bluuebunny/crossref_metadata_2025 huggingface dataset:
THE NEOPLASTIC POTENTIALITIES OF MOUSE EMBRYO TISSUES
Authors: Smith William E. , Rous Peyton
Published: June 2004

The observation that adenomas develop very rapidly in the pulmonary tissue of mouse embryos implanted together with methylcholanthrene, in adult animals, has led to tests of the neoplastic potentialities of this tissue in utero. C strain females in the latter half of pregnancy were injected with urethane and the lungs of their young were searched for adenomas. None could be perceived with certainty in embryos at term or in mice just born, but they were several times found 3 days after birth and they were frequent and much larger in 10-day-old animals. The controls showed none. After 60 to 70 days they were often visible in the gross. Corroboratory findings were obtained in A mice. No parallelism could be perceived in the incidence of the tumors in mothers and offspring.

The adenomas arose from tissue devoid of any sign of preliminary local disturbance. Mitoses were abundant in them and they grew rapidly for a while, but within 2 months cell division had almost ceased. By this time however many of the neoplasms were as big as any adenomas in the urethanized mother animals and in some instances twice as big. While growing fast they underwent little differentiation, but this took place when proliferation slowed and in consequence the tumors came to have the morphology of the spontaneous and induced adenomas of adults.

The neoplastic cells were derived from alveolar elements, yet in proportion as differentiation of them occurred they came to resemble the epithelial cells lining the small bronchioles. Occasionally the resemblance to bronchial epithelium was complete, save that the cytoplasm of the tumor cells was slightly basophilic. The following conclusions seem justified:—

1. The injection of urethane into pregnant female mice of the C strain frequently initiates the development forthwith of pulmonary adenomas in the young she is carrying.

2. Some of the pulmonary cells of mouse embryos well along toward term possess the ability to be neoplastic.

3. The adenomatous change finds swift expression in young creatures because of conditions implicit in their youth. The rapid proliferation of the tumor cells is almost entirely due to these conditions, not to the neoplastic state as such.

4. Adenomatous change prior to birth is intrinsically the same process as that occurring in the adult creature.

5. The adenomatous state does not prevent the cells of young mice from undergoing the maturation that takes place in normal elements of the same sort as the organism grows older. Though the proliferative activity natural to youth and the unnatural activity consequent on neoplastic change are summated in the young organism, they still are separable.
THE STRUCTURE OF HUMAN SKIN COLLAGEN AS STUDIED WITH THE ELECTRON MICROSCOPE
Authors: Gross Jerome , Schmitt Francis O.
Published: June 2004

1. The structure of the collagen fibrils of normal human skin corium has been investigated with the electron microscope.

2. Under the conditions of observation the fibrils ranged in width from about 700 to 1,400 A with 1,000 A as the value occurring most frequently. They showed little tendency to fray longitudinally as is characteristic of tendon fibrils; when fracture of fibrils occurred it was usually in planes transverse to the axis.

3. The axial repeating periods observed in fibrils stained with phosphotungstic acid or shadowed with chromium or platinum range from about 500 to 800 A, the maximum occurring between 620 and 660 A. The average period in fibrils from infant skin does not differ significantly from that of adult and aged skin.

4. Depending on conditions of preparation, intraperiod fine structure, in the form of cross-bands, was observed in varying detail. The most detailed pattern commonly observed contains six bands of characteristic density and position.

5. Shadowed plastic replicas of dried collagen fibrils reproduce much of the structure commonly seen in shadowed fibrils. Replicas of moist fibrils show considerably less surface contouring than do dried fibrils. Replicas from smears of connective tissue fragments on glass show detailed structure, indicating the feasibility of applying this technique to biopsy material.

6. Infant skin differs from adult skin in having considerably greater amounts of amorphous material, little of which is strongly adherent to the collagen fibrils.
HEREDITARY OSTEOPETROSIS OF THE RABBIT
Authors: Pearce Louise , Brown Wade H.
Published: June 2004

The manifestations and course of an hereditary disease of the rabbit are reported. The condition is present at birth and is invariably fatal, generally in the 4th and 5th weeks of age. Retardation and eventual cessation of growth with marked reduction in size are conspicuous characteristic symptoms.

The condition, which first occurred in the backcross progeny of a pure bred Dutch male rabbit, is inherited. It is determined by the expression of a simple recessive unit factor, affected individuals being homozygous for the factor. Rabbits heterozygous for the factor are identified only by appropriate breeding tests. The condition is not sex-linked.

The disease has a remarkable resemblance to osteopetrosis or marble bone disease of infants and children with respect to signs and general course and also, as may be stated in anticipation of later discussions (5, 6), to the characteristic abnormal condition of the skeleton.
THE ASSOCIATIVE REACTIONS OF PNEUMONIA VIRUS OF MICE (PVM) AND INFLUENZA VIRUSES: THE EFFECTS OF pH AND ELECTROLYTES UPON VIRUS-HOST CELL COMBINATIONS
Authors: Davenport Fred M. , Horsfall Frank L.
Published: June 2004

Combination between PVM and erythrocytes as well as between the influenza viruses and erythrocytes is inhibited at low electrolyte concentrations. Combination between PVM and lung particles as well as between the virus and erythrocytes can be dissociated in solutions of low electrolyte concentration. The rate of elution of influenza virus is decreased under similar conditions. PVM can combine with and be dissociated from erythrocytes repeatedly without affecting the combining capacity of the ceils and does not possess an enzyme-like activity similar to that of the influenza viruses. Because dissociation depends on electrolyte concentration and pH, it appears that the PVM-cell component complex may be in the nature of a weak salt.
MYOSITIS IN MICE FOLLOWING INTRAMUSCULAR INJECTION OF VIRUSES OF THE MOUSE ENCEPHALOMYELITIS GROUP AND OF CERTAIN OTHER NEUROTROPIC VIRUSES
Authors: Rustigian Robert , Pappenheimer Alwin M.
Published: June 2004

A study has been made of the local effects following intramuscular injection of various neurotropic viruses.

