bluuebunny/crossref_metadata_2025 huggingface dataset:
PLASMA PROTEIN AND HEMOGLOBIN PRODUCTION
Authors: Robscheit-Robbins F. S. , Miller L. L. , Whipple G. H.
Published: June 2004

Given healthy dogs fed abundant iron and protein-free or low protein diets with sustained anemia and hypoproteinemia, we can study the capacity of these animals to produce simultaneously new hemoglobin and plasma protein.

Reserve stores of blood protein-building materials are measurably depleted and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for weeks or months depending upon the intake of food proteins or amino acid mixtures. These dogs are very susceptible to infection and various poisons. Dogs tire of these diets and loss of appetite terminates many experiments.

Under these conditions (double depletion) standard growth mixtures of essential amino acids are tested to show the response in blood protein output and urinary nitrogen balance. As a part of each tabulated experiment one of the essential amino acids is deleted from the complete growth mixture to compare such response with that of the whole mixture.

Methionine, threonine, phenylalanine, and tryptophane when singly eliminated from the complete amino acid mixture do effect a sharp rise in urinary nitrogen. This loss of urinary nitrogen is corrected when the individual amino acid is replaced in the mixture.

Histidine, lysine, and valine have a moderate influence upon urinary nitrogen balance toward nitrogen conservation.

Leucine, isoleucine, and arginine have minimal or no effect upon urinary nitrogen balance when these individual amino acids are deleted from the complete growth mixture of amino acids during 3 to 4 week periods.

Tryptophane and to a less extent phenylalanine and threonine when returned to the amino acid mixture are associated with a conspicuous preponderance of plasma protein output over the hemoglobin output (Table 4).

Arginine, lysine, and histidine when returned to the amino acid mixture are associated with a large preponderance of hemoglobin output.

Various amino acid mixtures under these conditions may give a positive urinary nitrogen balance and a liberal output of blood proteins but there is always weight loss, however we may choose to explain this loss.

These experiments touch on the complex problems of parenteral nutrition, experimental and clinical.
RAIDING OF BODY TISSUE PROTEIN TO FORM PLASMA PROTEIN AND HEMOGLOBIN
Authors: Whipple G. H. , Miller L. L. , Robscheit-Robbins F. S.
Published: June 2004

Dogs with sustained anemia and hypoproteinemia due to bleeding and a continuing low protein or protein-free diet with abundant iron will continue to produce much new hemoglobin and plasma protein for many weeks.

The stimulus of double depletion (anemia and hypoproteinemia) leads to raiding of body and tissue protein to fill the demand for new hemoglobin and plasma protein. The blood proteins in these experiments take priority over the organ and tissue proteins. This is another illustration of the "ebb and flow" or dynamic equilibrium between organ or tissue protein and blood proteins.

The average dog cannot tolerate this drain of double depletion for more than 7 to 11 weeks and during this time may lose 30 to 40 per cent of body weight. Some dogs are much more resistant to this raiding than others. Some dogs show a high blood protein output during every week up to the danger point. With the largest blood protein output one usually observes the most rapid weight loss.

For every kilogram of weight loss we observe 50 to 140 gm. blood protein output. The weekly blood protein production ranges from 40 to 66 gm.

These experiments make heavy demands on the body protein and we expected to record a "premortal rise" in urinary nitrogen. No such observations are noted, rather a most frugal use of all protein and minimum figures for urinary nitrogen.

We suspect that "premortal rise" in many experiments means a terminal infection with the related catabolism of tissue protein and high urinary nitrogen.
ACTIVE IMMUNITY TO POLIOMYELITIS IN CHIMPANZEES FOLLOWING SUBCLINICAL INFECTION
Authors: Melnick Joseph L. , Horstmann Dorothy M.
Published: June 2004

This report is concerned with the production of subclinical poliomyelitis in the chimpanzee, and immunity to such infection. Subclinical infection was produced in eight chimpanzees by the administration of virus orally or intracutaneously, and was measured by the production of a virus carrier state and the development of neutralizing antibodies. Immunity was tested by attempting to induce the carrier state again by a challenge dose of virus by the same routes.

With an homologous strain as the challenge virus, immunity as defined here was produced in each of four chimpanzees tested. Neutralizing antibodies to the homologous strain were present about 1 month following the first exposure to virus by either the oral or cutaneous route.

In another group of two chimpanzees, one developed neutralizing antibodies and immunity to heterologous strains, and one did not.
AN EXPERIMENTAL STUDY OF SHOCK WAVES RESULTING FROM THE IMPACT OF HIGH VELOCITY MISSILES ON ANIMAL TISSUES
Authors: Harvey E. Newton , McMillen J. Howard
Published: June 2004

The spark shadowgram method of studying shock waves is described. It has been used to investigate the properties of such waves produced by the impact of a high velocity missile on the surface of water.

The method can be adapted for study of behavior of shock waves in tissue by placing the tissue on a water surface or immersing it in water. Spark shadowgrams then reveal waves passing from tissue to water or reflected from tissue surfaces.

Reflection and transmission of shock waves from muscle, liver, stomach, and intestinal wall are compared with reflection from non-living surfaces such as gelatin gel, steel, plexiglas, cork, and air. Because of its heterogeneous structure, waves transmitted by tissue are dispersed and appear as a series of wavelets.

