bluuebunny/crossref_metadata_2025 huggingface dataset:
LEVELS OF HOMOTYPIC NEUTRALIZING ANTIBODY IN HUMAN POLIOMYELITIS THREE YEARS AFTER INFECTION
Authors: Winsser Johan , Sabin Albert B.
Published: June 2004

Quantitative neutralization tests in monkeys were carried out on sera obtained from 7 patients, 3 months, and 3 years after an attack of poliomyelitis. The serum specimens were tested against 100 to 1000 PD50 of the patient's own strain of virus, recovered during the acute phase of the illness; all the strains were Type 1. The 6 patients, aged 6 months to 13 years, who had a paralytic attack of the disease, all exhibited very high levels of neutralizing antibody at 3 years as well as at 3 months after onset. The 50 per cent serum dilution titers ranged from about 1:180 to at least 1:860. Since the maximum titers were not established, it is not known to what extent, if any, the level of antibody may have dropped over the 3 year period. One of the patients, with a diagnosis of non-paralytic poliomyelitis, had a negligible or questionable antibody response during convalescence and no demonstrable antibody at 3 years; there is justifiable doubt as to whether the Type 1 poliomyelitis virus recovered from this patient had actually caused infection.

Tests for Lansing neutralizing antibody indicated that the 5 patients who had no evidence of previous infection with Type 2 poliomyelitis virus had not become infected with it during the 3 year period. This suggested that these patients did not live in an environment in which infection with poliomyelitis virus is frequent. It is concluded, therefore, that in human beings, paralytic infections due to Type 1 poliomyelitis virus produce large amounts of homotypic neutralizing antibody, which persists at high levels for a period of at least 3 years.
MUTANTS OF A BACTERIOPHAGE OF BACILLUS MEGATHERIUM
Authors: Murphy James S. ,   With the Technical Assistance of Robert L. Gosney, Jr.
Published: June 2004

Repeated transfers in 5 per cent peptone or asparagine media of sensitive B. megatherium cultures containing C phage have made possible the isolation of lysogenic bacteria which produce different strains of phage. This is probably due to the failure of C virus to make the lysogenic adjustment while those of its variants which can succeed are selected.

Four distinct plaque types have been isolated by this method and some of their reactions in mixedly infected bacteria are described.

It has been shown that it is possible to isolate either C or T analogues of each of the strains, bringing the reported plaque types of B. megatherium phage to eight.

No success was obtained in an attempt to isolate a wild type and a phage carrying two mutations when crosses were made of two phages each differing by one mutational step.
THE EFFECT OF X-RADIATION ON THE MULTIPLICATION OF RICKETTSIA MOOSERI IN EMBRYONATE EGGS
Authors: Greiff Donald , Chiga Masahiro , Blumenthal Herman T. , Pinkerton Henry
Published: June 2004

The multiplication of Rickettsia mooseri in fertile eggs is speeded up and quantitatively increased by single dose x-radiation given either 24 hours before or 48 hours after inoculation. This effect is noted at all dosage levels studied, ranging from 100 to 1500 r. The rickettsiostatic effects of high incubation temperature (40°C.) and of streptomycin are neutralized by radiation, but the rickettsiostatic actions of PABA, penicillin, and aureomycin are not altered. Possible mechanisms of action and implications of the observed effects are discussed.
THE ANTIMYCOBACTERIAL ACTIVITY OF VARIOUS AMINES RELATED TO SPERMINE IN CHEMICAL STRUCTURE
Authors: Hirsch James G.
Published: June 2004

A final concentration of 3 x 10–5 M spermine or spermidine inhibited the growth of mammalian tubercle bacilli in a modified Dubos liquid medium. Various related amino compounds, including isolated portions of the spermine molecule and the products of its chemical degradation, did not manifest similar antimycobacterial activity.
THE ESSENTIAL PARTICIPATION OF AN ENZYME IN THE INHIBITION OF GROWTH OF TUBERCLE BACILLI BY SPERMINE
Authors: Hirsch James G.
Published: June 2004

Spermine inhibits the multiplication of tubercle bacilli in vitro only if another tissue substance is present in the culture medium. This activating substance occurs as a chemical contaminant of the albumin in commercial bovine plasma fraction V ordinarily added to culture media; it is also found in whole bovine and sheep serum and in aqueous extracts of the guinea pig kidney. No detectable spermine activator is contained in whole human, guinea pig, or rabbit serum.

The serum constituent which renders spermine inhibitory for the growth of acid-fast bacteria has the properties of a protein of the alpha globulin classification. This protein is an enzyme which acts on spermine. Presumably, some product of the enzymatic reaction exerts a toxic effect on mammalian tubercle bacilli.
STUDIES ON ENTRY AND EGRESS OF POLIOMYELITIC INFECTION
Authors: Faber Harold K. , Silverberg Rosalie J. , Dong Luther
Published: June 2004

We have demonstrated a progressive centrifugal migration of poliomyelitis virus from the CNS into various peripheral ganglia and into peripheral nerves, including their distal portions. This phenomenon appears to be a regular occurrence in experimental animals, and is similar to that found in two other neurotropic infections, rabies and Borna disease.

Viremia appears to be secondary to primary neural infection.

The presence of virus in the lumen of the alimentary tract appears to be secondary to primary neural infection and not to viremia, and to be associated with the centrifugal spread of virus in peripheral nerves.

