periods quite as long. Their cells continued to differentiate, and in other respects underwent no significant change.

Urethane had no influence on the rate of growth of the adenomas exposed to it; methylcholanthrene, on the other hand, markedly retarded the enlargement both of them and of the mammary tumors. Its inhibitory influence was not passed on from cell to cell however; when freed of the carcinogen by further transplantation, the retarded tumors grew as fast as the controls. Furthermore the retardation caused no evident delay in the occurrence of cancerous changes in the adenomas.

One of the adenomas was maintained in twelve parallel lines while under test and new tumors arose in nine of them, the earliest appearing more than fifteen months after initial transfer of the growth. Always it was an adenoma solidum, this appearing almost concurrently in eight of the nine lines. In six of them it was soon followed by carcinomas, the sequence of events and the morphological findings both indicating that they had derived from it. Individually the cancers were widely various, but they were similar on the whole from line to line. Carcinomas of a wholly different aspect arose from the other adenoma undergoing cancerous change, and they were not preceded by adenoma solidum. In both instances the character of the superimposed neoplastic alterations seemed to have been determined by some inherent trait of the adenoma concerned.
AN INFECTIOUS HEPATITIS OF UNDETERMINED ORIGIN IN MICE
Authors: Jordan Janet , Mirick George S. ,   With the Technical Assistance of Marjorie G. Huck
Published: June 2004

A transmissible agent (AHA) causing ascites and hepatitis in mice has been described. No known pathogenic bacteria, fungi, protozoa, leptospira, rickettsia, or viruses have been demonstrated in the infected mice. AHA does not pass through a Seitz filter and differs in most respects from the agents previously described which produce hepatitis in mice.
STUDIES ON THE PATHOGENESIS OF ACUTE INFLAMMATION
Authors: Allison Fred , Smith Mary Ruth , Wood W. Barry
Published: June 2004

A special adaptation of the rabbit ear chamber has been devised to study in vivo, under high magnification, the acute inflammatory reaction to thermal injury. Systematic observations of the cellular response have led to the following conclusions.

1. Contrary to the commonly accepted view, vasodilatation does not always precede the adherence of leucocytes to vascular endothelium.

2. The fact that leucocytes often adhere to one another as well as to the endothelium indicates that the increased adhesiveness characteristic of the early stages of inflammation is not limited to the surfaces of the endothelial cells.

3. The sharing of erythrocytes and platelets in this increased stickiness suggests that a "plasma factor" is involved. There is indirect but as yet inconclusive evidence that the plasma factor may concern the clotting mechanism of the blood.

4. The adherence of leucocytes to the endothelium is usually first noted on the side of the vessel closest to the site of injury. This previously undescribed phenomenon of "unilateral sticking" is in keeping with the concept that the vascular reaction is caused by products of cellular damage which diffuse to the vessel from the site of injury.

5. Leucocytes always become adherent to the endothelium before penetrating the vessel wall. They often migrate about for some time on the endothelial surface before undergoing diapedesis.

6. Although no definite stomata are at any time visible in the endothelium, penetrating leucocytes may leave behind temporary defects through which other leucocytes and even erythrocytes may pass.

7. The diapedesis of leucocytes appears to depend primarily upon cellular motility. It may occur in static vessels where there is presumably little if any hydrostatic pressure.

8. The diapedesis of erythrocytes, on the other hand, is a passive process depending upon intravascular pressure. Its occurrence is greatly exaggerated in areas in which intravascular pressure becomes elevated. Such elevations occur as the result of proximal arteriolar dilatation and distal occlusion of vessels.

9. Once they have reached the extravascular tissues the leucocytes move about more or less at random, apparently uninfluenced by any compelling chemotactic force. Their resultant migration, however, is toward the site of injury around which they eventually tend to congregate.

10. The histiocytes normally present in the connective tissue appear to play no role in the type of acute inflammatory reaction produced in these experiments.
RED CELL STROMA IN DOGS
Authors: Robscheit-Robbins F. S. , Whipple G. H.
Published: June 2004

Normal red blood cells in dogs contain stroma in fairly uniform amounts. This red cell stroma is rich in proteins and lipides.

