bluuebunny/crossref_metadata_2025 huggingface dataset:
INHIBITION OF INFLUENZA VIRUS MULTIPLICATION BY ALKYL DERIVATIVES OF BENZIMIDAZOLE
Authors: Tamm Igor , Folkers Karl , Horsfall Frank L.
Published: June 2004

The activity of compounds which inhibit the multiplication of influenza virus can be measured in chorioallantoic membrane cultures in vitro by means of hemagglutination titrations on the medium. Studies on the reproducibility of virus reproduction in membrane cultures have revealed the major variables which affect the results and thus have led to the development of a precise technique. Under strictly controlled experimental conditions, the extent of reproduction of the virus in membrane cultures is predictable within narrow limits of variation.

With 105.5 EID50 of influenza B virus, Lee strain, and 5.75 cm.2 of chorioallantoic membrane per ml., the ratio of infective virus particles to susceptible allantoic cells appears to be approximately 1:28. Under these conditions, the evidence indicates that two cycles of multiplication occur and nearly maximal hemagglutination titers are found with culture medium at 36 hours. The extent of the deviation in the absolute titer in different experiments was only 0.112 log unit.

At a concentration of 0.0017 M, 2,5-dimethylbenzimidazole caused inhibition of the multiplication of influenza B virus, Lee strain, which persisted for at least 70 hours as measured by hemagglutination titrations on the culture medium. The degree of inhibition was closely comparable to that demonstrated by infectivity titrations on the membrane at the end of the first cycle of virus reproduction (1).
INHIBITION OF INFLUENZA VIRUS MULTIPLICATION BY ALKYL DERIVATIVES OF BENZIMIDAZOLE
Authors: Tamm Igor , Folkers Karl , Shunk Clifford H. , Heyl Dorothea , Horsfall Frank L.
Published: June 2004

The degree of inhibition of multiplication of influenza B virus, Lee strain, in membrane cultures in vitro appears to be directly related to the concentration of the inhibitory compounds used in this investigation. With each of the alkyl derivatives of benzimidazole, evidence for such a relationship was obtained in the range between 60 and 90 per cent inhibition of virus multiplication.

Alteration of the structure of benzimidazole by substitution of alkyl radicals at various positions in either the benzene or the imidazole ring resulted in diverse differences in the capacity to inhibit influenza virus multiplication in vitro. Minor increases in inhibitory activity resulted when one to three methyl groups were introduced at certain positions in the molecule. Marked increases in inhibitory activity were achieved by more extensive substitution in either the benzene or the imidazole ring. The position and nature of substituent groups appeared to be of decisive importance.

Among the more highly active compounds were 2,4,5,6,7-pentamethyl-benzimidazole, 5,6-diethylbenzimidazole, and 2-ethyl-5-methylbenzimidazole. Further extension of the alkyl chain at position 2 caused no significant change in the inhibitory activity of the derivative. The most active compounds studied caused 75 per cent inhibition of Lee virus multiplication in membrane cultures in vitro at concentrations of approximately 0.0002 M. Some of the implications of these findings are discussed.
THE PERMEABILITY OF HUMAN SWEAT GLANDS TO A SERIES OF SULFONAMIDE COMPOUNDS
Authors: Thaysen Jørn Hess , Schwartz Irving L.
Published: June 2004

A series of sulfonamide compounds, para-aminohippurate, and inulin were used to study the permeability of the epithelium of human sweat glands.

Inulin was not excreted in the sweat. The ratios of the concentrations in sweat to the concentrations in plasma, S/P, of sulfanilamide, sulfapyridine, sulfathiazole, sulfadiazine, and para-aminohippurate were found to be 0.69, 0.58, 0.13, 0.11, and 0.02 respectively, independent of the plasma concentrations and the sweating rates. The fact that the S/P ratios are thus unaffected by the absolute number of molecules transported suggests that these compounds enter into the sweat by simple diffusion and not via a specific secretory mechanism which could become saturated by increasing load. If this is so, the difference in the S/P ratios must be explained by an unequal permeability of the epithelium of the sweat gland to the various compounds and some explanation for these differences in the rate of excretion must exist in terms of physicochemical properties of the compounds.

A comparison between the S/P ratios and the pK values of the various sulfonamides indicates that the differences in their rates of excretion in the sweat depend upon the degree of ionization of the various compounds at the physiological pH. Compounds which are mainly non-ionized are excreted with high S/P ratios, whereas ionized compounds appear with low ratios. A quantitative relationship was shown to exist between the S/P ratio for each compound and the percentage of the compound which is non-ionized at pH 7.4.
THE RELATIONSHIP BETWEEN THE ACUTE PHASE RESPONSE AND ANTIBODY PRODUCTION IN THE RABBIT
Authors: Wood Harrison F.
Published: June 2004

The ability of an adjuvant and its individual constituents to induce the production of Cx-reactive protein in rabbits has been studied. It was found that the adjuvant stimulated rabbits to produce large amounts of the acute phase protein for 3 to 6 days. Melted aquaphor blended with saline stimulated the production of Cx-reactive protein for 3 or 4 days. Mineral oil was less effective in stimulating the production of the protein than either adjuvant or aquaphor. Heat-killed Jamaica strain tubercle bacilli suspended in mineral oil did not induce the Cx-protein response.

