bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON EXPERIMENTAL HYPERTENSION
Authors: Katz Yale J. , Goldblatt Harry
Published: June 2004

1. Extraction of finely ground fresh hog kidney with distilled water adjusted to pH 7.8 with sodium hydroxide, followed by successive treatment, as described, with trichloroacetic acid and acetone, gives renin in good yield of a purity suitable for physiological studies and a good starting material for further purification. It contains 15 dog units per mg. N.

2. Further successive purification of this material with ethyl alcohol and ammonium sulfate gives a preparation containing 130 dog units per mg. N. The purest preparation hitherto reported (15) contained 16.0 to 20.8 units per mg. N. Preliminary Tiselius electrophoresis studies suggest homogeneity, but further studies to establish purity are in progress.

3. The properties of the most purified renin indicate that it is a protein. Its chemical and physiological properties correspond to those of the material in crude renal extract which induces an elevation of blood pressure when it is injected intravenously.
RADIOACTIVE IRON ABSORPTION BY GASTRO-INTESTINAL TRACT
Authors: Hahn P. F. , Bale W. F. , Ross J. F. , Balfour W. M. , Whipple G. H.
Published: June 2004

Iron absorption is a function of the gastro-intestinal mucosal epithelium. The normal non-anemic dog absorbs little iron but chronic anemia due to blood loss brings about considerable absorption—perhaps 5 to 15 times normal. In general the same differences are observed in man (1).

Sudden change from normal to severe anemia within 24 hours does not significantly increase iron absorption. As the days pass new hemoglobin is formed. The body iron stores are depleted and within 7 days iron absorption is active, even when the red cell hematocrit is rising.

Anoxemia of 50 per cent normal oxygen concentration for 48 hours does not significantly enhance iron absorption. In this respect it resembles acute anemia.

Ordinary doses of iron given 1 to 6 hours before radio-iron will cause some "mucosa block"—that is an intake of radio-iron less than anticipated. Many variables which modify peristalsis come into this reaction. Iron given by vein some days before the dose of radio-iron does not appear to inhibit iron absorption.

Plasma radio-iron absorption curves vary greatly. The curves may show sharp peaks in 1 to 2 hours when the iron is given in an empty stomach but after 6 hours when the radio-iron is given with food. Duration time of curves also varies widely, the plasma iron returning to normal in 6 to 12 hours.

Gastric, duodenal, or jejunal pouches all show very active absorption of iron. The plasma concentration peak may reach a maximum before the solution of iron is removed from the gastric pouch—another example of "mucosa block."

Absorption and distribution of radio-iron in the body of growing pups give very suggestive experimental data. The spleen, heart, upper gastro-intestinal tract, marrow, and pancreas show more radio-iron than was expected.

The term "physiological saturation" with iron may be applied to the gastro-intestinal mucosal epithelium and explain one phase of acceptance or refusal of ingested iron. Desaturation is a matter of days not hours, whereas saturation may take place within 1 to 2 hours. We believe this change is a part of the complex protein metabolism of the cell.
AN OUTBREAK OF PSITTACOSIS IN PIGEONS, INVOLVING THE PRODUCTION OF INCLUSION BODIES, AND TRANSFER OF THE DISEASE TO MAN
Authors: Smadel Joseph E. , Wall M. J. , Gregg Alan
Published: June 2004

An epizootic disease in pigeons associated with atypical pneumonia in two persons handling the birds has been studied. Most of the observations made during the work were consistent with the idea that we were dealing with an infection caused by a member of the psittacosis-lymphogranuloma venereum group of viruses. The outbreak was peculiar, however, in that tissues of the diseased pigeons contained many intranuclear inclusions and that the viruses isolated from these birds produced both intranuclear inclusions and elementary bodies in the cytoplasm of cells of chorio-allantoic membranes of the developing egg. Whether the pigeons were simultaneously infected with two viruses or whether the virus of pigeon psittacosis can produce intranuclear inclusions under certain conditions remains to be determined.
THE STABILITY OF VARIOLA VIRUS PROPAGATED IN EMBRYONATED EGGS
Authors: Nelson John B.
Published: June 2004

After 24 transfers in embryonated eggs a strain of variola virus (Chinese) was established in the testis of the rabbit and maintained for 11 passages at intervals of 7 days. Residence in the rabbit testis was not accompanied by any significant alteration in the species identity of the virus.

A second strain of variola virus (Minnesota) was transferred 180 times in embryonated eggs with no apparent change in its behavior. Subsequent attempts, however, to maintain this strain in the rabbit by serial testicular passage were unsuccessful.

These observations are discussed in relation to the so called transformation of variola to vaccinia virus by animal passage.
THE OXIDATION OF p-AMINOBENZOIC ACID AND ANTHRANILIC ACID BY SPECIFICALLY ADAPTED ENZYMES OF A SOIL BACILLUS
Authors: Mirick G. S.
Published: June 2004

1. A soil bacillus has been isolated capable of developing specific adaptive enzymes which oxidize PABA apparently to carbon dioxide, water, and ammonia. A few related compounds which, however, do not give the diazo reaction are similarly attacked.

2. This bacillus is also capable of developing analogous but apparently independent adaptive enzymes specifically directed against anthranilic acid, the ortho isomer of PABA.