Anemia due to blood loss causes an increase in stroma protein. The highest levels of stroma protein are found in the severe anemias. As the anemia is corrected by red cell regeneration, the stroma protein level falls to normal.

Anemia due to blood destruction (phenylhydrazine) presents very high levels of stroma protein—almost double the increase noted in anemia due to blood loss.

Hypoproteinemia added to anemia due to blood loss causes no significant change on the stroma protein level.

Abscesses due to the subcutaneous injection of turpentine during the anemia cause slight decreases in the stroma protein levels. Chloroform poisoning has no effect on the stroma protein levels.

The total lipides of the stroma are rather stable and are little influenced by anemia. In certain experiments with hemolytic anemia and with hypoproteinemia, there is a significant rise in total lipide figures.
LYSIS OF T4 PHAGE BY THE SPECIFIC LIPOCARBOHYDRATE OF PHASE II SHIGELLA SONNEI
Authors: Jesaitis Margeris A. , Goebel Walther F.
Published: June 2004

When the specific lipocarbohydrate of Phase II Sh. sonnei and T4 phage react in vitro, the virus is rapidly inactivated and the content of the viral membrane is released into the surrounding medium. The reaction between phage and lipocarbohydrate proceeds only in the presence of a lipide constituent which can be extracted from the polysaccharide, rendering the latter inactive, and which can be replaced by certain fatty acids. It has been suggested that the lipocarbohydrate is the receptor substance of the Phase II bacillus which specifically combines with and brings about disintegration of the virus when the latter infects the host cell.
EFFECTS OF CORTICOSTERONE, HYDROCORTISONE, AND CORTICOTROPIN ON PRODUCTION OF ANTIBODIES IN RABBITS
Authors: Kass Edward H. , Kendrick Mary I. , Finland Maxwell
Published: June 2004

The effects of hydrocortisone, corticosterone, and pituitary adrenocorticotropin on antibody production were studied immunochemically in rabbits.

Hydrocortisone in doses as low as 2.5 mg. per day (approximately 1.0 mg. per kg. per day) markedly depressed antibody production whereas corticosterone in doses four times as large exerted no significant effect.

Corticotropin in doses of 15 units daily exerted an effect similar to that of corticosterone, but its effect was more like that of hydrocortisone when given in doses twice as great. This finding is in agreement with observations that the prolonged administration of corticotropin in sufficient dosage leads to increased output of hydrocortisone by the adrenal cortex of the rabbit.

Corticosterone did not antagonize the effect of hydrocortisone on antibody production, but seemed to act additively with it.

Although each of the hormones tested induced some adverse effect on nitrogen balance as measured by the weights of the animals, and hydrocortisone induced the more striking decreases in weight, there was no direct correlation between the effects of these hormones on antibody production and their effects on weight.
THE EFFECT OF DINITROPHENOL AND THYROXIN ON THE SUSCEPTIBILITY OF MICE TO STAPHYLOCOCCAL INFECTIONS
Authors: Smiths J. Maclean , Dubos René J.
Published: June 2004

Mice were given daily per os amounts of dinitrophenol or of thyroid extract sufficient to prevent or retard the normal weight gain of uninfected animals, but not large enough to cause their death.

When mice maintained on these regimens for 1 or 2 weeks were infected with staphylococci, most of them died within 12 days—much more rapidly than did mice fed a normal diet. Deaths occurred even when the organism injected was a non-virulent staphylococcus, unable to cause fatal disease in mice fed a normal diet.