The ability of subcutaneously administered adjuvant without antigen incorporated in the saline phase to potentiate the antibody response of rabbits to the intravenously administered antigens, C-reactive protein and human gamma globulin, was investigated. It was found that the adjuvant-treated animals produced more precipitating antibody to the two intravenously administered antigens than did the control animals given intravenous antigen alone.
STUDIES OF THE EFFECT OF BACTERIAL ENDOTOXINS ON RABBIT LEUCOCYTES
Authors: Berthrong Morgan , Cluff Leighton E.
Published: June 2004

Intravenous injection into rabbits of bacterial endotoxins results in an inhibition of migration of leucocytes from the buffy coat of their blood in tissue culture or in "slide cell" preparations. This effect was demonstrable 5 minutes after the intravenous injection and persisted for from 6 to 12 hours after the injection. It is as marked in rabbits receiving only a single intravenous injection of endotoxin as in those previously prepared intradermally and developing a severe local Shwartzman reaction on intravenous injection. The preparation of the skin for the Shwartzman reaction does not in itself result in appreciable changes of leucocyte migration. The production of the effect depends upon some action in vivo, since leucocytes of uninjected rabbits migrate normally from the buffy coat in plasma substrates to which large concentrations of endotoxin are added in vitro. The inhibitory effect, as observed in these experiments, also depends upon the added influence of centrifugation. Leucocytes from a rabbit receiving endotoxin intravenously migrate normally from uncentrifuged lung or spleen fragments and migrate normally in blood on the warm stage prior to centrifugation. Identical centrifugation does not affect leucocytes from uninjected animals. The heparin inhibition of the local Shwartzman reaction does not alter this effect of endotoxins on leucocytes. Its possible role in the production of leucopenia and of the local Shwartzman reaction is briefly discussed.
INHIBITION OF THEILER'S ENCEPHALOMYELITIS VIRUS (GDVII STRAIN) OF MICE BY AN INTESTINAL MUCOPOLYSACCHARIDE
Authors: Mandel Benjamin , Racker Efraim
Published: June 2004

A mucopolysaccharide has been obtained from intestinal tissue of adult mice which inhibits both infectivity and hemagglutination of Theiler's GDVII strain of encephalomyelitis virus of mice. The inhibitor is inactive against the FA and TO strains of Theiler's virus and against the Lansing strain of poliomyelitis virus. In the adult mouse, large amounts of the inhibitor are found only in the small intestine. The small intestine of infant mice, however, contains a considerably smaller amount of inhibitor. Inhibition, both in vivo and in vitro, appears to be the result of an interaction between virus and inhibitor. The intestines of man, monkey, rabbit, rat, cotton rat, hamster, sheep, cow, and pig contain relatively little inhibitor whereas guinea pig intestine contains as much as adult mouse intestine. An enzyme was found in the feces of mice, and several other animals, which is capable of destroying the inhibitory activity of the mucopolysaccharide with the liberation of reducing sugars.
SUSCEPTIBILITY OF MICE FREE OF THEILER'S VIRUS (TO STRAIN) TO INFECTION WITH TO VIRUS
Authors: Feltz Elmer T. , Mandel Benjamin , Racker Efraim
Published: June 2004

A method for the establishment and maintenance of a colony of mice free of Theiler's (TO) virus has been described. This colony has been maintained since 1947 with but one instance of contamination in 1948.

Studies on the susceptibility of these mice to TO virus show that smaller doses are required to establish an infection of the intestinal tract than of the CNS.

A mutant strain of TO(B) virus has been isolated which, following oral administration to mice free of TO virus, is able to cause infection of the CNS with paralysis. When fed to stock mice that carry TO virus, this TO(B) strain does not cause paralysis or other signs of CNS infection.
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: Nelson John B.
Published: June 2004

The mortality rate for 80 Swiss weanlings infected with mouse hepatitis was 2.5 per cent in comparison with 98 per cent for 140 Princeton weanlings.

In Swiss weanlings discrete lesions, which generally failed to progress, were observed in the liver from the 3rd through the 10th day after intraperitoneal injection. The causal virus was demonstrable in peritoneal washings through the 21st day and less regularly in the liver through the 14th day. It was also detectable in both loci after subcutaneous injection.

Infant Swiss mice were susceptible through the 10th day of life, intraperitoneal injection being commonly followed by death.

The pathogenicity and titer of the virus were significantly increased by successive passage in Swiss weanlings.

The virus was detected in the blood of Swiss weanlings on subcutaneous injection only after it had been modified by passage.
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: Nelson John B.
Published: June 2004

The hepatitis of Princeton weanlings was not prevented by the prior injection of terramycin nor was the virus inactivated by exposure to room temperature.

Eperythrozoon coccoides was not demonstrable in blood films from Swiss and Princeton mice infected with the corresponding type of hepatitis virus.

Combined infection with this virus and eperythrozoa, originally obtained by Dr. R. B. McGhee from mice in association with Plasmodium berghei, was attended by the appearance of numerous organisms in the blood.

The development of eperythrozoa in dually infected Princeton mice had no effect on the outcome of the hepatitis.

In Swiss mice, animals with high natural resistance to hepatitis virus, the pathogenicity of this agent was markedly enhanced by combined infection with eperythrozoa.

Eperythrozoa were maintained throughout 18 successive passages in normal Princeton and Swiss weanlings with intact spleens.

The combined infection of Princeton mice with eperythrozoa and the virus component of Gledhill, Dick, and Andrewes, which is nearly inactive when injected alone, resulted in acute hepatitis with fatal outcome.
A STUDY OF ILLNESS IN A GROUP OF CLEVELAND FAMILIES
Authors: Jordan William S. , Gordon Irving , Dorrance William R.
Published: June 2004

Feeding of stool supernates to volunteers has demonstrated that there are at least two different types—afebrile and febrile—of acute infectious non-bacterial gastroenteritis.