3. Sulfapyridine is bacteriostatic for this bacillus and this effect is inhibited as in the case of other bacterial species by PABA. Other effects of the sulfonamide drugs and sulfanilic acid upon the specific oxidative enzymes have been described.

4. The specific adaptive enzymes of this soil bacillus may be used for the identification of as little as 10 gamma of either PABA or OABA. A method is described for carrying out these determinations.

5. The possible advantages of this enzymatic method as compared with the more sensitive but less specific techniques which measure the activity of PABA as a growth factor for certain bacterial species have been discussed.
SUSCEPTIBILITY OF CEBUS CAPUCINA (THE SOUTH AMERICAN RINGTAIL MONKEY) AND CERCOPITHECUS CEPHUS (THE AFRICAN MUSTACHE MONKEY) TO POLIOMYELITIS VIRUS
Authors: Melnick Joseph L. , Paul John R.
Published: June 2004

1. The South American ringtail monkey, Cebus capucina, has been infected with the virus of poliomyelitis as found in ultracentrifuged concentrates from poliomyelitic human stools.

2. This species was also found susceptible to poliomyelitis virus found in rhesus and cynomolgus monkey cords, representing early generations of virus derived from two different human sources and from flies trapped in an epidemic area.

3. The Hartford strain of poliomyelitis has been successfully established in different generations in Cebus capucina monkeys.

4. The African mustache monkey, Cerocopithecus cephus, has been infected with poliomyelitis virus by the intra- and subcutaneous routes as readily as the green African monkey, Cercopithecus aethiops sabaeus, and the rhesus monkey, Macaca mulatta.
THE EFFECTS OF ROENTGEN RAYS ON CELL-VIRUS ASSOCIATIONS
Authors: Friedewald William F. , Anderson Rubert S.
Published: June 2004

The virus-induced papillomas of cottontail as well as domestic rabbits regress completely within a few weeks when exposed to 5,000 r of x-ray irradiation. The x-rays do not immediately kill the papilloma cells, but lead to death by inhibiting cellular division and producing pathological changes in the cells which then continue to differentiate. The virus associated with the growths, however, not only persists in undiminished amount during regression, but often an increased yield of it can be obtained on extraction.

The fibroma virus in crude extracts or in vivo is inactivated by far less irradiation than the papilloma virus. 10,000 r destroys 90 per cent or more of the infectivity of the fibroma virus, whereas at least 100,000 r is required to inactivate 50 per cent of the papilloma virus in extracts containing about the same amount of protein.

No variant of the papilloma virus or fibroma virus has been encountered as a result of the irradiation.
STUDIES ON HERPETIC INFECTION IN MICE
Authors: Berry George Packer , Slavin Howard B.
Published: June 2004

Passive immunity, naturally acquired from immune mothers or artificially induced through the administration of immune rabbit serum, conferred on suckling mice of the albino Swiss strain a high degree of resistance against herpetic infection following the intranasal instillation of the virus. Antibodies, which could be readily demonstrated in the blood of 2-week-old mice, were received by the offspring of immune mothers primarily by the mammary route. Naturally acquired immunity declined rapidly when suckling was interrupted. Herpes virus was not recovered from the fetuses of either immune or infected, non-immune mothers.
STUDIES ON HERPETIC INFECTION IN MICE
Authors: Slavin Howard B. , Berry George Packer
Published: June 2004

Intranasal instillation of herpes virus in suckling mice results in specific lesions widely distributed in the viscera. The lungs are infected by aspiration of the virus. Virus disseminated by way of the blood establishes itself in endothelium in certain situations where parenchymal lesions result by direct spread from the vascular foci. Evidence of blood-borne infection was found frequently in the liver and spleen, less frequently in the suprarenals, and, in one instance, in the bone marrow. Renal infection appeared to be uriniferous. Lymph carriage of the virus also occurs, and lymph nodes draining infected areas were often found to contain herpetic inclusion bodies. Herpes virus seems incapable of invading the central nervous system of suckling mice by the vascular route.
PRODUCTION OF A SCURVY-LIKE CONDITION BY FEEDING OF A COMPOUND STRUCTURALLY RELATED TO ASCORBIC ACID
Authors: Woolley D. W. , Krampitz L. O.
Published: June 2004

The feeding of glucoascorbic acid, an analog of ascorbic acid, to mice and cotton rats caused the production of a condition exhibiting many of the changes characteristic of scurvy as seen in susceptible species.

The condition was not prevented or cured by ascorbic acid, but was cured by removal of the glucoascorbic acid from the ration.

The condition was produced in mice fed a highly purified ration. It was not produced in mice fed a natural ration. The presence of a substance in certain plant products which prevented the production of the condition was demonstrated.
THE YIELD OF RABIES VIRUS IN THE CHICK EMBRYO
Authors: Sigurdsson Björn
Published: June 2004

Rabies virus was inoculated intracerebrally in 8 day old chick embryos and the virus activity of pools of embryos titered after incubation at 35–36°C. for different lengths of time. The virus reached a titer of 10–5.5 to 10–6.5 in 5 to to 6 days and remained at a rather constant level until the 9th day of the infection. The report by Kligler and Bernkopf that rabies virus will invade the very young embryo after inoculation on the chorioallantoic membrane was confirmed.
SELECTIVE REVERSIBLE INHIBITION OF MICROBIAL GROWTH WITH PYRITHIAMINE
Authors: Woolley D. W. , White A. G. C.
Published: June 2004