There was some suggestion that thyroid treatment interfered with the bactericidal mechanism in the liver, spleen, and kidneys of mice during the initial phase of infection. In contrast there was no clear evidence at any time thereafter that either thyroid extract or dinitrophenol caused the staphylococci to multiply more rapidly in the various organs.
THE ABILITY OF GROUP A STREPTOCOCCI KILLED BY HEAT OR MERCURY ARC IRRADIATION TO RESIST INGESTION BY PHAGOCYTES
Authors: Wiley Grove G. , Wilson Armine T.
Published: June 2004

Living group A streptococci which resist ingestion by human neutrophils in an in vitro test still do so after they have been killed by exposure to heat or to mercury are irradiation.
ANTITUBERCULOUS IMMUNITY INDUCED BY METHANOL EXTRACTS OF TUBERCLE BACILLI—ITS ENHANCEMENT BY ADJUVANTS
Authors: Weiss David W. , Dubos René J.
Published: June 2004

It is possible to prepare from tubercle bacilli a fraction soluble in methanol which is capable of eliciting in mice a marked degree of resistance against virulent tuberculous infection. The immunity was evident whether the infective dose was large and caused a disease with a rapid course, or was very small and caused a disease of many months duration.

Active material has been obtained by extraction with methanol at 55°C. of bacterial cells killed with 2 per cent phenol, and washed with acetone. The methanol extracts used in the present study have been prepared from the phenol-killed cells of a culture of BCG, and of the avirulent culture H37Ra.

Vaccination of mice bas been carried out by the intraperitoneal route, and the challenge infection (with a highly virulent bovine culture), by the intravenous route.

Weight for weight, the protective activity of the methanol extract is smaller than that of the bacterial cells from which it is extracted, but its primary toxicity for mice is also considerably lower. The protective activity can be increased, and the immunity prolonged, by using certain adjuvants as vehicle for injection of the vaccine. An oil adjuvant mixture, and small amounts of a highly purified preparation of the somatic antigen of typhoid bacilli, have been found capable of enhancing and prolonging the antituberculous immunity induced by the methanol extract.

Under appropriate conditions the resistance resulting from intraperitoneal injection of the methanol extract is of the same order as that which follows vaccination with whole killed tubercle bacilli or with living BCG.
THE IMMUNOLOGICAL SPECIFICITY OF TYPE II PNEUMOCOCCUS AND ITS SEPARATION INTO PARTIAL SPECIFICITIES
Authors: Heidelberger Michael , Adams John
Published: June 2004

The specificity of Type II pneumococcus determined by its capsular polysaccharide (S II) may be separated into three partial specificities, each characteristic of one of the three component sugars of S II, namely, glucuronic acid, glucose, and rhamnose.

By far the largest portion of antibodies in Type II antipneumococcus horse sera which cross-react with carbohydrates containing one or more of these sugars are reactive with those characterized by multiple groupings of glucuronic acid. This confirms, extends, and explains earlier observations.

In confirmation of predictions based upon existing information tamarind seed polysaccharide (jellose), in which much of the glucose exists as 1,4,6-branch points, was found to react in Type II antisera.

Several instances are given of cross-reactions in these antisera apparently due to the L-rhamnose component of the reacting polysaccharides.

The antisera contain far more antibody capable of precipitating with substances with multiple units of glucuronic acid than with those so far tested containing multiple 1,4,6-branch points of glucose or multiple groupings of rhamnose.

The long known increase of titer of gum arabic on partial hydrolysis is now fully explained and discussed, and a chemical picture is given of the change in "avidity."

The sum of the partial specificities measured does not equal the whole.

Quantitative data illustrating these points are given.
AN ENDEMIOLOGICAL STUDY OF ENTERIC VIRUS INFECTIONS
Authors: Honig Edward I. , Melnick Joseph L. , Isacson Peter , Parr Robert , Myers Ira L. , Walton Mary
Published: June 2004

An endemiological study of enteric viruses was conducted among 136 normal children, living in households in two socio-economic groups, over a 29 month period in Charleston, West Virginia.

A repeatable seasonal incidence of enteric virus excretion was noted with over 90 per cent of isolations occurring in the months of June to October. Of 592 stools examined in District I, a lower socio-economic group, 8.3 per cent yielded virus as compared to 3.1 per cent of 966 stools examined in District IV, an upper middle class district with good environmental sanitation. Among the 77 viruses isolated in tissue cultures of monkey kidneys, 44 per cent were ECHO or orphan viruses, 37 per cent Coxsackie viruses, and 19 per cent poliomyelitis viruses.