The afebrile illness, produced by the Marcy agent previously described, has an average incubation period of 60 hours and is characterized by watery diarrhea.

The agent (FS) responsible for the febrile illness has been carried through 3 human passages. The febrile disease has an average incubation period of 27 hours and is characterized by constitutional symptoms.

It is believed that the two agents are not the same because of the differences in incubation period, the clinical picture, and the absence of cross-immunity.

Intranasal instillation of throat washings obtained from 2 persons with gastroenteritis failed to produce illness in 2 groups of volunteers.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Bennett Ivan L. , Beeson Paul B. ,   With the Technical Assistance of Elizabeth Roberts
Published: June 2004

Injection of extracts or suspensions of various rabbit tissues was found to be without effect upon the body temperature of normal rabbits.

Occasionally, extracts of bone marrow produced transient fever, and saline extracts of acute inflammatory lesions of the Shwartzman and Arthus types were found to produce fever when injected intravenously.

Suspensions or extracts of polymorphonuclear leukocytes collected from sterile peritoneal exudates contain a heat-labile substance which produced fever whereas those of erythrocytes, macrophages, and lymphocytes failed to do so.

The cell-free supernatant fluid of sterile peritoneal exudates obtained at the stage when polymorphonuclear leukocytes predominate also proved capable of producing fever.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Bennett Ivan L. , Beeson Paul B. ,   With the Technical Assistance of Elizabeth Roberts
Published: June 2004

Further studies on fever production by injection of leukocyte extracts or cell-free supernatant fluids from peritoneal exudates in rabbits are reported.

Granulocytes collected from peripheral blood or from pleural exudates contain a heat-labile pyrogenic substance.

The material in extracts of leukocytes and in peritoneal fluids, which causes fever, is destroyed by heating for 30 minutes at 90°C. at pH 7.2 and at 70°C. at pH 4.5. It is active in producing fever over a pH range of 2.0 to 10.5 and maintains potency for as long as 6 months at 4°C.

The fever-producing substance in leukocyte extracts is not dialyzable. Its activity is not destroyed by trypsin, chymotrypsin, or ribonuclease. No evidence of plasma activator or inhibitor was detected.

Significant temperature elevation in the rabbit was effected by a quantity of leukocyte extract containing 0.76 mg. protein and 0.054 mg. polysaccharide.

The febrile response produced by the material under study was compared with that of Menkin's pyrexin as well as with that of bacterial pyrogens. Several significant differences were noted. The properties of pyrexin are similar to those of bacterial pyrogens.

Amidopyrine suppressed the febrile response to injection of leukocyte extracts, whereas neither amidopyrine nor cortisone influenced the appearance of pyrogenic material in induced peritoneal exudates.

Peritoneal fluids collected from rabbits made leukopenic by HN2 were found to contain a fever-promoting substance. Its character has yet to be determined.

It is concluded that there is present in polymorphonuclear leukocytes of rabbits a heat-labile factor capable of producing fever in rabbits and that the leukocyte is probably not the only source of such a factor.
STUDIES ON THE PATHOGENESIS OF KERNICTERUS
Authors: Vogel F. Stephen
Published: June 2004

Kernicteric pigment was extracted by means of chloroform from the brains of 3 infants. Solutions of it gave a positive diazo reaction, and, as determined electrophotometrically, gave maximum absorption of light having a wavelength of 425 mµ, being identical in these properties with chloroform solutions of crystalline mesobilirubin.

Experimental kernicterus was regularly induced by injecting crystalline mesobilirubin intracerebrally in newborn kittens, the pigment staining the cerebral tissues a bright canary-yellow and being deposited abundantly in the nerve cells, as microscopic examinations showed, although these latter were otherwise intact. Bilirubin, likewise injected intracerebrally in newborn kittens, had no such effects.

The possibility is discussed that the blood-brain barrier is altered in some infants with hyperbilirubinemia in such a way that bilirubin crosses it and is then reduced within the brain to mesobilirubin thus giving rise to the cerebral pigmentation of kernicterus. The fact that the pigment itself does not seem to damage the neurons, as the present studies show, makes it necessary to seek some other cause for the neuronal damage that is sometimes seen, in association with the pigmentation, in the naturally occurring disease.
REGRESSION OF TRANSPLANTED LYMPHOMAS INDUCED IN VIVO BY MEANS OF NORMAL GUINEA PIG SERUM
Authors: Kidd John G.
Published: June 2004

In the experiments here described transplanted lymphomas of two kinds regularly regressed following repeated injections of normal guinea pig serum intraperitoneally into mice carrying them, the animals meanwhile remaining lively and devoid of signs of illness or wasting. The lymphomas of untreated control mice, by contrast, usually grew progressively and killed their hosts within 20 to 30 days, and the same was true of the growth of other mice given repeated injections of horse serum or rabbit serum.

In similar experiments, the cells of a transplanted lymphosarcoma of rats were temporarily kept from proliferating by repeated intraperitoneal injections of guinea pig serum, though the cells of two transplanted mammary carcinomas of mice, and those of fibrosarcoma, grew unimpeded in hosts likewise treated.

Additional experiments related to the phenomenon here described, and a discussion of the findings as a whole, are given in an associated paper.
OSMOTIC ACTIVITY OF LIVER CELLS AND MELTING POINT OF LIVER
Authors: Opie Eugene L.
Published: June 2004

Depression of the melting point of liver tissue rapidly frozen by liquid nitrogen during life provides a means by which the molecular concentration within liver cells may be compared with that of solutions of sodium chloride or of blood or of blood serum.