Early massive necrosis of muscle fibers accompanied by edema and acute inflammatory reaction is produced by Jungeblut's SK virus even in low concentrations.

Similar but more slowly developing lesions follow the introduction of mouse encephalomyelitis GD-VII and FA strains. Strain 4727 (TO type) produces inflammatory changes with fibrosis in the intermuscular septa and necrosis of scattered individual fibers. The relatively avirulent FV strain (TO type) was not pathogenic for skeletal muscle.

The Mitchell strain of lymphocytic choriomeningitis virus gives rise to a profuse lymphocytic and monocytic infiltration of the fat and connective tissue but does not cause necrosis of muscle fibers.

No significant lesions resulted from intramuscular injection of the murine-adapted human poliomyelitis Lansing virus, the HF strain of herpes, a strain of Eastern equine encephalitis virus, or a still unidentified demyelinating mouse virus.

Evidence is presented that the mouse encephalomyelitis virus GD-VII and Jungeblut's SK virus multiply locally in the injected limb. The GD-VII virus has been passed through four muscle to muscle passages and muscle lesions have been elicited at the same time.

Specific and complete protection against myositis was obtained by anti-GD-VII and anti-SK rabbit sera.
CAPSULAR REACTIONS AND SOLUBLE ANTIGENS OF TORULA HISTOLYTICA AND OF SPOROTRICHUM SCHENCKII
Authors: Neill James M. , Castillo Carlos G. , Smith Robert H. , Kapros Charles E.
Published: June 2004

The present paper deals with reactions between antiserums and the capsules of Torula histolytica (Cryptococcus hominis or Torulopsis neoformans) and of Sporotrichum schenckii. The reactions, although similar in principle to the capsular swelling seen in Quellung tests of bacteria, present a special interest because the microorganisms are larger in size and more complex in structure than bacteria.

That the reactions on the capsules were caused by immunologically specific antibodies was shown by the fact that the capsular reactivity of the serums was directly related to their capacities to agglutinate suspensions and to precipitate soluble antigens of Torula and of Sporotrichum, and by the fact that the capsular reactivity was removed from the serums by absorption with soluble antigens of the respective fungi.

The soluble antigens included partially purified products from broth cultures of Torula and of Sporotrichum, a partially purified product from Sporotrichum-infected mice, and a purified polysaccharide from a culture of Torula grown in a synthetic medium. The purified polysaccharide was highly reactive in precipitation tests with unabsorbed serum, and its ability to absorb the Torula capsular reactivity from the serums indicates that the major antigens on the surface of encapsulated Torula cells are polysaccharides, identical with or similar to the product used in the present study.
ONE-STEP GROWTH CURVES OF VARIOUS STRAINS OF INFLUENZA A AND B VIRUSES AND THEIR INHIBITION BY INACTIVATED VIRUS OF THE HOMOLOGOUS TYPE
Authors: Henle Werner , Rosenberg Evelyn B.
Published: June 2004

One-step growth curves of five strains of influenza A, one strain of swine influenza, and three strains of influenza B virus have been analyzed.

The influenza A and swine influenza strains showed constant periods of 5 to 6 hours before newly formed virus was liberated from the infected cells, whereas 8 to 10 hours elapsed in the case of the influenza B strains.

The yield of virus in the allantoic fluids, i.e. the number of ID50 released for every ID50 of seed virus adsorbed, was consistently higher in the case of the influenza A and swine influenza strains than in that of the influenza B viruses.

Interruption of the cycle by injection of inactivated virus subsequent to infection can be achieved by any of the strains of the homologous type. However, cross-tests between influenza A and swine influenza virus led only to partial inhibition of virus growth.
THE SPECIFIC ANTIGENS OF VARIANTS OF SHIGELLA SONNEI
Authors: Baker Edgar E. , Goebel Walther F. , Perlman Ely
Published: June 2004

It has been shown that phase variation of Sh. sonnei is accompanied by changes in morphology and antigenic structure. Two mutants of the Phase I organism (IIS and IIR), which were studied, elaborate somatic antigens which are immunologically identical. The purified lipocarbohydrate-protein antigens of the Phase I and IIS microorganisms are chemically similar yet immunologically distinct and specific. By inference the same should hold true of the antigen of IIR, but it has not yet been investigated in this relation.

It is suggested that when Sh. sonnei undergoes variation from Phase I to IIS the immunological changes occurring are dependent upon a change in the enzyme systems responsible for the synthesis of the lipocarbohydrate-protein constituent.
DIETARY EFFECTS ON ANEMIA PLUS HYPOPROTEINEMIA IN DOGS
Authors: Robscheit-Robbins F. S. , Whipple G. H.
Published: June 2004

Doubly depleted dogs (anemic and hypoproteinemic) respond favorably to all the diet proteins used in the above experiments.

Egg products (whole egg, albumin, or egg yolk) are well utilized by these dogs. Egg proteins favor the production of plasma protein and in some experiments the output of plasma protein is actually more than the output of hemoglobin. In contrast fresh beef muscle favors hemoglobin production—the output being 3 or 4 times that of plasma protein.