Among poliovirus carriers, and 15 family contacts, 10 individuals had simultaneous heterotypic and type-specific antibody responses. The heterotypic ones were usually present at low levels and were transient in nature.

Family infection with certain orphan viruses was also evident from antibody development which occurred following isolation of virus in the sentinel child.
INFLUENZA VIRUS AND ITS MUCOPROTEIN SUBSTRATE IN THE CHORIOALLANTOIC MEMBRANE OF THE CHICK EMBRYO
Authors: Schlesinger R. Walter , Karr H. Valerie
Published: June 2004

The fate of heat-stable inhibitors (HI) of hemagglutination by influenza viruses in the infected chorioallantoic membrane has been studied. The amount of soluble HI extractable from the normal CAM is taken as a measure of the total mucoprotein substrate derived from the allantoic cells.

It has been shown that a decrease in HI is demonstrable when all or nearly all cells of the allantois are involved in the infectious process. Once this condition is fulfilled, viral multiplication in the CAM is associated with stepwise breakdown and partial restoration of HI. The periodicity of these steps is in close agreement with earlier reports by others on the duration of primary and secondary cycles of viral multiplication. Periodicity of viral multiplication and of HI breakdown with subsequent restoration is particularly pronounced in eggs pretreated with metaperiodate or with mixtures of periodate and glucose or glycerol.

The stepwise nature of the HI breakdown indicates that it is in some way related to intracellular phases of viral reproduction, and that individual cells produce virus in cycles rather than continuously. A possible mechanism of this process is proposed.
STUDIES ON SERUM PROTEOLYTIC ENZYME INHIBITION
Authors: Moll Frederic C. ,   With the Technical Assistance of Shirley Sunden And Burton Palmer
Published: June 2004

Serial studies of the serum levels of trypsin inhibitor have been performed on monkeys following injection of turpentine-falba, total body irradiation, thermal injury, splenectomy, administration of cortisone acetate and egg albumin. Following the injection of turpentine-falba mixture there was a prompt elevation in the trypsin inhibitor power of the serum. A similar response accompanied the administration of cortisone acetate. The response to cortisone was not inhibited by removal of the spleen. Animals premedicated with cortisone acetate for 3 and 4 weeks showed no statistically significant change in the level of the serum inhibitor following injection of the turpentine-falba.

Total body irradiation and immunization with egg albumin were accompanied by a very slight rise in the inhibitory power of the serum despite a prompt and extensive drop in the total white blood cell count in the irradiated animals, and development of precipitins in all of the immunized animals. The significance of these findings is discussed.
5-HYDROXYTRYPTAMINE AND HISTAMINE AS MEDIATORS OF THE VASCULAR INJURY PRODUCED BY AGENTS WHICH DAMAGE MAST CELLS IN RATS
Authors: Rowley Donald A. , Benditt Earl P. ,   With the Technical Assistance of Margaret Arase And Elizabeth Roeper
Published: June 2004

Each of the four agents, ovomucoid, dextran, 48/80, and testis extract, when injected beneath the skin of the dorsa of the paws of rats produces a local vascular injury characterized by a protein-rich edema. Each agent also produces damage to mast cells.

Either 5-hydroxytryptamine or histamine produces a response similar in the gross to that elicited by the agents which damage mast cells; however, neither of these two agents produces mast cell damage. On a weight basis 5-hydroxytryptamine is a much more potent edema-producing agent than histamine.

The edema-producing action of 5-hydroxytryptamine can be differentiated from the similar action of histamine by the use of specific antagonists; dibenamine is a 5-hydroxytryptamine antagonist and pyrilamine a histamine antagonist.

The edema produced by the mast cell-damaging agents is partially inhibited by dibenamine but is not diminished by pyrilamine. It is completely inhibited by treatment of rats with both drugs.

The drugs which inhibit edema do not prevent mast cell damage by ovomucoid, dextran, 48/80, or testis extract.