The rising temperature of frozen blood of guinea pig under the conditions of these experiments is retarded when melting occurs, pursues when plotted a prolonged linear course, and finally rises precipitously at –0.54°C. when melting is complete. With the melting of blood serum of guinea pig and of blood of cat and of rat, the temperature takes approximately the same course. The temperature changes are nearly the same as those of a frozen solution of sodium chloride isotonic with blood serum.

The temperature changes of frozen liver assumes when plotted a linear course at about –1.1°C., increases at intervals with step-like progress and finally rises precipitiously at –0.76°C. The temperature changes in melting liver of cat and of rat are similar. The melting of liver begins at a level which approximates that of a solution of sodium chloride isotonic with it.

The step-like course of temperature changes which occur during the melting of frozen liver are best explained by the assumption that the cells contain substances which successively and temporarily retard the rise of temperature.
THE EFFECT OF ADRENAL STEROIDS, CORTICOTROPIN, AND GROWTH HORMONE ON RESISTANCE TO EXPERIMENTAL INFECTIONS
Authors: Kass Edward H. , Lundgren Marguerite M. , Finland Maxwell
Published: June 2004

Cortisone acetate, hydrocortisone, and hydrocortisone acetate depress the resistance of mice to pneumococcal and influenza viral infections, although hydrocortisone acetate is somewhat less effective than the free alcohol, when given subcutaneously.

Pituitary adrenocorticotropin, even in highly purified form and in oil and beeswax, does not significantly alter the resistance of mice to these experimental infections, even when given in doses which may cause profound eosinopenia, lymphopenia, and weight loss, and which are at the limit of tolerance of the animals.

Corticosterone depresses resistance to pneumococcal infections significantly, but fails to alter resistance to influenza viral infections. The findings suggest that murine adrenals may produce one of the known adrenal steroids such as corticosterone along with another steroid, or may produce a steroid other than cortisone, hydrocortisone, or corticosterone.

When resistance is decreased by adrenal steroids, survival time is invariably shortened, and the effect of the steroid hormones is frequently demonstrable within the 1st day after infection with pneumococci, making it unlikely that the depression of resistance that is seen is primarily due to depression of antibody formation.

A single dose of 5 mg. of cortisone may cause depression of resistance and may decrease the survival time for 3 to 6 days afterward.

Growth hormone (somatotropic hormone) in highly purified form, and in the doses used, did not overcome the weight loss induced by cortisone, but the animals treated with growth hormone and cortisone regained their lost weight more rapidly than those receiving cortisone alone. Growth hormone alone caused a slight increase in the rate of gain in weight over controls.

Growth hormone alone did not increase resistance to infection, and did not increase the survival time, in mice infected with either pneumococci or influenza virus. Growth hormone in various dosages failed to overcome the effect of cortisone in depressing resistance to these infections.

Cortisone, hydrocortisone, corticosterone, and corticotropin did not alter significantly the titers of influenza virus attained in the murine lungs during the first 2 days after infection, but cortisone and hydrocortisone markedly delayed the rate at which virus titers declined during the subsequent 6 days. Corticosterone and corticotropin delayed the rate at which the titers declined but slightly, and growth hormone had no apparent effect, as compared with controls. Growth hormone did not overcome the effect of cortisone and hydrocortisone on viral titers. No detectable antibody was found as late as 6 days after infection, in controls or in hormone-treated animals.
SYNTHESIS OF ALL PLASMA PROTEIN FRACTIONS EXCEPT GAMMA GLOBULINS BY THE LIVER
Authors: Miller Leon L. , Bale William F.
Published: June 2004

Lysine-ϵ-C14-labeled plasma proteins produced by the normal rat and the isolated perfused rat liver have been fractionated by preparative zone electrophoresis. The isolated perfused liver incorporates lysine-ϵ-C14 into the plasma albumin, alpha globulin, and beta globulin (including fibrinogen) fractions. No significant C14 incorporation into the trichloracetic acid-precipitable proteins of the gamma globulin fraction was observed.

Presumptive evidence indicates that the alpha globulins turn over more rapidly than any other major plasma protein fraction.

The increased production of gamma globulins in liver disease is discussed.
PLASMA AND TISSUE PROTEINS PRODUCED BY NON-HEPATIC RAT ORGANS AS STUDIED WITH LYSINE-ϵ-C14
Authors: Miller Leon L. , Bly C. G. , Bale William F.
Published: June 2004

The non-hepatic tissues in a perfused "carcass" (caudal half of the rat) maintain some physiological functions for as long as 5 to 6 hours of perfusion, including good clearance of lysine-ϵ-C14 and glucose from the perfusate, and synthesis of both tissue and plasma proteins.

The perfused "carcass" tissues incorporate only small amounts of lysine-ϵ-C14 into the plasma proteins to an extent not markedly affected by the presence of the gastrointestinal tract, pancreas, spleen, or kidneys. This activity is found only in the globulin fraction obtained by sodium sulfate fractionation. No significant activity was detected in the plasma fibrinogen or albumin fractions.