The processed egg albumin fed in Table 4 was not well utilized and there was weight loss.

Beef muscle (fresh or processed) gives a total blood protein output about twice that with egg feeding and there is a striking preponderance of hemoglobin output.

Beef heart and salmon muscle show a pattern much like beef muscle. The total blood protein output is below that due to beef muscle.
STUDIES ON ACUTE DISSEMINATED ENCEPHALOMYELITIS PRODUCED EXPERIMENTALLY IN RHESUS MONKEYS
Authors: Kabat Elvin A. , Wolf Abner , Bezer Ada E.
Published: June 2004

Acute disseminated encephalomyelitis has been produced in rhesus monkeys by injection of their own brain tissue, removed surgically and incorporated with adjuvants.
A TYPE-SPECIFIC PROTEIN FROM PNEUMOCOCCUS
Authors: Austrian Robert , MacLeod Colin M.
Published: June 2004

The isolation and characterization of a type-specific M protein from pneumococcus are described. This protein is similar chemically in all respects studied to the M proteins of group A streptococci. No immunological crossreactions have been observed, however, between M proteins of the two species.

Strains of capsular type I pneumococcus have been encountered which contain different M proteins. The same is true for capsular type II pneumococcus. It is apparent, therefore, that the capsular polysaccharides and M proteins can vary independently of each other.
THE EFFECT OF LITHIUM PERIODATE ON CRYSTALLINE BOVINE SERUM ALBUMIN
Authors: Goebel Walther F. , Perlmann Gertrude E.
Published: June 2004

A study of the chemical, physicochemical, and immunological changes in bovine serum albumin, brought about by oxidation with lithium periodate, has been made. It has been shown that destruction of certain amino acids occurs, that a change in the absorption spectrum takes place, and that the electrophoretic behavior of the protein is altered. Prolonged contact of bovine albumin with lithium periodate destroys its ability to incite antibodies in experimental animals.
THE MECHANISM OF ACTIVE CEREBRAL IMMUNITY TO EQUINE ENCEPHALOMYELITIS VIRUS
Authors: Schlesinger R. Walter
Published: June 2004

Continued serial brain-to-brain passage of strains of W.E.E. virus in mice has yielded variants which kill mice with increased rapidity. Their rate of multiplication in the mouse brain has been found to be correspondingly increased.

At 1 hour after intracerebral inoculation of various amounts of W.E.E. virus, only 3.5 to 10 per cent of the expected amount of virus was recovered from the infected brains.

In infected mouse brains, the period of active viral multiplication was preceded by a latent phase which lasted a considerably shorter time in the case of a "fast" than in that of a "slow" variant.

In brains inoculated with various amounts in excess of minimal lethal doses the rates of multiplication tended to converge with the result that the maximum titer was reached after about the same period of time. After inoculation of smaller amounts, the rates of viral multiplication tended to parallel each other.

Vaccinated mice may be fully resistant to maximal intracerebral doses of a slowly multiplying strain while they are not at all or only partly protected against a rapidly multiplying one derived from it. This difference is demonstrable even though fast and slow variants are, as far as can be tested, serologically identical. The difference in response may be masked if animals are immunized with relatively large doses of vaccine.

The bearing of these findings on certain practical problems has been pointed out.
CARDIAC LESIONS PRODUCED IN RABBITS BY MASSIVE INJECTIONS OF BOVINE SERUM GAMMA GLOBULIN
Authors: More Robert H. , Waugh Douglas , Kobernick Sidney D.
Published: June 2004

Granulomatous lesions of the valves and valve rings have been produced in 52 per cent of rabbits treated by massive intravenous administrations of bovine gamma globulin in such a way as to establish a state of anaphylactic hypersensitivity in the animals. The incidence of the lesions is greater than has heretofore been reported as produced by the use of any type of foreign protein injection in rabbits.

The use of a purified protein antigen has resulted in the production of several different types of lesions; namely, a granulomatous inflammation of heart valves and valve rings, a glomerulonephritis, and an arteritis.

The lesions of the heart cannot be regarded as being identical with the lesions of human rheumatic fever, but they are considered to be sufficiently similar to warrant a continuation of this approach to the study of the etiology and pathogenesis of rheumatic fever in man.
A VIRUS RECOVERED FROM THE FECES OF "POLIOMYELITIS" PATIENTS PATHOGENIC FOR SUCKLING MICE
Authors: Dalldorf Gilbert , Sickles Grace M. , Plager Hildegard , Gifford Rebecca
Published: June 2004

A virus has been recovered from the feces of two children having symptoms similar to those of poliomyelitis. The virus is pathogenic for suckling mice and hamsters but not for rhesus monkeys. It induces striking lesions in the skeletal muscles of the experimental animal but not in the central nervous system. Other viruses inducing similar signs and lesions in suckling mice have been isolated from several other outbreaks of a poliomyelitis-like disease, including one large urban epidemic.
QUANTITATIVE AIR-BORNE TUBERCULOSIS IN THE RABBIT
Authors: Heppleston A. G.
Published: June 2004

1. Pulmonary tuberculosis in unselected rabbits, induced by primary quantitative air-borne infection with human type tubercle bacilli, may retrogress or progress. Some animals whose disease was in a stationary condition might have fallen into one of the above groups had the experiments been prolonged.

2. Within the limits of the observations natural resistance or susceptibility appears to be the chief factor in determining the course of the disease.

3. Following the development of the primary lesions the tuberculin reaction became positive but thereafter proved to be an unreliable indicator of the course of the disease.