The observations are consistent with the hypothesis that agents which damage mast cells, "release" both 5-hydroxytryptamine and histamine and that in the rat the edema associated with mast cell damage is mediated largely by 5-hydroxytryptamine.
RATES OF ANTIBODY SYNTHESIS DURING FIRST, SECOND, AND HYPERIMMUNE RESPONSES OF RABBITS TO BOVINE GAMMA GLOBULIN
Authors: Dixon Frank J. , Maurer Paul H. , Weigle William O. , Deichmiller Maria P.
Published: June 2004

Determinations of the rates of antibody synthesis during first, second, and hyperimmune responses to bovine gamma globulin using S35-labelle aminod acids indicate the following:

1. In all three responses the rate of antibody synthesis increases while antigen is circulating and then begins to decline rapidly after elimination of detectable circulating antigen.

2. The initial rates of decline of antibody synthesis are approximately the same for all three responses.

3. There is a relatively persistent source of antibody production which appears after repeated stimulation and increases in proportion to the number of repeated stimuli.
A STUDY OF THE EFFECT OF SERUM ON THE IMMUNOLOGICAL REACTION OF A BACTERIAL ENDOTOXIN
Authors: Cluff Leighton E.
Published: June 2004

Contact of a purified endotoxin from Shigella fiexneri Type Z with normal rabbit or human serum results in an alteration of its immunological reaction with antiserum, as determined by precipitation in gel. Analysis of fractions of normal serum obtained by zone electrophoresis in starch indicates that the component responsible for altering the immunological reaction of endotoxin is associated with beta globulin. Normal serum has no similar effect on the immunological reaction of a variety of other protein and polysaccharide antigens. Serum from rabbits made tolerant to the pyrogenic action of an endotoxin from Serratia marcescens (P-35) possesses the ability to alter the reaction of Shigella endotoxin with its specific antiserum, although the serum from tolerant rabbits does not significantly enhance the pyrogenicity of Shigella toxm. The component of normal rabbit serum responsible for the effect on the immunological reaction of Shigella endotoxin is not destroyed by heating at 56°C. The possible relationship of the effect of normal serum on the immunological reaction of endotoxin and the augmentation of fever induced by endotoxins is discussed.
AN EXPERIMENTAL ANALYSIS OF THE CURATIVE ACTION OF PENICILLIN IN ACUTE BACTERIAL INFECTIONS
Authors: Wood W. Barry , Smith Mary Ruth
Published: June 2004

Three strains of pneumococcus (types I and III), equally sensitive to penicillin, have been shown to be killed by the antibiotic in vitro when grown either in enriched beef infusion broth or in a thin serous exudate. Killing of the bacteria resulted promptly when the penicillin was added during the logarithmic phase of growth but failed to occur if addition of the antibiotic was delayed until the later "stationary" growth phase. In analogous experiments with thick purulent exudates from established subcutaneous abscesses, the pneumococci failed to grow rapidly, and added penicillin exerted only a relatively slow bactericidal effect.

The relevance of these in vitro observations to the curative action of penicillin was demonstrated in a systematic histologic study of the antimicrobial effect of the drug in experimental (type I) pneumococcal pneumonia. Evidence was obtained that at least two distinct processes are involved. The first, the direct bactericidal effect of the penicillin itself, was shown to operate in the outer edema zone of the spreading pneumonic lesion where the micro-organisms multiply rapidly in the thin serous exudate. The second, which predominates in the older more central portions of the lesion, was demonstrated to depend upon destruction of the pneumococci by phagocytosis. Here the bacteria, having presumably reached a relatively stationary phase of growth in the alveolar exudate, are resistant to the bactericidal action of the penicillin but are readily destroyed by the phagocytes.
STUDIES ON NON-PRECIPITATING ANTIBODY
Authors: Sternberger Ludwig A.
Published: June 2004

Reinjection of antigen into immunized rabbits usually results in an immediate increase of circulating antibody-antigen complex. This immediate formation of complex seems to depend upon the presence of non-precipitating antibody before reinjection. The complex disappears by the 2nd day after reinjection and reappears between the 4th to 7th day. This is earlier than its first appearance after a primary injection and may indicate an anamnestic response of the non-precipitating antibody responsible for the formation of circulating antibody-antigen complex.
THE PROPERDIN SYSTEM AND IMMUNITY
Authors: Wardlaw Alastair C. , Pillemer Louis
Published: June 2004

Methods for the preparation and standardization of reagents suitable for studies on the bactericidal action of the properdin system are described. The preparation and properties of serum free of properdin (RPb) are presented in detail because of the necessity for a suitable RPb in these studies.

