bluuebunny/crossref_metadata_2025 huggingface dataset:
THE HISTOGENESIS OF CELLS IN EXPERIMENTAL PNEUMONIA IN THE DOG
Authors: Loosli Clayton G.
Published: June 2004

The kinds of cells and the sequence in which they appeared in the inflammatory exudate were studied in a series of experimentally produced pneumonic lesions in dogs. There was a gradual and progressive change in the character of the exudate and the kinds of cells as the disease progressed. The microscopic findings could be more closely correlated with the age of the lesions than with their gross appearance or with the clinical condition of the animal at the time of death. The cells in the exudate came principally from the blood. The polymorphonuclear leucocytes were gradually replaced by larger phagocytic mononuclear cells. These were derived chiefly from the hypertrophy and transformation into larger phagocytic cells of the lymphocytes and monocytes of the blood after they entered the air spaces along with the polymorphonuclear leucocytes in the early stages of the disease. To follow the development of the hematogenous exudate cells into macrophages in the dog, the pneumonic process must be studied from its earliest inception and at close stages during the first 36 hours of the disease. The local septal cells contributed only in a minor way to the origin of the macrophages. Their principal reaction appeared to be one of enlargement without detachment from the alveolar walls. Consolidation of the lungs occurred as a result of the spread of the pneumococci through the air spaces by direct passage of the infected edema fluid from alveolus to alveolus through the pores of Kohn and from bronchiole to bronchiole from aspiration during breathing and coughing. The similarity of the histogenesis of the exudate cells in this series of experimentally induced pneumonic lesions in the dog and in those which occur spontaneously in man was discussed.
NUTRITIONAL DEFICIENCIES AS A CAUSE OF ELEVATED BLOOD PRESSURE IN RATS (WITH ESPECIAL REFERENCE TO THE VITAMIN B2 COMPLEX)
Authors: Calder Royall M.
Published: June 2004

The effects of dietary deficiencies on the blood pressure of rats were studied, with especial reference to vitamin B deficiencies. A deficiency of the entire vitamin B complex was followed by a slight fall in blood pressure. A deficiency of only thse heat-stable fractions was followed by a significant and persistent rise in pressure, which could be reversed by restoring these factors to the diet. Partial deficiencies were followed by a higher rise of blood pressure than were complete deficiencies, perhaps because of the debilitating effects of the latter.

Even an excessive intake of the heat-stable fractions of the vitamin B complex did not prevent entirely a rise of pressure if the diet was otherwise deficient. Under the latter conditions, the rise in pressure was slower and less marked than in those animals with a deficiency of the vitamin B2 complex only. It therefore appears that, while a deficiency of the vitamin B2 complex plays a dominant rôle in causing a rise of blood pressure in rats, other dietary factors as yet undefined are also involved. From analogy with other deficiency states, it is possible that thsese undefined nutritional factors cause their effects by interfering with absorption and utilization of the vitamin B2 complex.
SELECTIVE "STAINING" FOR ELECTRON MICROGRAPHY
Authors: Mudd Stuart , Anderson Thomas F.
Published: June 2004

The physical basis of contrast and image formation in electron micrography is considered in relation to the possibility of recording selective chemical effects on cell components. A technology of selective microchemical analysis, equivalent to differential staining, is suggested as practicable in electron micrography.

Electron pictures of bacteria after exposure to salts of heavy metals have shown the bacterial inner protoplasm, but not the cell walls, to be selectively darkened; shrinkage, coagulation, or escape of protoplasm from the injured cells may result and be recorded in the electron micrographs.

Recording of the action of germicidal agents on individual bacterial cells is indicated as one promising field of application of microchemical analysis with the aid of the electron microscope.
RADIOACTIVE IRON ABSORPTION IN CLINICAL CONDITIONS: NORMAL, PREGNANCY, ANEMIA, AND HEMOCHROMATOSIS
Authors: Balfour W. M. , Hahn P. F. , Bale W. F. , Pommerenke W. T. , Whipple G. H.
Published: June 2004

Radio iron is a tool which makes iron absorption studies quite accurate in dogs and reasonably satisfactory in human beings. This method is vastly superior to others previously used.

Normal human pregnancy without significant anemia may show active radio iron absorption—16 to 27 per cent of iron intake. The pregnant woman as a rule shows 2 to 10 times the normal absorption of radio iron.

Diseased states in which iron stores are known to be very abundant—pernicious anemia, hemochromatosis, familial icterus, and Mediterranean anemia —show very little absorption, probably less than normal. This is in spite of a severe anemia in all conditions except hemochromatosis.

Chronic infections in spite of anemia show no utilization of radio iron, whether it may be absorbed or not.

Leukemia shows little utilization of radio iron in red cells in spite of absorption (autopsy), probably because of white cells choking the red marrow.

Polycythemia shows very low values for iron absorption as do normal persons. Two pregnant women showed only normal iron absorption.

We believe that reserve stores of iron in the body, rather than anemia, control iron absorption. This control is exerted upon the gastro-intestinal mucosa which can refuse or accept iron under various conditions.
STUDIES IN RODENT POLIOMYELITIS
Authors: Jungeblut Claus W. , Feiner Rose R. , Sanders Murray
Published: June 2004

1. Murine SK poliomyelitis virus has been transferred from mouse to guinea pig with the establishment of a fixed strain of cavian passage virus.

