bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON RENAL JUXTAGLOMERULAR CELLS
Authors: Hartroft Phyllis Merritt , Hartroft W. Stanley
Published: June 2004

Accumulation of granules in the juxtaglomerular cells occurred in rats which were maintained for 5 to 6 weeks on a diet low in sodium, chloride. Cytological evidence suggests that this was probably a storage phase of secretion following a decrease in the rate of liberation of the granules. Administration of DCA (desoxycorticosterone acetate) to salt-deficient rats did not alter this appearance of the juxtaglomerular cells.

Two per cent sodium chloride taken in the drinking water consumed for 4 weeks by similar animals caused degranulation of the juxtaglomerular cells. This effect was enhanced by DCA. DCA administered to animals on a normal salt intake produced a lesser degree of degranulation. Cytological changes in degranulated cells suggested that these represent a stage of hyperactivity in the secretory cycle produced by an increase in the rate of liberation of granules.

A hypothesis is suggested that the juxtaglomerular cells are involved in the hormonal regulation of sodium metabolism and/or blood pressure.
UREA EXCRETION IN HUMAN SWEAT AS A TRACER FOR MOVEMENT OF WATER WITHIN THE SECRETING GLAND
Authors: Schwartz Irving L. , Thaysen Jørn Hess , Dole Vincent P.
Published: June 2004

Previous workers have found that the concentration of urea in human sweat exceeds the concentration of urea in plasma. This fact has been confirmed in the present work and extended by measurements of the concentrations of urea in the sweat and the corresponding concentrations of urea in the plasma over a range of 25- fold variation in the latter.

An analysis of the data showed that the ratio of the concentration of urea in sweat to the concentration of urea in plasma, S/P, was independent of the plasma concentration, independent of the absolute flux of urea or water, and independent of the calculated energy expenditure. Two experiments showed that the concentration of urea in sweat followed a rising concentration in plasma with a time lag of approximately 5 minutes; this fact indicates that the accumulation of urea in sweat is a continuous process which is in operation during the observed discharge.

These observations suggest that urea is carried into the gland in some precursor solution and subsequently raised to a higher concentration by the reabsorption from this solution of a constant fraction of the water.
STUDIES ON THE ACTIVATION OF SERUM PROTEASE BY AN ANTIGEN-ANTIBODY SYSTEM
Authors: Jemski Joseph V. , Flick John A. , Stinebring Warren R.
Published: June 2004

The results obtained in this study indicate that serum protease is not activated by either a rabbit or guinea pig antiovalbumin-ovalbumin system, in vitro.

A precipitin reaction occurring in the presence of a serum protease precursor of three species (human, rabbit, and guinea pig) failed to activate the protease precursor. Furthermore, particulate material as preformed precipitates could not be shown to activate the protease of either human or rabbit serum or their euglobulin fractions.

The material presented seems to be further evidence against the postulated role of serum protease in immunologic systems.
IN VITRO PRODUCTION OF NEW TYPES OF HEMOPHILUS INFLUENZAE
Authors: Leidy Grace , Hahn Eros , Alexander Hattie E.
Published: June 2004

Two new types of Hemophilus influenzae, Sab and Sad have been produced in vitro. Each exhibits the presence of the type specific polysaccharides of 2 types of E. influenzae within the same cell. In Sab the polysaccharides of types a and b have been demonstrated and in Sad those which characterize types a and d. The Sab and Sad traits are inherited.

Sab was produced by the action of DNA-containing extract isolated from type a on either type b cells or Rb cells (non-encapsulated non-type-specific cells derived from type b). Sad cells were formed as a result of the action of the DNA-containing extract isolated from type d on cells intermediate between Rab and Sab cells.

DNA-containing extracts isolated from Sab cells have induced the Sab trait in Rd cells with predictable regularity.

Evidence has been presented that the hereditary determinant of Sab cells is a new genetic substance with new functions. Therefore, the interaction of the DNA-containing substance from cells of one genetic type with living cells of a genetically different type has produced what appears to be a new individual which differs from each of the cells contributing the differing genetic traits but has at least one trait in common with each.

Sab cells derived presumably from a single cell show the appearance of type b cells sometime during the first 7 generations.
INDUCED MALIGNANCY IN CELLS FROM RAT MYOCARDIUM SUBJECTED TO INTERMITTENT ANAEROBIOSIS DURING LONG PROPAGATION IN VITRO
Authors: Goldblatt Harry , Cameron Gladys
Published: June 2004

In two strains of fibroblasts originating from fragments of myocardium from a 5 day old rat of the Slonaker-Addis strain, a strain known to develop tumors but rarely, abnormal morphologic alterations took place which eventuated in neoplastic changes. This happened only after repeated exposure of the cultures to an atmosphere of nitrogen (anaerobiosis) and did not occur in the control cultures of fibroblasts originating from the same rat heart, and grown continuously throughout the same period (2 ½ years) without exposure to nitrogen.
THE CYTOLOGICAL DISTRIBUTION IN PIGEON SKELETAL MUSCLE OF ENZYMES ACTING ON PHOSPHORYLATED NUCLEOTIDES
Authors: Kitiyakara Amara , Harman John W.
Published: June 2004

A procedure has been described for the centrifugal fractionation of the cytological components of pigeon breast muscle. An analysis of the distribution of enzyme activity among the different particles reveals a predominant location of magnesium-activated ATPase and myokinase in the cytochondria. The myofibrillar nuclear components are the site of calcium-activated ATPase and adenylic acid deaminase.
QUANTITATIVE STUDIES OF PROSTATIC SECRETION
Authors: Huggins Charles , Sommer John Lambert
Published: June 2004

The prostate of the dog was relocated permanently in the perineum where its size could be measured and correlated with the output of prostatic secretion during many months. The secretion of a submaxillary gland obtained through a fistula was utilized as an internal biologic standard of the effects of pilocarpine, the secretory stimulus employed, because the amount and route of administration of the alkaloid are critical factors in inducing secretion.