The properdin system is responsible for the bactericidal action of normal human serum against a variety of microorganisms. The present work shows that the removal of properdin from serum also removes bactericidal activity. Addition of properdin to properdin-deficient serum restores bactericidal activity. A quantitative relationship exists between the final properdin concentration and bactericidal activity against sensitive organisms. The possibilities of a bactericidal assay for properdin are discussed.

It is demonstrated that, in addition to properdin, the four components of complement (present in RPb) are necessary for the destruction of properdinsensitive bacteria. If any component is missing, bactericidal activity is lost; when the component is replaced, bactericidal activity is restored. Magnesium is also necessary for the bactericidal activity of the properdin system. Maximal bactericidal activity is obtained with magnesium concentrations similar to that of normal human serum (10–3 to 10–4 M). The bactericidal activity of the properdin system occurs only at temperatures above 15°.

Resistant strains have been encountered in species of bacteria sensitive to the properdin system. Resistance or sensitivity is a characteristic of the individual strain and not of the species.

The widespread occurrence of the properdin system in normal mammalian serum and the variety of bacteria destroyed by it suggest that the properdin system is a factor in natural resistance.
PHAGOCYTIN: A BACTERICIDAL SUBSTANCE FROM POLYMORPHONUCLEAR LEUCOCYTES
Authors: Hirsch James G.
Published: June 2004

A technique has been developed for collecting large numbers of polymorphonuclear leucocytes from peritoneal exudates in rabbits. These cells are obtained essentially free from other cell types and from debris.

When microphages so procured are disrupted by physical methods and extracted with aqueous salt solutions, the soluble fraction manifests striking bactericidal activity, especially on Gram-negative enteric bacilli. The susceptible microorganisms are not lysed.

This bactericidal substance, which has been called phagocytin, appears to be limited in distribution mainly to the polymorphonuclear leucocyte. No phagocytin is present in extracts of rabbit heart, kidney, or skeletal muscle, and rabbit liver and spleen contain much less than do packed leucocytes.

Extracts of human and of guinea pig microphages show less bactericidal activity than rabbit cell preparations. Similar extracts of rat and mouse polymorphonuclear leucocytes contain no demonstrable phagocytin.

As indicated by its behavior on dialysis, on exposure to proteolytic enzymes, and on salt fractionation, phagocytin appears to be a protein with general properties characteristic of a globulin. It is clearly different from lysozyme and from properdin.

Although phagocytin is reasonably stable at temperatures of 65°C. and lower for several hours, solutions of it gradually lose bactericidal activity on standing for prolonged periods at 4°C. This instability, and also the ease with which phagocytin is inactivated, presumably by adsorption, on exposure to a variety of materials, have thus far rendered fruitless efforts to isolate it.
EFFICIENCY OF GLUTAMYL PEPTIDE POLYMERS AS PLASMA VOLUME EXTENDERS
Authors: Rosenthal William S. , O'Connell Daniel J. , Axelrod D. Robert , Bovarnick Max
Published: June 2004

A series of polymers of polyglutamic acid have been tested as plasma volume expanders. The results indicate that those polymers prepared from backbones of 40,000 molecular weight or over and side chains of 3,000 molecular weight or over, will have plasma volume retention half-life of 15 hours or longer.

Measurements of the oncotic efficiency of these polymers in vivo indicated a blood stream fluid retention of approximately 51 ml./gm. of polymer. Similar measurements of polymer-serum albumin solutions in vitro showed a retention of 52 ml./gm. of polymer.