2. The disease thus produced in guinea pigs is characterized by the occurrence of flaccid paralysis. Typical poliomyelitic lesions are found in the anterior horn of the spinal cord.

3. Guinea pigs are susceptible to infection with murine virus by the intracerebral, intravenous, intraperitoneal, and subcutaneous route; cavian passage virus produces paralysis only upon intracerebral or intravenous injection. Neither virus paralyzes guinea pigs by feeding or nasal instillation.

4. The potency of the virus (murine or cavian) in guinea pigs is considerably lower than in mice and compares with the titer of the original SK strain in monkeys. In paralyzed guinea pigs the virus is found only in the central nervous system and not in extraneural sites, such as blood or abdominal viscera.

5. Attempts to cultivate cavian passage virus in tissue culture have yielded evidence of some in vitro propagation but no passage virus has as yet been obtained by this method.

6. Cross neutralization tests with cavian passage virus in guinea pigs and with murine virus in mice have established the serological identity of the two viruses. Inactivation of cavian passage virus in guinea pigs by poliomyelitis-convalescent monkey sera is irregular. Complete neutralization has been obtained with a concentrated poliomyelitis horse serum.

7. Resistance to reinfection with potent virus can be demonstrated in convalescent guinea pigs as well as in guinea pigs which have survived a symptomless infection with either murine or cavian virus. This immunity is demonstrable by the power of the serum of such animals to neutralize the virus in vitro and by the ability of nerve tissue to dispose in vivo of the infectious agent.

8. Cavian passage virus has a limited pathogenicity for rhesus monkeys. Of a total of 35 monkeys injected intracerebrally with guinea pig passage virus 26 failed to respond with any manifest symptoms of disease; 8 monkeys showed various signs of definite involvement of the central nervous system consisting of tremor, convulsions, facial palsy, and localized pareses; 1 monkey developed typical flaccid paralysis.

9. Following injection with cavian virus the virus may be recovered from the tissues of normal monkeys but not from the tissues of convalescent monkeys shortly after a paralyzing attack of poliomyelitis due to SK or Aycock virus.

10. Immunization of monkeys with early cavian passage virus by the subcutaneous route has given no clear-cut evidence of protection against intracerebral reinfection with SK poliomyelitis virus. Neither has there been any evidence of effective interference in monkeys injected intravenously with early cavian passage virus and intracerebrally with RMV poliomyelitis virus.

11. The bearing of the experimental data upon the epidemiology of the human disease is discussed.
DISTRIBUTION OF THE Rh FACTOR IN AMERICAN INDIANS
Authors: Landsteiner Karl , Wiener Alexander S. , Matson G. Albin
Published: June 2004

Erythrocytes from 120 full blooded American Indians and 155 Indians of mixed ancestry were tested for the Rh agglutinogen. Only a single blood among the full blooded Indians appeared to lack this factor, and in the Indians known not to be full blooded, the distribution of this (and other) blood properties was found to be intermediate between that for whites and pure Indians according to expectation. A variant of Rh demonstrable by a special human serum was more than twice as frequent in full blooded Indians as in white individuals.
THE PATHOGENESIS AND PATHOLOGY OF EXPERIMENTAL TYPE I PNEUMOCOCCIC PNEUMONIA IN THE MONKEY
Authors: Loosli Clayton G.
Published: June 2004

The pathogenesis of lobar consolidation and microscopic pathology of induced Type I pneumococcic pneumonia in a series of fourteen monkeys, killed at close intervals of time after infection, have been studied. The inflammatory process which resulted in consolidation was primarily intraalveolar and intrabronchial. The pneumococci spread within the air spaces as a result of the dissemination of the infected edema fluid directly from alveolus to alveolus through the pores of Kohn and from bronchiole to bronchiole as a result of repeated aspiration during breathing. The pneumonic process within the air spaces developed and progressed independently of the reaction in the interstitial tissues. The organisms spread to the interstitial tissue secondarily from the alveolar spaces. Once in the interstitial tissues they appeared to be the important source of infection producing bacteremia but not important in the mechanism by which consolidation was produced.

The exudate cells came chiefly from the blood. The large mononuclear cells which replaced the polymorphonuclear leucocytes were derived principally from the hypertrophy and transformation of lymphocytes and monocytes into macrophages after they entered the exudate in the early stages of the disease. The part the local septal cells played as the source of the macrophages could not be accurately determined. The reaction of the septal cells appeared to be chiefly one of swelling without detachment and occasional proliferation to form binucleated attached cells. To follow the transformation of the hematogenous mononuclear cells into macrophages in the exudate, the inflammatory reaction must be examined at frequent intervals during the first 36 hours of the disease.

The similarity of the pathogenesis of lobar consolidation in human pneumonia to that observed in the experimentally induced disease in monkeys and dogs was discussed.
STUDIES ON THE NUTRITION OF HEMOPHILUS INFLUENZAE
Authors: Hoagland Charles L. , Ward S. M. , Gilder Helena , Shank Robert E.
Published: June 2004

The metabolic activity of H. influenzae can be followed quantitatively by measurement of the nitrite produced in a medium containing 0.2 per cent potassium or sodium nitrate.

When X-factor, or hemin, and other specific substances required for the optimum growth of H. influenzae, are present in excess, the nitrite produced by this organism is quantitatively related to the concentration of V-factor, or total coenzyme. This quantitative relationship has been demonstrated for five strains of H. influenzae.

