bluuebunny/crossref_metadata_2025 huggingface dataset:
ANTIGENICITY OF RAT COLLAGEN
Authors: Rothbard Sidney , Watson Robert F.
Published: June 2004

Reverse anaphylactic shock was induced in rats by intravenous injection of serum containing complement-fixing antibodies, obtamed by immunization of rabbits with purified preparations of rat tail collagen. Normal rabbit serum or serum containing antibodies to collagen from tunica of carp swim bladder was without effect. The clinical and pathological findings resembled those described by previous workers studying direct and reverse anaphylactic reactions induced in the rat with other antigens. Thrombocytopenia, leukopenia with rebound leukocytosis, delayed blood coagulability, lowering of serum complement and the development of a refractory state to the antibody after the initial shock—all compatible with anaphylaxis—were demonstrated. The reacting substance was found to be in the gamma globulin fraction of the serum, and the antibody titer appeared to be correlated with the degree of shock and vascular injury.

Collagen injury in rats dying from acute shock or in those injected with repeated sublethal doses was not demonstrated by the methods employed; techniques by which lesions of collagen might be induced are discussed.

Absorption experiments indicated that anti-rat collagen rabbit serum is specifically directed to a substance, apparently collagen, in the rat; it is likely that the combination of the antibody and collagen induces anaphylactic shock. These studies, made in vivo, provide further evidence of antigenic and immunological differences between acid-soluble rat and fish collagens.
THE BEHAVIOR OF VIRULENT AND AVIRULENT STAPHYLOCOCCI IN THE TISSUES OF NORMAL MICE
Authors: Smith J. Maclean , Dubos René J.
Published: June 2004

The fate of hemolytic staphylococci injected intravenousiy into albino mice was followed by determining quantitatively the numbers of living organisms present in the various tissues at different intervals of time after infection.

Irrespective of the strain of staphylococcus used, most of the organisms disappeared rapidly from the blood, liver, spleen, and kidneys. This was true even when the infective dose consisted of large numbers of virulent, coagulase-positive staphylococci, capable of producing a fatal disease in a high percentage of the infected mice. The initial rate of removal or destruction of staphylococci was particularly high in the lungs and kidneys. In all cases on the other hand, a few living staphylococci persisted in the various organs for several weeks after infection, even when the organisms were non-virulent and coagulase-negative.

Although virulent as well as avirulent staphylococci were eliminated extremely rapidly and efficiently from the kidneys during the initial stage of infection, the microorganisms soon began to multiply in this organ, causing abscesses first detected in the cortex. Death of the animals infected with virulent cultures appeared to be due to the destruction of renal tissue by these abscesses. The abscesses caused by the avirulent strains eventually became sterile, and healed.

No convincing difference could be recognized amongst seven strains in their resistance to the bactericidal power of the mouse tissues during the initial phase of the infection. In contrast, marked quantitative differences came to light in their subsequent behavior in the kidneys. The multiplication of the coagulase-negative staphylococci in this organ soon came to an end in all animals and never proceeded far enough to result in fatal disease. The staphylococci of a weakly coagulase-positive strain multiplied somewhat more extensively in the kidneys than did the coagulase-negative, but never sufficiently to cause the death of any animal within the period of observation of 1 month. The three coagulase-positive strains tested yielded the largest bacterial population in the kidneys and caused the death of many of the infected animals. These three virulent strains differed quantitatively amongst themselves with regard to both the rapidity and extent of their multiplication in the kidneys and the lethal power of a given infective dose.

Taken together, the findings indicate that the hemolytic strains of staphylococci can be arranged in a continuous spectrum according to their ability to cause disease in albino mice. Although virulence for these animals appeared to be correlated with the production of coagulase, it did not seem to depend upon the ability of this substance to interfere with the bactericidal mechanisms of the mouse organs during the early phase of the infection. Virulence manifested itself chiefly by the production in the kidneys of progressive abscesses originating from the few staphylococci which were not destroyed during the initial bactericidal reaction.
THE INCORPORATION OF ACETATE-1-C14 INTO CHOLESTEROL AND FATTY ACIDS BY SURVIVING TISSUES OF NORMAL AND SCORBUTIC GUINEA PIGS
Authors: Bolker H. I. , Fishman S. , Heard R. D. H. , O'Donnell V. J. , Webb J. L. , Willis G. C.
Published: June 2004

The synthesis of cholesterol and fatty acids from acetate-l-C14 by the isolated liver, adrenal, and aorta of scorbutic and pair-fed control guinea pigs has been studied. It was found that ascorbic acid deficiency does not affect the rate of incorporation of C14-acetate into cholesterol and fatty acids by the tissues investigated, under our experimental conditions. The relatively high metabolic activity of the artery with regard to cholesterogenesis and lipogenesis was noted. The elevation of serum cholesterol and hexosamine in scurvy has been confirmed.
NUTRITION OF THE HOST AND NATURAL RESISTANCE TO INFECTION
Authors: Schneider Howard A. , Zinder Norton D.
Published: June 2004

The double strain inoculation test as used for the assay of nutritional factors capable of enhancing survivorship in mouse salmonellosis has been modified and improved. The modification has been based on the use of genetically marked strains of S. typhimurium, and substitutes for survivorship a bacteriological datum, a certain minimum population size of the virulent salmonellae in the mouse spleen at a certain time. The analysis permitting this substitution and the economies achieved by the modification has been presented.