Prostatic secretion was found to be profoundly affected by androgenic and estrogenic compounds, in contrast to salivation. The curves of the secretory response of the prostate and submaxillary glands to pilocarpine proved to be similar and a mathematical formula has been constructed to represent them.

When testosterone propionate was administered in increasing quantities for periods of weeks at each level, the volume of the prostate increased in a series of flattened curves. This volume, under the conditions mentioned, was found to stand in a simple arithmetic relationship to the amount of testosterone propionate administered.

Moderate quantities of testosterone propionate masked the effects of small amounts of stilbestrol on the prostate. The reverse was also true and the critical amounts of these compounds were defined.

The amounts of stilbestrol were determined which lowered the quantity of prostatic secretion resulting from the simultaneous administration of moderate amounts of testosterone propionate in castrate dogs, the result being a level and flat secretory curve which was maintained for many weeks. We designate this effect the plateau phenomenon. When this amount of estrogen was continued, and the dosage of testosterone propionate greatly augmented, the prostatic secretion did not increase in volume. Very slight increases above the critical amount of stilbestrol, however, caused the secretory curve to fall to new and still lower levels though the secretion was never completely suppressed. The acid phosphatase content of the prostatic secretion in the regions of secretory plateaus was similar to that of castrate dogs injected with androgen alone. The plateau phenomenon is due to simultaneous physiologic action of androgenic and estrogenic compounds on the prostatic cells.

The depression of prostatic secretion resulting in the plateau phenomenon is due to both functional and structural changes in the prostatic epithelium. They are best explained on the assumption that differences in steroid threshold exist in groups of cells within the prostate, those of the anterior rim of the gland being least susceptible to estrogenic activity.
THE INFECTION BY PLASMODIUM LOPHURAE OF DUCK ERYTHROCYTES IN THE CHICKEN EMBRYO
Authors: McGhee R. Barclay
Published: June 2004

Certain morphological differences render it possible to recognize duck erythrocytes after introduction into the circulating blood of chick embryos infected with P. lophurae. 4 hours afterward, considerable numbers of merozoites have entered duck erythrocytes, while the parasitemia of the chick itself remains essentially unchanged in degree. By estimating the numbers of potentially invading merozoites from blood films made at the time of introduction of duck cells, it was learned that a relatively constant rate of invasion into duck cells by merozoites was maintained. In counter-distinction there was an ever increasing merozoite death rate in embryos not receiving duck cells concurrent with the increase in numbers of parasites. After the injection into parasitized embryos of duck erythrocytes showing but few parasites, no difference was apparent in the rate of merozoite invasion into the introduced cells and the host cells, respectively; but when the percentage of duck cells was greater, the rate of merozoite penetration diminished to zero. The selective penetration of duck erythrocytes which, under the experimental conditions obtaining, constituted only 30 per cent of the total cell numbers of most, and the inability of the merozoites to move independently, taken together, suggest that the greater susceptibility of the duck erythrocyte may be due to greater numbers of accessible areas on its surface. The decreased susceptibility following parasitization indicates that the presence of the parasite alters the cell in such wise that entry of additional parasites is rendered more difficult.
STUDIES ON THE PSITTACOSIS-LYMPHOGRANULOMA GROUP
Authors: Allen Emma G. , Girardi Anthony J. , Sigel M. Michael , Klein Morton
Published: June 2004

The findings presented indicate that aureomycin could become associated with tissue of the chick embryo by both hematogenous distribution and direct adsorption.

Treatment of chick embryos infected with MP virus with 1 mg. of aureomycin by the allantoic route caused an inhibition of virus growth in the allantoic membrane.

The drug had no effect on "inert" virus, and appeared to have little effect on adsorption of virus to host tissue.

Complete inhibition of growth during the time interval corresponding to the first cycle of multiplication could be achieved only if the drug was administered within 6 to 8 hours after virus inoculation.

Partial inhibition of virus multiplication could be achieved even if the administration was delayed as late as 24 hours after infection.

In these experiments the chief role of the antibiotic appeared to be one of virustasis reflected in a prolongation of the latent period (non-infectious phase). The virus was able to resume its growth when a critical low level of the drug in the allantoic membrane was reached.

When infectivity titrations were carried out using various tissues and organs of treated and untreated embryos, it was found that no virus was detectable in the brains of treated embryos as late as 192 hours after inoculation of virus. This was in contrast with the findings in allantoic membranes and livers of such embryos; these organs showed virus at 120 and 144 hours, respectively. In untreated controls, virus appeared in membranes at 24 hours, in the liver at 48 hours, and in the brain at 72 hours.
STUDIES ON THE ANTIBODIES IN RABBIT ANTISERA RESPONSIBLE FOR SENSITIZATION OF HUMAN SKIN
Authors: Vaughan John H. , Kabat Elvin A.
Published: June 2004

The capacity of rabbit anti-egg albumin sera to sensitize human skin has been studied.