It has been shown that various media, which in the past have been used for the determination of coenzyme by growth of H. influenzae, have in many instances been deficient in X-factor and that this substance rather than coenzyme has been the specific factor limiting growth.

When 0.5 per cent blood is added to a basal proteose-peptone medium the specific requirements for optimum growth and metabolic activity of H. influenzae, other than coenzyme, are met, and a large number of specific biocatalysts and nutritive substances added to this medium are without effect in stimulating further growth.

The foregoing studies have formed the basis for a quantitative method for the determination of total coenzyme in blood and tissue. This method is being described elsewhere.
HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER
Authors: Whipple G. H. , Robscheit-Robbins F. S.
Published: June 2004

Human liver tissue has been assayed to determine the amount of hemoglobin production factors in normal and abnormal states. Standardized dogs made anemic by blood removal have been used in this biological assay. Normal animal liver as control is rated as 100 per cent.

Normal human liver tissue as compared with the normal animal control contains more of these hemoglobin production factors—a biological assay ratio of 120 to 160 per cent. Infections, acute and chronic, do not appear to modify these values, the concentration of hemoglobin-producing factors falling within the normal range.

Pernicious anemia and aplastic anemia both show large liver stores of hemoglobin-producing factors—a biological assay ratio of 200 to 240 per cent. Therapy in pernicious anemia reduces these liver stores as new red cells are formed.

Secondary anemia presents a low normal or subnormal liver store of hemoglobin-producing factors—an assay of 60 to 130 per cent.

Hemochromatosis, erythroblastic anemia, and hemolytic icterus in spite of large iron deposits in the liver usually show a biological assay which is normal or close to normal.

Polycythemia shows low reserve stores of hemoglobin-producing factors. Leukemias present a wide range of values discussed above.

Hypoproteinemia almost always is associated with low reserve stores of hemoglobin-producing factors in the liver—biological assays of 60 to 80 per cent. Hypoproteinemia means a depletion of body protein reserve stores including the labile protein liver reserves—a strong indication that the prehemoglobin material (or globin) is related to these liver stores.

Pregnancy, eclampsia, and lactation all may present subnormal liver stores of hemoglobin-producing factors. Exhaustion of protein stores lowers the barrier to infection and renders the liver very susceptible to many toxic substances.

It should not be difficult to correct hypoproteinemia under these conditions and thus relieve the patient of a real hazard.
A GENERALIZED VISCERAL DISEASE OF GUINEA PIGS, ASSOCIATED WITH INTRANUCLEAR INCLUSIONS
Authors: Pappenheimer Alwin M. , Slanetz Charles A.
Published: June 2004

A spontaneous generalized visceral disease of guinea pigs, characterized by the presence of intranuclear inclusion bodies of the herpes type, is described.

The possible relation of this disease to the salivary gland virus infection of guinea pigs is discussed.
STUDIES ON EASTERN EQUINE ENCEPHALOMYELITIS
Authors: King Lester S.
Published: June 2004

50 per cent glycerine injected intraperitoneally, intramuscularly, or intravenously, greatly enhances the activity of equine encephalomyelitis virus injected intramuscularly, increasing its virulence up to 100-fold. The same effect is produced by very concentrated sodium chloride. The result appears due to dehydration of the nervous system, suddenly produced. Gradual withdrawal of body fluids, produced by depriving animals of drinking water, results in sharp concentration of the blood, equal to that produced by glycerine or salt. But such deprivation of water alone does not result in significant dehydration of the brain, nor does it have any effect on virus action. The facilitation effect is not produced by drastic procedures involving shifts of electrolytes without loss of total water from the brain. Glycerine has no facilitating action when the virus is administered intranasally or intraocularly, suggesting a fundamental difference in pathogenesis between these routes and the intramuscular.
SIMULTANEOUS RENAL AND HEPATIC EXCRETION OF WATER, CYANOL, AND AZOFUCHSIN I IN RABBITS
Authors: Ehrich William E.
Published: June 2004

1. The renal and hepatic excretion of water, cyanol, and azofuchsin I was studied in rabbits under various conditions. It was observed that under the conditions of our experiments the urine rate was independent of the bile rate, and vice versa. The renal excretion of these dyes also was independent of their hepatic excretion except in cases in which the liver was severely damaged. On the other hand, the hepatic excretion of these dyes depended also on their renal elimination.

2. The relationship between the renal and hepatic excretion of cyanol and azofuchsin I could be expressed in the form of hyperbolas.

3. In the use of dyes as a measure of renal function, no noteworthy error is introduced by their hepatic excretion except in cases in which the liver is severely damaged.
THE CONTROL OF THE RENAL EXCRETION OF WATER
Authors: Shannon James A.
Published: June 2004

Water and electrolyte excretion has been studied in a series of dogs with diabetes insipidus, in which the extent of neurological damage was subsequently determined. The animals were studied before and after the introduction of variables which produce marked changes in the state of hydration,—administration and restriction of water and the substitution of 0.5 per cent sodium chloride for it as a drinking fluid. Observations were made on those factors, both general and renal, which appear to be important in determining the excretion of water and electrolyte, or which may be expected to yield information on the mechanisms by which the regulation of such excretion is achieved. These are the volume of extracellular fluid and plasma and the concentration of the contained electrolyte, glomerular filtration rate, and the excretion of electrolyte, urea, and water itself, as well as the tonicity of the urine.
QUANTITATIVE ALTERATIONS IN THE HYPEREMIA RESPONSES TO LOCAL ISCHEMIA OF THE SMALLEST BLOOD VESSELS OF THE HUMAN SKIN FOLLOWING SYSTEMIC ANOXEMIA, HYPERCAPNIA, ACIDOSIS, AND ALKALOSIS
Authors: DiPalma Joseph R.
Published: June 2004