C14-labeled plasma proteins obtained from the eviscerated surviving rat 6 hours after intravenous lysine-ϵ-C14 have been separated by zone electrophoresis. The gamma globulins contain most of the C14 activity, with small but measurable activity in the beta and alpha globulins, and no activity in the albumin fraction.
PLAQUE FORMATION AND ISOLATION OF PURE LINES WITH POLIOMYELITIS VIRUSES
Authors: Dulbecco R. , Vogt Marguerite
Published: June 2004

Plaques have been produced with the three types of poliomyelitis viruses on monolayer tissue cultures of monkey kidney and monkey testis. The number of plaques was proportional to the concentration of the virus. Each plaque originates, therefore, from a single virus particle, defined as the virus unit that is unseparable by dilution. The plaques are due to the specific action of the virus since they are suppressed by type-specific antiserum.

Pure virus lines were established by isolating the virus population produced in single plaques. These derived virus lines had the same morphological, serological, and pathogenic properties as the parent strain.

High titer virus stocks, with titers up to 7 x 108 plaque-forming particles per ml., were obtained.
THE BINDING OF PENICILLIN IN RELATION TO ITS CYTOTOXIC ACTION
Authors: Eagle Harry
Published: June 2004

1. Bacteria exposed to C14- or S35-labelled penicillin bound and concentrated the antibiotic. The amount bound from low concentrations (0.001 to 0.01 µg. per ml.) was related to the penicillin sensitivity of the strain; and highly sensitive organisms such as Streptococcus pyogenes concentrated the antibiotic as much as 200-fold. The material bound by highly sensitive strains from these low concentrations of penicillin was removed to only a minor extent by washing. Penicillin inactivated with penicillinase, by hot H2SO4 or by cold HCl was not similarly concentrated.

2. Despite wide differences in their sensitivity to penicillin, at equieffective (LD99.9) levels, four of the five strains here studied had bound comparable amounts of antibiotic. That lethal intracellular concentration averaged 1.7 to 4 µg. per gm., and 1600 to 3300 molecules per cell.

3. Bacteria in the logarithmic phase of growth, "resting" organisms, and cell-free sonic extracts, had roughly the same reactivity with penicillin. The differences in the amount of penicillin bound by bacteria of varying sensitivity therefore do not rest on differences in the permeability of the cell.

4. Escherichia coli (K12)-inactivated penicillin within the cell; and that inactivation adequately explains its low binding affinity, and its relative resistance. The other species here studied inactivated the diffusible cellular penicillin to only a minor degree, and not enough to explain the differences in their penicillin-sensitivity. The working hypothesis is suggested that their varying sensitivity is instead determined by differences in the reactivity of vital cell components with the antibiotic.

5. At high concentrations of antibiotic (1 to 1000 µg. per ml.), there was non-specific binding by all the cell strains and cell extracts here studied, unrelated to their sensitivity, and masking the specific differences in reactivity noted at low concentrations. At these high levels, penicilloic acid was bound to the same degree as the active antibiotic.
THE EFFECT OF UNDERNUTRITION ON CHOLESTEROL ATHEROSCLEROSIS IN THE RABBIT
Authors: McMillan Gardner C. , Whiteside J. H. , Duff G. Lyman
Published: June 2004

Experiments were done to determine whether undernutrition with consequent loss of weight or failure to gain weight inhibited the development or promoted the regression of the aortic lesions of experimental cholesterol atherosclerosis in the rabbit. The experiments were conducted in such a way as to determine whether undernourished and adequately nourished rabbits fed the same daily doses of cholesterol would manifest different degrees of atherosclerosis at the end of an experiment.

Different experiments tested the effect of undernutrition in young, growing animals that failed to gain weight normally (Experiments 1 and 2); in young rabbits subjected to marked undernutrition both before and during cholesterol feeding (Experiment 3); in fully grown, mature rabbits that lost weight during undernutrition (Experiment 4); and in rabbits that had completed a period of cholesterol feeding before caloric restriction was begun (Experiment 5).

In every experiment it was observed that, if two groups of rabbits were fed cholesterol, one group being subjected to caloric restriction while the other received an adequate diet, no difference in aortic atherosclerosis was observed between the two groups at the termination of the experiment. Furthermore, no obvious effect of undernutrition on the regression of atherosclerotic lesions was observed in the rabbit.

At the same time, undernutrition was found to promote hypercholesterolemia in the rabbit fed cholesterol. The possible significance of this result was discussed.
GLYCOGEN, AN IMMUNOLOGICALLY SPECIFIC POLYSACCHARIDE
Authors: Heidelberger Michael , Aisenberg Alan C. , Hassid William Z. ,   With the Technical Assistance of Arnold Powell
Published: June 2004

Glycogens from various animal and vegetable sources precipitate antipneumococcal horse sera of Types II, VII, IX, XII, XX, and XXII.

Fractionated glycogen and glycogen recovered after reprecipitation, acetylation, and deacetylation precipitate the antisera, but glycogen degraded by saliva does not.

A fraction of the antibody is precipitated in the antisera by glycogen. Possible chemical relationships accounting for these instances of cross-precipitation are discussed in terms of the structures of glycogen and the type-specific polysaccharides of pneumococcus and the quantitative theory of specific precipitation.

Amylopectin also gives cross-reactions of smaller magnitude. Quantitative data on these are withheld until irregularities have been eliminated.
VIREMIA IN HUMAN POLIOMYELITIS
Authors: Horstmann Dorothy M. , McCollum Robert W. , Mascola Anne D.
Published: June 2004

Poliomyelitis virus was isolated from the blood of 6 of 33 individuals infected with a Type 1 strain. Of the 27 negative for viremia, 18 already had Type 1 antibodies.

Type 1 virus was isolated from the throat swabs of all 6 who had viremia, and from the 5 rectal swabs tested. These specimens were all collected at the same time as the positive blood specimens.