4. Tubercle bacilli can be recovered from macroscopically normal lung tissue of rabbits several weeks after primary infection.

5. Reinfection did not induce the formation of new lesions nor alter the course of the disease caused by the primary infection.
SEROLOGICAL STUDIES IN RHEUMATIC FEVER
Authors: Fischel Edward E. , Pauli Ruth H.
Published: June 2004

1. An attempt was made to repeat and extend various tests which have been presumed to demonstrate specific antigens and antibodies in rheumatic fever.

2. The "phase reaction" appears to be an inconstant phenomenon probably related to a colloidal abnormality of the serum, rather than to a specific antigen-antibody system.

3. No specific autoantibodies to human tissue extracts were demonstrable by complement fixation or by the collodion particle technique. Variable results were noted with the same test sera on different occasions, and positive reactions with control tissues and control sera were observed.

4. The possibility should be considered that autoantibodies are not necessarily specific for rheumatic fever but may be manifestations of the occurrence of a type of reaction similar to a biologically false positive Wassermann reaction.
OBSERVATIONS ON THE RELEASE OF SERUM FIBRINOLYSIN BY SPECIFIC ANTIGEN, PEPTONE, AND CERTAIN POLYSACCHARIDES
Authors: Ungar Georges , Mist Shirley H.
Published: June 2004

Formation of fibrinolysin from its inactive precursor in serum was observed under the following conditions: (a) by adding the specific antigen to serum from sensitized guinea pigs; (b) by mixing normal guinea pig serum with peptone, agar, hyaluronic acid, chondroitinsulfuric acid, glycogen, pneumococcal polysaccharides, and heparin.

Activation of profibrinolysin by these agents differs from chloroform or streptokinase activation in that it requires the presence of some serum constituent non-precipitable with the euglobulin fraction and destroyed by heating at 56°C.

The bearing of these observations on the mechanism of anaphylactic and anaphylactoid reactions is discussed. The findings reported support the concept that proteolysis is part of the process determining the release of histamine and other toxic products.

It is suggested that the presence of fibrinokinase may be responsible for the toxicity of serum induced in vitro by a number of agents.
TREATMENT OF EXPERIMENTAL DIETARY CIRRHOSIS OF THE LIVER IN RATS
Authors: György Paul , Goldblatt Harry
Published: June 2004

Dietary cirrhosis of the liver was produced in 223 rats, and then therapy of the condition attempted. Administration of lipotropic factors (casein, methionine, choline) was followed not only by reduction of fat infiltration and by regeneration of hepatic parenchyma but, by a reduction of the degree of the fibrosis. In one group of rats, comparison of sections obtained by biopsy, before treatment, with findings at necropsy, after completed therapy, indicated apparent reduction of the fibrosis and of the amount of ceroid and considerable restoration of architecture. This improvement, however, was obtained neither with complete regularity nor in a short time. In very severe cirrhosis, as a rule, the effect of a lipotropic diet was disappointing, even after prolonged treatment up to 200 to 240 days. It is assumed that factors determining prevention are beneficial only to a limited extent in treatment. The therapy of very severe cirrhosis may require the interaction of further beneficial factors (nutritional and hormonal).

Best therapeutic results were obtained by the combination of an adequate amount of casein with methionine or liver extract, and by the combination of methionine with liver extract.

Methionine and thiouracil, both of which, singly, are effective in the prevention of dietary hepatic cirrhosis in rats, have proved to be less effective for the therapy of cirrhosis, when administered together, than methionine given alone for the same purpose.

Under identical conditions, female rats have shown greater resistance to the production of dietary hepatic cirrhosis and a more favorable response to therapeutic dietary factors, than male rats.
THE INHIBITION OF SURFACE PHAGOCYTOSIS BY THE CAPSULAR "SLIME LAYER" OF PNEUMOCOCCUS TYPE III
Authors: Wood W. Barry , Smith Mary Ruth
Published: June 2004

Five strains of type III pneumococcus have been shown to possess wide capsular slime layers during the logarithmic phase of growth in serum broth.

The slime layer stains metachromatically with methylene blue and can be visualized under the electron microscope as a fuzzy halo which extends well beyond the surace of the capsule proper and causes centrifugates of the organism to be of extremely large volume.

This outer capsular structure is most readily demonstrated in vivo and in nutrient broth containing glucose and serum. It disappears from the surface of the cell with aging of the culture, and is easily removed by dilute alkali, alcohol, and heat.

Exposure of slime-covered type III pneumococci to homologous antibody and to type III polysaccharidase reveals that the slime layer contains the same type-specific polysaccharide that is present in the rest of the capsule.

From a type III strain producing a prominent slime layer an intermediate mutant has been isolated which forms small non-mucoid colonies on blood agar and possesses a relatively small capsule with a barely discernible slime layer.

The wide slime layer protects virulent type III pneumococci from surface phagocytosis. Whenever the type III cells lose their broad slime layer, whether from aging of the culture, from mutation, from exposure to injurious chemicals, or from the action of type III polysaccharidase, they become susceptible to phagocytosis by the surface mechanism. Once phagocyted the type III pneumococci are promptly destroyed, even in the absence of antibodies.
THE INFLUENCE OF DIET ON IRON ABSORPTION
Authors: Kinney Thomas D. , Hegsted D. Mark , Finch Clement A.
Published: June 2004

Rats placed on a corn grit diet and added iron absorbed large amounts of iron in contrast to control groups.