Growth of many microbial species was inhibited by pyrithiamine, the pyridine analog of thiamine. Growth of many other species was not influenced. In a series of bacteria, yeasts, and molds, it was found that inhibition of growth occurred only in those in which growth was stimulated by thiamine or its component pyrimidine and thiazole portions. The amount of pyrithiamine required for inhibition was correlated with the type of thiamine requirements of various species. The least amount was needed to inhibit organisms which required intact thiamine. Those which could use the pyrimidine and thiazole portions were not so readily inhibited. In the case of the former organisms, half maximal inhibition was produced by as little as 0.03 γ per cc. In all instances, the inhibition was overcome by sufficient amounts of thiamine. The synthesis of thiamine by insusceptible species was studied, and it was concluded that formation of thiamine or other antagonistic substance did not provide an adequate explanation of the resistance of these species to the action of pyrithiamine.
BIOCHEMICAL STUDIES ON SHOCK
Authors: Russell Jane A. , Long C. N. H. , Engel Frank L.
Published: June 2004

The changes in the blood levels of amino nitrogen, glucose, lactate, and pyruvate were compared in eviscerate (liverless) rats and eviscerate rats subjected to hemorrhage, in order to establish the rôle of the peripheral tissues in the blood changes during shock. It was found that:—

1. The blood amino acids accumulate at a more rapid rate in the bled liverless rats than in the control liverless animals.

2. The blood sugar falls more rapidly in the liverless rat after hemorrhage, both in animals with intact suprarenal glands and those with enucleated suprarenal medullae.

3. The blood lactate and pyruvate rise slowly in the liverless rat, but maintain a constant relation to each other except terminally when convulsions occur. In the bled liverless rat both lactate and pyruvate increase much more rapidly than in the control liverless rat, and the lactate/pyruvate ratio also increases.

These data are interpreted to indicate that a decrease in liver function during hemorrhagic shock serves to make apparent a considerable increase in peripheral protein catabolism and accentuates the effects of an increased carbohydrate utilization by the periphery. The lactate and pyruvate changes are determined chiefly by anoxia of the peripheral tissue and probably indicate an increasing predominance of anaerobic over aerobic metabolism of carbohydrate in muscle. The liver plays a negligible rôle in the lactate and pyruvate changes in shock.
VARIATION IN MORBIDITY AND MORTALITY OF MURINE TYPHUS INFECTION IN MICE WITH CHANGES IN THE ENVIRONMENTAL TEMPERATURE
Authors: Moragues Vicente , Pinkerton Henry
Published: June 2004

Murine typhus rickettsiae injected intraperitoneally in mice of the dba strain caused a uniformly fatal rickettsial peritonitis if the animals were kept at a room temperature ranging from 65–73°F. or from 70–80°F. With an environmental temperature range of 85–98°F., a mortality of less than 25 per cent was observed.

By utilizing different strains of mice and controlling the environmental temperature, conditions may be created under which murine typhus will have any desired degree of mortality. Such conditions have obvious advantages for the evaluation of therapeutic measures in typhus infection.
THE SIZE OF INFLUENZA VIRUS
Authors: Stanley W. M.
Published: June 2004

The sedimentation behavior of influenza virus in dilute solutions of electrolyte was found to be quite variable. At times the virus activity appeared to sediment at a rate comparable with that of particles about 80 to 120 mµ in diameter, at other times at a rate comparable with that of particles about 10 mµ in diameter, and at still other times the bulk of the activity appeared to sediment at a rate comparable with that of the larger particles and the residual activity at a rate comparable with that of the smaller particles. However, in the presence of a sucrose density gradient, the virus activity was always found to sediment with a rate comparable to that of particles about 80 to 120 mµ in diameter; hence it appeared that the variable sedimentation behavior in dilute electrolyte solution was due to convection or mechanical disturbances during centrifugation.

About 30 per cent of the high molecular weight protein present in the allantoic fluid of chick embryos infected with the F 12 strain of influenza virus was found to consist of a component having a sedimentation constant of about 30 S, and hence a probable particle diameter of about 10 mµ. The residual protein of high molecular weight was present in the form of a component having a sedimentation constant of about 600 S, and hence a probable particle diameter of about 70 mµ. The proportion of the 30 S component in allantoic fluid of chick embryos infected with the PR8 strain of influenza virus was found to be considerably less. The 600 S and 30 S components of F 12 allantoic fluid were purified and separated by differential centrifugation. The purified preparations of the 600 S component were found to possess a specific virus activity from 100 to over 10,000 times that of the purified preparations of the 30 S component, the difference in activity apparently depending only on the degree of fractionation of the two components. The purified 30 S component was found to sediment normally in the presence of 12 per cent sucrose, whereas the small residual virus activity of such preparations was found to sediment in the presence of a sucrose density gradient with a rate comparable to that of much heavier particles. It is concluded that influenza virus activity is not associated with material having a particle diameter of about 10 mµ, but is associated solely with material having a sedimentation constant of about 600 S and hence a probable particle diameter of about 70 mµ.
PARA-AMINOBENZOIC ACID PRODUCTION BY STAPHYLOCOCCI
Authors: Spink Wesley W. , Wright Lemuel D. , Vivino Jean J. , Skeggs Helen R.
Published: June 2004

1. Strains of staphylococci produce diazotizable materials which can be converted to a dye, and the intensity of the color reaction can be quantitated in the same manner as p-aminobenzoic acid. The sulfonamide-resistant strains which we have studied produce more diazotizable substance than non-resistant strains.