It has been shown that passive transfer by these sera is completely unrelated to the egg albumin-anti-egg albumin system, as demonstrated by a failure of passive transfer by some antisera containing ample anti-egg albumin and persistence of passive transfer in other antisera from which all anti-egg albumin had been removed by precipitation with homologous antigen. Three preparations of non-precipitating anti-egg albumin have been shown to have sensitizing capacities which bear no relation to their non-precipitating anti-egg albumin contents. From a portion of one of these the non-precipitating anti-egg albumin was removed without impairing its sensitizing ability, while in another portion obliteration of the sensitizing capacity was accomplished without reducing the anti-egg albumin.

Evidence is presented to show that there are at least two possible antibodies in anti-egg albumin sera which are capable of inducing skin sensitivity and that they are antibodies against egg white impurities in crystalline egg albumin other than anti-conalbumin, anti-ovomucoid, and anti-lysozyme.

The usefulness of a suitable quantitative precipitin technic for the analysis for antibodies against antigen impurities and for their selective absorption from sera is illustrated. The principle governing the procedure is described. The technic allows for the determination of a given trace antibody by working with such small concentrations of its purified specific antigen that whatever other antigen-antibody compounds are formed simultaneously with that to be determined will be below their solubility levels and consequently will not contribute appreciably to the precipitate.
IMMUNOCHEMICAL STUDIES OF ANTITOXIN PRODUCED IN NORMAL AND ALLERGIC INDIVIDUALS HYPERIMMUNIZED WITH DIPHTHERIA TOXOID
Authors: Kuhns William J.
Published: June 2004

The Arthus reaction was studied in guinea pigs passively immunized with human diphtheria antitoxin. Diphtheria toxoid was given intradermally 24 hours following the intravenous administration of antitoxin and the subsequent reactions were graded and measured.

The intensity of Arthus reactions was dependent upon the relative amounts of precipitating antitoxin and toxoid used. Severe lesions were caused by intravenous sensitization with 0.48 mg. precipitating antitoxin N and intradermal challenge with 0.05 or 0.17 toxoid N. Reactions of lesser intensity were caused by smaller amounts of antitoxin and toxoid.

The nature of the antibody used for sensitization was of importance in the severity of Arthus reactions. In contrast to the behavior of precipitating antitoxin, amounts of non-precipitating antitoxin equivalent to 0.48 mg. N did not cause severe Arthus reactions when 0.05 or 0.17 mg. toxoid N was given intradermally.

Precipitating antitoxic whole serum is altered by heating at 56°C. for 5 hours so that its precipitability is lost without any appreciable loss of antitoxic strength. This modified antitoxin produced Arthus reactions of only intermediate severity in guinea pigs sensitized with 0.48 mg. antitoxin N. When fractions of precipitating antitoxic serum were obtained using a cold ethanol technique described by Deutsch (16), a mixture of the purified γ2-globulin and the crude albumin fraction heated together at 56°C. for 5 hours behaved similarly to whole serum. However, γ2-globulin alone was not affected by the heating procedure, remained precipitable by toxoid, and was able to cause a severe Arthus reaction following sensitization with 0.48 mg. antitoxin N.
THE MECHANISM OF ACTION OF CORTISONE IN EXPERIMENTAL HYPERSENSITIVITY
Authors: Germuth Frederick G.
Published: June 2004

Cortisone markedly suppressed the cardiovascular and renal lesions of serum sickness type hypersensitivity which ordinarily develop following the intravenous injection of bovine albumin. The inhibitory effect of cortisone on the allergic granulomatous lesions of the spleen was less striking; the lesions were less extensive, but the percentage of animals affected was unchanged.

Cortisone in the dosage employed had no effect on the elimination of antigen following its intravenous administration or on the appearance of circulating antibody. These findings indicate that inhibition of the lesions of serum sickness by cortisone does not depend on the suppression of antibody production. Therefore, it is inferred that cortisone somehow protects the animal from the damaging effects of antigen-antibody union.
CHRONIC SODIUM CHLORIDE TOXICITY IN THE ALBINO RAT
Authors: Meneely George R. , Tucker Robert G. , Darby William J. , Auerbach Stewart H.
Published: June 2004

Sustained arterial hypertension developed in male, albino rats chronically fed diets rich in sodium chloride with demineralized drinking water available ad libitum. After 12 months of the experimental regimen a positive, linear correlation (r = 0.91) was found between the systolic blood pressure and the concentration of sodium chloride in the diet.

A syndrome of edema and renal failure was observed in 18 per cent of the group fed at the level of 7.0 to 9.8 per cent of sodium chloride. Significant histologic changes occurred in the kidneys and certain other organs in rats consuming rations containing these levels of NaCl.

The relative volume of the radiosodium space was increased in the rat by high dietary sodium chloride.
INFLAMMATION AND PROTEIN METABOLISM STUDIES OF CARBON-14-LABELED PROTEINS IN DOGS WITH STERILE ABSCESSES
Authors: Yuile C. L. , Lucas F. V. , Jones C. K. , Chapin S. J. , Whipple G. H.
Published: June 2004

Carbon-14-labeled plasma proteins given by mouth to dogs with sterile abscesses undergo decreased absorption, presumably owing to impaired digestion of protein.

The turnover of plasma albumin is greatly accelerated but the globulins, excluding fibrinogen, show little change during the acute stage of the sterile inflammation.