In the course of development of the new assay evidence was obtained that the nutrient entity or entities responsible for enhanced survivorship, as measured by the bacteriological correlate, are not stored in the mouse. A deficiency state was achieved 24 hours after supplying the basal synthetic diet. Similarly, positive effect of active nutrients was evident as soon as 24 hours after feeding.
STUDIES ON THE O ANTIGEN OF SALMONELLA TYPHOSA
Authors: Johnson Arthur G. , Gaines Sidney , Landy Maurice
Published: June 2004

Quantitative studies have demonstrated that a purified lipopolysaccharide (endotoxin) derived from the O-901 strain of Salmonella typhosa markedly enhanced the antibody response of rabbits when given separately or in conjunction with protein antigens. The augmentation of antibody levels varied from 2- to 40-fold with the number of injections, the dosage of antigen and endotoxin, and the route of administration. This antibody-enhancing property was found to be common to a broad group of endotoxins from Gram-negative bacilli and was not restricted to the lipopolysaccharide derived from S. typhosa.

Factors affecting this enhancement were investigated, and data are presented which indicate that host susceptibility to endotoxin is a prerequisite for elevation of antibody levels; the intact lipopolysaccharide, as isolated, might not be essential for this activity; and the rate of clearance of antigen from the circulation of rabbits was accelerated when endotoxin was given in conjunction with protein.

The data obtained are discussed in relation to postulated mechanisms on the antibody-enhancing action of endotoxin.
ON THE NATURE OF PARABIOSIS INTOXICATION: SHOCK AS THE PRECIPITATING CAUSE
Authors: Hall C. E. , Hall O.
Published: June 2004

Spinal transection of one of a parabiotic pair of rats is immediately followed by a state indistinguishable in visual and hematologic characteristics from spontaneous "parabiosis intoxication." The transected rat develops erythremia, hyperhemoglobinemia, and an increased hematocrit count; whereas the twin concurrently shows anemia characterized by a decrease in hemoglobin, erythrocyte count, and hematocrit reading, and often also lipemia.

These findings are ascribed to whole blood transfusion of one rat by the other followed by adjustments compensatory to the resulting distortion in the respective blood volumes. It is suggested that parabiosis intoxication is a manifestation of this same process and is not due, as has been contended, to an immune response.
THE PREPARATION AND FUNCTION OF THE HYPERTENSIN-CONVERTING ENZYME
Authors: Skeggs Leonard T. , Kahn Joseph R. , Shumway Norman P.
Published: June 2004

It has been shown by use of isolated, perfused rat kidneys that hypertensin II is a potent vasoconstrictor substance while hypertensin I is not. Hence it would appear that in intact animals the pressor activity of hypertensin I results from its rapid conversion to hypertensin II.

An enzyme which effects this conversion has been procured from horse plasma in a semipurified form by means of ammonium sulfate fractionation and isoelectric precipitation. A method is described for estimating the activity of the enzyme. An example of the use of the preparation in converting purified hypertensin I to hypertensin II has been described.
ANTIGENIC VARIANTS OF INFLUENZA A VIRUS (PR8 STRAIN)
Authors: Gerber Paul , Hamre Dorothy , Loosli Clayton G.
Published: June 2004

Four successive generations of antigenic variants of influenza PR8-S virus, each derived from the previous one by serial passage in the lungs of mice immunized with the homologous agent, were compared with the original parent PR8-S virus with respect to their serological and immunological character. It was demonstrated by means of H.I., complement-fixation and in ovo-neutralization tests that the variants exhibited a progressively decreasing reactivity with the parent PR8-S antiserum while retaining the ability to elicit antibody to PR8-S influenza virus and to their respective predecessors. Accompanying these changes was a progressive reduction in antigenicity without any significant changes in pathogenicity for mice. Experimental evidence was presented which indicates that the serological changes observed with the variants are not related to the P-Q phenomenon.

Antibody absorption tests showed that the variants share antigens with PR8-S virus but differ from it by the presence of specific antigenic components; these increase in quantity with each successive variant while the amount of related antigens shows a progressive decrease.

The importance of evaluating the significance of antigenic changes of influenza viruses with active immunity tests was emphasized by the fact that PR8-S vaccine protected mice against fatal infection with lethal doses of the variant strains although the latter had a progressively decreasing serological reactivity with PR8-S antiserum.

The inheritable character of the new antigenic properties of the variant strains was demonstrated by their persistence in the absence of thea selective environment following 18 to 24 serial intranasal passages with large inocula in normal mice and following limiting dilution passage in fertile eggs.
THE RELATION OF ANGIOTONIN AND L-NOREPINEPHRINE TO ESSENTIAL HYPERTENSION AS DETERMINED BY THE REACTION OF THE NAILFOLD CAPILLARY BED
Authors: Greisman Sheldon E.
Published: June 2004

Further evidence has been obtained that L-norepinephrine infusions markedly decreases cutaneous capillary blood flow in the nailfold. Sustained ischemia of the capillary bed occurred prior to the attainment of hypertensive diastolic arterial blood pressure levels. Corroborative evidence of this nailfold capillary ischemia was obtained from the capillary reactive hyperemia that followed the abrupt discontinuance of the L-norepinephrine infusions.