When the accoustical impedance (density x wave velocity) of a medium is less than that in which the wave is moving, reflection will occur with inversion of the wave; i.e., a high pressure wave will become a low pressure wave. This inversion occurs at an air surface and is illustrated by shadowgrams of reflection from stomach wall, from a segment of colon filled with gas, and from air-filled rubber balloons.

Bone (human skull and beef ribs) shows good reflection and some transmission of shock waves.

When steel is directly hit by a missile, clearly visible elastic waves pass from metal to water, but a similar direct hit on bone does not result in elastic waves strong enough to be detected by a spark shadowgram.
MODE OF ACTION OF STREPTOMYCIN ON TYPE b H. INFLUENZAE
Authors: Alexander Hattie E. , Leidy Grace
Published: June 2004

1. Of fourteen patients with type b H. influenzae infections treated with streptomycin alone ten recovered promptly; in three of the four remaining cases failure was proved to be due to emergence of resistance of the organisms to streptomycin.

2. The rapid development of resistance to 1000 units of streptomycin per cc. during treatment argues against metabolic adaptation of the bacteria.

3. Careful study of large samples of initial bacterial populations shows resistant members in all ten strains examined. The incidence varies from 1 in 1.1 billion to 1 in 13.8 billion organisms.

4. The proportion of resistant members is not significantly higher, before treatment, in patients who do poorly than in those who respond promptly.

5. The results indicate that emergence of resistance is the result of a selective process; after elimination of sensitive members the very few resistant ones, apparently present in all strains, make up most or all of the population in the cultures taken after commencement of treatment.

6. The survival of organisms which can grow in high concentrations of streptomycin, either in patients or in vitro, is influenced more by the size of the bacterial population than by any other known factor.

7. Since the bacterial population is relatively small in those patients with mild or moderately severe infections the likelihood of a significant number of very resistant members being present is remote.

8. The traits responsible for resistance of the organisms are apparently inherited: (a) The resistant state of one strain has been transmitted in vitro without change in degree through over one hundred subcultures in the absence of streptomycin, (b) Persistence of resistant organisms in the nasopharynx of one patient during a one year period raises an important public health problem.
IMPAIRMENT OF ANTIBODY RESPONSE IN PYRIDOXINE-DEFICIENT RATS
Authors: Stoerk Herbert C. , Eisen Herman N. , John Hedda M.
Published: June 2004

Striking impairment of the antibody response to sheep erythrocytes was found in pyridoxine-deficient rats. Deficiencies in the three other B factors required by the rat, and low protein feeding, having effects on body weight comparable to pyridoxine deficiency, failed to influence the antibody response studied.

Confirming previous observations, a striking loss of thymic and lymphoid tissue occurred in the pyridoxine-deficient animals. A marked deficit in thymus weight also resulted from the feeding of a diet low in thiamin. Histologically, however, lymphoid atrophy was less pronounced in thiamin-deficient rats than in those deprived of pyridoxine.
STUDIES ON STREPTOCOCCAL FIBRINOLYSIS
Authors:   Commission on Acute Respiratory Diseases
Published: June 2004

A method for the measurement of fibrinolysin production by beta hemolytic streptococci is described. The test was shown to be highly accurate in that repeated determinations showed only small variations. A study of 766 strains of beta hemolytic streptococci isolated from normal soldiers and patients with respiratory disease showed that fibrinolysin was produced by Lancefield groups A, C, and G, and, in addition, by a few strains of groups B and F.

Group A streptococci produced more fibrinolysin on the average than the other groups. The median titers were 117 for group A, 61 for group C, and 20 for group G streptococci. In a study of 388 typed group A streptococci from different subjects the fibrinolytic capacity of an organism was shown to be related to the serological type. The importance of this observation in relation to the role of streptococcal fibrinolysis in infections is discussed.

Finally, it was demonstrated that strains of streptococci which produced large amounts of fibrinolysin were capable of stimulating antifibrinolysin formation in patients whereas strains that produced small amounts only occasionally caused antibody formation.
THE OCCURRENCE DURING ACUTE INFECTIONS OF A PROTEIN NOT NORMALLY PRESENT IN THE BLOOD
Authors: McCarty Maclyn
Published: June 2004

A procedure is described for the isolation and crystallization from human serous fluids of the C-reactive protein, a substance which appears in the blood especially in the early phase of certain acute infectious diseases. Immunological studies confirm earlier work in showing that the protein is highly antigenic and serologically specific, and demonstrate that crystallization of the protein effectively separates it from normal serum proteins.
THE ANTIRICKETTSIAL EFFECT OF THIONINE DYES
Authors: Peterson Osler L. , Fox John P.
Published: June 2004

Methylene blue (MB) and toluidine blue (TB) when administered in maximum tolerated oral doses to mice and to cotton rats are highly effective in preventing the usual lethal outcome of intraperitoneally induced infections with R. orientalis. This activity is manifest even when dye administration is delayed until a systemic infection has been well established. Methylene blue is also effective in cerebral infections in mice.

The toxicity of MB, however, limits parenteral (subcutaneous) administration of the dye to dosage levels which are much less effective than the maximum tolerated oral levels. The inability of mice to tolerate an adequately effective parenteral dose of MB suggests that the properties of the dye responsible for its toxicity may be separated from those upon which its antirickettsial effect depends.