The responsiveness of the smallest blood vessels of the human skin was measured in systemic anoxemia, hypercapnia, acidosis, and alkalosis. A method was used which measured quantitatively the reactive hyperemia produced by a standardized period of local ischemia of these fine vessels. By timing the clearing period of the threshold hyperemia response a direct indication of blood flow in these fine vessels was obtained. The following conclusions were reached concerning the responses of the smallest blood vessels of the skin.

1. Systemic anoxemia causes a decrease in sensitivity to local ischemia and a slowing of the blood flow.

2. Hypercapnia prevents the changes resulting from anoxemia.

3. These changes in the smallest blood vessels of the skin occur independently of changes in pulse rate, blood pressure, and respiratory rate and depth.

4. With systemic acidosis there is a decrease in sensitivity to local ischemia and a slowing of blood flow. The exact opposite takes place in systemic alkalosis.

5. The view is advanced, after due consideration of the facts, that the carbon dioxide concentration of the blood, or something directly associated with it, is the most important factor determining the sensitivity of these vessels, rather than oxygen saturation or changes in blood pH.
LIVER INJURY, LIVER PROTECTION, AND SULFUR METABOLISM
Authors: Miller L. L. , Whipple G. H.
Published: June 2004

Protein-depleted dogs are very susceptible to injurious agents—in particular, chloroform. Methionine given shortly before chloroform anesthesia will give complete protection against chloroform. Methionine (or cysteine plus choline) given 3 or 4 hours after chloroform anesthesia will give significant protection against the liver injury of chloroform anesthesia. Methionine given more than 4 hours after chloroform anesthesia gives no protection against liver injury. Choline alone given before chloroform gives no protection against liver injury.

The protein-depleted dogs have livers which are deficient in both nitrogen and sulfur, but sulfur is depleted more than is the nitrogen. The N/S ratio therefore rises. Methionine or cystine feeding promptly makes up this liver sulfur deficit. Viable liver cells are necessary for this uptake of sulfur.

Livers of fetuses in utero or of newborn pups tolerate a chloroform anesthesia which will cause fatal liver injury in adults. The nitrogen and sulfur values of these fetus or pup livers are within the high normal values for adults. Blood-forming cells are present in the fetus or pup livers during this period. When these blood islands are eliminated during the 3rd or 4th week of life, the liver then becomes normally susceptible to chloroform liver injury.

Methionine or methionine-rich protein digests (e.g. casein) or various proteins by mouth or by vein should prove useful to protect the liver against certain types of injury and to aid in organ repair.
A NATURAL ANTIBODY THAT REACTS IN VITRO WITH A SEDIMENTABLE CONSTITUENT OF NORMAL TISSUE CELLS
Authors: Kidd John G. , Friedewald William F.
Published: June 2004

The foregoing experiments have shown that complement fixation takes place when the blood serum of normal adult rabbits is mixed with fresh saline extracts of normal rabbit tissues under controlled conditions. A natural antibody, which reacts in vitro with a sedimentable constituent of normal tissue cells, is responsible for the phenomenon.
THE METABOLISM OF THE CENTRAL NERVOUS SYSTEM IN EXPERIMENTAL POLIOMYELITIS
Authors: Racker E. , Kabat Herman
Published: June 2004

1. During paralysis, the brain of the mouse infected with poliomyelitis virus shows on test after mincing a decrease in anaerobic glycolysis with no significant change in oxygen utilization. The decrease in anaerobic glycolysis varies from 5 per cent to 50 per cent.

2. Sodium fluoride produces a greater inhibition of anaerobic glycolysis in normal than in poliomyelitic brain.

3. Dehydrogenase activity is higher for poliomyelitis-infected brain without added substrate. This difference from normal disappears when substrates are added.

4. The ratio of

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for the sliced motor cortex is higher than

for sliced visual cortex of the dog and cat.

5. The oxygen consumption of the anterior horn of the sliced spinal cord of dog and cat is much less than that of the cerebral cortex.

6. The findings are in keeping with the view that, at a certain stage of the infection, the nerve cells may be reversibly injured but not yet destroyed by the virus.
STUDIES ON HYPOALBUMINEMIA PRODUCED BY PROTEIN-DEFICIENT DIETS
Authors: Elman Robert , Davey Harriet Wolf
Published: June 2004

1. It proved possible to correct dietary hypoalbuminemia in dogs by large plasma transfusions (about 50 cc. per kilo per day). After 1 week of injections the increase of plasma protein exceeded the normal level although but 10 to 13 per cent of the injected protein remained in the blood. There was an associated increase in plasma volume and a marked diuresis. During the following 2 weeks the plasma volume and protein returned to their previous low levels.