The infusion of angiotonin into persons with normal blood pressure did not induce sustained ischemia of the nailfold capillary vessels, even after definite hypertensive diastolic arterial blood pressure levels were attained. Corroboration of the adequacy of nailfold capillary blood flow was obtained by noting the absence of capillary reactive hyperemia following the abrupt cessation of the angiotonin infusions.

The nailfold capillary bed in persons with angiotonin-induced hypertension could not be distinguished from that of persons with essential hypertension by direct microscopic examination.

During the infusion of angiotonin into subjects with normal cardiovascular systems, the reactivity of the nailfold capillary bed to circulating L-norepinephrine was significantly increased, approaching the levels found in persons with essential hypertension.

From the standpoint of its effects upon the nailfold capillary bed, angiotonin, unlike L-norepinephrine, is one substance which possesses the properties required of the hypothetical humoral pressor substance of essential hypertension.
COLICINE K
Authors: Goebel Walther F. , Barry Guy T. , Shedlovsky Theodore
Published: June 2004

An apparatus for maintaining the pH of an actively growing bacterial culture at constant level has been described. Using this apparatus it has been shown that the production of maximal amounts of colicine K from a strain of E. coli known as K235 is dependent upon an enriched nutrient medium which is maintained at pH 7.0.
STUDIES OF THE BACTERICIDAL ACTION OF PHAGOCYTIN
Authors: Hirsch James G.
Published: June 2004

The bactericidal activity of phagocytin on Gram-negative enteric bacilli is influenced by the reaction of the medium; the more acid the environment, the more marked is the activity.

Phagocytin exerts approximately the same action whether citrate, acetate, or phosphate salts are used as buffer, and the addition of glucose, casein hydrolysate, or cation binding agents does not produce notable change. Although proteins in general have but little effect, the inclusion in the medium of a high concentration of bovine plasma albumin neutralizes the lethal action of phagocytin on enteric bacilli. Very high concentrations of magnesium or calcium ions antagonize but do not completely block the bactericidal effect.

The bactericidal activity of phagocytin is essentially independent of the numbers of bacteria exposed; a 100-fold increase m the numbers of enteric bacilli results in approximately a 2-fold increase in the concentration of phagocytin required to kill 90 per cent of them.

When susceptible microorganisms are exposed to phagocytin at 0°C., practically no killing takes place. At higher temperatures the bactericidal action is rapid, being well advanced in 5 minutes and complete within 30 minutes.
ACTION OF X-RAYS ON MAMMALIAN CELLS
Authors: Puck Theodore T. , Marcus Philip I.
Published: June 2004

The effects of x-irradiation have been quantitatively studied on single cells of a human cervical carcinoma (HeLa) under conditions such that 100 per cent of the unirradiated cells reproduce in isolation to form macroscopic colonies. This technique eliminates complexities due to interactions of members of large cell populations.

Survival of single cells (defined as the ability to form a macroscopic colony within 15 days) yields a typical 2 hit curve when plotted against x-ray dose. The initial shoulder extends to about 75 r, after which a linear logarithmic survival rate is obtained, in which the dose needed to reduce survivors to 37 per cent is 96 r. This radiation sensitivity is tens to hundreds of times greater than that of any microorganism for which the equivalent function bas been studied.

Evidence, though not proof, is presented that the lethal effect is due to a radiation-induced genetic defect which, however, cannot be a simple single gene inactivation. The locus of the action could be chromosomal.

Beginning at doses of 100 r, or possibly earlier, growth-delaying effects of radiation are visible.

Cells in which the ability to reproduce has been destroyed by doses below 800 r, can still multiply several times. At higher doses even a single cell division is precluded.

A large proportion of the cells killed by radiation at any dose gives rise to one or more giant cells. These metabolize actively, grow to huge proportions but never reproduce under the experimental conditions employed. Methods of preparing large populations of giant cells are described. These giants are particularly susceptible to virus action.

Some of the irradiated cells disappear from the plate, presumably by disintegration. This action of radiation is by far the least efficient, since even after 10,000 r, 5 to 10 per cent of the original cell inoculum is recoverable as giants.
THE LOCALIZATION OF SKIN-SENSITIZING ANTIBODY IN THE SERA OF RAGWEED-SENSITIVE INDIVIDUALS BY ELECTROPHORESIS
Authors: Sehon Alec H. , Harter John G. , Rose Bram ,   With the Technical Assistance of P. L. Rojowski
Published: June 2004

Starch electrophoresis was used to separate allergic sera into electrophoretically distinct albumin, α-, ß-, and γ-globulin fractions. The identity of the various fractions was established by free and paper electrophoresis. The γ-globulin fractions were also characterized by ultracentrifugation.