2. The development of a color by the diazotizable substance can be inhibited by exposing the substance to a soil bacillus (Mirick) specifically adapted to oxidize PABA.

3. The diazotizable substance produced by staphylococci inhibits the anti-staphylococcic action of sodium sulfathiazole to approximately the same degree as equivalent amounts of pure p-aminobenzoic acid.

4. Two microbiological methods for assaying p-aminobenzoic acid were employed for quantitating the amount of this material produced by staphylococci. In general, the sulfonamide-resistant strains produced more p-aminobenzoic acid than the sulfonamide-sensitive strains. The inconstant results obtained with these biological assays are discussed.
STUDIES ON THE DENATURATION OF ANTIBODY
Authors: Wright George G.
Published: June 2004

Diphtheria antitoxin has been shown to be inactivated in the presence of urea. In 7.5 molar area at pH 7.82 nearly half the activity is destroyed in 24 hours, as measured by the neutralizing power of toxin. The reaction appears to be first order with respect to antitoxin, since the initial rate is independent of the antitoxin concentration, but the rate decreases rapidly with time. Higher or lower pH of the presence of M/10 sodium sulfite increases the antitoxin inactivation.

The meaning of the results is discussed.
ISOLATION FROM NORMAL MICE OF A PNEUMOTROPIC VIRUS WHICH FORMS ELEMENTARY BODIES
Authors: Nigg Clara , Eaton Monroe D.
Published: June 2004

1. A pneumotropic virus which forms elementary bodies has been isolated from apparently normal albino Swiss mice.

2. The antigenic relationship of this virus to those of meningopneumonitis, lymphogranuloma venereum, hamster pneumonia (7), and human pneumonitis (8) was established either by cross-immunity or complement fixation or both.

3. In spite of a relationship to other viruses, the virus could be differentiated from all the others studied by certain of its properties.
THE EFFECT OF CHEMICAL CARCINOGENS ON VIRUS-INDUCED RABBIT PAPILLOMAS
Authors: Rous Peyton , Friedewald William F.
Published: June 2004

The application of methylcholanthrene and tar to virus-induced papillomas of the domestic rabbit caused them to become carcinomatous with great rapidity, and the malignant changes were frequently multiple. In bringing on the cancers the chemical agents acted in their specific capacity as carcinogens, not as ordinary stimulants of cell proliferation. The cancers derived from the virus-infected cells and were of the same types as arise from these elements spontaneously after a much longer time.

The evidence would seem to indicate that the chemical carcinogens acted by way of the virus.
HETEROGENETIC ANTIBODIES IN ACUTE HEPATITIS
Authors: Eaton Monroe D. , Murphy William D. , Hanford V. Lee
Published: June 2004

A heterogenetic antibody showing fixation of complement with human liver and agglutination of sheep erythrocytes was found in certain cases of acute infective hepatitis.

The antigen concerned in these reactions was apparently heat stable and alcohol soluble.

Differences from other heterogenetic antigen-antibody systems have been noted.

The possible relation of the heterogenetic antibody to liver damage was considered.
AMINO ACID MIXTURES EFFECTIVE PARENTERALLY FOR LONG CONTINUED PLASMA PROTEIN PRODUCTION. CASEIN DIGESTS COMPARED
Authors: Madden S. C. , Woods R. R. , Shull F. W. , Whipple G. H.
Published: June 2004

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications.

The ten growth essential amino acids of Rose plus glycine will maintain nitrogen balance and produce as much new plasma protein as will good diet proteins. This good utilization is demonstrated over periods of several months when the amino acids are given either orally or parenterally. There is no evidence of toxicity in general nor to unnatural forms of these synthetic amino acids in particular.

Given parenterally appropriate mixtures of these amino acids are well tolerated even upon rapid injection. The minimal daily requirements for a 10 kilo dog may be given intravenously in 10 minutes without reaction. Subcutaneously a 10 per cent solution may be given rapidly without reaction.

Among various mixtures tested Vt approximates a minimum for a 10 kilo dog. It contains in grams (dl-threonine 0.7, dl-valine 1.5, l-(-) leucine 1.5, dl-isoleucine 1.4, dl-lysine hydrochloride 1.5, l(-) tryptophane 0.4, dl-phenylalanine 1.0, dl-methionine 0.6, l(+)-histidine hydrochloride 0.5, l(+)-arginine hydrochloride 0.5, and glycine 1.0. The presence of glycine improves tolerance to rapid intravenous injection, but excess glycine does not improve utilization of the mixture. Over a long period this mixture appears suboptimal in quantity. Doubled it is more than ample.

Of two casein digests tested the one prepared by enzymatic hydrolysis provided good nitrogen retention and fairly good plasma protein production but was much less tolerable upon intravenous injection than certain mixtures of pure amino acids. The other one prepared by acid hydrolysis and tryptophane fortification afforded bare nitrogen equilibrium and produced virtually no plasma protein.