The relationship between the response of mice to oral treatment with MB and such factors as the size of the infecting dose and the times of initiation and of withdrawal of treatment may be summarized as follows:

1. With a constant infecting dose, the time of initiation of treatment largely determines the degree of therapeutic effect.

2. The interval after infection beyond which further treatment does not increase the survival rate depends not upon the previous duration of treatment but upon the size of the infecting dose. Paradoxically, treatment can be discontinued sooner after a massive infecting dose than after a smaller one.
HISTOLOGICAL AND SEROLOGICAL SEQUENCES IN EXPERIMENTAL HYPERSENSITIVITY
Authors: Hawn Clinton Van Zandt , Janeway Charles A.
Published: June 2004

1. Groups of normal rabbits were given, single intravenous injections of foreign proteins in doses of 1 gm. per kilo, bled at regular intervals for serologic studies, and sacrificed after varying lengths of time for pathological studies. The protein solutions used were of crystallized bovine serum albumin, bovine serum gamma globulin, and bovine serum. The experiments were planned, first, to correlate the sequence of pathological and immunological changes, and second, to compare the responses to two chemically and immunologically distinct plasma protein fractions and to the whole serum of the same species.

2. (a) The principal pathological lesions in rabbits given bovine serum were similar to those which have been previously observed following, the injection of horse serum and were characterized by widely dispersed but segmental acute inflammatory lesions of the arteries. These lesions were at their height 2 weeks after injection and showed marked repair at 4 weeks.

(b) Crystallized bovine serum albumin produced lesions almost exclusively confined to the arteries which were at their height at 2 weeks, were healing at 3, and healed by 4 weeks. The lesions were less numerous and less intense than in animals given whole serum and were only found in some of the animals.

(c) Bovine serum gamma globulin elicited quite different histologic sequences. The most striking lesions involved the glomeruli of the kidneys, and to a lesser degree, the heart. Lesions in the liver and joints were present but less conspicuous, and arterial lesions were rare and slight in degree. The lesions not only differed from those in rabbits given albumin in distribution but in timing, since they were most widespread and acute at 1 week and were healing at 2 weeks after injection. Moreover, lesions were observed in almost every animal.

3. Results of immunological studies were consistent with the interpretation that the pathological lesions were due to an antigen-antibody reaction in the tissues, as shown by the following:

(a) Acute lesions were only observed when antigen was present and before antibody appeared in the circulation.

(b) Healing of lesions was only observed (with one exception) when antigen had almost or completely disappeared from the circulation, usually with the appearance of antibody.

(c) There was a correlation between the rapidity of evolution of the lesions and the rapidity with which the antigen disappeared from the circulation.

(d) There was a rough correlation between the proportion of animals showing lesions and the proportion developing antibodies after the injection of a particular protein solution.
ABSORPTION FROM THE PULMONARY ALVEOLI
Authors: Drinker Cecil K. , Hardenbergh Esther
Published: June 2004

Experiments upon dogs anesthetized with nembutal and lasting 4 hours, in which the right lymphatic duct and thoracic duct have been cannulated and collection of lung lymph and blood specimens was accomplished after intratracheal instillation of dog plasma, purified bovine serum albumin, crystallized egg albumin, and hemoglobin, have shown that the absorption of such molecules is slight. Experiments in which pyrex glass spheres averaging 4 micra in diameter were instilled failed to disclose entrance of these distinctive foreign particles into the lymph stream, though the fact that lung phagocytes were often found containing the particles or covered with them, indicated that eventually these particles would be found in lung lymphatics and in lymph nodes. The protection against absorption from the lung alveoli is in the main due to intact alveolar epithelium through which molecules of the dimensions of the proteins. commonly entering the alveoli, as a result of trauma or disease, pass very slowly and are found in small traces in lung lymph and even to a less degree in blood.
INFECTION OF MICE WITH MAMMALIAN TUBERCLE BACILLI GROWN IN TWEEN-ALBUMIN LIQUID MEDIUM
Authors: Pierce Cynthia , Dubos René J. , Middlebrook Gardner
Published: June 2004

Introduction of the bacilli by the mtravenous route or by feeding gives rise to a disease predominantly localized in the lungs. Following intracerebral infection, the bacilli first multiply rapidly in the brain tissue, and then invade other organs, producing lesions especially in the lungs. Injection of the bacilli by the intraperitoneal route is less effective than by either the intravenous or intracerebral routes; however, admixture of the bacilli with some of the components of egg yolk increases both the infectivity and the pulmonary localization.

Different strains of mice differ markedly in their susceptibility to experimental tuberculous infection; the highest susceptibility was observed among the pigmented strains (line 1 dba and C57 black). Greater resistance does not appear to depend on the ability to prevent the establishment of infection, but rather corresponds to a slower rate of progression of the infectious process.