Fibrinogen shows very rapid production and utilization during acute inflammation. Large amounts of C14 are incorporated in fibrinogen within a few hours after ingestion of the labeled material. The labeled fibrinogen largely disappears within 2 to 4 days after its production.

The appearance of C14 in new red cells from labeled protein or amino acid sources is reduced by inflammation—evidence of impaired synthesis.

The pus of the sterile abscess contains a good deal of C14 activity which at times is as much as that found in the liver. Pus cell C14 activity per milliliter is similar after injection of labeled plasma and ingestion of labeled plasma or lysine. However, the pus cell fraction contains 3 to 4 times more C14 activity per milliliter than does the supernatant fluid when the isotope is fed. In the supernatant fluid the activity is all within precipitable protein, much of which is probably derived from the blood plasma.

In spite of increased loss of C14 as CO2 in the expired air and in the pus, there is evidence of conservation of protein-building materials for maintenance of new plasma proteins and tissue proteins in the more active organs (e.g. liver)—a shift of protein C14 from the less active tissues (muscle and skin).
EXPERIMENTAL ATHEROSCLEROSIS IN CEBUS MONKEYS
Authors: Mann George V. , Andrus Stephen B. , McNally Ann , Stare Fredrick J.
Published: June 2004

Atherosclerosis has been produced in Cebus monkeys by dietary means. This disease has been produced by feeding diets high in cholesterol and low in sulfur amino acids over periods of 18 to 30 weeks. Within 2 to 8 weeks this regimen caused the concentration of cholesterol in the serum to rise to 300 to 800 mg. per cent. The hypercholesterolemia could be largely prevented by feeding 1 gm. per day of dl-methionine or l-cystine as supplements to the diet. After the serum concentration had become elevated, it could be restored to normal by feeding 1 gm. of dl-methionine but only partially restored by 0.5 gm. of l-cystine daily.

The vascular lesions were in the ascending aorta but extended from the valves of the left ventricle to the proximal portions of the carotid and femoral arteries. Minimal lesions have been observed in the coronary arteries. The aortic lesions were chiefly characterized by the presence of lipid-laden phagocytes and increase in collagen and elastic fibers. The lipids were in part cholesterol derivatives. Visceral cholesterolosis was not associated with this disease.
ACTIVATION OF PROFIBRINOLYSIN BY ANTIGEN-ANTIBODY REACTION AND BY ANAPHYLACTOID AGENTS; ITS RELATION TO COMPLEMENT
Authors: Ungar Georges , Damgaard Evelyn , Hummel Fred P.
Published: June 2004

The activation of profibrinolysin in sensitized guinea pig serum when mixed in vitro with the homologous antigen was confirmed with a more accurate and more reliable method than the one previously used. A study was made of some of the conditions required for obtaining maximum activation.

Profibrinolysin activation was also induced in normal guinea pig serum by addition of certain "anaphylactoid" agents such as peptone, tween 20, morphine, octylamine, octadecylamine, and 48/80.

The specific antigen and the anaphylactoid agents produce activation only when added to whole, fresh, unheated serum. Profibrinolysin activation by these agents, as opposed to activation by streptokinase, seems to require the intervention of a kinase system (serofibrinokinase) inactivated by fractionation of serum and by heating to 56°C.

Whenever serum was submitted to treatments which caused fractionation, fixation or inhibition of complement, serofibrinokinase was also inactivated. Under the conditions investigated the behavior of this kinase was indistinguishable from that of complement.
THE ESTIMATION OF CIRCULATING ANTIBODY-ANTIGEN COMPLEX
Authors: Sternberger L. A. , Maltaner Frank , DeWeerdt Jacob
Published: June 2004

Immune sera were subjected to treatment with alkali in the cold to cause dissociation of antigen-antibody complexes. Precipitates and a capacity to fix complement developed in some of these sera subsequent to such treatment.

The specific immunologic nature of these phenomena and their observation in relation to disappearance of free antigen and appearance of free antibody in circulation are discussed. The phenomena observed appear to be consistent with the assumption that a circulating antibody-antigen complex is revealed as a result of treatment.
STUDIES OF HYPERSENSITIVITY TO LOW MOLECULAR WEIGHT SUBSTANCES
Authors: Eisen Herman N. , Belman Sidney
Published: June 2004

2,4-dinitrophenylsulfenyl chloride (DSCl) and 2,4-dinitrophenylthiocyanate (DSCN) elicited allergic reactions of the delayed type when applied to the skin of guinea pigs and of human beings who had been sensitized by prior exposure to 2,4-dinitrofluorobenzene (DF). DSCl and DSCN, together with 2,4-dinitrobenzene sulfonate (DSO3), constitute a clearly defined group of allergenic dinitrophenyl compounds in that they all combined with skin protein in vivo through reaction with cysteine or cystine. In vitro, these compounds combine with free SH groups, and with —S—S— groups of hair and epidermis, but not with —S—S— groups of oxidized glutathione or of bovine gamma globulins. DSO3, DSCl, and DSCN did not react with amino groups in vivo, but did react with protein amino groups in vitro at pH values of about 10.

Another group of dinitrophenyl compounds (DF, DCl, and DBr) previously had been shown to combine with lysine ϵ-NH2 groups of epidermal proteins. In the present work it was found that these compounds do not react with the disulfide groups of these proteins, either in vivo or in vitro. Moreover, they did not seem to react with SH groups of viable skin, although they are highly reactive with sulfhydryl in vitro. This apparent discrepancy between reactivity with SH groups in vitro and in vivo may be due to the fact that the chromatographic technique employed was relatively insensitive for the sulfhydryl derivative.