Skin lesions observed after 10 to 20 weeks of synthetic diet probably reflect a deficiency of some member or members of the vitamin B2 group. A persistent slight weight loss in the face of a strongly positive nitrogen balance may accompany this deficiency.
GELATIN—ITS USEFULNESS AND TOXICITY
Authors: Robscheit-Robbins F. S. , Miller L. L. , Whipple G. H.
Published: June 2004

Gelatin given by vein to doubly depleted dogs (anemic and hypoproteinemic) gives no immediate toxic response, no anaphylactoid reactions, and may contribute something to the building of new hemoglobin and plasma protein.

Gelatin given by vein during 1 to 2 weeks (total 3 to 17 gm. per kilo) usually causes serious disturbances—inhibition of blood protein production, signs of intoxication, much weight loss, and even death.

Gelatin given by vein for 2 to 3 days (total 1 to 3 gm. per kilo) may not cause any recognizable abnormalities, but dogs vary greatly in their response to gelatin by vein. Some dogs may tolerate a total of 7 gm. per kilo without significant disturbance and other dogs may be seriously intoxicated by 2 to 3 gm. per kilo. No one can predict which animal will be least tolerant.

Some experiments with gelatin by vein for 2 to 3 days (total gelatin 1 to 2 gm. per kilo) given with and followed by amino acids or casein digests do show absence of intoxication and ample production of new hemoglobin and plasma protein during the weeks following the injection of gelatin. This may suggest possible usefulness of gelatin with amino acids or casein digests in acute emergencies (shock, hemorrhage).

These doubly depleted dogs are very susceptible to various injurious agents as compared to normal dogs. They may serve as sensitive testing machines for evaluating plasma substitutes.

Where the gelatin by vein inflicts its damage is not clear and there is little if any significant histological evidence but the disturbance of blood protein production implicates the liver.

Gelatin of smaller molecular weight (degraded by autoclaving) is no less toxic than the standard gelatin.

Gelatin by mouth may contribute to but cannot alone support the production of new hemoglobin and plasma protein.

Gelatin by vein has definite limitations in dogs and, by implication, when used in human cases the amount given should be very carefully watched.
HEMATOLOGICAL FINDINGS IN THE GOLDEN HAMSTER (CRICETUS AURATUS)
Authors: Stewart Mabel O. , Florio Lloyd , Mugrage Edward R.
Published: June 2004

Values for hemoglobin, erythrocytes, volume of packed cells, leucocytes, and their distribution, and red blood cell diameter are presented as determined on a group of 114 hamsters of both sexes and of various ages.
INDUCED RESISTANCE OF THE CENTRAL NERVOUS SYSTEM TO EXPERIMENTAL INFECTION WITH EQUINE ENCEPHALOMYELITIS VIRUS
Authors: Schlesinger R. Walter , Olitsky Peter K. , Morgan Isabel M.
Published: June 2004

Although vaccination of guinea pigs with formalin-inactivated Western equine encephalomyelitis virus rendered them specifically immune to an intracerebral challenge dose of 1,000 M.L.D. of Western virus, it failed to protect their central nervous system against the initial effects of the virus: the intracerebral challenge dose was followed by an abortive infection of 20 to 30 hours' duration characterized by fever and histopathological changes which simulated the response at that early stage of non-vaccinated control animals.

During the abortive infection of immune animals, virus could occasionally be demonstrated in their brains; indeed, it was detected with about the same frequency it was isolated from brains of similarly inoculated, non-immune guinea pigs during corresponding early phases of the infection. About one week after the abortive infection there was found a marked transitory accumulation of specific neutralizing antibody in the brain tissue.

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equalled at this time 1:1 to 1:10 instead of the value of about 1:300 found under physiological conditions.

Guinea pigs which had recovered from an abortive infection with Western virus were resistant for a limited period of time to the effects of intracerebral inoculations of the immunologically distinct viruses of Eastern equine encephalomyelitis or vesicular stomatitis.
THE PATHOGENESIS OF TUMORS OF THE LIVER PRODUCED BY BUTTER YELLOW
Authors: Opie Eugene L.
Published: June 2004

A conspicuous feature of the cirrhosis that is produced by butter yellow is the new formation of bile ducts that sprout from ducts of the larger portal spaces and penetrate between "portal units" to anastomose with liver cell columns at the periphery of these units.

Hyperplasia of the liver may occur with butter yellow administration in the absence of cirrhosis or other change associated with widespread destruction of liver tissue; it occurs as diffuse or focal lesions and affects both parenchymal cells and newly formed ducts.

Focal hyperplasia is a precursor of trabecular and adenomatous hepatomas which arise as multiple tumors.

Butter yellow causes localized cystic dilatation of newly formed bile ducts unaccompanied by acute or chronic inflammation and liver cells adjacent to them may undergo hyperplasia.

Cystic ducts by proliferation of their epithelium may form cyst-adenomas.

Butter yellow causes newly formed ducts to undergo dilatation, and with acute inflammation and fibrosis to produce circumscribed macroscopically recognizable lesions (cholangiofibrosis).

Cholangiofibrosis is the precursor of tumors that reproduce the histological characters of small bile ducts (cholangiomas), and often proceed to the formation of scirrhous carcinoma.