The serum skin-sensitizing antibody to ragweed pollen was shown to be associated with the γ-globulins in fourteen allergic sera by means of passive transfer technique. The mobility of the skin-sensitizing antibody corresponded to that of γ–1 and/or γ–2 globulins. All the other serum fractions were devoid of reaginic activity.

Reaginic activity per se was not directly related to protein concentration.

The discrepancies between these results, and those obtained by others and ourselves previously are discussed.
STUDIES ON COPPER METABOLISM. XIX
Authors: Bush J. A. , Jensen W. N. , Athens J. W. , Ashenbrucker Helen , Cartwright G. E. , Wintrobe M. M.
Published: June 2004

Ferrokinetic studies were performed in three copper-deficient swine and the results have been compared with similar studies in 18 normal pigs. The mean value for the plasma iron turnover rate in the deficient swine was 1.76 mg./kg. day; for the red cell iron incorporation rate, 1.24 mg./kg. day; for the red cell iron turnover rate, 1.18 mg./kg. day; for the red cell life span, 13 days. Corresponding figures in the normal swine were 1.11 mg./kg. day, 1.01 mg./kg. day, 0.59 mg./kg. day and 63 days, respectively.

The red cell life span was measured by the use of radioactive chromium in a total of 26 pigs. The mean erythrocyte half-life of normal cells transfused into normal pigs was 17 days. The mean half-life of erythrocytes from copperdeficient swine transfused into copper-deficient swine was 9 days. The mean half-life of red cells from control animals transfused into copper-deficient swine was 16 days while that of erythrocytes from copper-deficient swine transfused into normal pigs, was 13 days. The mean half-life of cells from iron-deficient pigs transfused into iron-deficient pigs was 19 days.

It is concluded that copper deficiency anemia results from both a shortened erythrocyte survival time and limited capacity of the bone marrow to produce red cells. It is suggested that copper is an essential component of erythrocytes in swine.
STUDIES ON BACTERIEMIA
Authors: Rogers David E.
Published: June 2004

During the course of studies on the characteristics of experimental bacteriemia, staphylococci were swiftly cleared from the blood stream of rabbits during the initial 10 to 15 minutes following intravenous injection of microorganisms. A subsequent abrupt decline in the rate of clearance ensued, resulting in a low grade bacteriemia which was demonstrable for many hours.

The experiments reported have indicated that this strain of staphylococcus is rapidly phagocyted within the vascular system of rabbits, and that viable staphylococci circulate within the cytoplasm of polymorphonuclear leukocytes.

The removal mechanisms contained within the liver and spleen appear to preferentially trap circulating extracellular staphylococci. When most of the circulating staphylococci are contained within leukocytes, splanchnic removal declines or virtually ceases.

These observations suggest that viable, intracellular microorganisms are responsible for the persistence of staphylococcal bacteriemia in rabbits following the phase of rapid removal from the blood stream.
AN ASCITES TUMOR APPEARING DURING THE PASSAGE OF EPERYTHROZOON COCCOIDES IN MICE
Authors: Nelson John B.
Published: June 2004

A strain of Eperythrozoon coccoides was maintained in a pure state for 16 months in unsplenectomized Princeton mice by the intraperitoneal injection of parasitized blood, at intervals of 1 to 3 weeks. In the 39th passage three out of five mice developed marked ascites with innumerable neoplastic cells in the peritoneal fluid. By passage of this fluid the tumor cells and the eperythrozoon were transferred together, with the rapid development of ascites and early death of the animals. On continued passage of ascitic fluid and blood from the mice of the 39th successive group both the tumor and the eperythrozoon were ultimately obtained in a pure state. Development of the passaged tumor was uninfluenced by the eperythrozoon but growth of the latter appeared enhanced in the presence of the neoplastic cells. Throughout 50 passages in mice the ascites tumor has not altered in character.

The intraperitoneal injection of ascitic fluid was irregularly followed by the appearance of tumor cells in the blood, the rate of the carriage being 26 per cent in sixty-five animals. The subcutaneous and intramuscular injection of the fluid resulted in solid, highly invasive, local growths which did not metastasize. The solid growths proved transferable in series yet after 20 passages still produced the ascites tumor on intraperitoneal injection of their cells.
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Liu Oscar C. , Paucker Kurt , Henle Werner
Published: June 2004

Certain aspects of the formation of non-infectious hemagglutinins (NIHA) in the chick embryo infected with influenza virus have been analyzed.

It was shown by the use of combined in ovo-deembryonation technics that little or no NIHA is released following infection with small doses of standard virus during the most active and constant growth periods of the virus extending to about the 36th hour of incubation in spite of the fact that multiple infection of cells must have taken place in the latter half of that period. A slight decrease in the ID50/HA ratios of the yields obtained after the 36th hour, coinciding with the falling off of virus production and release may possibly be explained in terms of inactivation of completed virus or leakage of as yet incompleted virus from damaged cells.

Exposure of the entodermal cells of the allantois of eggs deembryonated shortiy after injection of saturation or near saturation inocula of standard seed to large quantities of infectious virus added to the media at various times after infection and not extending over more than 2 hours resulted in a decrease of the ID50/HA ratios of the progenies only during the first 2 or possibly 4 hours after the primary inoculation. Later addition did not influence the yields. As discussed, such sudden and heavy exposures of cells are not expected to occur during the infectious process induced by small inocula of standard seed.