2. The nitrogen introduced was retained and produced no change in urinary excretion during the week of plasma injections, but in the following 2 weeks there was an increased nitrogen output. The inference would seem to be that the large amounts of plasma injected in these experiments were not permanently utilized by the body as nitrogenous nourishment but after some delay were largely excreted in the urine.
QUANTITATIVE STUDIES OF SULFONAMIDE RESISTANCE
Authors: Kirby William M. M. , Rantz Lowell A.
Published: June 2004

1. In vitro experiments were performed with E. coli, using a method designed for the quantitative study of various aspects of sulfonamide resistance.

2. Resistance was found to be a gradually developing process, and was demonstrated for all four drugs tested, sulfanilamide, sulfapyridine, sulfathiazole, and sulfadiazine.

3. It was shown that the degree of resistance developed was correlated with the bacteriostatic potency of the sulfonamides, and that organisms resistant to certain bacteriostatic concentrations of one sulfonamide were equally resistant to similar bacteriostatic concentrations of the other sulfonamides.

4. These observations were interpreted as indicating that the development of sulfonamide resistance represents an interaction between the organisms and the one common structural unit of all the sulfonamides, namely, the p-amino nucleus. It is also suggested that this interaction may involve the same enzyme system (or systems) as those concerned in the antagonism of the sulfonamides by para-aminobenzoic acid.

5. The relation of these findings to the broader aspects of sulfonamide resistance is discussed, and it is postulated that, despite reports to the contrary, all organisms susceptible to the bacteriostatic action of the sulfonamides are capable of becoming resistant to all of the sulfonamides.
THE SWINE LUNGWORM AS A RESERVOIR AND INTERMEDIATE HOST FOR SWINE INFLUENZA VIRUS
Authors: Shope Richard E.
Published: June 2004

1. During a 3 year study of the lungworm as intermediate host for the swine influenza virus 98 transmission experiments, using 216 swine, have been conducted. Of these, 50 gave negative results. In the remaining 48, transmission of swine influenza virus by way of the lungworm was demonstrated in one or more animals of each experiment. Irregularities in the results would appear to be due not so much to lack of transmission of masked virus by the lungworms as to failure to evoke its pathogenic capabilities.

2. The stimulus of choice that was most successful in the provocation of swine influenza consisted of multiple intramuscular injections of H. influenzae suis. In several experiments pigs developed swine influenza virus infections 9 to 17 days after infestation with infected lungworms in the absence of any known provocative stress. In these instances an immune response of the swine to the lungworms themselves is suspected of having furnished the provocation.

3. During May, June, July, and August, swine prepared by the ingestion of lungworms carrying virus were absolutely refractory to the provocation of influenza, and they were relatively refractory in September and October. The masked virus was activated most readily during the first 4 months of the year.

4. In a single experiment we succeeded in demonstrating by direct means the presence of swine influenza virus in the neighborhood of lungworms at the base of the lung at a time when the virus was not demonstrable anywhere else in the respiratory tract.

5. Masked swine influenza virus was found to be present in lungworm ova obtained either from the respiratory tracts or the feces of infected swine.

6. In a number of instances, masked swine influenza virus has been found to persist for over a year in lungworm larvae within the earthworm intermediate hosts, and in one case its presence was demonstrated after 32 months.

7. Two varieties of a single species of earthworm, namely, Allolobophora caliginosa f. typica (Savigny) and A. caliginosa f. trapezoides (Dugès), have been found separately capable of serving as intermediate hosts for virus-infected lungworms.

8. Lungworm ova, obtained from convalescent swine which are no longer carrying swine influenza virus in infectious form in their respiratory tracts, contain masked virus.
COMPLEMENT FIXATION WITH THE NEUROTROPIC VIRUSES
Authors: Havens Walter P. , Watson Dennis W. , Green Robert H. , Lavin George I. , Smadel Joseph E.
Published: June 2004

Antigens capable of fixing complement specifically with the appropriate antibodies have been prepared from brain tissue of hamsters and mice infected with the viruses of St. Louis, Japanese, Western, and Eastern encephalitis, and with the West Nile virus. The antigens were freed of the material which reacts with normal serum by means of centrifugation at relatively high speed. In addition, the infectivity of the preparation was destroyed by irradiation with ultraviolet light.

Cross reactions were demonstrated by means of the complement-fixation technique with materials from animals infected with the viruses of Eastern and Western equine encephalitis. No relationship was detectable by this procedure between St. Louis, Japanese, and West Nile viruses. These findings emphasize the need for further investigation and correlation of the immunological reactions of the groups of neurotropic viruses, since the equine agents are apparently unrelated when studied by neutralization and cross-immunity tests while these methods provide evidence of the presence of common antigenic structures in the St. Louis, Japanese, and West Nile agents.
THE DISTRIBUTION OF WATER AND ELECTROLYTES BETWEEN BLOOD AND SKELETAL MUSCLE IN EXPERIMENTAL HYPERTENSION
Authors: Eichelberger Lillian ,   With the Technical Assistance of Michael Roma
Published: June 2004

The effect of an abnormal renal circulation and a resulting hypertension on the distribution of water and electrolytes in skeletal muscle of dogs was as follows: (1) By analysis of the muscle the total content of sodium and chloride was found increased and the total potassium content decreased. (2) A redistribution of water occurred in the muscle involving a shift of water from the muscle cells to the extracellular phase. The calculated mean values per kilo of muscle were, extracellular phase (F) = 254, ± 54 gm.; intracellular water (H2O)C = 532, ± 47 gm., and total solids (S) = 214, ± 8 gm. This extracellular phase volume of 254 gm. represents an increase of 65 per cent over that found in normal dog muscle.