Hepatomas, cyst-adenomas, and cholangiomas may become malignant with formation of metastases in which the characteristics of the parent tumor are reproduced.
THE ESSENTIAL DIFFERENCE BETWEEN THE TWO OPTIMUM PROPORTIONS FLOCCULATION RATIOS
Authors: Boyd William C. , Purnell Marjorie A.
Published: June 2004

The fact that the optimum proportion flocculation ratio is different when determined by the α (Dean and Webb) and ß (Ramon) procedures is pointed out. It is demonstrated that this difference is a consequence of the difference in the two methods, and that the two optima, though they may in certain cases lie near together, can never coincide. A new ratio (the ϵ ratio), intermediate between the α and ß ratios, and having theoretical advantages over both of them, is defined.
NUTRITIONAL REQUIREMENTS AND FACTORS AFFECTING THE PRODUCTION OF TOXIN OF CLOSTRIDIUM SEPTICUM
Authors: Bernheimer Alan W. ,   With the Technical Assistance of Margaret T. Spencer
Published: June 2004

A medium consisting of a complete acid hydrolysate of casein supplemented with cystine, tryptophan, growth accessory factors, glucose, and inorganic salts, has been developed for the cultivation of Clostridium septicum. Toxin equivalent to 400 to 700 L.D50 per ml. has been obtained regularly in this medium. The principal factors found to affect the yield of toxin are:—

(a) Phase of strain employed: Cultures of Cl. septicum may contain a number of variants. Some of these may be characterized by their colonial morphology on blood agar as: (1) rough, non-hemolytic colonies; (2) smooth, non-hemolytic colonies; (3) smooth, hemolytic colonies. Of these three variants, only the last produces toxin.

(b) Quantity of growth and length of time cultures were incubated: The toxin and hemolysin content of cultures increases as the bacterial population increases, reaching a maximum value when the number of bacteria is at a maximum, or shortly thereafter. Upon further incubation, the toxin and hemolysin content decreases.

(c) Presence of a hemolysin-inactivating factor: A substance, possibly lipid, and present in cooked meat, is capable of inactivating hemolysin produced in casein hydrolysate medium and can account for the absence of hemolysin from cultures grown in cooked-meat broth.
POLIOMYELITIS BY ACCIDENTAL CONTAGION IN THE CHIMPANZEE
Authors: Howe Howard A. , Bodian David
Published: June 2004

Poliomyelitis virus was isolated from the stools of two uninoculated chimpanzees which had been quartered for 6 months in cages adjoining those of rhesus monkeys receiving intranasal inoculations of potent human stools. Upon arrival, and for 4 months thereafter, neither chimpanzee had antibody against the virus eventually isolated from it. However, antibody had developed against the animals' own virus strains at the time these were isolated from the feces.
STUDIES ON A NON-HEMOLYTIC STREPTOCOCCUS ISOLATED FROM THE RESPIRATORY TRACT OF HUMAN BEINGS
Authors: Mirick George S. , Thomas Lewis , Curnen Edward C. , Horsfall Frank L.
Published: June 2004

A single serological type of non-hemolytic streptococcus, designated streptococcus MG, has been isolated from the lungs of fatal cases of primary atypical pneumonia, from the sputa of patients with this disease, and occasionally from the respiratory tracts of normal human beings. Certain biological characteristics of this microorganism have been studied. All of the 59 strains isolated have been shown to belong to a homogeneous bacteriological group with characteristics which serve to distinguish it from any other well defined species of streptococcus. It has been suggested that this microorganism probably represents a distinct and hitherto undifferentiated species of streptococcus.
PLASMA PROTEIN METABOLISM—NORMAL AND ASSOCIATED WITH SHOCK
Authors: Fink R. M. , Enns T. , Kimball C. P. , Silberstein H. E. , Bale W. F. , Madden S. C. , Whipple G. H.
Published: June 2004

Labeled plasma proteins are produced by administering to dogs the amino acid lysine synthesized with heavy nitrogen. Such labeled proteins are apparently indistinguishable biologically from proteins of normal isotope concentration.

Labeled plasma proteins, as plasma, injected into normal dogs pass out of the blood stream at an initially rapid but constantly decreasing non-logarithmic rate. This outflow is balanced by a simultaneous inflow of plasma proteins from the tissues. Fifty per cent of the labeled protein is out of the blood stream in about 24 hours; 75 per cent in about 6 days.

Shock due to trauma of intestine or leg shows a dilution curve of labeled plasma protein not unlike that of the normal dog. If anything, dilution appears a little less rapid in shock. Since the usual shrinkage of plasma volume and plasma protein mass is present in these shocked dogs, these data are compatible with a decreased inflow of protein into the plasma during shock.

Methods are described which are suitable for the use of heavy nitrogen incorporated in the epsilon group of lysine and its subsequent analysis in body fluids.

These data may indicate that the plasma proteins are normally in constant and rapid exchange with a mobile pool of body protein.
ADJUVANTS IN IMMUNIZATION WITH INFLUENZA VIRUS VACCINES
Authors: Friedewald William F.
Published: June 2004

Subcutaneous inoculation, of PR8 allantoic fluid, or watery suspensions of the virus obtained from allantoic fluid by high-speed centrifugation or by elution after adsorption on red cells induced serum antibodies in experimental animals, which reached the highest levels within 2 weeks after inoculation and were gradually lost thereafter. The addition of killed acid-fast bacteria (Myco. tuberculosis or butyricum), paraffin oil, and a proprietary adsorption base (Falba) to form a stable water-in-oil emulsion of influenza virus suspensions greatly enhanced and maintained immunity and antibody response to the virus. These adjuvants provided a much more effective method of increasing antibody production to the virus than the use of concentrated preparations of virus alone.