The possible role of destruction of cell receptors in NIHA production has been analyzed in several ways. The addition of receptor-destroying enzyme (RDE) to the media of deembryonated eggs after near saturation inocula of standard seeds, if anything, increased the ID50/HA ratios of the progenies, and that only when added during the first few hours following infection, presumably by reducing the changes for high multiplicity of infection of cells. In contrast, ultraviolet-inactivated virus, which retains its enzymatic activity, lowered, if anything, the ID50/HA ratios of the progenies, when present in the media of deembryonated eggs from the 2nd to 4th or possibly 6th hour after infection. Excessive amounts of irradiated virus may still cause some degree of interference under these conditions. Later addition of irradiated viruses were without effect with respect to NIHA production or interference. In attempts to alter the cell receptors prior to infection by potassium periodate (KIO4), it was noted that the addition of glycerol led to the appearance and partial retention for at least 24 hours of substances in the allantoic fluids which were capable of inactivating considerable proportions of standard virus. These data indicate that destruction of external cell receptors plays little if any role in NIHA production.

The implications of these findings are discussed.
THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS
Authors: Hirsch Robert L. , Kellner Aaron
Published: June 2004

Mice rendered hyperlipemic by means of intravenous or subcutaneous injections of triton WR 1339 were found to have an increase in the total amount of cholesterol in their bodies. This observation indicates that the injected surface-active agent affects the metabolism of cholesterol and brings about hyperlipemia by augmenting the synthesis of lipides, or by interfering with their degradation or excretion, or by some combination of these factors. The implications of the findings for the pathogenesis of the hyperlipemia induced by triton are discussed further in the accompanying paper (16).
THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS
Authors: Hirsch Robert L. , Kellner Aaron
Published: June 2004

Rabbits subjected to subtotal hepatectomy failed to develop increased serum cholesterol levels following parenteral injection of triton WR 1339, the finding indicating that the liver is essential for the establishment of the hypercholesterolemia induced by surface-active agents.

The cholesterol content of the livers of rabbits rendered hyperlipemic by means of triton remained unchanged both during the rapid rise of the serum cholesterol levels and during the return to normal values. By contrast, the cholesterol content of the livers of rabbits fed cholesterol rose progressively over a period of 5 weeks, concommittant with the increase in serum cholesterol levels. The findings provide support for the hypothesis that surface-active agents bring about hyperlipemia by altering the circulating lipoproteins in some manner so that they are retained in the circulating body fluids.
STRUCTURE AND DEVELOPMENT OF VIRUSES OBSERVED IN THE ELECTRON MICROSCOPE
Authors: Morgan Councilman , Rose Harry M. , Moore Dan H.
Published: June 2004

Rods and spheres believed to represent viral particles were observed at the free surface of entodermal cells of the chorioallantoic membrane 6 to 44 hours after infection. Although occasional short rods revealed poorly defined internal bodies, the majority, as well as all the longer rods (filaments), exhibited no visible internal structure. The spheres presumed to lie central to the plane of section contained an inner body 20 to 22 mµ in diameter. Both forms possessed a dense, sharply defined limiting membrane 30 A thick and a diffuse external coat of lesser density. Where superimposition within the section was minimal, the viral particles were separated by a relatively constant distance. Measured to include this spacing, on the assumption that it reflected the presence of a component of the outer coat, the diameters of a majority of the rods were 50 to 60 mµ, whereas the spheres averaged 60 to 70 mµ. The rods appeared to form by a process of extrusion from the cell wall and became detached either singly or in bundles of variable length. The spheres seemed to differentiate at the cell surface and to acquire the inner body, limiting membrane, and outer coat as they migrated through the membrane of the host cell. No characteristic changes were seen in the nuclei or adjacent cytoplasm, and recognizable viral particles were never encountered in these areas of the cell. No support was obtained for the assumption that the spheres developed primarily by segmentation of the rods. It is suggested that the spherical form of the virus is the elemental infectious unit and that the filamentous form is largely or completely non-infective.
THE AMINO ACID SEQUENCE OF HYPERTENSIN II
Authors: Skeggs Leonard T. , Lentz Kenneth E. , Kahn Joseph R. , Shumway Norman P. , Woods Kenneth R.
Published: June 2004

The amino acid sequence of horse hypertensin II has been determined by the use of chymotrypsin, the fluorodinitrobenzene method, and stepwise phenylisothiocyanate degradation. The results indicate that the amino acids of hypertensin II are arranged in the following order: asp-arg-val-tyr-iso-hist-pro-phe.
OBSERVATIONS ON RENAL PROTEIN METABOLISM
Authors: Lathem Willoughby , Benjamin Alvin D.
Published: June 2004

No significant difference was demonstrated in the free and total alpha amino nitrogen content of arterial, renal venous, and inferior vena caval blood of normal anesthetized dogs during fasting and following the administration of 3 to 6 gm. of hemoglobin. These results do not provide evidence of renal protein reabsorption and metabolism in the dog under the conditions employed in this study.
THE LETHAL EFFECT OF ENDOTOXINS ON THE CHICK EMBRYO
Authors: Smith Richard T. , Thomas Lewis ,   With the Technical Assistance of Donna G. Gellerman
Published: June 2004