After subjecting the hypertensive dogs to large increases in total body water produced by the intravenous injection of normal isotonic salt solution, the total bulk of 1 kilo of muscle increased a mean average of 103 gm. of which one half was attributed to the extracellular phase and the other half to the swelling of the muscle cells.

Whether the changes found in this study are the result of the functional disturbances caused by the experimental renal abnormalities, or the hypertension, or a combination of both is uncertain at this time. The significance of the results is that there is quantitative evidence that a redistribution of water has occurred in skeletal muscle so that a real extracellular edema exists.
THE STATE OF THE VESSELS OF THE MESENTERY IN SHOCK PRODUCED BY CONSTRICTING THE LIMBS AND THE BEHAVIOR OF THE VESSELS FOLLOWING HEMORRHAGE
Authors: Page Irvine H. , Abell Richard G.
Published: June 2004

1. Direct observations of the arteries, arterioles, capillaries, veins, and lymphatics in the mesentery of anesthetized cats put into shock by incomplete occlusion of the circulation of the limbs showed that:

(a) Marked constriction of the arteries and arterioles, produced by muscular contraction, occurred usually within an hour after incomplete occlusion of the limbs, lasted several hours, and finally gave way in most instances to relaxation an hour or more before death. The constriction reduced the blood supply to the mesentery and intestine and the venous return from them. It did not, however, interrupt the blood flow. No pooling or stagnation of blood was seen even as a terminal phenomenon.

(b) The veins of the mesentery also became constricted but showed less tendency to dilate as death approached. The lymphatics likewise became somewhat narrowed. Even during the terminal stage the leukocytes moved along without change in shape or sticking to the walls of the capillaries or venules.

(c) Hematocrit determinations showed progressive hemoconcentration of moderate degree.

(d) Autopsy usually showed the presence of small hemorrhages in many parts of the body, especially the heart, liver, spleen, and lungs.

(e) Bilateral nephrectomy, suprarenalectomy, and pancreatectomy did not significantly alter the morphological picture elicited by shock induced by restriction of the circulation to the limbs.

2. Removal of large amounts of blood was always followed within a short time by constriction of arteries, arterioles, veins, and lymphatics of the mesentery.

3. Fall in arterial pressure produced by pithing was not accompanied by change in diameter of the arteries, arterioles, veins, or lymphatics, or by blanching of the mesentery or gut.
STUDIES ON THE NATURE OF THE VIRUS OF INFLUENZA
Authors: Chambers Leslie A. , Henle Werner
Published: June 2004

A considerable fraction of the influenza A virus contained in infected allantoic fluid of the developing chick is not sedimentable under conditions which remove virus activity almost completely from filtrates of emulsified mouse lung. The infectious unit from tissue suspensions is about 100 mµ in diameter and is of the same chemical composition as particles of the same size and abundance separated from normal tissues by an identical procedure. Evidence has been presented showing that the infectivity can be, and probably is, carried on such normal cell components as an adsorbate. Other non-infective particles such as erythrocytes may also become infectious units through adsorption of the virus.

The virus occurs in allantoic fluid in two states of dispersion. A variable percentage is associated with particles considerably less than 100 mµ in diameter, probably more nearly 10 mµ, while the remainder is reversibly aggregated. Reversal to the more disperse state may be effected by dilution, sonic vibration, or moderate heat treatment.
STUDIES ON THE NATURE OF THE VIRUS OF INFLUENZA
Authors: Chambers Leslie A. , Henle Werner , Lauffer Max A. , Anderson Thomas F.
Published: June 2004

The pathogenic agent of influenza A has been sedimented from infected extra-embryonic fluids of the developing chick, embryo by ultracentrifugation. Material so obtained contains two fractions resolvable in the analytical centrifuge cell. The first, a homogeneous fraction, showed a sedimentation constant S20 = 20 to 31 x 10–13. The second showed a sedimentation constant S20 = about 800 ± 100 x 10–13, was much less homogeneous than the first, and was shown to consist principally of aggregated particles of the more disperse fraction. Both fractions contained the virus in essentially equal amounts per unit of protein weight as calculated from nitrogen determinations.

Electron micrographs of the isolated virus protein indicated that the predominating unit is roughly spherical in shape and has a modal particle diameter of about 11 mµ, in good agreement with the sedimentation data in indicating a molecular weight of about 650,000.

Approximately 300 of the particles having molecular weight of 650,000 were present in the minimal dose producing infection in mice after nasal instillation.

The influenza A virus may now be regarded as one of the smallest pathogenic agents thus far isolated. Preliminary analyses indicate that it is also one of the least complex, being composed principally of nucleoprotein.
MAMMALIAN RED CELLS AS A SOURCE OF "SMALL PARTICLES"
Authors: Sigurdsson Björn
Published: June 2004

1. Small particles essentially similar to those previously isolated from other tissues have been isolated from mammalian red blood cells (horse blood).