The histological picture was that of progressive hemosiderosis of the hepatic parenchyma and of the reticuloendothelial system. On chemical analysis, the iron content of the liver was found to be greatly increased. This supports the concept that the liver represents the chief storage organ for iron so absorbed.

These data indicate that a normal block for iron absorption may be overcome under certain circumstances.
THE INFLUENCE OF DIET ON IRON ABSORPTION
Authors: Hegsted D. Mark , Finch Clement A. , Kinney Thomas D.
Published: June 2004

Rats fed a corn grit diet containing large amounts of ferric citrate absorb and deposit excessive amounts of iron in their livers. Undoubtedly various factors are involved in iron absorption, but these studies indicate that the low level of dietary phosphate was primarily responsible.

The addition of phosphate salts to this diet has shown that the amount of iron deposited in the liver was inversely related to the phosphorus content of the diet.

It is possible to obtain excessive iron deposits in the livers of animals receiving a normal diet, by adding large amounts of iron salts to the diet. This is not associated with losses of body weight in these animals.

It is concluded that the absolute amount of iron and/or phosphorus in the diet as well as the iron-phosphorus ratio influences the amount of iron absorbed.
NUCLEIC ACIDS AND THE PRODUCTION OF ANTIBODY BY PLASMA CELLS
Authors: Ehrich William E. , Drabkin David L. , Forman Carolyn
Published: June 2004

A study has been made of the relationship of antibody formation and the changes in amount of the nucleic acids in rabbit lymph nodes draining areas injected with typhoid vaccine.

The increase in DNA was found to parallel the increase in weight of the nodes, as might be expected from the active multiplication of cells.

The peak of PNA increase occurred between the 4th and 6th days after vaccine injection when antibody formation was at its maximum.

A histologic study of methyl green- and pyronine-stained sections of the nodes revealed that during the first 6 days of the experiment the cellular reaction was chiefly one of plasma cells. During the first 3 days plasmoblasts predominated; on the 5th and 6th days mature plasma cells were the prevailing cells. Most of the PNA was contained in the plasma cells.

The lymphocytes began to proliferate in significant numbers on the 3rd and 4th days, and germinal centers began to appear on the 4th and 5th days. They showed their greatest activity only on the 9th day when PNA and antibody formation had passed their peaks.

These results are interpreted as indicating that the plasma cell and not the lymphocyte is responsible for antibody formation.
A MURINE VIRUS (JHM) CAUSING DISSEMINATED ENCEPHALOMYELITIS WITH EXTENSIVE DESTRUCTION OF MYELIN
Authors: Bailey Orville T. , Pappenheimer Alwin M. , Cheever F. Sargent , Daniels Joan B.
Published: June 2004

A description has been given of the pathologic changes produced experimentally in animals by the inoculation of a virus material obtained from a mouse with spontaneous encephalomyelitis. The most distinctive feature of the lesions in the central nervous system is the widespread destruction of myelin. Giant cells derived from a variety of tissue elements characterize the early lesions. The liver in the majority of cases is the seat of focal necrosis. In some mice, infected with large doses by the intravenous route, there is produced massive necrosis of the liver, with fat infiltration and calcification. Giant cells are occasionally found in lymphatic tissue, but no significant changes were noted in other organs. Inclusions or elementary bodies were not demonstrated in the lesions.

Similar lesions were produced by the inoculation of mouse virus into hamsters. In rats, the lesions were of a more chronic character.

The relation of this disease to other demyelinating diseases of man and animals is discussed.
THE RELATIVE SIGNIFICANCE OF GRADED IMMUNIZING AND CHALLENGE DOSES IN MEASURING THE POTENCY OF VACCINES
Authors: Batson H. C.
Published: June 2004

A study of the effect of graded immunizing doses of typhoid vaccine and graded challenge doses of S. typhosa in 5 per cent mucin on the degree of gradation of response (survival or death) elicited in successive groups of mice is reported.

In the range of doses employed the effect of graded immunizing doses was markedly greater than was the effect of graded challenge doses. Statistically the difference exceeded the 0.1 per cent level of significance.

It was concluded that the use of graded immunizing doses was preferable to the use of graded challenge doses as a basis for the immunological assay of typhoid vaccine, since with the former there was obtained (a) a greater significance of differences in response of groups given graded doses even with smaller fold increments in successive doses, (b) a greater slope of the dosage-response curve which permitted estimation of ED50 values with smaller standard errors, and (c) an effect on response apparently less dependent on the sex of mice used.
STUDIES ON BACTERIOPHAGE
Authors: Miller Elizabeth M. , Goebel Walther F.
Published: June 2004

Phase I and Phase II Sh. sonnei exhibit differences in their susceptibility to the T series of bacteriophages. Both microorganisms are lysed by T2 and T6, but only the Phase II bacillus is lysed by T3, T4, and T7.

Lysis of the Phase I or Phase II bacillus by T2 or T6 is not inhibited by the homologous type-specific antigen. In the presence of an appropriate cofactor, however, the lysis of Phase II Sh. sonnei by T3, T4, and T7 is specifically inhibited by the homologous somatic antigen but not by the Phase I antigen.

The significance of these observations is discussed in respect to the nature of the virus receptor of these microorganisms.
PLASMA AND RED CELL RADIOIRON FOLLOWING INTRAVENOUS INJECTION
Authors: Yuile C. L. , Bly C. G. , Stewart W. B. , Izzo A. J. , Wells J. C. , Whipple G. H.
Published: June 2004

Sterile inflammation induced by repeated subcutaneous injections of turpentine in non-anemic, non-iron—deficient dogs, leads to a fall in plasma iron concentration, the development of a moderate anemia, and a marked delay in the uptake by the red blood cells of intravenous radioiron.