The clinical response to infusion of solutions of these polymers indicated no untoward pharmacological properties. Although the number of trials presented is too small for ultimate conclusion regarding either the physiological or clinical effects of these polymers, they do provide a strong indication of the desirability of further clinical testing of this polymer and a sound basis on which to plan the larger scale preparation of polymer. Both measures are currently under way.
ELEVATION OF PROPERDIN LEVELS IN MICE FOLLOWING ADMINISTRATION OF BACTERIAL LIPOPOLYSACCHARIDES
Authors: Landy Maurice , Pillemer Louis
Published: June 2004

The administration of a single small dose of bacterial lipopolysaccharide produces in mice a considerable rise in properdin levels. This is accompanied by an early, transient, non-specific increase in resistance to certain bacterial infections. Bacterial lipopolysaccharides were shown to possess far greater activity than other substances previously studied in bringing about an elevation of properdin levels.

After the injection of bacterial lipopolysaccharides, high molecular weight substances appear in the circulation, which interfere with the combination of properdin with zymosan and thus affect the assay of properdin.

The administration of small amounts of bacterial lipopolysaccharides to mice at appropriate times before experimental infection "conditions" the mice so that they maintain normal or elevated properdin titers during the infectious process in contrast to control mice which show a progressive decline in properdin to low levels and death.

The significance of this observation and its relationship to natural resistance to Gram-negative pathogens are considered.
ANALYTICAL PATHOLOGY
Authors: Ortega Louis G. , Mellors Robert C.
Published: June 2004

The principal objective of this investigation was to define the roles of injected and autogenous, kidney-localizing antibodies in the pathogenesis of rat nephrotoxic nephritis by relating data obtained with fluorescent antibody techniques to clinical and histologic observations.

Such an analysis of the nephritis that developed in 28 rats after injection with the crude γ-globulin fraction of nephrotoxic serum has led us to the following conclusions:—

The renal localization of nephrotoxic antibodies is primarily and, perhaps, exclusively in the membranes of the glomerular tufts. These antibodies are demonstrable, as antigens, in the glomeruli for up to 3 months after injection.

In the acute stage of the nephritis, non-antibody, autogenous globulins are present in the glomerular tufts, probably as components of edema fluid. From 6 and 9 days to 3 months after injection, autogenous antibodies are localized in the glomerular tufts in a pattern that corresponds closely to that of the nephrotoxins.

The essential requirements for the operation of the mechanism postulated by Kay are fulfilled in rat nephrotoxic nephritis.
NATURE OF FLUIDS WHICH FUNCTIONALLY DISTEND THE KIDNEY
Authors: Swann H. G. , Valdivia Luis , Ormsby A. A. , Witt W. T.
Published: June 2004

The nature of the fluid draining from the kidney, after its artery was occluded, was investigated. Samples of systemic arterial blood, renal venous blood and urine were also analyzed. It was found that the fluid draining from the kidney after occlusion is a mixture of vascular blood and another fluid designated as "diluting fluid," each contributing half to the composite mixture. In volume the mixture is 26 per cent of the functionally distended kidney. With the assumption that the renal extracellular fluid can be considered a simple mixture of blood plasma and a cell-free fluid, the composition of the "diluting fluid" was deduced from the known compositions of vascular blood and total fluid draining. The ratios of its content in a given substance to that in systemic (or renal venous) plasma are: for Na and Ca, 1.0; K, 1.5; Cl, 1.2; PO4, 2.0; urea, 1.8; plasma protein, 0.3; albumin, 0.4; glucose, 0.4, and osmolarity, 1.2. The fluid bears little or no relation to urine, especially since the urine varied considerably between individual dogs whereas the "diluting fluid" was relatively constant in composition. It was also found that the hematocrit of the fluid draining after arterial occlusion progressively decreased as it flowed out, until the last portion contained only 5 per cent red cells.

It is concluded that since renal lymph has approximately the same composition in protein, urea, glucose, and inulin as does "diluting fluid," the latter is, in all probability, renal interstitial fluid. Under the conditions of the experiment, it drains out of the kidney slowly relative to blood drainage. It is large in volume, particularly when compared with the capillaries that nourish it. Its high protein content explains the observation that the kidney is apparently naturally distended with a fluid disproportionately rich in plasma protein.