2. About one-third of the dry weight of the particles is lipids.

3. The particles produce hemolysins against the homologous erythrocytes when inoculated into a foreign species.

4. The fact that the particles can be isolated from mammalian red cells which do not contain visible granules is taken to indicate that some at least of the particles isolated from whole organs represent disintegrated "stroma."
MORPHOLOGICAL STRUCTURE OF RICKETTSIAE
Authors: Plotz Harry , Smadel Joseph E. , Anderson Thomas F. , Chambers Leslie A.
Published: June 2004

The morphological structures of the rickettsiae of epidemic and endemic typhus fever, Rocky Mountain spotted fever, and Q fever are similar to one another and to certain bacteria. The rickettsial organisms in common with the elementary bodies of vaccinia virus and all bacteria would appear to have a limiting membrane which surrounds a substance that seems to be protoplasmic in nature; numbers of dense granules are embedded in the inner protoplasm.
INDUCED RESISTANCE OF THE CENTRAL NERVOUS SYSTEM TO EXPERIMENTAL INFECTION WITH EQUINE ENCEPHALOMYELITIS VIRUS
Authors: Olitsky Peter K. , Schlesinger R. Walter , Morgan Isabel M.
Published: June 2004

Under none of the experimental conditions here described was treatment of the infection induced by the virus of Western equine encephalomyelitis in mice and guinea pigs with specific hyperimmune rabbit serum effective if begun after the onset of signs of encephalitis. In mice, after intracerebral inoculation of virus, serum was ineffective when given even before that stage. After peripheral introduction of virus in guinea pigs the disease was completely arrested in certain animals by single or multiple doses of antiserum if treatment was begun within 24 to 48 hours after virus inoculation. In others the incubation period was prolonged to 2 or even as long as 7 weeks.

In untreated guinea pigs, injection of virus alone led to active immunity in those which survived. Antiserum blocked the antigenicity of active virus in the serum-treated animals. The decrease in titer in the sera of all antiserum-treated animals proceeded at the same rate as in those of control guinea pigs which received antiserum alone. Thus it was not possible to predict which ones would survive and which would succumb after a prolonged incubation period. Delayed fatal disease occurred at a time when the neutralizing antibody of the treated guinea pigs had fallen to a low titer. It is therefore likely that the virus which persisted throughout this long incubation period had been prevented from passing to and infecting other cells but reached them when antibody fell to an ineffective level in the surrounding medium. The relative frequency of such delayed reactions limits to a further extent the degree to which antiserum can be depended on for effective treatment of infection with the virus of equine encephalomyelitis.
BIOCHEMICAL STUDIES ON SHOCK
Authors: Engel Frank L. , Winton Mary G. , Long C. N. H.
Published: June 2004

During and following the production of shock by hemorrhage in the normal, suprareno-demedullated, and suprarenalectomized rat, the following significant changes in amino acid and carbohydrate metabolism have been observed.

1. In the intact, suprareno-demedullated, and suprarenalectomized rat there is a progressive rise in the whole blood and plasma amino acid nitrogen levels during and after a fatal, shock-inducing hemorrhage. The rate of rise varies inversely with the survival time. In animals surviving the hemorrhage there is little or no elevation in whole blood amino acid levels during the 8 hours following hemorrhage, and a decrease in 24 hours due to hemodilution. The plasma amino acids, however, rise slightly.

2. The blood amino acid nitrogen elevation occurs only after the blood pressure has fallen to between 85 and 90 mm. of Hg.

3. The blood keto acids, as pyruvate, and the blood lactate become elevated during shock in the normal, suprareno-demedullated and suprarenalectomized rat.

4. In the normal fasted rat with low liver glycogen stores the blood sugar may rise moderately or may not rise at all during hemorrhagic shock. In animals with high liver glycogen levels (fed rats or fasted rats previously fed high protein diets) shock generally induces a marked hyperglycemia. In both groups hypoglycemia may occur terminally.

5. In the suprareno-demedullated and suprarenalectomized rats shock is always accompanied by a fall in the blood sugar.

6. There is no significant difference between the liver glycogen levels of suprareno-demedullated rats fasted 48 hours and those similarly fasted but surviving 24 hours after a hemorrhage.

The blood chemical changes have been interpreted as due to a decrease in hepatic function resulting from early anoxia of the liver and to the later effects of anoxia on the peripheral tissues causing an increased rate of protein breakdown and of glucose utilization and an accumulation of lactate and pyruvate in the blood and tissues.
A METHOD FOR THE DETERMINATION OF THE BLUE DYE T-1824 IN PLASMA
Authors: Phillips Robert Allan
Published: June 2004

A method for the estimation of the concentration of the blue dye, T-1824, in plasma has been developed. The method is based on the fact that the dye can be reduced to a colorless compound by Na2S2O4, in alkaline solution. The extinction coefficient is determined under specified conditions before and after reduction of the dye. Under the conditions employed hemoglobin does not interfere, even if partly present as HbCO or as methemoglobin; the absorption of light by the hemoglobin is the same before and after reduction of the dye. Absorption of light by suspended lipids and plasma pigments is also unaltered by the Na2S2O4. Hence variations from sample to sample in hemolysis or degree of lipemia do not affect the accuracy with which T-1824 is determined.
THE IMMUNOLOGICAL PROPERTIES OF THE HETEROPHILE ANTIGEN AND SOMATIC POLYSACCHARIDE OF PNEUMOCOCCUS
Authors: Goebel Walther F. , Adams Mark H.
Published: June 2004

1. The lipocarbohydrate or F polysaccharide derived from a rough variant of Type I pneumococcus (I R) is antigenic in rabbits and gives rise to precipitins and sheep cell hemolysins. The somatic or C carbohydrate on the other hand is not antigenic.