When a compound of either group was applied to the skin surface, dinitrophenyl-amino acids were recovered from the epidermis but not from the dermis.

The results are discussed from the viewpoint of the epidermal localization of dinitrophenyl-protein conjugates.
THE ERGASTOPLASM
Authors: Weiss Jules M.
Published: June 2004

The fine structure of the ergastoplasm of the pancreatic exocrine cell of Swiss albino mice has been studied with the electron microscope. It was found that this material consists of sac-like structures, which may be called ergastoplasmic sacs, embedded in an amorphous granular ground substance, the cytoplasmic matrix. The membranous wall of the ergastoplasmic sac is a structure approximately 250 A wide. Except for its greater electron density and granular structure, the ergastoplasmic membrane is similar in appearance to the nuclear, plasma, and mitochondrial membranes. From data available in the literature, and from our own evidence, the conclusion can be drawn that the ergastoplasmic membrane contains ribonucleic acid.

The mode of formation of the ergastoplasm and secretory granules was studied in animals which were first fasted and subsequently fed. It was found that ergastoplasm is formed within the cytoplasm, near the nuclear membrane, and possibly from the plasma membrane. The secretory granules were observed to arise by accumulation of materials within small ergastoplasmic sacs.
THE ANTIGENIC COMPOSITION OF INFLUENZA VIRUS MEASURED BY ANTIBODY-ABSORPTION
Authors: Jensen Keith E. , Francis Thomas
Published: June 2004

The application of methods herein described for the absorption of antibody from sera by influenza virus adsorbed to erythrocytes has greatly facilitated absorption studies with this virus and has resulted in a more comprehensive demonstration of strain differences and relationships. It is now evident that there are at least 18 different antigenic components which can be measured in Type A strains of influenza virus. Utilization of quantitative absorption technics allows the simultaneous detection of variable quantities of several different antigens so that the antigenic composite of the strain is more clearly defined than was previously possible. The wide sharing of antigenic components leads to the conclusion that no completely new antigens have formed of late nor have the antigenic components of strains isolated several years ago disappeared. Some mechanisms for antigenic variation among strains are suggested, and the significance of the variation in antigenic components is discussed in relation to specifications for an effective vaccine.
SUSCEPTIBILITY OF GRAVID MICE TO COXSACKIE VIRUS INFECTION
Authors: Dalldorf Gilbert , Gifford Rebecca
Published: June 2004

Gravid mice become progressively more susceptible to infection with the pancreatic line of Group B-1 Coxsackie virus during the last week of pregnancy. A Group A-8 strain did not have such an effect.

The young that survive despite the fact that their mothers are infected with a B-1 strain appear to be normal in the gross and microscopically, to grow at the usual rate, to be free of demonstrable virus, and to be susceptible on challenge with a homologous strain.
MECHANISMS INVOLVED IN THE ANTIMYCOBACTERIAL ACTIVITY OF CERTAIN BASIC PEPTIDES
Authors: Hirsch James G.
Published: June 2004

The antimycobacterial activity of thymus peptide under certain conditions in vitro can be partially neutralized by increasing the concentration of sulfate ions in the medium, and to a lesser extent by the addition of certain organic compounds which contain sulfur. It is suggested that thymus peptide suppresses the growth of tubercle bacilli by interfering with the normal sulfur metabolism of these microorganisms.

Polylysine peptide and pituitary adrenocorticotropic hormone, other basic peptides derived from animal tissues, also inhibit the multiplication of tubercle bacilli in vitro, and their antimycobacterial activity is also antagonized by sulfate ions. Basic peptide hormones prepared from the posterior pituitary gland do not affect the growth of acid-fast bacteria under the conditions of the test.
THE COMBINED ACTIONS OF CHLORAMPHENICOL AND OF BACTERICIDAL ANTIBODY PLUS COMPLEMENT ON SALMONELLA TYPHOSA
Authors: Treffers Henry P. , Muschel Louis H.
Published: June 2004

Quantitative determinations, employing turbidimetric growth assays, have been made of the inhibitory actions of choramphenicol, and of specific antibody plus complement, separately, and in combination. In experiments with the Ty2 strain of S. typhosa the combined activities of the two groups of reagents have been predicted, within 3 per cent, from the activities of the separate components, on the hypothesis of joint, independent action (additive inhibitions). A fourfold increase in resistance to chloramphenicol of the 0901 strain of S. typhosa has been shown to have little, if any, effect on its susceptibility to the bactericidal action of anti-O antibody and complement. Indirect evidence indicates that the latter may not be a general effect but may vary with the particular strain.
ONE-STEP GROWTH CURVE OF WESTERN EQUINE ENCEPHALOMYELITIS VIRUS ON CHICKEN EMBRYO CELLS GROWN IN VITRO AND ANALYSIS OF VIRUS YIELDS FROM SINGLE CELLS
Authors: Dulbecco R. , Vogt Marguerite
Published: June 2004

The rate of adsorption of WEE virus onto chicken embryo cells in vitro was determined both on a cell layer and on a cell suspension.

One-step growth curves were determined in cell suspensions and on cell layers. The latent period varied between 2 and 3½ hours; it was shorter on cell layers and decreased with higher multiplicity of infection. The shortest period is probably the real latent period.