Inoculation of the CAM of the 10-day chick embryo with endotoxin preparations derived from the meningococcus and other Gram-negative microorganisms has been shown to result in multiple hemorrhages and death of the embryo within a few hours. Evidence has been presented to indicate that this lethal effect is specific for the general class of endotoxins derived from Gram-negative bacteria. Susceptibility to endotoxin was maximal in 10-day old embryos, and younger or older embryos showed little or no response. The optimal incubation temperature for the effect of endotoxin was 39.5°C., and embryos incubated at 28°C. were completely protected. The lethal effect was prevented by small amounts of cortisone, hydrocortisone, and 9-alpha fluorohydrocortisone, but not by cholesterol, desoxycorticosterone, or 1-dehydrocortisone.
THE CARBOHYDRATE OF γ-GLOBULIN AND MYELOMA PROTEINS
Authors: Müller-Eberhard H. J. , Kunkel Henry G.
Published: June 2004

Various preparations of γ-globulin homogeneous in the ultracentrifuge showed a similar content of hexose, hexosamine, fucose, and sialic acid. Subfractionation of Fr. II γ-globulin by zone electrophoresis revealed multiple components of different mean mobilities but containing similar amounts of carbohydrate.

Gamma globulin isolated directly from normal serum by zone electrophoresis showed a heavy component in addition to the usual 7 S material. The heavy component (s20, w = 19 S) concentrated by preparative ultracentrifugation was found to be considerably richer in carbohydrate than the rest of the γ-globulin and accounted for small differences in carbohydrate content between different preparations of γ-globulin.

Pathological sera with marked elevation in γ-globulin showed a carbohydrate-protein ratio for the γ-globulin similar to that found for the corresponding 7 S fraction in normal serum. This was only partially true of the myeloma proteins with a mobility in the γ-globulin region. Certain of these proteins showed slight but significant differences. The myeloma proteins of faster mobility (ß-myelomas) contained considerably more carbohydrate. The possible role of these carbohydrates in accounting for some of the mobility and immunological differences in the myeloma proteins is discussed. The pathological proteins found in two cases of macroglobulinemia showed a high carbohydrate content similar to but slightly lower than the normal 19 S component of γ-globulin.
SEQUENCE OF MORPHOLOGICAL CHANGES IN EPITHELIAL CELL CULTURES INFECTED WITH POLIOVIRUS
Authors: Reissig Magdalena , Howes David W. , Melnick Joseph L.
Published: June 2004

A sequential study is reported of the cytological changes induced in cultures of monkey kidney epithelial cells by poliovirus. The pattern of cytological changes was followed through a single cycle of virus multiplication. Morphological alterations were correlated with the appearance of new infective virus within the cells and in the culture fluid.

Alteration of the chromatin pattern of the nucleus, and Type B acidophilic intranuclear inclusions, were seen as early as 4 hours after virus inoculation. Later wrinkling and shrivelling of the nucleus occurred, and eosinophilic cytoplasmic masses appeared. The rounded, pycnotic cell, customarily used as an index of the cytopathic response, was found only during the last stages of the infective process. On the basis of these changes, infected cells could be classified into six different types. Differential cell counts were made on the stained cultures, and the stage of cytopathic degeneration was correlated with the appearance of virus in the cells and in the culture fluid. Newly formed virus could be detected within the infected cells at about the same time that the first nuclear alterations and intranuclear inclusions were seen.

The virus-induced morphological changes exhibited a specificity distinct from the classical pycnosis of autolytic degeneration.
FOCAL DESTRUCTION OF NERVOUS TISSUE BY FOCUSED ULTRASOUND: BIOPHYSICAL FACTORS INFLUENCING ITS APPLICATION
Authors: Ballantine H. T. , Hueter T. F. , Nauta W. J. H. , Sosa D. M.
Published: June 2004

Ultrasound at frequencies of 1.0 mcps and 2.5 mcps can be focused by a suitable lens system to produce a small region of high vibrational intensity. The concentrated energy within and around the focal region can be used to destroy structures of the central nervous system.

The extent of destruction depends upon: (a) the size of the focal region, which varies inversely with the frequency, (b) the ultrasonic intensity, (c) the duration of exposure, and (d) the physical and physiologic characteristics of the tissue under irradiation.

With proper choice of ultrasonic dosage, mice were rendered monoplegic by destruction of one-half of the spinal cord without demonstrable injury to the skin or subcutaneous tissues through which the converging ultrasonic beam had been transmitted. In similar fashion, focal lesions were produced in the basal ganglia of living cats by stereotaxic transdural application of a focused ultrasonic beam delivered through the superior aspect of the cerebral hemispheres.

Histologic studies of mouse spinal cords and cat brains offered evidence that the fiber tracts of the central nervous system are more vulnerable to ultrasonic irradiation than aggregates of cell nuclei or vascular structures.