The presence of virus in "extraneural" tissues is not per se referable to infection of their constituent cells but rather to infection of their supplying nerves or, in some instances, to their content of virus-bearing blood.

The finding of virus in the vagus nerve may throw light on some of the electrocardiographic changes noted in certain cases of human poliomyelitis.

The presence of virus in peripheral nerves may throw light on the etiology of the most frequent clinical manifestations of human poliomyelitis, localized pain and tenderness.
OSMOTIC HOMEOSTASIS MAINTAINED BY MAMMALIAN LIVER, KIDNEY, AND OTHER TISSUES
Authors: Opie Eugene L. , Rothbard Mary B.
Published: June 2004

Osmotic pressure maintained by liver or kidney tissue measured by its water equilibrium with solutions of sodium chloride remains unchanged from 5 minutes up to 1½ hours following removal of the tissue from the body. Then with autolytic increase of molecular concentration within the cytoplasm of cells it reaches a higher level. Osmotic pressure maintained by pancreas or submaxillary gland, as ascertained in the same way, remains unchanged during ½ hour and later increases.

Liver tissue of rat, mouse, guinea pig, rabbit, and cat maintains an osmotic pressure greater than twice that of the blood, and kidney tissue maintains an osmotic pressure somewhat less than twice that of blood.

Fasting throughout a period of 7 days has little influence upon osmotic pressure maintained by cells of liver or kidney.

Low protein diet has been found to depress osmotic pressure of liver cells after about 4 weeks, and with degenerative changes in the parenchyma, notably fatty infiltration, this pressure has remained at a diminished level during approximately 90 days.

Increase of pressure within the common bile duct and the changes following biliary obstruction are accompanied by depression of the osmotic pressure maintained by liver tissue and ligation of the ureter diminishes the osmotic pressure maintained by kidney tissue. In both instances osmotic pressure tends later to rise to its former level.

The osmotic pressure maintained by liver or by kidney tissue preserves an approximately uniform level under normal conditions and may be little changed by conspicuous injury to the organ. When this osmotic homeostasis is impaired by severe injury the pressure maintained by the tissue returns to its former level with recovery from the injury.
SYNTHESIS OF TYPE III PNEUMOCOCCAL POLYSACCHARIDE BY SUSPENSIONS OF RESTING CELLS
Authors: Bernheimer Alan W.
Published: June 2004

The capsular polysaccharide (SIII) of type III pneumococci was removed enzymatically, and the cells thus deprived of preformed SIII were washed and examined for capacity to synthesize SIII anew. The washed, decapsulated cocci lost their capacity to be agglutinated in type-specific antiserum but again became agglutinable and formed readily measurable amounts of SIII, after suspension in a solution containing only glucose and salts.

Maximal SIII synthesis required the presence of glucose, magnesium, potassium and phosphate ions, and oxygen. Other fermentable sugars could be substituted for glucose but then the yield of SIII was reduced. Synthesis of SIII occurred anaerobically but was increased four- to fivefold by oxygenation of the suspension. The effects of pH and of enzyme poisons on the capacity of the cocci to form SIII are described.
AN ANTIVIRAL SUBSTANCE FROM PENICILLIUM FUNICULOSUM
Authors: Shope Richard E.
Published: June 2004

Helenine exerts a therapeutic effect against Semliki Forest virus infections of mice. Cures, that is to say the survival of treated animals, were more frequently observed in Semliki Forest virus infections than they were in SK virus infections. It is believed that this difference in end-result probably represented only a quantitative difference in the therapeutic effect of helenine against these two viruses and not a qualitative difference in its mechanism of therapeutic action.

The findings reported in this paper with regard to the treatment of Semliki Forest virus infections with helenine parallel very closely those described in an accompanying paper which deals with the action of helenine on SK. virus infections.
THE OCCURRENCE OF CHANGES RESEMBLING THE INFLAMMATORY IN SKIN INJURED AND INCUBATED AFTER EXCISION
Authors: Cooke Jean V. , Goldring David , Kahn Lawrence I.
Published: June 2004

Observations are reported on the changes which occurred in excised rabbit and human skin after mild trauma and incubation at body temperature. These changes resembled those of chronic inflammation, in that perivascular and diffuse infiltration by histiocytes occurred in the corium and subcutaneous tissue, but they developed within a few hours. The experiments have shown that even after removal from the body certain tissue elements may retain the ability to react with proliferative changes in response to tissue injury if kept under artificially simulated physiological conditions. The possible significance of these changes in relation to the inflammatory process is discussed.
STUDIES ON THE PROPAGATION IN VITRO OF POLIOMYELITIS VIRUSES
Authors: Scherer William F. , Syverton Jerome T. , Gey George O.
Published: June 2004

The cells of a human epithelial cancer cultivated en masse have been shown to support the multiplication of all three types of poliomyelitis virus. These cells (strain HeLa of Gey) have been maintained in vitro since their derivation from an epidermoid carcinoma of the cervix in February, 1951. As the virus multiplied it caused in from 12 to 96 hours degeneration and destruction of the cancer cells. The specific destructive effect of the virus was prevented by adding homotypic antibody to the cultures but not by adding heterotypic antibodies.

Methods for the preparation of large numbers of replicate cultures with suspensions of strain HeLa cells were described. The cells in suspension were readily quantitated by direct counts in a hemocytometer. A synthetic solution that maintains cellular viability was employed for viral propagation.