The clinical circumstances under which viremia was detected included the minor illness, the asymptomatic infection, and one instance in which the virus was isolated several days before the onset of a mild non-paralytic attack.

In one instance, virus was isolated from a blood specimen which also contained Type 1 antibodies.

The possible role of viremia in the pathogenesis of poliomyelitis is discussed.
SELECTIVE NECROSIS OF CARDIAC AND SKELETAL MUSCLE INDUCED EXPERIMENTALLY BY MEANS OF PROTEOLYTIC ENZYME SOLUTIONS GIVEN INTRAVENOUSLY
Authors: Kellner Aaron , Robertson Theodore
Published: June 2004

Focal necrosis of cardiac and skeletal muscle was produced regularly in rabbits by means of a single intravenous or intra-arterial injection of a solution of crude papain. Similar lesions were produced in rats and mice injected with this material. The intravenous injection of solutions of ficin, trypsin, and streptokinase also resulted in comparable lesions of cardiac and skeletal muscle in rabbits.

The lesions in the myocardium became apparent within 6 hours after injection of the enzyme; they consisted essentially of focal degeneration and necrosis of the sarcoplasm and myofibrils within a segment of muscle fiber. An inflammatory reaction consisting of a small number of polymorphonuclear leukocytes and considerable numbers of mononuclear cells, and often multi-nucleated giant cells, was present within the lesions. In some instances severely damaged fibers were replaced by fibrous tissue and in others proliferation of muscle cell nuclei and restitution of the fiber appeared to take place. Similar changes of a lesser degree were also observed in skeletal muscle.

The findings are discussed in connection with the pathogenesis of the anatomical lesions of rheumatic fever, periarteritis nodosa, and other hypersensitivity states.
STUDIES ON SUSCEPTIBILITY TO INFECTION FOLLOWING IONIZING RADIATION
Authors: Hammond Carolyn W. , Colling Margaret , Cooper Dorothy B. , Miller C. Phillip
Published: June 2004

Mice were inoculated by mouth at different times (2 hours, 5 days, and 11 days) after a single exposure to 550 r total body x-irradiation. The inocula contained approximately 107 Pseudomonas aeruginosa which was found to be quite harmless for unirradiated mice.

Comparison of the cumulative mortality curves and of the incidence of Pseudomonas bacteremia showed their susceptibility to infection by this route to be greatest on the 11th day, somewhat less on the 5th day post irradiation, and least of all directly after irradiation. Since damage to the intestinal mucosa has been found to be maximal within the first few hours after exposure to doses of x-irradiation in this range, it seems reasonable to conclude that the increased susceptibility is not due to increased permeability of the mucosa of the gut, but to impairment of the animal's natural defenses against infection.
STUDIES ON THE FACTORS ESSENTIAL TO THE INITIATION AND MAINTENANCE OF MULTIPLICATION OF PSITTACOSIS VIRUS (6BC STRAIN) IN DEFICIENT CELLS IN TISSUE CULTURE
Authors: Hare John D. , Morgan Herbert R.
Published: June 2004

The growth of psittacosis virus (6BC) was studied in cultures of minced whole chick embryo tissue maintained in either Hanks-Simms solution or Hanks's balanced salt solution (BSS), and in neither medium could sustained, long-term virus growth take place. Addition of beef embryo extract (BEE) to cultures at a time when virus multiplication was declining reversed this general trend and resulted in greater virus growth. This virus-stimulating action of BEE was only partially diminished by colchicine, a mitotic inhibitor, indicating that the action of BEE was not due entirely to the development of a larger population of cells as a result of its enhancement of cell proliferation.

Chick embryo tissue cultivated for 13 days in BSS prior to infection lost its ability to support the growth of psittacosis virus, but this capacity could be restored by the addition of BEE, alone or with colchicine, at the time of infection. A significant amount of virus was adsorbed to tissue in BSS alone, indicating that the failure of virus to grow in depleted tissue maintained only in BSS after infection was not due entirely to failure of virus to attach to and invade the cells.

It was found that an ultrafiltrate and a dialysate of BEE contained the major part of the stimulating capacity of the whole extract, indicating that the active materials were substances of low molecular weights. Autoclaved lactalbumin hydrolysate was an active stimulator, suggesting that the materials responsible for its activity were relatively heat-stable.

Since a chemically defined medium (Parker 199) was equally effective in stimulating viral growth, it should be possible eventually to define the chemical nature of the virus stimulators.

The implications of the findings are discussed with special reference to their application in the study of tissue tropisms and of latency in viral infections of cells.
MYOCARDIAL NECROSIS PRODUCED IN ANIMALS BY MEANS OF CRYSTALLINE STREPTOCOCCAL PROTEINASE
Authors: Kellner Aaron , Robertson Theodore
Published: June 2004

Focal myocardial necrosis that was often extensive was found in a high percentage of rabbits, guinea pigs, and mice given a single intravenous injection of crystalline streptococcal proteinase.

The findings are discussed in relation to their possible implications for the pathogenesis of the cardiac lesions of rheumatic fever.
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: Oliver Jean , MacDowell Muriel , Lee Yin Chen
Published: June 2004

When proteins pass the glomerular filter they are in part directly absorbed by the epithelial cells of the proximal convolution of the nephron with no apparent alteration of the cytological pattern. If the capacity of the tubule cells to thus absorb protein from the tubule fluid is exceeded either by the amount or the nature of the protein the accessory mechanism of droplet formation occurs. This accessory mechanism is an intracellular process in which cytoplasmic elements, the mitochondria with their enzymes, and the absorbed protein combine to form droplets. As the droplets form and then disappear from the renal cells their evolution presents a constantly changing picture depending on the varying nature of their protein and cytoplasmic content.