The destructive action of the ultrasound is apparently a result of mechanical strain combined with a rise in temperature at the focus of the beam. The heating factor was found to assume greater importance under conditions of high intensity and continuous (rather than pulsed) irradiation.

Trypan blue staining and radioautography using P32 have been employed to identify the lesions 1 hour after irradiation. This has been a valuable adjunct in our attempts to determine the accuracy of placement of the lesions and their size. Perhaps more important, however, is the indication from these studies that ultrasonically produced lesions may offer a useful method for investigation of the nature of the blood-brain barrier.

"Target studies" were undertaken to determine the precision with which lesions of predetermined size could be placed at predetermined sites in the basal ganglia of the cat. Results to date have been promising, but it is our opinion that further technical improvement will be necessary before ultrasound can be used as an accurate method for placing discrete lesions within the human brain.
LOSS OF MYOCARDIAL CONTRACTILITY INDUCED IN ISOLATED MAMMALIAN HEARTS BY STREPTOLYSIN O
Authors: Kellner Aaron , Bernheimer Alan W. , Carlson Arthur S. , Freeman Elizabeth B.
Published: June 2004

When solutions containing minute quantities of streptolysin O, previously activated with cysteine, were added to a salt and glucose medium that was being perfused by way of the coronary arteries through the vigorously beating isolated hearts of guinea pigs, rabbits, and rats, the amplitude of myocardial contraction decreased abruptly, often to zero. The effect was usually accompanied by a diminution in the flow of perfusion fluid, probably owing to spasm of the coronary arteries. The diminution in coronary flow was transitory, however, lasting as a rule only 2 or 3 minutes, while the loss of myocardial contractile power was permanent and irreversible. No decrease in myocardial contractility was obtained when the streptolysin O was not previously activated with cysteine, or when the streptolysin O was inhibited by cholesterol or by specific antibody, the findings pointing to streptolysin O as the active cardiotoxic agent.
INCREASED RESISTANCE TO INFECTION AND ACCOMPANYING ALTERATION IN PROPERDIN LEVELS FOLLOWING ADMINISTRATION OF BACTERIAL LIPOPOLYSACCHARIDES
Authors: Landy Maurice , Pillemer Louis
Published: June 2004

It has been shown that injection of lipopolysaccharides, derived from a variety of Gram-negative bacterial species, evokes in mice a rapidly developing rise in resistance to infection with Gram-negative pathogens. This is accompanied by an elevation in properdin titer, at times to levels 2 to 3 times the normal. The rate, magnitude, and duration of these responses are dependent on many factors, the most important of which are the quantity and timing of the lipopolysaccharide administered.

The increased resistance to infection evoked in mice by lipopolysaccharides was effective against infections produced by endotoxin-bearing organisms-bacterial species highly susceptible in vitro to the bactericidal action of the properdin system.

Properdin titers of mice prior to infection provide an incomplete picture of the subsequent reaction of the host to the infective agent. Following infection with Gram-negative organisms, properdin levels accurately reflect the bacteriologic course and outcome of the infection. Thus, in control animals, properdin titers progressively declined and the animals died, while in mice appropriately treated with lipopolysaccharide, properdin levels were either maintained in the normal range or increased, depending on the dose and time of administration of lipopolysaccharide; this was always accompanied by successful management of the infection.

The complex nature of the alterations produced in the host by lipopolysaccharides is stressed. It is pointed out that the increase in the ability of the host to cope with Gram-negative infections may be the result of stimulation of other defense mechanisms, in addition to the properdin system.
GROWTH CHARACTERISTICS OF INFLUENZA VIRUS. PROPERTIES OF THE INITIAL CELL-VIRUS COMPLEX
Authors: Ishida Nakao , Ackermann W. Wilbur
Published: June 2004

The rate has been determined at which the initial stable complex is formed between cells of the chorioallantoic membrane and the PR8 strain of type A influenza virus.

Characterization of the complex revealed the following properties: (a) stability to dilution and to simple washing with buffered saline, (b) insensitivity to the action of receptor-destroying enzyme (obtained from cholera vibrio), (c) sensitivity to the inhibitory effect of anti-viral immune serum, (d) formation of the complex at low temperatures, 3°C., (e) accompanied by a loss of detectable viral infectivity from the reaction mixture, (f) stability at 3°C. but transformation at 37°C. to a state which is resistant to the inhibitory action of a specific anti-viral serum. The rate of this latter transformation has been determined. The infectious process in more than 50 per cent of the cells can be influenced by immune serum 2 hours after the completion of the initial reaction with virus.
ON THE RELATION OF WHITE BLOOD CELLS AND PLATELETS TO VENOM HEMOLYSIS
Authors: Turner Joseph C. ,   With the Technical Assistance of E. Ann Pearson
Published: June 2004

Removal of the white cells and platelets from suspensions of red cells usually produces substantial reduction in the hemolytic activity of venoms.

Guinea pig red cells constitute a notable exception and may be lysed by a direct action of venom.

White blood cells and platelets appear to contribute to hemolysis by serving as sources of phosphatides for the formation of lysophosphatides.

No correlation could be found between phospholipase activity and direct hemolytic activity of venoms.