The experimental results demonstrate the usefulness of strain HeLa cells for (a) the quantitation of poliomyelitis virus, (b) the measurement of poliomyelitis antibodies, and (c) the production of virus.
ASPERMATOGENESIS IN THE GUINEA PIG INDUCED BY TESTICULAR TISSUE AND ADJUVANTS
Authors: Freund Jules , Lipton Murray M. , Thompson George E.
Published: June 2004

The injection into the dorsal skin of a suspension of guinea pig testis or spermia incorporated in a water-in-oil emulsion containing killed mycobacteria induces aspermatogenesis in guinea pigs. The injury begins with the inhibition of the maturation of spermia and proceeds through the degeneration and exfoliation of spermatids, spermatocytes, and finally spermatogonia. These germinal cells pass from the seminiferous tubules into the epididymis. The process is not associated with inflammation. No significant changes occur in the intertubular spaces and the Leydig cells do not seem to be affected. The seminal vesicles and the prostate remain normal. The aspermatogenesis may begin in 10 days and it lasts for more than 5 months. The process may lead to atrophy of the seminiferous tubules and fibrosis. Guinea pigs which receive a suspension of their own testis or spermia and adjuvants develop a similar injury.

The "mitochondrial" fraction of the testis of guinea pig is effective while repeated injections of alcoholic extract of testis emulsified with paraffin oil containing mycobacteria do not cause aspermatogenesis. The presence of acid-fast bacilli in the water-in-oil emulsion containing testis or spermia seems to be essential for the production of testicular lesions; the injection of antigen and mycobacteria into different sites is ineffective.

When guinea pig testis is replaced by guinea pig liver or kidney or rabbit testis no testicular damage occurs.

The injection of rabbit spinal cord combined with adjuvants results in allergic encephalomyelitis in a large proportion of guinea pigs, accompanied by a great loss of weight. The testes of a few of these animals show a varying degree of aspermatogenesis. When guinea pig brain is combined with adjuvants and administered subcutaneously the incidence of testicular injury is high, although the damage is, in general, mild. From the standpoint of mechanism, the inhibition of spermatogenesis which occurs in these animals may be unrelated to the injury which follows the injection of germinal cells.

Aspermatogenesis follows the injection of killed mycobacteria in paraffin oil into the testis as well as into certain sites related to the gonad: the abdominal cavity, the subcutaneous tissue over the abdomen, and the skin of the inguinal region.

Antibodies fixing complement in the presence of spermia are demonstrable in the sera of guinea pigs injected with testis or spermia and adjuvants. When the mycobacteria are omitted the titers are low and no testicular injury occurs. Although there seems to be a correlation between testicular damage and complement-fixing titer, this may not be a causal relationship.

Antibodies which neutralize guinea pig hyaluronidase and those which immobilize spermia have also been demonstrated in the sera of these guinea pigs.
VIRUS AND CELL INTERACTION WITH ION EXCHANGERS
Authors: Puck Theodore , Sagik Bernard
Published: June 2004

At pH 7 the bacteriophages T1 and T2 attach to anionic exchangers when suspended either in distilled water or in salt solutions. They attach to cationic exchangers only in the presence of salt. T2 requires approximately ten times higher a salt concentration than does T1 virus, a relationship which is duplicated in the attachment of these phages to their common host cell, E. coli B.

The host cell, E. coli B, attaches to anionic exchangers when suspended either in salt or distilled water, but does not attach to cationic exchangers even in 0.2 M NaCl.

These observations support the hypothesis previously advanced that the role of cations in effecting union of viruses to their host cells is to neutralize the repulsive electrostatic potential due to the excess of negative charges on the surfaces of both bodies.

Influenza virus similarly requires salt for attachment to cationic exchangers, and unites to anionic exchangers even in the absence of salt. It is therefore proposed that the same general principles which govern the behavior of the bacteriophage system, may also apply to host cell attachment of at least some mammalian viruses.

T1 bacteriophage and influenza virus are readily eluted from cationic exchangers. T2 bacteriophage cannot be recovered in active form.

Experiments with P32- and S35-labelled T2 bacteriophage reveal that shortly after its attachment to the resin, the virus is split into its phosphorus-containing DNA, and the sulfur-containing protein fraction.

It is proposed that the splitting of phage into its protein and DNA components that occurs ordinarily at the surface of a cell is a result of the establishment of the primary electrostatic bonds, just as in the attachment to cationic exchange resins.

The affinity of cationic resins for influenza virus is great enough to remove the virus almost completely from red cells to which it has become attached.
MORPHOLOGIC VARIATION IN PNEUMOCOCCUS
Authors: Austrian Robert
Published: June 2004

The interaction of each of the four morphologic variants of pneumococcus with the transforming principles of the heterologous morphologic variants of the same species has been studied and has resulted in the isolation of eighteen of the twenty variants predicted to arise through such interactions. The analogy of the findings to the recombination of independently heritable characters in sexually reproducing forms has been noted.
SULFATE-SULFUR METABOLISM IN THE RAT FETUS AS INDICATED BY SULFUR-35
Authors: Dziewiatkowski Dominic D.
Published: June 2004

Twenty-four hours after the intraperitoneal injection of sodium sulfate-S35 into pregnant rats, sulfur-35 was found in the embryos. The amount of the sulfur-35 retained by the embryos was directly related to their degree of development in utero.

A large fraction of the sulfur-35 found in the embryos was insoluble in 5 per cent trichloroacetic acid. At the 9th to 10th day of development, about 40 per cent of the sulfur-35 was present in this fraction. In 20-day-old embryos this fraction accounted for nearly 90 per cent of the total.