2. Antisera for the rough variant of Type 1 pneumococcus contain also bacterial agglutinins immunologically unrelated to the C and F precipitins and the heterophile antibody.

3. A study has been made of the quantitative precipitin reaction of the C and F polysaccharides in the serum of rabbits immunized with the IR pneumococcus clarifying certain of these relationships.
ANTIGENIC RELATIONSHIP OF BRITISH SWINE INFLUENZA STRAINS TO STANDARD HUMAN AND SWINE INFLUENZA VIRUSES
Authors: Hudson N. Paul , Sigel M. Michael , Markham F. S.
Published: June 2004

The antigenic relationships of Type A (PR 8, WS) and Type B (Lee) human strains and the Shope and British (Cambridge, North Ireland) swine strains were studied by specific antiserum inhibition of chicken red cell agglutination by the influenza virus.

The Cambridge and North Ireland strains were found to be closely related to the Type A strains and differentiated from the Shope virus.

The distinctive antigenicity of the Lee strain of Type B was confirmed.

Specific antibodies were developed in chickens following single intraperitoneal injections of influenza virus. Inhibition tests yielded results, in the antigenic analysis of the influenza viruses examined, comparable to those obtained with ferret antisera.

Specific inhibition of hemagglutination by influenza virus proved an effective method for the study of strain relationships.
IMMUNITY TO YELLOW FEVER ENCEPHALITIS OF MONKEYS AND MICE IMMUNIZED BY NEURAL AND EXTRANEURAL ROUTES
Authors: Fox John P.
Published: June 2004

Monkeys and mice surviving cerebral infection with yellow fever virus of relatively avirulent strains have been found to resist maximal intracerebral doses of yellow fever virus of a highly neurotropic strain. Such animals, however, do not resist more than very small doses of intracerebrally inoculated virus of Eastern equine encephalomyelitis.

Animals immunized by extraneural routes, on the other hand, are not uniformly resistant to neural infection with neurotropic yellow fever virus. Monkeys which have undergone systemic infection with virus of the avirulent 17D strain or of several jungle strains resist only small intracerebral doses of neurotropic virus; while mice, even when possessed of very high serum-antibody levels as the result of intraperitoneal hyperimmunization, manifest only an irregular resistance to intracerebral challenge inocula.

The difference in the resistance of neurally and extraneurally immunized animals is not related to similar differences in the levels of protective antibody in the sera. Indeed, the average of the serum-antibody titers of the hyperimmune mice is several times that of the intracerebral immunes.

A possibly significant relation does exist, however, between the resistance of mice to neural infection and the content of protective antibody in the brain. The protective activity of suspensions of brains from mice surviving cerebral infection was found to be several times that of brain suspensions from the hyperimmunized animals.

It is concluded that the superior resistance to neural infection of animals whose immunity results from a previous non-fatal infection of the nervous system is effected by a specific local mechanism which is based at least in part upon an increased concentration of antibody in the cerebral tissue.
NON-FATAL INFECTION OF MICE FOLLOWING INTRACEREBRAL INOCULATION OF YELLOW FEVER VIRUS
Authors: Fox John P.
Published: June 2004

Observations have been reported which indicate that mice inoculated intracerebrally with active yellow fever virus may develop an infection which is not only non-fatal but may also be completely inapparent.

The most extensive observations were made on mice which showed signs of infection but were still alive 22 days after inoculation with virus of one or another of several 17D substrains. In such cases, the infection usually progressed no further and partial or complete recovery often ensued. Agents other than yellow fever virus were excluded as a significant cause of such nonfatal infections by the failure of repeated attempts to isolate other infective agents, by the demonstration of antibodies against yellow fever virus in the sera of the mice, and by the demonstration of a high degree of resistance on the part of such surviving mice to reinoculation with large doses of neurotropic yellow fever virus.

Completely inapparent infections with 17D virus were also shown to occur. Studies of apparently normal survivors of 17D virus titrations revealed a small but significant number of animals resistant to intracerebral challenge with neurotropic yellow fever virus. Further, pooled sera from such mice were shown to contain specific protective antibodies.

The occurrence of non-fatal infections with 17D virus was found related to virus dose and substrain. Small doses of virus provoked a significantly higher proportion of non-fatal infections than large doses; while different 17D substrains, tested over equivalent ranges of virus dose, varied greatly with respect to the proportion of infections which did not terminate with death. In the case of two substrains (17DD low and 17D3), non-fatal infections (as demonstrated by resistance to intracerebral challenge with neurotropic virus) were sufficiently frequent to cause an increase, when included in the computation of the infective titers, of 25 per cent above the figures based on deaths alone. The demonstration of non-fatal infections, thus, may be important to the accuracy of quantitative determinations of infectivity.

Limited observations with virus of the French neurotropic and the pantropic Asibi strains revealed that non-fatal infections do occur, but only rarely.

Somewhat more extensive observations with unmodified virus of strains isolated from Brazilian cases of jungle yellow fever, in contrast, revealed an occurrence of non-fatal infections much greater than that observed with the most productive 17D substrains. With these jungle strains, the demonstration of non-fatal infections proved indispensable to any measure of the level of infectivity of virus preparations.

The demonstration of the proportional occurrence in mice of non-fatal infections with yellow fever virus provides an additional means by which different virus strains and substrains may be characterized.