It is possible to produce in mice tuberculosis presenting any desired degree of acuteness or chronicity by controlling certain factors which condition the initiation and the progression of the infection.
ANTIPROTEINS IN HORSE SERA
Authors: Heidelberger Michael
Published: June 2004

The antiprotein in an antipneumococcus horse serum resulting from intravenous injections of infected pleural exudate showed a precipitin type of reaction with pneumococcus nucleoprotein rather than the antitoxin type of response.
THE ENHANCING EFFECT OF CONCURRENT INFECTION WITH PNEUMOTROPIC VIRUSES ON PULMONARY TUBERCULOSIS IN MICE
Authors: Volkert Mogens , Pierce Cynthia , Horsfall Frank L. , Dubos René J.
Published: June 2004

The course of pulmonary tuberculosis in the mouse appears to be accelerated as a result of concurrent infection of the lung with either of two pneumotropic viruses. This effect is obtained with virus inocula sufficiently small as to induce little or no definite viral pneumonia.
STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMONIA DUE TO FRIEDLÄNDER'S BACILLUS
Authors: Sale Llewellyn , Wood W. Barry
Published: June 2004

Experimental pneumonia due to Friedländer's bacillus was produced in white rats by the intrabronchial inoculation of the bacilli suspended in mucin. The pneumonia was lobar in type, was almost uniformly fatal, and simulated the acute form of the natural disease in human beings.

The pathogenesis of the pneumonic lesion was studied by examination of microscopic sections of the lungs of animals killed at frequent intervals during the course of the infection. The histologic characteristics of the various stages of the pneumonia were essentially the same as those previously described in experimental pneumococcal (Type I) pneumonia except for the following differences: (1) In isolated areas of the lung in Friedländer's pneumonia many more bacteria were encountered in the alveoli than were ever noted in experimental pneumococcal pneumonia. (2) Abscess formation was common in the late stages of Friedländer's infection, whereas it was not noted in the pneumococcal lesion. (3) Organization of the alveolar exudate, rarely observed in experimental pneumococcal pneumonia, was a prominent feature of the pneumonia due to Friedländer's bacillus.

The mechanism of spread of Friedländer's lesion appeared to be the same as that of pneumococcal pneumonia. Likewise there was noted the same phagocytosis of organisms in the lungs of even bacteremic animals dying of the infection.
STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMONIA DUE TO FRIEDLÄNDER'S BACILLUS
Authors: Sale Llewellyn , Smith Mary Ruth , Wood W. Barry
Published: June 2004

Sulfonamide chemotherapy was found to cure rats of an otherwise fatal form of experimental Friedländer's bacillus pneumonia when treatment was begun 6 hours after inoculation. Most of the pneumonic lesions cleared completely, but an occasional animal exhibited small residual abscesses in the previously consolidated lung.

The recovery process taking place in the lungs was studied histologically at various intervals during therapy. As in the case of pneumococcal pneumonia, the principal action of the sulfonamide was upon the bacteria in the advancing edema zone at the periphery of the pneumonic lesion. The bacteriostatic action of the drug appeared to stop the spread of the pneumonia, and the Friedländer bacilli were ultimately ingested and destroyed by the phagocytic cells in the alveolar exudate.

The phagocytosis of bacteria in the lung was shown to be unrelated to the presence of antibody in the blood.
PLASMA ESTERASE ACTIVITY IN PATIENTS WITH LIVER DISEASE AND THE NEPHROTIC SYNDROME
Authors: Kunkel Henry G. , Ward Sylvia M.
Published: June 2004

By a study of plasma esterase in various hypoproteinemic states information was gained concerning the synthesis of a protein by the liver, which may be applicable to the problem of albumin synthesis. Patients with infectious hepatitis and cirrhosis showed defective formation of plasma esterase that paralleled the defect in albumin formation. The defect could only be altered in patients with cirrhosis by very prolonged therapy indicating that liver function itself had to improve before the proteins could be formed in a normal manner. Patients with the nephrotic syndrome showed a normal or hypernormal formation of plasma esterase. Following spontaneous remissions or the administration of albumin the esterase level showed a marked rise which was in direct contrast to the difficult alterability of the enzyme level in patients with severe liver involvement. It is suggested that the defect in protein synthesis by patients with the nephrotic syndrome may be due to the lack of certain essential materials, one of which may be albumin itself, rather than to any abnormality in the liver.
PREPARATION OF DRIED HEMOGLOBIN WITHOUT LOSS OF ACTIVITY
Authors: Farr Lee E. , Hiller Alma , Van Slyke Donald D. ,   With the Technical Assistance of John Plazin
Published: June 2004

The technique for freezing, drying, and preserving in vacuo which is in common use for plasma can be successfully applied to hemoglobin solutions when the hemoglobin is first deoxygenated to the extent of 99.7 per cent or more.

In confirmation of Morrison and Hisey, the preliminary deoxygenation of the solution is found necessary to avoid formation of methemoglobin during drying. If a solution of oxyhemoglobin is frozen and dried, 20 to 30 per cent is changed to methemoglobin.

Deoxygnated hemoglobin dried and preserved in vacuo retained all its oxygenbinding activity for 180 days, when stored at temperatures from 4° to 30°C. Storage at 38°C. for 92 days, or at 56° for 7 days, caused no loss in activity. The dried hemoglobin had a foam structure which caused it to dissolve immediately upon contact with water.