Radioautographs of sections of embryos fixed in a solution of formaldehyde revealed that the sulfur-35 was most highly concentrated in the cartilaginous portion of the skeleton. All other tissues gave much weaker autographic reactions, comparable with the over-all reaction obtained when sections from embryos fixed in a solution of formaldehyde saturated with barium hydroxide were used.

By analysis for the sulfur-35 content of individual tissues the concentration of the sulfur-35 in humeri from 20-day-old embryos was found to be about 30 times that in the maternal sternum. The concentration of the isotope in the skeletal muscle, brain, heart, and skin of the same embryos was also higher than in the corresponding maternal tissues. On the other hand, the concentration of the sulfur-35 in the maternal gastrointestinal tract plus contents was higher than in the gastrointestinal tract and contents of the embryos.
THE INFLUENCE OF CALCIUM IONS ON THE INACTIVATION OF HUMAN COMPLEMENT AND ITS COMPONENTS BY PLASMIN
Authors: Lepow Irwin H. , Pillemer Louis , Ratnoff Oscar D. ,   With the Technical Assistance of Leona Wurz
Published: June 2004

Ca++ potentiates the inactivation of human complement by streptokinase-activated plasmin and chloroform-activated bovine plasmin. The optimum concentration of Ca++ varies between 10–2 M and 10–3 M, decreasing with increasing concentrations of streptokinase.

The susceptibility of the components of complement to inactivation by plasmin is different in the presence and absence of Ca++. C'2 and C'4 are most readily inactivated by plasmin in the presence of Ca++, while C'1 disappears first in the absence of Ca++. A large part of this C'1 disappearance is due to spontaneous inactivation.

Similarities are pointed out between the influence of Ca++ on the inactivation of the components of complement by antigen-antibody systems and by plasmin.
THE EGESTION OF PHAGOCYTIZED PARTICLES BY LEUKOCYTES
Authors: Wilson Armine T.
Published: June 2004

Streptococci that were phagocytized by human or mouse leukocytes were usually enclosed in a digestive vacuole. At times the vacuole emptied itself, discharging the cocci to the outside. Whether the egested streptococci then multiplied in the extracellular environment appeared to depend upon how long they had been in the vacuole.

The phenomenon of egestion also involves particles other than bacteria, as shown by observation of an erythrocyte that was phagocytized by a human leukocyte and was hemolyzed intracellularly, forming a cell ghost that was then egested.
THE RELATIONSHIP BETWEEN THE ACUTE PHASE RESPONSE AND ANTIBODY PRODUCTION IN THE RABBIT
Authors: Wood Harrison F.
Published: June 2004

It has been found that some rabbits respond to the administration of either human C-reactive protein or human gamma globulin with the production of an acute phase substance, Cx-reactive protein. A correlation was found to exist between the amount of Cx-protein produced and the subsequent production of significant titers of precipitating antibody to the two antigens employed.
INHIBITION OF THEILER'S ENCEPHALOMYELITIS VIRUS (GDVII STRAIN) OF MICE BY AN INTESTINAL MUCOPOLYSACCHARIDE
Authors: Mandel Benjamin , Racker Efraim
Published: June 2004

A mucopolysaccharide inhibitor of Theiler's GDVII virus has been purified from intestinal tissue of adult mice. The purified material has been shown to consist chiefly of carbohydrate. Following acid hydrolysis of the inhibitor, several amino adds were found to be present. The carbohydrate components shown to be present thus far are galactose, hexosamine, N-acetylhexosamine, methylpentose, hexurornic acid; an indication has been obtained that sedoheptulose is also present. The available evidence strongly suggests that this mucopolysaccharide, and not some other substance present in minute amounts, is the inhibitor of the GDVII virus.
REGRESSION OF TRANSPLANTED LYMPHOMAS INDUCED IN VIVO BY MEANS OF NORMAL GUINEA PIG SERUM
Authors: Kidd John G.
Published: June 2004

In an extension of the experimental studies recorded in an associated paper; attempts were made to isolate and characterize the constituent of guinea pig serum responsible for inducing regression of transplanted lymphomas in vivo. The active material was precipitated readily from the whole serum, along with some of the globulins, by means of ammonium sulfate in concentrations of 2.0 molar or greater; it withstood heating at 56°C. for 20 or 30 minutes, but was inactivated upon heating at 66°C. for similar periods; it was completely inactivated by chymotrypsin in concentrations of 1 or 2 mg./cc. during 6 hours at 37°C. Furthermore, the inhibitory effects of small amounts of the guinea pig serum in vivo were enhanced upon admixture with immune sera prepared by injecting the lymphosarcoma cells into rabbits. The facts as a whole suggest that the active material is a protein, and that it may be one or another of the components of complement; yet they do not suffice to establish its identity.

Microscopic studies showed that the cells of subcutaneous lymphomas rapidly died and were resorbed following injections of relatively large amounts of guinea pig serum intraperitoneally into mice carrying them, while similar changes followed more gradually after repeated injections of smaller amounts of guinea pig serum. No changes referable to the guinea pig serum were seen in the normal tissues or organs of mice receiving it.

Mouse lymphoma cells, suspended artificially as individuals in a physiological saline solution, regularly remained viable following incubation in vitro in mixture with guinea pig serum during 6 hours at 37°C. The finding provides strong evidence that the regression of lymphomas that follows injection of guinea pig serum in vivo is brought about through some reaction in which the guinea pig serum and the host both participate.