Similar periods of inflammation in anemic, iron-deficient dogs on a diet low in iron cause no increase in the degree of anemia and no inhibition of red blood cell uptake of intravenous radioiron.

Radioiron appears only in traces in abscess exudates.

Intravenous iron disappearance curves following a single injection are uninfluenced by sterile inflammation in either anemic or non-anemic dogs.

The impairment of hemoglobin synthesis caused by inflammation is at most a relative matter, since the anemia that develops is seldom severe or progressive, and since the inhibition can be overcome if the marrow is sufficiently stimulated by the demands of a severe continuing anemia.
THE DISTRIBUTION AND STORAGE OF BLUE ANTIGENIC AZOPROTEINS IN THE TISSUES OF MICE
Authors: Kruse Heinz , McMaster Philip D.
Published: June 2004

Intensely blue dye-azoproteins have been prepared by diazotization and coupling of the highly indiffusible blue dye T-1824, Evans blue, with various serum proteins and egg albumin. The products, whether purified by precipitation with alcohol or by chromatography, have a constant dye-to-protein ratio and tests have shown them to be essentially free from unlinked dye. An extremely diffusible dye, echt-säure-blau, has also been coupled to bovine γ-globulin. These materials are adapted to physiological experimentation. They seem to behave in the bodies of mice like other proteins; they fail to appear in either the bile or urine of normal animals, and they are strongly antigenic.

When these soluble antigenic azoproteins are injected into the blood stream of mice for the first time they enter reticulo-endothelial cells in almost every organ of the body; the final distribution is like that of intravenously injected, finely divided particulate matter. The azoproteins appear in the cells which classical immunological studies have shown to be active in removing particulate antigenic materials or bacteria from the blood or body fluids. The Kupffer cells of the liver and sinus and reticular cells in lymph nodes, especially the great mesenteric node, are particularly active in the removal of the blue antigens from the blood, but many other R-E cells are active to a lesser degree. The storage of the antigenic material is in the cytoplasm only; it has not been seen within nuclei, nor has it been seen within cells of the brain.

Serological methods disclose that the blue material seen within Kupffer cells of the liver after as long a period as 2 days is still antigenic in its reactions. The blue azoproteins, therefore, serve excellently as tracer antigens, especially since they can be seen directly in fresh and fixed tissue preparations and in the body fluids.
BILE SALT METABOLISM AS INFLUENCED BY PURE AMINO ACIDS AND CASEIN DIGESTS
Authors: Hawkins W. B. , Hanson P. C. , Coon R. W. , Terry R.
Published: June 2004

A non-protein diet supplemented with vitamins fed to a bile fistula dog caused marked reduction in cholic acid and taurocholic acid formation.

A mixture of pure amino acids, essential for growth, promoted taurocholic acid production for a limited period.

A mixture of amino acids composed of 2 fractions of a casein digest fortified with dl-methionine and dl-tryptophane, (Merck Vuj-N-ix), also resulted in increased taurocholic acid excretion.

A casein digest, Amigen, supported cholic acid production, but there was very low taurocholic acid excretion. Addition of methionine to the Amigen brought about increased taurocholic acid excretion with reduction in the amount of free cholic acid in the bile.

A bile fistula animal was maintained for a year in excellent condition and produced bile salt on a non-protein diet supplemented by vitamins, Amigen, and methionine.

Unhydrolyzed alcoholic filtrate of bile contained traces of taurine, valine, glutamic acid, and aspartic acid.

Acid-hydrolyzed alcoholic filtrate of bile contained large amounts of taurine, and significant amounts of leucine, valine, alanine, glycine, serine, glutamic acid, and aspartic acid.
SERIAL RENAL CLEARANCES IN DOGS WITH NEPHROGENIC AND SPONTANEOUS HYPERTENSION
Authors: Stamler J. , Katz L. N. , Rodbard S.
Published: June 2004

Evidence is presented on the occurrence of spontaneous hypertension in dogs.

All dogs with spontaneous hypertension exhibited normal renal plasma flow and glomerular filtration rate.

Clearances on nephrogenic hypertensive dogs revealed that some exhibited normal kidney function, while others had significant depression of renal plasma flow and glomerular filtration rate. In the latter, the filtration fraction may or may not be elevated.

Serial renal clearances were done at intervals on 3 dogs with spontaneous hypertension during their 3rd year of known hypertension. They exhibited no tendency to develop impaired renal function in the face of prolonged benign hypertension.

Serial renal clearances on nephrogenic hypertensive dogs revealed no tendency for kidney function to become progressively impaired. This was true, whether the immediate postoperative clearance values were normal or depressed. It was also true regardless of the duration of the hypertension.

It is suggested that mechanisms other than elevated blood pressure per se operate to produce progressive kidney damage and impairment of renal function.

No tendency was revealed over the course of a year or more for the kidney function to improve in Goldblatt dogs exhibiting depressed clearances immediately postoperatively. This is interpreted as evidence against the postoperative development in persistently hypertensive Goldblatt dogs of a renal collateral circulation sufficient to augment significantly effective renal blood flow.

Pathological studies on 2 dogs with spontaneous hypertension revealed slight to moderate chronic focal lesions in the kidneys, and bilateral adrenal cortical adenomatous hyperplasia. Both lesions may have no pathogenetic significance.

In accord with previous observations, autopsies on 3 Goldblatt dogs revealed minimal renal changes in one, and unilateral kidney atrophy with contralateral hypertrophy in the 2 others. The adrenals were normal.