The growth curves of the virus showed an initial exponential rise and reached a maximal constant value after 6 to 8 hours. The maximum virus yield per cell varied between 200 and 1000 on the cell layer, and between 100 and 200 in suspended cells.

The yield of single infected cells was determined. An analysis of the distributions of the individual yields obtained after various periods of virus growth led to two main conclusions: (1) that virus is released from the same cell over a long period of time; (2) that one phase of the intracellular virus growth is exponential.
INHIBITION OF INFLUENZA VIRUS MULTIPLICATION BY N-GLYCOSIDES OF BENZIMIDAZOLES
Authors: Tamm Igor , Folkers Karl , Shunk Clifford H. , Horsfall Frank L.
Published: June 2004

Chloro derivatives of benzimidazole were found to be 2 to 3 times more active than corresponding methyl derivatives in causing inhibition of Lee virus multiplication in chorioallantoic membrane cultures in vitro. The most active benzimidazole derivative thus far tested is 5,6-dichloro-1-ß-D-ribofuranosylbenzimidazole (DRB); it caused 75 per cent inhibition of Lee virus multiplication in membrane cultures at a concentration of 0.38 x 10–4 M. On the other hand, 5,6-dimethyl-1-alpha;-D-ribofuranosylbenzimidazole, the moiety present in vitamin B12, failed to inhibit Lee virus multiplication at a concentration of 35 x 10–4 M. Other N-glycosides of 5,6-dichlorobenzimidazole were considerably less active than DRB.

In single cycle experiments, the degree of inhibition of Lee virus multiplication by DRB in membrane cultures was not dependent on the amount of virus in the inoculum. This compound did not inactivate the infectivity of extracellular Lee virus, had no effect on virus-erythrocyte interaction, did not interfere with the adsorption of the virus by the host tissue, nor affect the release of newly formed virus from the membrane. The inhibitory effect of DRB on Lee virus multiplication, in contrast to that of 2,5-dimethylbenzimidazole, persisted after transfer of infected membranes into fresh culture medium not containing the compound. Both DRB and the 2,5-dimethyl compound caused 99 per cent inhibition of Lee virus multiplication without affecting oxygen uptake of the membrane. Tissue proliferation of membrane pieces in roller tube culture was not significantly affected by DRB at inhibitory concentration, whereas at equivalent concentration the 2,5-dimethyl compound did restrict cellular growth. At higher concentrations, both compounds caused retardation of cell proliferation. This effect was reversible on removal of either compound from the medium. The multiplication of several strains of influenza A and B viruses, i.e. Lee, MB, PR8, and FM1, was inhibited to the same degree by each of the two compounds; DRB was 35 times more active than the 2,5-dimethyl compound relative to each of the strains.

DRB caused inhibition of Lee virus multiplication in intact embryonated chicken eggs and in mice without causing significant signs of toxicity in either host. Some of the implications of these findings are discussed in relation to the mechanism of the inhibition of influenza virus multiplication.
THE EFFECT OF CORTISONE ON THE SERUM LIPIDS AND ON THE DEVELOPMENT OF EXPERIMENTAL CHOLESTEROL ATHEROSCLEROSIS IN THE RABBIT
Authors: Gordon Dina , Kobernick Sidney D. , McMillan Gardner C. , Duff G. Lyman
Published: June 2004

An experiment was performed to determine the effect of cortisone on the serum lipids and on the development of experimental cholesterol atherosclerosis in the rabbit. Litter mate rabbits of the same sex were employed; both sexes were represented in the experiment. The report is based upon four experimental groups comprising (1) 12 rabbits fed cholesterol and treated with cortisone vehicle; (2) 12 rabbits fed cholesterol and treated daily with cortisone; (3) 11 rabbits treated with cortisone; and (4) 7 rabbits that received cortisone vehicle.

It was observed that: (1) There was less aortic atherosclerosis in the cholesterol-fed cortisone-treated rabbits as judged by both morphological and chemical means than in the rabbits fed cholesterol without cortisone treatment. (2) Cortisone depressed appreciably the hypercholesterolemia resulting from the feeding of cholesterol to rabbits. (3) Cortisone treatment caused a moderate hypercholesterolemia in normal rabbits. (4) Cortisone caused a moderate increase in serum lipid phosphorus equal to that produced by cholesterol feeding alone. (5) The combination of cholesterol feeding and cortisone did not result in a higher phospholipidemia than either one of these agents alone. (6) Cortisone caused a great increase in serum-neutral fat; it was not apparent whether cholesterol feeding affected the neutral fat lipemia due to cortisone treatment alone. (7) The total cholesterol to lipid phosphorus ratio was about normal in the rabbits that received cortisone only. It was doubled in the animals receiving both cholesterol and cortisone, and it was increased about four times in those that received only cholesterol.

The significance of the alterations in the serum lipids induced by cortisone is discussed in relation to the inhibition of the development of aortic atherosclerosis that occurred in the cholesterol-fed rabbits treated with cortisone.
THE ANTIGENICITY OF RAT COLLAGEN
Authors: Watson Robert F. , Rothbard Sidney , Vanamee Parker
Published: June 2004

A method is described for preparing purified collagen from the tail tendons of rats with minimal alteration from its native state.

This purified collagen is soluble in dilute acetic acid and when injected intraperitoneally into rabbits induces complement-fixing antibodies in low titer.

It has been demonstrated by the use of certain immunological tests, enzymatic analyses, and electron microscopy that these antibodies are probably directed specifically toward collagen rather than toward accompanying impurities such as tissue proteins or polysaccharides.