Deoxygnated hemoglobin in the dry state was partly converted to methemoglobin by even momentary contact with oxygen. When, however, the deoxygnated hemoglobin was dissolved before it was exposed to air, the hemoglobin in solution was relatively stable, and could be stored for months at 4° in contact with air without significant loss of activity.
RENAL EFFECTS OF HEMOGLOBIN INFUSIONS IN DOGS IN HEMORRHAGIC SHOCK
Authors: Hamilton Paul B. , Hiller Alma , Van Slyke Donald D.
Published: June 2004

The immediate effects of treating hemorrhagic shock in dogs by replacing lost blood with 7 per cent hemoglobin solution were favorable, both on renal function and on general condition. However, subsequent transitory depression of the urea clearance for several days, shown by some of the treated animals, but not by untreated bled controls, indicates sufficient possibility of renal damage by the hemoglobin solution to prevent its recommendation at present as a blood substitute.
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS
Authors: Chase Merrill W.
Published: June 2004

Evidence is presented to show that guinea pigs actively sensitized to simple chemical compounds form serum antibodies capable of sensitizing the skin of normal guinea pigs. Skin sites prepared as for the Prausnitz-Küstner test develop immediate-type ("evanescent") reactions with erythema and edema, upon subsequent injection of the corresponding simple compounds or protein conjugates thereof, and give effects resembling transferred reaginic reactions as seen in human beings. The antibodies were obtainable after sensitization by acyl chlorides, acid anhydrides, and also substances of lesser reactivity, picryl chloride and 2:4 dinitrochlorobenzene, which are human allergens. Observations are reported on the specificity of the antibodies and on various details of the reaction.

Like effects result when antiprotein immune sera and their corresponding antigens are employed for the test, making it highly probable that the antibodies secured after sensitization to drugs result from immunization by conjugates formed in vivo.

The sera obtained after sensitization with simple chemical compounds readily confer passive anaphylaxis, and their capacity for sensitizing the skin declines gradually with progressive heating.

It was observed that following a reaction of substantial degree in guinea pig skin the area involved does not fully recover for some days its capacity to react, the effect being a manifestation, it would seem, of what has been termed "non-specific antianaphylaxis."
STUDIES OF THE DISTRIBUTION OF POLIOMYELITIS VIRUS
Authors: Brown Gordon C. , Francis Thomas , Ainslie John
Published: June 2004

The occurrence and duration of the carrier state in familial associates of recognized cases of poliomyelitis was studied by the examination for virus of stool specimens collected from the members of four families at regular intervals for a period of over 2 months. The results indicate that: (1) virus may persist in their stools continuously for 4 to 5 weeks; (2) virus may be encountered intermittently in the stools; (3) in some instances virus may be present for brief periods only; (4) children are more likely to maintain virus than are adults in the same family; (5) infection of a family takes place rapidly, suggesting again simultaneous infection from a common source.
THE LETHAL EFFECT OF RELATIVE HUMIDITY ON AIR-BORNE BACTERIA
Authors: Dunklin Edward W. , Puck Theodore T.
Published: June 2004

The viability of pneumococcus, Type I, sprayed into the atmosphere from a liquid suspension was measured as a function of the relative humidity. When broth, saliva, or 0.5 per cent saline solution is employed as the suspending medium, a very high mortality rate is observed at relative humidities in the vicinity of 50 per cent. However, at humidities above or below this value the microorganisms survive for long periods.

Measurement of the rate of settling of droplets employed in these experiments demonstrated that the disappearance of microorganisms from the air is a true lethal process, rather than a manifestation of aerosol collision processes.

When a saline-free fluid was used, the sharp peak in death rate at intermediate relative humidities disappears.

The lethal effect of intermediate relative humidities on pneumococci atomized from a saline-containing suspension is increased when the particle size of the atomized droplets is increased or when the temperature is raised.

Cultures of hemolytic streptococcus group C and staphylococcus sprayed from a broth medium exhibit the same general survival pattern as a function of relative humidity although the mortality rates are smaller than that of the pneumococcus.

These effects can be explained by assuming the existence of a critical degree of cellular dehydration at which microorganisms become much more sensitive to toxic agents than in states where either more or less water is bound to the cell.

The results presented here may be significant in elucidating certain aspects of the epidemiology of air-borne infections.
THE EFFECT OF DESOXYCORTICOSTERONE ACETATE ON BLOOD PRESSURE, RENAL FUNCTION, AND ELECTROLYTE PATTERN IN THE INTACT RAT
Authors: Friedman Sydney M. , Polley John R. , Friedman Constance L.
Published: June 2004

Small doses of DCA administered at intervals in pellet form are capable of raising the blood pressure, altering renal function, and changing the electrolyte pattern in the intact rat. The concomitant feeding of 1 per cent saline intensifies the process.

The elevation in blood pressure occurs prior to demonstrable changes in renal excretory function.

The alteration in renal function consists first of a reduction in CPAH with the maintenance of a normal filtration rate. Filtration fraction is elevated while there is no reduction in renal plasma flow per unit of tubular excretory tissue. Later, filtration is interfered with and renal ischemia occurs.

The electrolyte change is characterized by a sustained fall in plasma K and Cl, a rise in plasma Na, an increase in the Na/Cl ratio, and finally an elevation of Na plus K. Plasma Ca is unaffected.