The droplet is therefore not a cytological structure of fixed characteristics (hyaline droplet) but a locus of metabolic activity and varied structural aspect.
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: Lee Yin Chen
Published: June 2004

1. The cells of the proximal convolutions of the rat can be filled with fine droplets by the administration of certain amino acids in non-toxic dosage.

2. These minute droplets resemble in their Gram positivity and in their phospholipid and PNA content on biochemical analysis (3) the larger droplets that form in the cells of the proximal convolution during the absorption of certain proteins.

3. The positive or negative reaction to 3 specific histochemical procedures of the fine droplets forming after administration of 7 amino acids gave such a high positive correlation with theoretical assumption as to warrant the following inferences: (a) that the methods are specific under the conditions of the experiment; (b) that the droplets contain a higher concentration of the administered amino acid than the general cytoplasm of the cells which contain them.

4. The mitochondrial rodlets of epithelium of the proximal convolution contain sulfhydryl in high concentration, a finding which correlates well with their enzymatic activity.
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: Kretchmer N. , Cherot Francis J.
Published: June 2004

Parenteral injection of amino acids resulted in the formation of Gram-positive droplets in the cytoplasm of the proximal convoluted tubule cells of the kidney of the rat within 15 minutes after intravenous administration.

At this time the free alpha amino nitrogen in the cortex of the kidney had increased 2-fold. At the end of 1 hour this level was still somewhat higher than that of the control animals.

The administration of increasing amounts of the amino acid disclosed the existence of a maximal concentration level in the renal cortex. When it was reached droplets appeared.

Fractionation of the cells 15 minutes after the injection of lysine resulted in the recovery of free amino acid in the supernatant fluid but 1 hour after the injection lysine was contained within the particulate protein of the fractions which contain droplets. The increase in lysine was of the order of 2- 3-fold.

It is concluded that the mitochondria-droplet complex is a locus of amino acid concentration and metabolism within the cytoplasm of the renal cell.

A method is described for the determination of lysine in micro quantities.
Combination of Isoflurane and Caspase Inhibition Reduces Cerebral Injury in Rats Subjected to Focal Cerebral Ischemia
Authors: Inoue Satoki , Drummond John C. , Davis Daniel P. , Cole Daniel J. , Patel Piyush M.
Published: June 2004

Background

Recent data indicate that the neuroprotective efficacy of isoflurane is not sustained. Delayed neuronal death, mediated in part by apoptosis, contributes to the gradual increase in the size of the infarction. These data suggest that isoflurane may not be able to inhibit delayed neuronal death. The prevention of apoptosis by a caspase inhibitor might provide neuroprotection in addition to that provided by isoflurane. The current study was conducted to determine whether isoflurane-mediated neuroprotection can be made more durable with the administration of z-VAD-fmk, a nonspecific caspase inhibitor.

Methods

Fasted Wister rats were allocated to awake-zVAD, awake-vehicle, isoflurane-zVAD, or isoflurane-vehicle groups (n = 16/group). Animals were subjected to focal ischemia for 60 min by filament occlusion of the middle cerebral artery. In the awake groups, isoflurane was discontinued after occlusion of the middle cerebral artery. In the isoflurane groups, isoflurane anesthesia was maintained at 1.5 minimum alveolar concentration during occlusion of the middle cerebral artery. Before and after ischemia, daily injections of z-VAD-fmk or vehicle were administered into the lateral cerebral ventricle for 14 days. Neurologic assessment was performed 14 days after ischemia. The volume of cerebral infarction and the number of intact neurons in the periinfarct cortex were determined by image analysis of hematoxylin and eosin-stained coronal brain sections.

Results

Infarction volume was less in the isoflurane-zVAD group (23 +/- 11 mm, mean +/- SD) than in isoflurane-vehicle, awake-vehicle, and awake-zVAD groups (82 +/- 31, 86 +/- 31, and 59 +/- 25 mm, respectively; P < 0.05). In comparison with the awake-vehicle and isoflurane-vehicle groups, the administration of z-VAD-fmk significantly decreased infarction volume (P < 0.05). The infarction volume between the awake-vehicle and isoflurane-vehicle groups was not different. The number of intact neurons within the periinfarct cortex was significantly less in the awake-vehicle group than in the other three groups (P < 0.05). The isoflurane-zVAD group demonstrated better neurologic function than the awake-vehicle group (P < 0.05).

Conclusion

These findings are consistent with the premise that ongoing delayed neuronal death, in part mediated by apoptosis, contributes to the progression of cerebral infarction during the recovery period, and its inhibition can provide sustained neuroprotection.
Inducible Nitric Oxide Synthase Mediates Delayed Cardioprotection Induced by Morphine In Vivo
Authors: Jiang Xiaojing , Shi Enyi , Nakajima Yoshiki , Sato Shigehito
Published: June 2004

Background

It is not known whether morphine induces delayed cardioprotection against ischemia and reperfusion. The authors measured the delayed preconditioning induced by morphine and determined the role of inducible nitric oxide synthase (iNOS) in mediating this effect using a pharmacological inhibitor and iNOS gene-knockout mice.

Methods

Adult male wild-type and iNOS gene-knockout (B6, 129) mice were treated with morphine (0.3 or 0.1 mg/kg intraperitoneal) or saline. Twenty-four hours later, mice were subjected to 45 min of coronary artery occlusion followed by 120 min of reperfusion. S-methylthiourea sulfate (3 mg/kg, intraperitoneal) was given 30 min before the occlusion to block iNOS. Infarct size as a percentage of the area at risk was determined by triphenyltetrazolium chloride staining. iNOS and endothelial nitric oxide synthase expression were measured by Western blot.