Some of the implications of the findings are discussed.
RECOMBINATIONS OF MUTANT PHAGES OF BACILLUS MEGATHERIUM 899A
Authors: Murphy James S. ,   With the Technical Assistance of Robert L. Gosney, Jr.
Published: June 2004

A group of mutant phages stemming from the virus of B. megatherium 899a (lysogenic), growing on a sensitive B. megatherium strain (KM), have been studied with respect to their recombination reactions. All these mutants and many of their recombinations can be recognized by a characteristic plaque morphology. A similar group of phages have been isolated directly from a culture of B. megatherium 899a in this laboratory.

Previous work has shown that when two different plaque mutant phages both infect essentially all the bacteria in a culture, a characteristic per cent of recombinants is produced. This percentage depends on the two recombinants used, each pair having its own value. Hershey and coworkers (2–5) have demonstrated with coli-phage T2, that the percentages of recombination found can be handled mathematically and that they demonstrate the existence of a relationship between the mutations entirely comparable to crossover percentages as used in gene locus maps in genetics. This has been found to hold true for the phages studied in the present work.

Only one "linkage group" has been detected and all the mutants studied showed low percentages of recombination (0.8 to 7.6).

B. megatherium 899a phage and some of its mutants have been examined with an electron microscope and no differences have been detected between the different mutant strains.
MYOCARDITIS AND PULMONARY ARTERITIS IN MICE ASSOCIATED WITH THE PRESENCE OF RICKETTSIA-LIKE BODIES IN POLYMORPHONUCLEAR LEUCOCYTES
Authors: Pappenheimer Alwin M. , Daniels Joan B.
Published: June 2004

A previously undescribed disease of mice, characterized by acute interstitial myocarditis, and by periarterial pulmonary lesions, is reported.

The transmissibility of this disease has been shown, but a large proportion of inoculated mice appears to be resistant.

Microorganisms, rickettsial in form but not positively identified as such, are consistently present in the lesions. They are found predominantly in the cytoplasm of polymorphonuclear leucocytes.

Filtrates of fecal material from normal mice of the Harvard breeding stock may produce lesions in myocardium and pulmonary arteries indistinguishable from those occurring in this disease. Rickettsia-like bodies are also found in these lesions.
THE SERUM DIPHENYLAMINE (DPA) REACTION IN EXPERIMENTAL ARTHRITIS
Authors: Coburn Alvin F. , Haninger Joan
Published: June 2004

The passive Arthus arthritis in the guinea pig provides an experimental model for studying reactions comparable to those which occur in rheumatic fever. The joint swelling in the Arthus reaction is followed by tissue injury which is reflected 24 hours later by a rise in the DPA level. The height of this rise is determined by the degree of injury, which in turn is determined both by the strength of the antibody injected and also by the number of antigen depots created.

The swelling reaction and the DPA rise can be suppressed by sodium salicylate, cortisone, or splenin A. The amount of drug required to block a DPA rise (DPA unit) is approximately tenfold the amount required to inhibit the joint swelling by 50 per cent (Arthus unit). Even when the Arthus arthritis has completed the swelling phase, treatment with appropriate amounts of these drugs suppress a rise in DPA.

It was pointed out that the DPA rise appears to be associated with the tissue injury that follows joint swelling; that the degree of a DPA rise is determined by the severity of the inflammatory process; and that the amount of an anti-inflammatory agent required to suppress a DPA rise depends on the intensity of the reaction.
THE EFFECT OF LIGATION OF THE COMMON BILE DUCT ON CHOLESTEROL SYNTHESIS IN THE RAT
Authors: Fredrickson Donald S. , Loud Alden V. , Hinkelman Beverly T. , Schneider Henny S. , Frantz Ivan D.
Published: June 2004

The effect on cholesterol synthesis of ligation of the common bile duct was studied in the rat. The bile ducts of rats were ligated; 24 to 48 hours later, estimates of the rate of cholesterol synthesis were made, either by injection of labelled water or acetate into the intact animal, or by incubation of slices or homogenates of the liver in the presence of 1-C14-acetate. These various criteria all indicated that cholesterol synthesis was increased following ligation of the bile duct. The average ratios of the rate of synthesis in the experimental animals to that in the controls were as follows:

1. Synthesis from C14-carboxyl-labelled acetate: (a) in the intact rat fed ad libitum, 19; (b) in liver slices from the fasted rat, 23; (c) in liver slices from the rat fed ad libitum, 4; (d) in cell-free homogenates from the fasted rat, >27; (e) in cell-free homogenates from the rat fed ad libitum, 17.

2. Synthesis from tritium-labelled water in the intact rat fed ad libitum, 4.
GROWTH CHARACTERISTICS OF INFLUENZA VIRUS: THE INFLUENCE OF A SULFONIC ACID
Authors: Ackermann W. Wilbur , Maassab Hunein F.
Published: June 2004

The growth characteristics of influenza virus in an isolated tissue maintained in vitro have been described. When compared with previously reported results using the embryonate egg, a considerably shorter latent period was observed. The release or liberation of the virus occurred throughout a period of many hours. There was no evidence of a general "burst" phenomenon, and the destruction of a cellular membrane did not seem to be essential to or concomitant with the release of virus.