These observations suggest the possible etiological significance of the adrenal cortex in some types of hypertension.
THE INACTIVATION OF BIOLOGICALLY ACTIVE PROTEINS, AND THE VIRUS OF WESTERN EQUINE ENCEPHALOMYELITIS BY PERIODIC ACID
Authors: Goebel Walther F. , Olitsky Peter K. , Saenz Arturo C.
Published: June 2004

The action of periodic acid on two biologically active proteins, crystalline ribonuclease and pneumococcus Type III immune globulin, and on the virus of Western equine encephalomyelitis has been studied. The biological activity of the two proteins and the pathogenic action of the virus were destroyed by the reagent; the specific antigenicity of the immune globulin was retained, however, but that of the equine virus was lost. The bearing of these reactions on the chemical alteration of the respective substances has been discussed.
THE DETERMINATION OF THE CONCENTRATION OF THE DYE T-1824 IN NORMAL AND LIPEMIC PLASMAS
Authors: Chinard Francis P. , Eder Howard A.
Published: June 2004

A method is presented for estimating the concentration of T-1824 in lipemic plasma. The plasma is mixed with acetone, which precipitates the proteins, dissolves or precipitates the lipids, and yields a clear solution for photometric measurement of the dye. The method is not sensitive to changes in the degree of lipemia and is relatively insensitive to hemolysis.
PROTEINURIA RELATED TO HYPERPROTEINEMIA IN DOGS FOLLOWING PLASMA GIVEN PARENTERALLY
Authors: Terry Roger , Hawkins David R. , Church Edwin H. , Whipple G. H.
Published: June 2004

Proteinuria in normal dogs can be produced at will by parenteral injections of dog plasma.

As the plasma injections are continued the plasma protein concentration rises and at some point protein begins to appear in the urine. The level of plasma protein concentration at which proteinuria appears in normal dogs ranges from 9.6 to 10.4 gm. per cent. This may be termed the renal threshold for proteinuria. Repeat experiments in the same dog show threshold levels to be practically identical.

An interval of days (4 to 26 days) has been noted between the start of plasma protein injections and the appearance of the proteinuria. Larger doses of plasma shorten this interval and the critical plasma protein level is attained sooner.

Considerable amounts of protein may appear in the urine—298 gm. protein during a 52 day period in one instance studied—yet the urine clears in 1 to 4 days after cessation of protein injections. Autopsy shows undamaged kidneys.

Maximal levels of plasma protein concentration range from 10.0 to 11.5 gm. per cent. The highest levels are usually associated with maximal output of protein in the urine.

It seems clear that plasma proteins readily pass cell barriers (or membranes) within the body, including the endothelium and epithelium of the renal glomerulus.
CIRRHOSIS AND OTHER HEPATIC LESIONS PRODUCED IN DOGS BY THYROIDECTOMY AND BY COMBINED HYPOPHYSECTOMY AND THYROIDECTOMY
Authors: Chajkoff I. L. , Gillman T. , Entenman C. , Rinehart J. F. , Reichert F. L.
Published: June 2004

1. The reactions of the dog's liver to (a) thyroidectomy and (b) both hypophysectomy and thyroidectomy are described.

2. Fatty changes of varying severity were detected in 8 of the 9 hypophysectomized-thyroidectomized dogs, hepatic fibrosis in 7, and severe cirrhosis in 4 animals of this group.

Among the thyroidectomized animals histologically demonstrable fatty livers were present in all 8, mild fibrosis was observed in 4, while early and mild cirrhosis was diagnosed in only one dog.

3. Two pathogenetically distinct forms of cirrhosis were present in the livers of dogs with the two operations, namely (a) cirrhosis initiated and developing around the radicles of the hepatic veins, and (b) periportal cirrhosis.

Both forms of cirrhosis occurred in dogs that were subjected to the same experimental procedures, and both forms could be found in the same liver.

The pathogenesis of these two forms of cirrhosis is described.

4. The relation between fatty change in the liver and the genesis of fibrosis is discussed, and it is suggested that, while fatty change may facilitate the evocation of cirrhosis, this reaction on the part of the supporting and vascular elements of the liver is not solely dependent on the fatty change in the liver cells.

5. The relation between the endocrines and hepatic cirrhosis is discussed. Since cirrhosis was slight in the fatty livers of thyroidectomized dogs, whereas it was often advanced in hypophysectomized-thyroidectomized dogs, it is suggested that in the absence of the pituitary cirrhogenic mechanisms are facilitated in the dog.
THE REACTIVITY OF VARIOUS HUMAN SERA WITH MUMPS COMPLEMENT FIXATION ANTIGENS
Authors: Henle Gertrude , Harris Susanna , Henle Werner
Published: June 2004

Human sera taken at various stages of mumps have been analyzed in regard to their reactivity with two serologically distinct complement fixation antigens which were derived from the infected chick embryo. Antibodies to the soluble or S antigen appear earlier in the disease and, as a rule, reach high levels before antibodies against the virus-bound or V antigen commence to rise. In early convalescence, both antibodies reach high levels. Subsequently antibodies against the S antigen decrease usually at a faster rate than those against V, so that after a period of several years, frequently only anti-V may be left.

These findings were found helpful in diagnostic procedures. The use of both the V and S antigens has permitted the early diagnosis of manifestations of mumps in the absence of parotitis, such as meningoencephalitis, since the finding of high levels of anti-S and of low titers of, or no, anti-V is considered diagnostically significant for the first few days of illness. For the determination of resistance the use of the V antigen appears more useful.