Evidence is presented suggesting that collagen exhibits species specificity.
Endocytosis as a Mechanism for Tyrosine Kinase-dependent Suppression of a Voltage-gated Potassium Channel
Authors: Nesti Edmund , Everill Brian , Morielli Anthony D.
Published: June 2004

The voltage-gated potassium channel Kv1.2 undergoes tyrosine phosphorylation-dependent suppression of its ionic current. However, little is known about the physical mechanism behind that process. We have found that the Kv1.2 alpha-subunit protein undergoes endocytosis in response to the same stimuli that evoke suppression of Kv1.2 ionic current. The process is tyrosine phosphorylation-dependent because the same tyrosine to phenylalanine mutation in the N-terminus of Kv1.2 that confers resistance to channel suppression (Y132F) also confers resistance to channel endocytosis. Overexpression of a dominant negative form of dynamin blocked stimulus-induced Kv1.2 endocytosis and also blocked suppression of Kv1.2 ionic current. These data indicate that endocytosis of Kv1.2 from the cell surface is a key mechanism for channel suppression by tyrosine kinases.
Autonomic Nervous System Response to Epidural Analgesia in Laboring Patients by Wavelet Transform of Heart Rate and Blood Pressure Variability
Authors: Deschamps Alain , Kaufman Ian , Backman Steven B. , Plourde Gilles
Published: June 2004

Background

Epidurals are effective in relieving labor pain but result in a sympathectomy that may compromise maternal hemodynamic stability and fetal perfusion. Decreases in blood pressure and heart rate can be corrected, but markers of autonomic activity would be useful to predict and prevent such changes. The goal of this study was to find markers describing the changes in autonomic nervous system activity with epidural anesthesia in laboring patients.

Methods

The authors analyzed heart rate variability and blood pressure variability in 13 laboring patients using wavelet transform, a time-frequency analysis that accommodates rapid changes in autonomic activity. Heart rate and blood pressure variability were obtained 5 min before and 10 min after injection of 20 ml bupivacaine, 0.125%, and 50 microg fentanyl in the epidural space.

Results

Blood pressure and heart rate were not affected by epidural analgesia. However, high-frequency power of heart rate variability increased after epidural (increase in parasympathetic drive). The ratio of low-frequency:high-frequency power of heart rate variability decreased. High- and low-frequency power of blood pressure variability decreased (decrease in sympathetic outflow).

Conclusions

Indices of parasympathetic and sympathetic activity after neuraxial blockade in laboring patients can be obtained by analysis of both heart rate variability and blood pressure variability. The analysis by wavelet transform can discern changes in autonomic activity when values of blood pressure and heart rate do not vary significantly. Whether this technique could be used to predict and prevent hemodynamic compromise after neuraxial blockade merits further studies.
Evidence That Intravenous Vasopressors Can Affect Rostral Spread of Spinal Anesthesia in Pregnancy
Authors: Cooper David W. , Jeyaraj Leo , Hynd Ryan , Thompson Rebekah , Meek Tim , Ryall David M. , Kokri Manmohan S.
Published: June 2004

Background

The authors have previously observed an apparent association between rostral spread of spinal anesthesia and choice of intravenous vasopressor given to maintain maternal systolic arterial pressure during cesarean delivery. This study tested the hypothesis that an intravenous infusion of phenylephrine can reduce rostral spread of spinal anesthesia in pregnancy, compared with ephedrine.

Methods

The study was randomized and double blind. It compared phenylephrine 100 microg/ml (phenylephrine group, n = 30), and ephedrine 3 mg/ml (ephedrine group, n = 30), given by infusion, to prevent maternal hypotension during combined spinal-epidural anesthesia for cesarean delivery. Two ml intrathecal plain levobupivacaine, 0.5%, combined with 0.4 ml intrathecal fentanyl, 50 microg/ml, and 10 ml epidural saline was given with the patient in the sitting position. The upper level of neural blockade to cold and light touch sensation was recorded at 10 and 20 min postspinal. Epidural space pressure was recorded at 5, 10, 15, and 20 min.

Results

At 20 min, the upper dermatome blocked to cold sensation was median T3 (interquartile range, T2-T4) for the phenylephrine group, compared with T1 (T1-T2) for the ephedrine group (P = 0.001). At 20 min, the upper dermatome blocked to light touch sensation was median T5 (T4-T8) for the phenylephrine group, compared with T3 (T2-T6) for the ephedrine group (P = 0.009). The mean epidural space pressure in the phenylephrine group was 16 (13-19) mmHg, compared with 16 (13-18) mmHg in the ephedrine group (P = 0.63).

Conclusions

This study provides evidence that intravenous phenylephrine can decrease rostral spread of spinal anesthesia in pregnancy, compared with intravenous ephedrine. Further work is required to investigate possible mechanisms and to assess its clinical significance.
Effect of ONO1714, a Specific Inducible Nitric Oxide Synthase Inhibitor, on Lung Lymph Filtration and Gas Exchange during Endotoxemia in Unanesthetized Sheep
Authors: Koizumi Tomonobu , Ogasawara Hitoshi , Yamamato Hiroshi , Tsushima Kenji , Ruan Zonghai , Jian Mingyuan , Fujimoto Keisaku , Kubo Keishi
Published: June 2004

Background

The effect of nitric oxide synthase inhibitor on acute lung injury remains controversial. The current study was designed to examine effects of a newly synthesized and selective inducible nitric oxide synthase inhibitor, ONO1714, on endotoxin-induced lung injury in unanesthetized sheep.