An early phase in the development of virus was described which is sensitive to the action of α-amino-p-methoxyphenylmethanesulfonic acid and it is by virtue of this that virus multiplication is prevented. If this phase was allowed to go on to completion, replication of virus occurred even in the presence of the sulfonic acid, but the release of virus from the tissue was impaired.

It is suggested that the sulfonic acid may interfere with the adsorption or penetration of the virus and that the initiation of infection and the liberation of new virus may be processes which share some common character.
EXPERIMENTAL STAPHYLOCOCCUS INFECTION IN THE HAMSTER CHEEK POUCH: THE PROCESS OF LOCALIZATION
Authors: Young G.
Published: June 2004

Small amounts of staphylococcus suspensions were injected into the cheek pouches of hamsters. Within 5 hours, the organisms were recovered from all outlying areas of the pouches, and in the following hours the entire structures showed vasodilation, edema, petechiae, and accumulation of leukocytes in the venules. Leukocytosis also occurred at this time.

Between 24 and 48 hours, well defined abscesses developed at the sites of injection, and there was a sharp decrease in the bacteria in all other areas. From the 3rd day onward, organisms were only occasionally recovered from tissue outside the abscesses. At this period of localization, the generalized edema and petechiae also subsided, as did the leukocytosis.

Localization of infection was not due to a walling off process, since the bacteria were disseminated through the entire pouches in the 1st few hours, but these organisms diminished rapidly, while those at the original injection sites continued to grow and reproduce for several days.

Localization of infection appeared to be due to the inability of the bacteria carried away from the site of injection to reproduce. This in turn may have been due to dilution, to lack of sufficient toxin to produce a necrotic substrate, or to greater accessibility of these organisms to phagocytes.
THE EXPERIMENTAL PRODUCTION OF COMBINATION FORMS OF VIRUS
Authors: Gotlieb Tamar , Hirst George K.
Published: June 2004

The simultaneous inoculation of influenza A and B strains into eggs was found to result in the formation of virus which had antigenic properties of both parent strains. The hemagglutinin of the new virus could be inhibited by both A and B antisera and the agent was also neutralized by both sera. This X particle displayed the characteristics of what we have previously called X1. It did not reproduce itself on multiplying in the egg, but instead yielded parent types.

Limiting infectious dilutions of influenza virus were studied in eggs by inoculating two different strains at once to act as markers for singly or doubly initiated infections. A base line was thus established for the frequency of single and mixed infections at virus dosages which were fractions of one ID50. These frequencies were compared with those obtained with X viruses. X1 virus from A-B infections did not initiate an unusual number of mixed infections at the end point. By contrast, X1 and X2 (M-W type) gave much higher numbers of mixed infections than did the control virus.

In the discussion it is proposed (a) that doubly antigenic viruses are due to an effect known as phenotypic mixing and (b) that the ability of individual virus particles to give rise to two separate strains is due to heterozygosis or diploidy.
STUDIES OF INFLUENZA VIRUS INFECTION IN THE CHICK EMBRYO USING FLUORESCENT ANTIBODY
Authors: Watson Barbara K. , Coons Albert H.
Published: June 2004

As evidenced by specific staining with fluorescent antibody, the major sites of multiplication of the PR8 and Lee B strains of influenza virus in chick embryos injected by the amniotic route were in the cells lining the amnion and in the epidermal and pharyngeal epithelium. Varying amounts of virus were also present in the epithelium of the allantois and less frequently in the peritoneum. No virus was detectable in any of the other tissues of 25 embryos injected between the 7th and 11th days of incubation and examined 48 hours later. Three out of five of the embryos inoculated with the PR8 strain of influenza virus on the 12th day of incubation, on the other hand, showed in addition extensive involvement of the cells lining the respiratory tract.

Specific staining of the tissues was first detectable when the ID50 of the amniotic fluids attained a level of greater than 4.5, which corresponded to the time of the appearance of hemagglutinins. With the inocula used this was generally achieved sometime between the 18th and 24th hour of the infection with the PR8 strain of virus and between the 24th and 48th hour of the infection with the Lee B strain of virus.

Cytologically, the multiplication of the influenza viruses was characterized by a diffuse type of immunospecific staining which was first detectable in the nuclei and later in the cytoplasm of the cells. The infection progressed rapidly and despite the restricted distribution of the viruses resulted in the death of the embryo in from 3 to 6 days.

The results obtained in the present experiments are compared with the findings previously reported in similar studies of mumps virus (6).
MECHANISM OF CELL WALL PENETRATION BY VIRUSES
Authors: Puck Theodore T. , Lee Howard H.
Published: June 2004

Treatment of radioactively labelled host cells with T1 or T2 bacteriophages induces a leakage of cellular P and S into the medium.

Evidence is presented showing that this increased cell permeability is not the result of complete lysis of a small fraction of the cells, but rather is made up of contributions from all or most of the infected population.

This leakage of cellular constituents exhibits the following characteristics: (a) Infection of a cell with a single virus suffices to evoke the reaction; (b) Increasing the multiplicity up to 7 to 8 virus particles per cell does not affect the extent of leakage produced; (c) Some leakage does occur at 0°C., but much less than at 37°C.; (d) Infection by T1 virus results in a smaller amount of leakage than in the case of T2, but the pattern of response to varying virus multiplicity is the same; (e) The P resulting from such leakage contains no DNA and chemically resembles that which elutes in smaller amounts from uninfected cells; (f) At 37°C. the virus-induced leakage reaction appears within a matter of seconds, and usually decreases after 2 to 3 minutes; (g) The reaction is inhibited by 0.025 M Mg++.