Following vaccination or skin testing, antibodies against both antigens may develop; those against V increase more regularly and to higher titers than those against S.
THE EFFECT OF SPHINGOMYELIN ON THE GROWTH OF TUBERCLE BACILLI
Authors: Dubos René J.
Published: June 2004

All preparations of sphingomyelin tested, whatever the tissues from which they originated, were found to enhance the growth of tubercle bacilli in vitro. Cerebrosides were inactive in this respect.

Sphingomyelin promotes growth through two independent mechanisms:

(a) It neutralizes the toxicity of long chain fatty acids probably by forming with them inert complexes. This protective effect facilitates initiation of growth from small inocula.

(b) It supplies to the bacteria lignoceric acid (or its amide) which is utilized for growth. The base sphingosine, another component of sphingomyelin, does not favor and probably inhibits proliferation of tubercle bacilli.
THE RATE OF BACTERICIDAL ACTION OF PENICILLIN IN VITRO AS A FUNCTION OF ITS CONCENTRATION, AND ITS PARADOXICALLY REDUCED ACTIVITY AT HIGH CONCENTRATIONS AGAINST CERTAIN ORGANISMS
Authors: Eagle Harry , Musselman A. D.
Published: June 2004

1. The concentrations of penicillin G which (a) reduced the net rate of multiplication, (b) exerted a net bactericidal effect, and (c) killed the organisms at a maximal rate, have been defined for a total of 41 strains of α- and ß-hemolytic streptococci, Staphylococcus aureus and Staphylococcus albus, Diplococcus pneumoniae, and the Reiter treponoma.

2. The concentration which killed the organisms at a maximal rate was 2 to 20 times the minimal effective level ("sensitivity" as ordinarily defined). With some organisms, even a 32,000-fold increase beyond this maximally effective level did not further increase the rate of its bactericidal effect. However, with approximately half the strains here studied (all 4 strains of group B ß-hemolytic streptococci, 4 of 5 group C strains, 5 of 7 strains of Streptococcus fecalis, 2 of 4 other α-hemolytic streptococci, and 4 of 9 strains of staphylococci), when the concentration of penicillin was increased beyond that optimal level, the rate at which the organisms died was paradoxically reduced rather than increased, so that the maximal effect was obtained only within a relatively narrow optimal zone.

3. There were marked differences between bacterial species, and occasionally between different strains of the same species, not only with respect to the effective concentrations of penicillin, but also with respect to the maximal rate at which they could be killed by the drug in any concentration. Although there was a rough correlation between these two factors, there were many exceptions; individual strains affected only by high concentrations of penicillin might nevertheless be killed rapidly, while strains sensitive to minute concentrations might be killed only slowly.

4. Within the same bacterial suspension, individual organisms varied only to a minor degree with respect to the effective concentrations of penicillin. They varied strikingly, however, in their resistance to penicillin as measured by the times required to kill varying proportions of the cells.
A MEANS OF INCREASING THE TUBERCULOSTATIC EFFECT OF KNOWN CHEMOTHERAPEUTIC AGENTS
Authors: Eiseman B.
Published: June 2004

By incorporating a known tuberculostatic agent on one end of a surface-active molecule, an increased in vitro effect on the tubercle bacillus has been obtained.

This activity is presumably due to the concentration of the drug molecules at or beneath the mycobacterial cell boundary.

Whether the surface-active drug actually penetrates the lipid, or lipoprotein complex that is so characteristic of the mycobacteria is only problematic. According to comparable purely physical-chemical experiments, such a penetration is quite likely.

Increase in tuberculostatic effect of over 1000-fold has been attained by rendering surface-active the drugs included in this study. The quantitative evaluation of this increase in activity has been obtained by measuring drug action both when its surface-active properties are functional, and when these properties have been selectively abolished by a specific surface-active antagonist.

It is believed that the molecular orientation of a surface-active drug about a bacterial cell accounts for one component of its antibacterial action. Certain previously described surface-active antituberculous drugs and antibiotics have been examined in light of this interpretation.

It may be anticipated that the more potent tuberculostatic drugs such as streptomycin could be made more effective by incorporating the molecule into a surface-active compound, according to the principles herein described.
STUDIES ON NEWCASTLE DISEASE VIRUS
Authors: Bang F. B.
Published: June 2004

The virus of Newcastle disease of chickens resembles those of the encephalitis group in its ability to spread throughout the developing egg and embryo, but it is similar to influenza virus in the high concentration of it found in the allantoic fluid before death. No effect of the size of the inoculum on the final titer of virus in the allantoic fluid was detected. Good growth occurred at temperatures from 35° to 41°C., apparently more rapid at 40°C. than at 35°C. No appreciable development of virus capable of agglutinating red cells but of low embryo infectivity was found. Although virus multiplication was not immediately perceptible after inoculation, this cannot on present evidence be attributed to a real lag phase.
OBSERVATIONS ON THE FEVER CAUSED BY BACTERIAL PYROGENS
Authors: Bennett Ivan L.
Published: June 2004

The relationship of the fever caused in rabbits by bacterial pyrogens to the fever produced by the injection of the sterile exudates of acute inflammation was investigated by recording the responses of normal and pyrogen-tolerant animals to injections of exudate. Exudates were produced by the intrapleural injection of turpentine in dogs.