In general, data on renal clearances showed correlation with postmortem kidney findings. However, normal renal clearances are found in the presence of anatomically abnormal kidneys.

The findings in canine spontaneous and nephrogenic hypertension are compared and contrasted with data obtained in human essential hypertension. Pathogenetic relationships are discussed.
THE EFFECT OF PODOPHYLLOTOXIN ON TISSUE METABOLISM AND ENZYME SYSTEMS
Authors: Miller Zelma Baker , Davison Clarke , Smith Paul K.
Published: June 2004

Podophyllotoxin, 10–3M, inhibits the respiration in vitro of rat lymph nodes, thymus, kidney, tumor, spleen, liver, brain, testis, and chicken embryo. Lymph node and spleen respiration are most sensitive, and the degree of inhibition increases with time.

The injection of podophyllotoxin into tumor-bearing mice (20 mg. per kg.) causes a dramatic reduction in the respiration of tumor slices. Within 6 hours, the respiration approaches zero. Inhibition is evident 2 hours after injection of the drug. Spleen respiration is reduced 50 per cent within 6 hours. Kidney and liver respirations remain within normal limits.

Marked reductions in the respiration of spleen, lymph nodes, and thymus glands of normal rats are produced by the injection of 15 mg. per kg. Thymus gland is the most sensitive of these three tissues, and its respiration is reduced 66 per cent 24 hours after injection of the drug.

The injection of 0.8 microgram podophyllotoxin into the yolk sac of chicken eggs bearing 5 day embryos has no effect on the respiration of the embryo within 8 hours, although this is a sufficiently toxic dose to kill 80 per cent of the embryos (within 24 hours).

Kidney respiration in the presence of acetate, glucose, alanine, and glutamate is inhibited to approximately the same degree as in the absence of added substrate. Succinate and pyruvate oxidation by rat kidney slices appear to be less sensitive.

Oxidation of acetate and butyrate by rabbit kidney homogenate is more sensitive to podophyllotoxin than oxidation by rabbit kidney homogenate without added substrate. Glucose oxidation by this preparation is not inhibited by 10–3M podophyllotoxin.

The anaerobic glycolysis of chicken embryo, rat brain, and rat testis is stimulated by 10–5 and 10–6M podophyllotoxin, and is inhibited by 10–3M.

The following enzymes are not inhibited by 10–3M podophyllotoxin: succinoxidase from pigeon breast muscle, choline, xanthine and tyrosine oxidase from rat liver homogenate, and leucine oxidase from Proteus vulgaris; alkaline and acid phosphatase from dog serum; adenosine triphosphatase from rat liver; choline esterase from rat brain homogenate; ribonucleodepolymerase from spleen mince and thymonucleodepolymerase from dog serum.

High concentrations of podophyllotoxin do not influence the viscosity and degree of polymerization of thymonucleic acid.
THE INHIBITION OF STREPTOCOCCAL DESOXYRIBONUCLEASE BY RABBIT AND HUMAN ANTISERA
Authors: McCarty Maclyn
Published: June 2004

Rabbit antisera against partially purified streptococcal desoxyribonuclease inhibit the action of the enzyme on its substrate. The activity of pancreatic desoxyribonuclease is not affected by these antisera. Similarly antibody against pancreatic nuclease does not inhibit the streptococcal enzyme.

Certain patients develop inhibitory antibody to streptococcal desoxyribonuclease following streptococcal infections, occasionally in very high titer, although the proportion of patients showing an antibody response appears to be lower than in the case of streptokinase and streptolysin O.

The pattern of antibody response to desoxyribonuclease has been compared to that of streptokinase and streptolysin O in a group of ninety patients from an epidemic of scarlet fever.
CELLULAR MECHANISMS OF ANTIBACTERIAL DEFENSE IN LYMPH NODES
Authors: Smith Ralph O. , Wood W. Barry
Published: June 2004

Acute pneumococcic lymphadenitis produced in rats by intradermal inoculation of the foot-pad is characterized by rapid infiltration of polymorphonuclear leucocytes into the intermediary sinuses of the node, and prompt phagocytosis of pneumococci by both the macrophages of the sinuses and the recently arrived leucocytes. After 5 to 7 hours the polymorphonuclear leucocytes are found densely congregated about the hilar region, and 9 hours after inoculation most of the phagocyted organisms have been digested. At the end of the 24 hour period the popliteal node presents the picture of a subsiding inflammation with a marked macrophage reaction and regenerating lymph follicles.

Phagocytosis of encapsulated pneumococci in the foot-pad and popliteal node occurs in less than 30 minutes after inoculation. It is assumed that this prompt phagocytosis is effected by the non-antibody mechanism of "surface phagocytosis."

The majority of polymorphonuclear leucocytes that enter the sinuses of the inflamed node appear to come from capillaries within the node itself rather than from the primary site of inflammation in the foot-pad. The prompt inflammatory response of the nodal tissues serves as an active defense against lymph-borne infection.

Macrophages invade nodal sinuses only after most of the pneumococci have been destroyed by polymorphonuclear leucocytes. It is suggested that the macrophage reaction follows removal of the primary inflammatory stimulus by the granulocytes, and thus constitutes only a late phase of recovery.