Theoretical considerations are presented suggesting the place of this reaction in the sequence of events constituting the virus penetration reaction; its relationship to the phenomenon of lysis-from-without; and its resemblance to the leakage reaction produced by electrostatic binding of ionized compounds to cell surfaces. The existence of similar effects in avian-mammalian virus systems is noted.
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: Kretchmer N. , Dickerman H. W.
Published: June 2004

1. Shifts of enzymatic activity have been followed during the formation and evolution of the droplets that form in the cells of the proximal convolution of the nephron of the rat after the injection of a 50 per cent solution of egg white in isotonic saline.

2. Twelve hours after injection there is a 35 to 40 per cent decrease in succinoxidase and cytochrome oxidase activities in the fraction containing the larger particles; i.e. mitochondria and droplets in equal concentration. Although after 30 hours the quantitative proportion of droplets and mitochondria is the same as previously, the activities of the fraction have returned to the normal observed originally in the uninjected rat in a corresponding fraction consisting of mitochondria only.

3. The microsome fraction shows an average increase of 35 per cent in oxidative enzyme activities during the early period following injection, and decreases to the original figure in the later period of droplet formation.

4. It is concluded from the shifting pattern of localization of oxidative enzyme activity within the cell particulates that the absorption droplets arise by the incorporation of the mitochondrial elements, which originally contain the highest enzyme activity, with absorbed protein through the intermediate stage of smaller (microsomal) particles.
Tissue Monocytes/Macrophages in Inflammation
Authors: Brack Alexander , Labuz Dominika , Schiltz Anu , Rittner Heike L. , Machelska Halina , Schäfer Michael , Reszka Regina , Stein Christoph
Published: June 2004

Background

Opioid-containing leukocytes migrate to peripheral sites of inflammation. On exposure to stress, opioid peptides are released, bind to opioid receptors on peripheral sensory neurons, and induce endogenous antinociception. In later stages of Freund's complete adjuvant-induced local inflammation, monocytes/macrophages are a major opioid-containing leukocyte subpopulation, but these cells also produce proalgesic cytokines. In this study, the role of tissue monocytes/macrophages in hyperalgesia and in peripheral opioid-mediated antinociception was investigated.

Methods

After intraplantar injection of Freund's adjuvant, leukocyte subpopulations and opioid-containing leukocytes were analyzed by flow cytometry in the inflamed paw in the presence or absence of monocyte/macrophage depletion by intraplantar injection of clodronate-containing liposomes (phosphate-buffered saline and empty liposomes served as controls). Paw volume was measured with a plethysmometer. Hyperalgesia was determined by measuring heat-induced paw withdrawal latency and paw pressure threshold. Paw pressure threshold was also measured after swim stress and injection of fentanyl.

Results

At 48 and 96 h of inflammation, it was found that (1). monocytes/macrophages were the largest leukocyte subpopulation (> 55% of all leukocytes) and the predominant producers of opioid peptides (71-77% of all opioid-containing leukocytes in the paw), (2). clodronate-containing liposomes depleted monocytes/macrophages by 30-35% (P < 0.05), (3). hyperalgesia was unaltered by liposome injection (P > 0.05), and (4) opioid-containing leukocytes and swim stress but not fentanyl-induced antinociception were significantly decreased by clodronate-containing liposomes (P < 0.05, P > 0.05, all by t test; opioid-containing cells and swim stress-induced increase of paw pressure threshold were reduced by 35-42% and 20%, respectively).

Conclusion

Partial depletion of tissue monocytes/macrophages impairs peripheral endogenous opioid-mediated antinociception without affecting hyperalgesia.
Adenosine A1 Receptor Antagonist and Mitochondrial ATP-Sensitive Potassium Channel Blocker Attenuate the Tolerance to Focal Cerebral Ischemia in Rats
Authors: Yoshida Mitsuyoshi , Nakakimura Kazuhiko , Cui Ying Jun , Matsumoto Mishiya , Sakabe Takefumi
Published: June 2004

Involvement of adenosine and adenosine triphosphate-sensitive potassium (KATP) channels in the development of ischemic tolerance has been suggested in global ischemia, but has not been studied extensively in focal cerebral ischemia. This study evaluated modulating effects of adenosine A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) and mitochondrial KATP channel blocker 5HD (5-hydroxydecanoate) on the development of tolerance to focal cerebral ischemia in rats. Preconditioning with 30-minute middle cerebral artery occlusion (MCAO) reduced cortical and subcortical infarct volume following 120-minute MCAO (test ischemia) given 72 hours later. The neuroprotective effect of preconditioning was attenuated by 0.1 mg/kg DPCPX given before conditioning ischemia (30-minute MCAO), but no influence was provoked when it was administered before test ischemia. DPCPX had no effect on infarct volume after conditioning or test ischemia when given alone. The preconditioning-induced neuroprotection disappeared when 30 mg/kg 5HD was administered before test ischemia. These results suggest a possible involvement of adenosine A1 receptors during conditioning ischemia and of mitochondrial KATP channels during subsequent severe ischemia in the development of tolerance to focal cerebral ischemia.
Brain Function Early after Stroke in Relation to Subsequent Recovery
Authors: Nhan Hoang , Barquist Kristin , Bell Kathleen , Esselman Peter , Odderson Ib R. , Cramer Steven C.
Published: June 2004