A recently described method (8) of paper chromatographic separation of phospholipides has been used successfully in part of the work.
SELECTIVE INHIBITION BY PREPARATIONS OF STREPTOCOCCAL FILTRATES OF THE OXIDATIVE METABOLISM OF MITOCHONDRIA PROCURED FROM RABBIT MYOCARDIUM
Authors: Carlson Arthur S. , Kellner Aaron , Bernheimer Alan W.
Published: June 2004

When solutions of streptolysin O were added to Warburg flasks containing, among other constituents, suspensions of mitochondria from the myocardium of rabbits and citrate, fumarate, or alpha-ketoglutarate as the substrate, there followed regularly a sharp reduction, and eventually complete cessation, of oxygen consumption. This phenomenon was not observed when succinate was the substrate in the flasks, the finding pointing to a selective interference with DPN as the underlying change.

The agent in the solutions of streptolysin O responsible for this effect was shown to be a streptococcal product, and to be non-dialyzable and heat-labile. It differed from streptolysin O in that it did not appear to require prior activation with cysteine, and its effectiveness was not diminished by treatment with cholesterol or antistreptolysin globulins.
VARIATION IN THE GROUP-SPECIFIC CARBOHYDRATE OF GROUP A STREPTOCOCCI
Authors: McCarty Maclyn
Published: June 2004

Soil organisms have been isolated which elaborate induced enzymes capable of attacking group A and variant (V) streptococcal carbohydrates. The V enzyme hydrolyzes V carbohydrate extensively to dialyzable split products with resultant total loss of precipitating activity with homologous antisera. The split products inhibit the reaction between intact V carbohydrate and its antiserum: evidence is presented which indicates that rhamnose oligosaccharides are responsible for the inhibitory effect. The serological specificity of the V carbohydrate thus appears to be primarily dependent on a rhamnose-rhamnose linkage.

The effect of the A enzyme on A carbohydrate is characterized by the removal of 50 to 70 per cent of the total glucosamine in the form of free N-acetyl-glucosamine. As a result of this treatment, the residual carbohydrate loses its reactivity with specific group A antisera and at the same time develops markedly increased cross-reactivity with V antisera. This cross-reactivity is in turn eliminated by treatment with V enzyme. The evidence suggests that the specificity of group A carbohydrate is determined to a large extent by side chains of N-acetyl-glucosamine which also serve to mask underlying rhamnose-rhamnose linkages with V specificity.
STUDIES ON THE TRANSFER OF LYMPH NODE CELLS
Authors: Harris T. N. , Harris Susanna , Farber Miriam B.
Published: June 2004

Leucocytes were obtained from the blood of rabbits, incubated in vitro with soluble antigenic material derived from Shigella paradysenteriae, washed, and transferred to irradiated recipient animals. On the 4th day after cell transfer, agglutinins to Shigella appeared in the sera of the majority of such recipients. The distribution of maximum agglutinin titers was substantially lower in these animals than in recipients of lymph node cells similarly incubated, as reported in earlier studies. Recipients of iodoacetate-treated cells showed no agglutinins. Similar results were obtained with cells of peritoneal exudates obtained 9 days after the intraperitoneal injection of lanolin and light mineral oil.

When cells of peritoneal exudates obtained 1 or 2 days after the injection of this irritant were incubated with the antigenic material and transferred to irradiated recipients, agglutinins did not appear in the sera of the latter. Similar results were obtained with cells from peritoneal exudates obtained a few days after the intraperitoneal injection of heavy mineral oil. The preponderant cell types in the suspensions from these two sources were the polymorphonuclear neutrophils and monocytes, respectively.
THE FATE OF MYCOBACTERIUM TUBERCULOSIS IN MOUSE TISSUES AS DETERMINED BY THE MICROBIAL ENUMERATION TECHNIQUE
Authors: McCune Robert M. , Tompsett Ralph , McDermott Walsh
Published: June 2004

Populations of tubercle bacilli of human origin exposed in vivo to pyrazinamide and a companion drug, vanished from the tissues of the mouse in so far as could be determined by microscopy, culture, or guinea pig subinoculation. The vanishing did not represent a complete elimination of the tubercle bacilli from all the animals. 90 days after the completion of treatment, tubercle bacilli could be cultured from approximately one-third of the animals examined at that time. This complete disappearance of the tubercle bacilli thus meets the definition of a truly latent infection in that the infection is present but is hidden beyond the limits of diagnostic reach. All but one of the strains of tubercle bacilli which survived in the animals and were detectable in the posttreatment period, were susceptible to pyrazinamide when tested under appropriate conditions in vitro.

Only two factors could be identified which were essential for the uniform occurrence of the disappearance of tubercle bacilli: the administration of the pyrazinamide in a high daily dosage for at least eight of a total of 12 weeks of antimicrobial therapy; and the concurrent or prior exposure of the microbial populations to isoniazid or in some cases to other antituberculous drugs.

The observations suggest that the ability of pyrazinamide-containing chemotherapies to bring about the disappearance of a tubercle bacillus is closely related to the occurrence of some alteration in the bacillus, essential for maximal pyrazinamide action, in response to environmental influences, including other antituberculous drugs present in the environment.