Fibrin formation in the sinuses of the lymph node is rare during acute lymphadenitis. This finding may be related to the observation that within 5 minutes after entrance of bacteria into the node, heparin-containing granules from mast cells are strewn throughout the sinuses.
CELLULAR MECHANISMS OF ANTIBACTERIAL DEFENSE IN LYMPH NODES
Authors: Smith Ralph O. , Wood W. Barry
Published: June 2004

The origin of the polymorphonuclear leucocytes found in the intermediary and subcapsular sinuses of the popliteal lymph node during acute bacterial lymphadenitis, and the effect of this leucocyte infiltration on the passage of bacteria through the lymph node have been investigated. It has been demonstrated that:

1. The polymorphonuclear leucocytes in the nodal sinuses originate both from blood vessels of the lymph node and from the primary inflammatory focus in the tissues.

2. Granulocytes invading the intermediary sinuses of the infected lymph node arise primarily from capillaries lining these sinuses.

3. Most of the polymorphonuclear leucocytes in the subcapsular sinus, on the other hand, originate from the inflammatory focus in the tissues and appear to traverse the node by way of this peripheral sinus.

4. The bacteremia following direct intralymphatic injection of pneumococci is suppressed by the presence of preformed inflammatory exudate in the nodal sinuses indicating that the filtering capacity of the node is thereby greatly increased.
THE EFFECT OF THE SIZE OF THE INOCULUM AND THE AGE OF THE INFECTION ON THE CURATIVE DOSE OF PENICILLIN IN EXPERIMENTAL INFECTIONS WITH STREPTOCOCCI, PNEUMOCOCCI, AND TREPONEMA PALLIDUM
Authors: Eagle Harry
Published: June 2004

The amount of penicillin which suffices to abort pneumococcal and streptococcal infections in white mice and rabbits, as well as syphilitic infection in rabbits, has been shown to increase markedly with the number of organisms inoculated. The curative dose increases also with the age of the infection, presumably owing to the interim increase in the number of organisms in the nfected host.

The necessity for the larger doses of penicillin is attributed to the longer itime for which effectively bactericidal concentrations of penicillin must then be provided in order to kill the larger number of organisms.
LOCALIZATION OF ANTIGEN IN TISSUE CELLS
Authors: Coons Albert H. , Kaplan Melvin H.
Published: June 2004

Improvements in a method for the specific microscopic localization of antigen in tissue cells are described. This method employs antibody labelled with fluorescein isocyanate as a histochemical stain, the specific antigen-antibody precipitate being made visible under the fluorescence microscope.

Two isomeric series derived from nitrofluorescein are described.
FURTHER STUDIES ON THE ASSOCIATIVE REACTIONS OF PNEUMONIA VIRUS OF MICE (PVM) AND INFLUENZA VIRUSES
Authors: Davenport Fred M. , Horsfall Frank L.
Published: June 2004

Tissue particles from a wide variety of animal tissues possess the capacity to combine with PVM. Various adsorbents also combine with the virus. Elution of PVM from combination with either tissue particles or adsorbents can be achieved by appropriately altering the ionic environment. Influenza viruses also are adsorbed on and eluted from adsorbents under similar conditions. Reasons are presented for thinking that combination of PVM with tissue particles results from the action of adsorptive forces between virus and tissue particles.
THE PRODUCTION OF FEVER BY INFLUENZAL VIRUSES
Authors: Wagner Robert R. , Bennett Ivan L.
Published: June 2004

The effect of treating rabbits with materials which destroy the cell receptors for influenzal viruses upon the ability of these animals to respond with fever to injection of the PR8 and Lee strains of influenza virus and Newcastle disease virus (NDV) is described. In general, both cholera vibrio and Cl. welchii filtrates produced diminution of febrile responses. The effect of sodium periodate upon the pyrogenic reaction was not significant.

Near-lethal amounts of these materials were necessary to demonstrate their protective effects against virus challenge. In order to rule out general debility as a factor in lessening the fever, it was shown that the ability of animals to respond to the pyrogenic effect of typhoid vaccine was unimpaired by injection of receptor-destroying substances.

The substances tested were more effective in abolishing the febrile response to PR8 virus than to Lee virus or NDV. This finding is compatible with previous studies of the protective effect exerted by homologous and heterologous viruses.

These findings give support to the hypothesis that union of virus and host receptor substance plays a part in the production of fever by these viruses.
AGE AS AFFECTING THE OSMOTIC AND MECHANICAL FRAGILITY OF DOG ERYTHROCYTES TAGGED WITH RADIOACTIVE IRON
Authors: Stewart W. B. , Stewart J.M. , Izzo M. J. , Young L. E.
Published: June 2004

Radioactive iron was administered to three normal dogs, two of which had previously been bled, in order to tag a group of erythrocytes of approximately known age.

The osmotic fragility of the newly formed tagged cells was significantly greater than that of the general cell population during the first few days after injection of the iron, while the mechanical fragility of the young cells was less than that of the general red cell population. As the cells aged and approached the end of their life span, their susceptibility to destruction by trauma inflicted by rolling glass beads exceeded that of the general cell population. The osmotic behavior of the old cells was not distinctive.

The increased mechanical fragility of senescent cells suggests that the life span of erythrocytes may be limited at least in part by changes within the cell which render it more susceptible to destruction by mechanical wear and tear in the circulation. It is emphasized, however, that the trauma produced by rolling glass beads may be quite unlike that inflicted upon red cells in vivo.

A decrease in circulating radioactive iron was observed in each experiment soon after the mechanical fragility of the tagged cells began to exceed that of the total cell population. The lowest point on the curve representing circulating radioiron was noted at 119, 119, and 122 days respectively after injection of iron in the three experiments. Estimates of the life span of dog erythrocytes obtained in this way agree with those provided by other methods.