Paraffin oil and Falba without the acid-fast bacilli were less effective as adjuvants, although the antibody levels induced were higher than those produced by watery suspensions of the virus and were maintained at a constant level for at least 6 months. Myco. butyricum appeared to be more effective in producing antibodies against the virus than the tubercle bacilli in the emulsions of paraffin oil and Falba. Immunization with these adjuvants and suspensions of influenza virus obtained from allantoic fluid induced antibodies not only against the virus but against antigenic material contained in normal allantoic fluid, although the latter titers were considerably lower.

A suspension of influenza virus (sedimented by high-speed centrifugation) and Myco. butyricum in sesame oil induced about four times as much antibody as when the virus was suspended in saline, in sesame oil alone, or in combination with typhoid bacilli.
THE SEDIMENTATION RATE OF THE BIOLOGICAL ACTIVITIES OF INFLUENZA A VIRUS
Authors: Lauffer Max A. , Miller Gail Lorenz
Published: June 2004

The sedimentation rates of the mouse infectivity principles of the PR8 and the F12 strains of influenza A virus were shown by studies in the separation cell to have values which are not significantly different from sedimentation rates of the principal components of purified preparations. It was shown further that the bulk of the chicken red blood cell agglutinating activity and of the chick embryo infectivity of PR8 influenza virus preparations sediments at the same rate as that of the 100 mµ. component. Some activity was shown to be associated with aggregates. These results lend strong support to the assumption that the three biological activities are associated with the particles characterized as spheres with a diameter of about 100 mµ.
BIOPHYSICAL PROPERTIES OF PREPARATIONS OF PR8 INFLUENZA VIRUS
Authors: Lauffer Max A. , Stanley W. M.
Published: June 2004

The biophysical properties of several preparations of PR8 influenza virus have been studied. Electron micrographs showed slightly irregular, circular particles with an average diameter of 115 mµ and a standard deviation of the distribution of diameters of 15 per cent. The specific volume was determined with a pycnometer to be 0.79. The sedimentation rate was found to vary inversely with the concentration of virus. The extrapolated value for one preparation was 722 Svedberg units and the value for another preparation was 658 units. Sedimentation studies in sucrose solutions of varying densities showed a non-linear dependence of sedimentation rate upon solvent density, indicating that the density in solution increases with increasing sugar concentration. The virus particles floated in a sugar solution with a density of 1.18. The density in the absence of sucrose was estimated to be about 1.1. The virus was shown not to lose infectivity very rapidly in sucrose solutions. The spreading of the boundary during sedimentation was shown to be represented by a standard deviation of the sedimentation rate equal to 8 per cent of the mean. This corresponds to a distribution of diameters with a standard deviation of 4 per cent of the mean. A more slowly sedimenting component was observed with the ultracentrifuge in the highest concentrations of several of the preparations. The intrinsic viscosities, calculated on the basis of concentrations expressed as grams per cubic centimeter, of several highly purified preparations were determined to be between 11.3 and 16.5. The variation of sedimentation rate with concentration was shown to be due entirely to the variation of solution viscosity with concentration. The viscosity of the virus preparations can be explained as being due in great part to the presence of the slower sedimenting contaminating components which possess a very high intrinsic viscosity.

The average particle diameter of the anhydrous PR8 virus particle was calculated from sedimentation and specific volume data to be about 80 mµ. The discrepancy between this value and that obtained from the electron micrographs, the greater size distribution from the electron micrographs, the slight irregularities in some of the particles as observed in the electron micrographs, the behavior of the sedimentation process in sucrose solutions of different densities, and the inactivation of the virus by withdrawal of electrolytes can all be explained in a straightforward manner if it is assumed that the virus particles in solution contain, in addition to the constituents shown by chemical analysis, about 60 per cent by weight of water. It is estimated that such hydrated virus particles are about 100 mµ in diameter.
ELECTROPHORETIC STUDIES ON PR8 INFLUENZA VIRUS
Authors: Miller Gail Lorenz , Lauffer Max A. , Stanley W. M.
Published: June 2004

Crude preparations of PR8 influenza virus, obtained by high-speed centrifugation, contain two electrophoretically distinct components. One of these, present to the extent of 10 to 20 per cent, was identified by electrophoresis, centrifuge, and activity tests, as an impurity similar to or identical with a high molecular weight acidic substance shown by Knight to be elaborated by normal uninfected embryos. The other component, present to the extent of 80 to 90 per cent, appeared to represent the active virus. The virus fraction was separated from the impurity by repeated fractional centrifugation. It then appeared homogeneous in the analytical centrifuge and in the Tiselius apparatus, and possessed an isoelectric point at pH 5.3 as measured by the micro-electrophoresis method.
CHEMICAL STUDIES ON BACTERIAL AGGLUTINATION
Authors: Kabat Elvin A. , Miller C. Phillip , Kaiser Hilda , Foster Alice Z.
Published: June 2004

1. The quantitative method for the estimation of agglutinins has been applied to antimeningococcal horse, rabbit, and chicken sera and to the sera of humans convalescing from meningococcus meningitis. The type-specific and group-specific agglutinin N can be measured, using homologous and heterologous suspensions of meningococci.

2. Type I horse, rabbit, and chicken antimeningococcal sera contain considerable amounts of antibody which cannot be removed either by Type II meningococcus suspension or by preparations of the Type I specific polysaccharide. This residual type-specific antibody has marked potency in protecting mice against subsequent infection with meningococci.