The duration of the febrile response in rabbits after a single dose of exudate was found to be much shorter than the fever following an injection of bacterial pyrogen.

Animals given daily injections of exudate demonstrated no tolerance to its fever-promoting effect.

Animals tolerant to bacterial pyrogens showed no diminution in responsiveness to exudates.

Daily injections of exudate failed to establish tolerance to bacterial pyrogens in rabbits.

It is concluded that the fever-promoting property of sterile exudates is not due to the presence of bacterial pyrogen.
STUDIES ON THE RELATIONSHIP OF PTEROYLGLUTAMIC ACID TO THE GROWTH OF PSITTACOSIS VIRUS (STRAIN 6BC)
Authors: Morgan Herbert R.
Published: June 2004

p-Aminobenzoic and pteroic acids antagonize the inhibition of the growth of psittacosis virus (strain 6BC) by sulfadiazine in a competitive manner. Pteroylglutamic acid exerts a non-competitive type sulfonamide antagonism.

The effects of certain analogues of pteroylglutamic acid and of pteroic acid on the growth of psittacosis virus and its inhibition by sulfadiazine are reported.

The implications of these findings with regard to the possible synthesis of pteroylglutamic acid by psittacosis virus and its suggested rôle as an essential factor for growth of this virus are discussed.
EPIDEMIC DIARRHEAL DISEASE OF SUCKLING MICE
Authors: Cheever F. Sargent , Mueller J. Howard
Published: June 2004

Four strains of mice—Harvard, Schwentker, CFW (Carworth Farms), and C (National Cancer Institute)—have been kept and bred underidentical conditions over the course of a year in order to determine the effect of strain, of litter, and of season upon the incidence of diarrheal disease among the suckling mice.

1. Significant strain differences were limited to CFW mice. A consistently lower percentage of these mice were weaned in comparison to the others.

2. The effect of litter was definite and consistent: In all four strains first litters fared worse than second and third ones, while fourth and fifth litters showed the highest percentage of mice weaned.

3. The effect of season seemed clear cut only in the case of one strain CFW; the highest percentage of mice weaned were observed during the summer months and the lowest during the autumn and early winter.
INFLUENZA VIRUS INFECTION IN THE HAMSTER
Authors: Friedewald William F. , Hook Edward W.
Published: June 2004

A study of influenza virus infection in the hamster has yielded the following results:

1. Two influenza A strains (Ga. 47 and PR8) multiplied readily in the hamster lung, although no lung lesions were produced during six serial passages. On further passage both viruses abruptly acquired the capacity to produce pulmonary consolidation and death of the animals.

2. Extracts of the lungs during the early passages contained complement-fixing antigen and infectious virus, as revealed by titration in mice and embryonated eggs. Agglutinins for chicken, human, and guinea pig red cells, however, were not demonstrable at this time. With further passage a close correlation was observed between the capacity of the virus to produce lung lesions in the hamster and to agglutinate mammalian types of red cells. In addition, quantitative changes in the virus population were demonstrated in the lung extracts by complement fixation tests and titrations in mice and eggs.

3. Incubation at 37°C. was effective in bringing out agglutinins in high titer for chicken red cells in lung extracts, which originally failed to agglutinate chicken cells but agglutinated mammalian red cells. This method did not increase the titers of mammalian cell agglutinins.

4. The body temperature of the hamster was found to decrease within 1 to 4 days after inoculation of influenza virus. In the early passages the temperature returned to normal within 24 hours, but with the development of the pathogenic strain of virus the temperature remained at subnormal levels until death.

5. The Lee strain of influenza B virus produced pulmonary lesions in the hamster on the first passage and no increase in pathogenicity of the virus occurred during eleven serial passages. Virus was demonstrable in extracts of the lungs by all the methods used and no difference was observed in its capacity to agglutinate fowl and mammalian types of red cells.

The implications of these findings are considered briefly in the discussion.
THE EFFECT OF CHICK EMBRYO EXTRACT ON THE GROWTH AND MORPHOLOGY OF TUBERCLE BACILLI
Authors: Bloch Hubert
Published: June 2004

Aqueous extracts of 11-day-old chick embryos enhance the growth of tubercle bacilli in oleic acid-albumin media.

These extracts also increase the tendency of virulent strains to exhibit the serpentine pattern of growth and confer this property on avirulent variants which normally grow unoriented in clumps.

Growth in the presence of chick embryo extract slightly increases the virulence of the virulent strains but does not confer virulence on the avirulent variants.
THE PRODUCTION OF A PERSISTENT ALTERATION IN INFLUENZA VIRUS BY LANTHANUM OR ULTRAVIOLET IRRADIATION
Authors: Björkman Sven E. , Horsfall Frank L.
Published: June 2004

The rates of elution from RBC of the Lee and PR8 strains of influenza virus were studied by means of a step-wise elution technique. By means of a single treatment with lanthanum acetate or irradiation with ultraviolet and subsequent passage in chick embryos, it was possible to alter the elution rate of the Lee strain so that it was similar to that of the PR8 strain. This alteration proved to be persistent on serial passage in the absence of the agent which caused it. As far as was determined, the elution rate of the virus appeared to be the only property which was altered. The phenomenon can be most readily understood on the assumption that the difference in elution rates of the two strains is due to a heterogeneous population of virus particles in the Lee strain with respect to elution rate.