Methods

Thirteen unanesthetized sheep chronically instrumented with a lung lymph fistula and vascular catheters for monitoring were prepared. Animals were randomly allocated into two experimental groups. In experiment 1, sheep (n = 6) were infused only with endotoxin (1 microg/kg) for 30 min. In experiment 2, sheep (n = 7) were pretreated with ONO1714 (0.1 mg/kg) before 30 min of endotoxin administration, and the endotoxin was infused in the same manner as in experiment 1. Mean pulmonary arterial pressure, left atrial pressure, systemic arterial pressure, and lung lymph flow were measured. Observation was continued over 5 h after endotoxin administration.

Results

ONO1714 did not cause any pulmonary hemodynamic changes at baseline or exert any influences on transient pulmonary hypertension and increased pulmonary vascular resistance during endotoxemia. However, inducible nitric oxide synthase inhibition with ONO1714 significantly reduced lung lymph filtration and improved abnormal oxygenation during endotoxemia. In addition, increased nitrate-nitrite in plasma and lung lymph in response to endotoxin was prevented by treatment with ONO1714.

Conclusions

These findings suggest that nitric oxide release by the inducible nitric oxide synthase pathway partially contributes to the increased permeability of pulmonary edema and decreased oxygenation during endotoxemia in sheep.
A Novel Liposomal Bupivacaine Formulation to Produce Ultralong-Acting Analgesia
Authors: Grant Gilbert J. , Barenholz Yechezkel , Bolotin Elijah M. , Bansinath Mylarrao , Turndorf Herman , Piskoun Boris , Davidson Elyad M.
Published: June 2004

Background

Currently available local anesthetics have relatively brief durations of action. An ultralong-acting local anesthetic would benefit patients with acute and chronic pain. The authors prepared and characterized a novel liposomal bupivacaine formulation using remote loading of bupivacaine along an ammonium sulfate gradient and assessed its efficacy in humans.

Methods

A large multivesicular liposomal bupivacaine formulation was prepared by subjecting small unilamellar vesicles to successive freeze-and-thaw cycles. Bupivacaine hydrochloride was then remotely loaded into the liposomes along an ammonium sulfate gradient ([(NH4)2SO4)]intraliposome/[(NH4)2SO4)]medium > 1000). The liposomes were then characterized for size distribution; drug-to-phospholipid ratio; in vitro release profile at 4 degree, 21 degree C, and 37 degree C; sterility; and pyrogenicity. Six subjects each received six intradermal injections in the lower back with 0.5 ml of 0.5, 1.0, and 2% liposomal bupivacaine; 0.5% standard bupivacaine; saline; and "empty" liposomes. Duration of analgesia was assessed using pinprick testing of the skin directly over the injection sites. Results were compared using the log-rank test.

Results

The mean large multivesicular vesicle size was 2439 +/- 544 nm, with a drug-to-phospholipid ratio of 1.8, fivefold greater than results previously reported. In vitro release was slowest at 4 degree C. The median duration of analgesia with 0.5% standard bupivacaine was 1 h. The median durations of analgesia after 0.5, 1.0, and 2.0% liposomal bupivacaine were 19, 38, and 48 h, respectively. Neither saline nor "empty" liposomes produced analgesia.

Conclusions

This novel liposomal formulation had a favorable drug-to-phospholipid ratio and prolonged the duration of bupivacaine analgesia in a dose-dependent manner. If these results in healthy volunteers can be duplicated in the clinical setting, this formulation has the potential to significantly impact the management of pain.
Injuries Associated with Regional Anesthesia in the 1980s and 1990s
Authors: Lee Lorri A. , Posner Karen L. , Domino Karen B. , Caplan Robert A. , Cheney Frederick W.
Published: June 2004

Background

The authors used the American Society of Anesthesiologists Closed Claims Project database to identify specific patterns of injury and legal liability associated with regional anesthesia. Because obstetrics represents a unique subset of patients, claims with neuraxial blockade were divided into obstetric and nonobstetric groups for comparison.

Methods

The American Society of Anesthesiologists Closed Claims Project is a structured evaluation of adverse anesthetic outcomes collected from closed anesthesia malpractice insurance claims of professional liability companies. An in-depth analysis of 1980-1999 regional anesthesia claims was performed with a subset comparison between obstetric and nonobstetric neuraxial anesthesia claims.

Results

Of the total 1,005 regional anesthesia claims, neuraxial blockade was used in 368 obstetric claims and 453 of 637 nonobstetric claims (71%). Damaging events in 51% of obstetric and 41% of nonobstetric neuraxial anesthesia claims were block related. Obstetrics had a higher proportion of neuraxial anesthesia claims with temporary and low-severity injuries (71%) compared with the nonobstetric group (38%; P <or=0.01) and a lower proportion of claims with death or brain damage and permanent nerve injury compared with the nonobstetric group (P <or= 0.01). Cardiac arrest associated with neuraxial block was the primary damaging event in 32% of obstetric and 38% of nonobstetric neuraxial anesthesia claims involving death or brain damage. Eye blocks accounted for 5% of regional anesthesia claims.

Conclusion

Obstetric claims were predominately associated with minor injuries. Permanent injury from eye blocks increased in the 1990s. Neuraxial cardiac arrest and neuraxial hematomas associated with coagulopathy remain sources of high-severity injury.