This study aimed to characterize brain activation and perfusion early after stroke within cortical regions that would later change activation during recovery. Patients were studied serially after stroke (mean t1, = 16 days after stroke, t2 = 3.5 months later) using perfusion-weighted imaging and functional magnetic resonance imaging during finger movement. Controls (n = 7) showed no significant change in regional activation volumes over time. Among stroke patients (n = 8), however, recovery was accompanied by several patterns of functional magnetic resonance imaging change, with increased activation volumes over time in five patients and decreased in two. Most regions increasing activation over time were in the stroke hemisphere. Of the five patients showing increased activation over time, specific activation foci enlarged at t2 were already activated at t1 in four patients, and at least one focus growing from t1 to t2 was in a different arterial distribution from the infarct in all five patients. Perfusion of sensorimotor cortex at t1 was generally not reduced in the stroke hemisphere (94% of noninfarcted hemisphere). Improved clinical outcome was related to increased activation within sensory cortices of both brain sides, including bilateral secondary somatosensory areas. Early after stroke, cortical activation that will later increase in parallel with recovery is often already identifiable, can be remote from the vascular territory of the infarct, and is not likely hindered by reduced perfusion. The findings may be useful for restorative interventions introduced during the weeks after a stroke.
Laser Speckle Flowmetry for the Study of Cerebrovascular Physiology in Normal and Ischemic Mouse Cortex
Authors: Ayata Cenk , Dunn Andrew K. , Gursoy-Özdemir Yasemin , Huang Zhihong , Boas David A. , Moskowitz Michael A.
Published: June 2004

Laser speckle flowmetry (LSF) is useful to assess noninvasively two-dimensional cerebral blood flow (CBF) with high temporal and spatial resolution. The authors show that LSF can image the spatiotemporal dynamics of CBF changes in mice through an intact skull. When measured by LSF, peak CBF increases during whisker stimulation closely correlated with simultaneous laser-Doppler flowmetry (LDF) measurements, and were greater within the branches of the middle cerebral artery supplying barrel cortex than within barrel cortex capillary bed itself. When LSF was used to study the response to inhaled CO2 (5%), the flow increase was similar to the response reported using LDF. For the upper and lower limits of autoregulation, mean arterial pressure values were 110 and 40 mm Hg, respectively. They also show a linear relationship between absolute resting CBF, as determined by [14C]iodoamphetamine technique, and 1/τc values obtained using LSF, and used 1/τc values to compare resting CBF between different animals. Finally, the authors studied CBF changes after distal middle cerebral artery ligation, and developed a model to investigate the spatial distribution and hemodynamics of moderate to severely ischemic cortex. In summary, LSF has distinct advantages over LDF for CBF monitoring because of high spatial resolution.
The NAD+Precursor Nicotinamide Governs Neuronal Survival During Oxidative Stress Through Protein Kinase B Coupled to FOXO3a and Mitochondrial Membrane Potential
Authors: Chong Zhao Zhong , Lin Shi-Hua , Maiese Kenneth
Published: June 2004

Nicotinamide, a ß-nicotinamide adenine dinucleotide (NAD+) precursor and an essential nutrient for cell growth and function, may offer critical insights into the specific cellular mechanisms that determine neuronal survival, since this agent significantly impacts upon both neuronal and vascular integrity in the central nervous system. The authors show that nicotinamide provides broad, but concentration-specific, protection against apoptotic genomic DNA fragmentation and membrane phosphatidylserine exposure during oxidative stress to secure cellular integrity and prevent phagocytic cellular demise. Activation of the protein kinase B (Akt1) pathway is a necessary requirement for nicotinamide protection, because transfection of primary hippocampal neurons with a plasmid encoding a kinase-deficient dominant-negative Akt1 as well as pharmacologic inhibition of phosphatidylinositol-3-kinase phosphorylation of Akt1 eliminates cytoprotection by nicotinamide. Nicotinamide fosters neuronal survival through a series of intimately associated pathways. At one level, nicotinamide directly modulates mitochondrial membrane potential and pore formation to prevent cytochrome c release and caspase-3–and 9–like activities through mechanisms that are independent of the apoptotic protease activating factor-1. At a second level, nicotinamide maintains an inhibitory phosphorylation of the forkhead transcription factor FOXO3a at the regulatory sites of Thr32and Ser253and governs a unique regulatory loop that prevents the degradation of phosphorylated FOXO3a by caspase-3. Their work elucidates some of the unique neuroprotective pathways used by the essential cellular nutrient nicotinamide that may direct future therapeutic approaches for neurodegenerative disorders.
Development of electrodeposited chromium composite by amphoteric surfactant
Authors: Omar A.M.A. , Azzam E.M.S.
Published: June 2004

A chromium‐silicon carbide electrodeposited composite coatings were obtained by suspending silicon carbide (SiC) particles in a trivalent chromium plating solution. This composite was improved by adding the synthesized 1‐ethyl‐1‐cetyl‐2‐sulfonate‐4(hydroxy ethyl)‐piprazine (A16) as dispersing agent for SiC. The adsorption of A16 on SiC was determined. The relation between the zeta potential and codeposition of SiC was investigated by studying the effect of the additive (A16) concentration on mobility (dispersion) and the zeta potential of SiC. The results show that the zeta potential of SiC is more positive at critical micelle concentration of the additive and stimulation results from the adsorption of A16 on the SiC particles. Morphology resistance of the coating was determined and compared with free chromium deposits. These results were discussed according to the obtained adsorption isotherm of the additive.