Results

Infarct size was significantly reduced in wild-type mice from 43.1 +/- 5.3% in the saline group to 22.4 +/- 4.4% in the higher-dose morphine group (0.3 mg/kg) (P < 0.05). This cardioprotective effect was abolished by S-methylthiourea sulfate (43.3 +/- 3.9%) and was absent in iNOS gene-knockout mice (42.3 +/- 4.7%). Pretreatment with the lower dose of morphine (0.1 mg/kg) did not reduce infarct size (41.1 +/- 5.4%). A significant increase in myocardial iNOS expression was observed 24 h after morphine administration (0.3 mg/kg but not 0.1 mg/kg; P < 0.05), whereas endothelial nitric oxide synthase remained unchanged.

Conclusions

: Pretreatment with morphine induces delayed cardioprotection in mice. The authors demonstrated an obligatory role for iNOS in mediating morphine-induced delayed cardioprotection.
Anesthetics Inhibit Acetylcholine-promoted Guanine Nucleotide Exchange of Heterotrimeric G Proteins of Airway Smooth Muscle
Authors: Sakihara Chie , Perkins William J. , Warner David O. , Jones Keith A.
Published: June 2004

Background

Anesthetics inhibit airway smooth muscle contraction in part by a direct effect on the smooth muscle cell. This study tested the hypothesis that the anesthetics halothane and hexanol, which both relax airway smooth muscle in vitro, inhibit acetylcholine-promoted nucleotide exchange at the alpha subunit of the Gq/11 heterotrimeric G protein (Galphaq/11; i.e., they inhibit muscarinic receptor-Galphaq/11 coupling).

Methods

The effect of halothane (0.38 +/- 0.02 mm) and hexanol (10 mm) on basal and acetylcholine-stimulated Galphaq/11 guanosine nucleotide exchange was determined in membranes prepared from porcine tracheal smooth muscle. The nonhydrolyzable, radioactive form of guanosine-5'-triphosphate, [S]GTPgammaS, was used as the reporter for Galphaq/11 subunit dissociation from the membrane to soluble fraction, which was immunoprecipitated with rabbit polyclonal anti-Galphaq/11 antiserum.

Results

Acetylcholine caused a significant time- and concentration-dependent increase in the magnitude of Galphaq/11 nucleotide exchange compared with basal values (i.e., without acetylcholine), reaching a maximal difference at 100 microm (35.9 +/-2.9 vs. 9.8 +/-1.2 fmol/mg protein, respectively). Whereas neither anesthetic had an effect on basal Galphaq/11 nucleotide exchange, both halothane and hexanol significantly inhibited the increase in Galphaq/11 nucleotide exchange produced by 30 microm acetylcholine (by 59% and 68%, respectively).

Conclusions

Halothane and hexanol interact with the receptor-heterotrimeric G-protein complex in a manner that prevents acetylcholine-promoted exchange of guanosine-5(')-triphosphate for guanosine-5'-diphosphate at Galphaq/11. These data are consistent with the ability of anesthetics to interfere with cellular processes mediated by heterotrimeric G proteins in many cells, including effects on muscarinic receptor-G-protein regulation of airway smooth muscle contraction.
Ultrasound Guidance in Caudal Epidural Needle Placement
Authors: Chen Carl P. C. , Tang Simon F. T. , Hsu Tsz-Ching , Tsai Wen-Chung , Liu Hung-Pin , Chen Max J. L. , Date Elaine , Lew Henry L.
Published: June 2004

Background

This study was conducted to investigate the feasibility of using ultrasound as an image tool to locate the sacral hiatus accurately for caudal epidural injections.

Methods

Between August 2002 and July 2003, 70 patients (39 male and 31 female patients) with low back pain and sciatica were studied. Soft tissue ultrasonography was performed to locate the sacral hiatus. A 21-gauge caudal epidural needle was inserted and guided by ultrasound to the sacral hiatus and into the caudal epidural space. Proper needle placement was confirmed by fluoroscopy.

Results

In all the recruited patients, the sacral hiatus was located accurately by ultrasound, and the caudal epidural needle was guided successfully to the sacral hiatus and into the caudal epidural space. There was 100% accuracy in caudal epidural needle placement into the caudal epidural space under ultrasound guidance as confirmed by contrast dye fluoroscopy.

Conclusions

Ultrasound is radiation free, is easy to use, and can provide real-time images in guiding the caudal epidural needle into the caudal epidural space. Ultrasound may therefore be used as an adjuvant tool in caudal needle placement.
Guest editorial: the 2001 UK census: remarkable resource or bygone legacy of the ‘pencil and paper era’?
Authors: Boyle Paul , Dorling Danny
Published: June 2004

National censuses are expensive. They are conducted infrequently. They collect information that some feel infringes their human rights, and people are required by law to complete them. The outputs are not perfect, and in some situations may be misleading. Some suggest that censuses hark back to a period when regularly collected administrative data were not available. These are some of the views held about national censuses. Why, then, would others argue that they are an essential resource? In this paper, we consider some of the pros and cons of conducting national censuses, before introducing a series of papers that draw on early data available from the 2001 UK census. We argue that these papers, and the wealth of research that will be conducted in the future with 2001 census data, make a strong case for supporting the compulsory collection of personal information about the ‘entire’ population every ten years.