3. Most human convalescent sera contain group-specific antibody. Small amounts of protective antibody and of antipolysaccharide are also formed.

4. Type I antisera absorbed with Type I polysaccharide and with Type II meningococci could be used as a guide in the purification of this new antigen.
IMMUNOLOGIC RELATIONSHIP OF DONOVANIA GRANULOMATIS TO GRANULOMA INGUINALE
Authors: Anderson Katherine , Goodpasture E. W. , DeMonbreun W. A.
Published: June 2004

1. A washed bacterial suspension of Donovan microorganisms cultivated in the yolk of chick embryos was used as an antigen in intracutaneous tests in 6 cases of granuloma inguinale in the active stage of the disease. These injections were responded to by an extensive erythematous and edematous reaction that reached its height in 24 hours and disappeared within 48 hours later. Four control cases without granuloma inguinale did not react to the injection to any greater extent than would be expected from the slight trauma incident to them. The skin of the reacting patients responded in a similar manner but to a lesser extent to a filtrate of infected yolk. Simultaneous control injections of filtered normal yolk demonstrated that sensitivity to normal yolk was not responsible for the reactions.

2. A mucoid material present in infected yolk, soluble in N/100 NaOH, and precipitable by N/100 HCl was recovered and purified by repeated acid precipitation, extraction with ether, washing in distilled water, and dissolution in N/100 NaOH. We regard this material to be of capsular origin.

3. The presumptive capsular material injected intradermally elicited a somewhat different and milder reaction in patients with active granuloma inguinale, but we regard it as specific.

4. The "capsularrdquo; material in suitable dilution elicited distinct precipitation reactions when mixed with the serum from 18 of 19 cases of active granuloma inguinale. Serum from 1 active case showed no precipitation. Sixty-four serums, including 6 from lymphopathia venereum patients and 18 from Wassermann- or Kahn-positive patients, and 1 from an early chancroid failed to precipitate. Two serums from a total of 66 used as controls showed a precipitate in the presence of the capsular material. These patients gave no history or evidence of granuloma inguinale.

5. The "capsular" material fixed complement in the presence of serum from patients with granuloma inguinale. Serum from 12 of 15 cases of granuloma inguinale demonstrated complement fixation. Three failed to fix complement. Of 19 control serums 18 failed to fix complement in the presence of the capsular material and 1 fixed only a very slight amount of complement. None of these serums nor the capsular material itself was anticomplementary.

6. The high proportion of precipitation and complement fixation reactions obtained from patients with active granuloma inguinale is indicative of a specific immunological relationship of the Donovan microorganism cultivated in embryonic yolk to the disease, granuloma inguinale.

7. We suggest that one or all of these methods might be so standardized as to be of distinct diagnostic value.
AN ELECTRON MICROSCOPE STUDY OF ISOLATED MITOCHONDRIA
Authors: Claude Albert , Fullam Ernest F.
Published: June 2004

1. The present paper constitutes a preliminary study of the morphology of mitochondria by means of electron microscopy.

2. The mitochondria that were the subject of this investigation were obtained from a lymphosarcoma of the rat. They were separated from the other components of the leukemic cells by a method of differential centrifugation, and thus made available for direct examination in the electron microscope.

3. In the purified form the mitochondria appeared as spherical bodies, the majority of them varying in size approximately from 0.6 to 1.3 µ in diameter.

4. Certain aspects of mitochondria in the electron microscope suggest that these elements are surrounded by a differentiated membrane. In some cases the limiting membrane seemed to be responsible for maintaining the general shape of the mitochondria, even when most of the mitochondrial substance had been lost.

5. By means of the electron microscope, it is possible to distinguish small elements, 80 to 100 mµ in diameter, within the body of certain mitochondria. Further work is suggested to establish whether these small granules are normal constituents of mitochondria, and what relation may exist between them and ordinary microsomes.

6. The nature of mitochondria as morphological units is discussed. Present evidence indicates that mitochondria constitute definite physical entities which can persist in the absence of the cytoplasm.
THE RÔLE OF THE LYMPHOCYTE IN ANTIBODY FORMATION
Authors: Harris T. N. , Grimm E. , Mertens E. , Ehrich W. E.
Published: June 2004

Following the injection of typhoid antigen or sheep erythrocytes into the pad of the rabbit's hind foot, lymph from the efferent lymphatic of the popliteal lymph node was collected and analyzed for antibody content.

On separating the lymphocytes from the lymph plasma, it was found that the antibody titer of the cell extract was substantially and consistently higher than that of the surrounding fluid. This difference was greatest at the time of greatest rate of increase of antibody titer in the whole lymph, rather than when the antibody titer of the lymph plasma was highest.

These results can only be interpreted to mean that the lymphocytes either produce antibodies or take them up from the lymph plasma. Incubation in vitro of lymphocytes containing one species of antibody with lymph plasma containing another showed that antibodies pass from the cells to the supernatant lymph fluid to reach approximate equilibrium; acquisition of antibody from supernatant lymph fluid was not observed. Similar results were obtained when normal lymphocytes were allowed to incubate in vivo in their own lymph fluid to which antibodies had been added. It was again found that antibodies were not absorbed or adsorbed by lymphocytes. These results seem to indicate that lymphocytes are instrumental in the formation of antibodies.