bluuebunny/crossref_metadata_2025 huggingface dataset:
HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER
Authors: Whipple G. H. , Robscheit-Robbins F. S.
Published: June 2004

Biological assay of the human liver in various types of anemia shows conspicuous differences in the concentration of hemoglobin producing factors.

Pernicious anemia shows very high values and the liver in untreated cases may show maximal storage of the hemoglobin producing factors. Liver therapy reduces this store as the missing factor is supplied and new hemoglobin and red cells can be turned out by the marrow.

Aplastic anemia likewise shows high concentration of hemoglobin producing factors as there is no outlet for this material through the red marrow.

Secondary anemia due to loss of blood will show low normal values but even long standing severe anemia will not seriously deplete this store of hemoglobin producing factors in the liver.

Secondary anemia due to blood destruction within the body shows higher values and some excess store of hemoglobin producing factors and iron.

Leukemia gives a biological assay like secondary anemia due to blood loss and always presents definite anemia.

Iron analyses show conspicuous differences and iron concentration within the liver parenchyma does not in any way parallel the concentration of hemoglobin producing factors. The highest values for iron concentration are found in aplastic anemia (70 mg. per cent)— high values in pernicious anemia (51 mg. per cent)—normal values in leukemia (13 mg. per cent)—and low values in anemia due to loss of blood (5.3 mg. per cent).

These findings should aid in a more complete understanding of the pathogenesis and internal metabolism of various anemias.
THE EFFECT OF PROTEOLYTIC DIGESTION PRODUCTS ON MULTIPLICATION AND MORPHOLOGICAL APPEARANCE OF MONOCYTES
Authors: Baker Lillian E.
Published: June 2004

It has been found that the enzymatic digestion products of proteins cause a rapid proliferation of blood monocytes in vitro. Digestion mixtures having anywhere from 12 to 68 per cent of their nitrogen in the amino form possess this property.

For continued proliferation, heparin plasma or serum must be repeatedly supplied with the digests. Without them, multiplication continues for only a few days, the coagulum in which the cells are embedded liquefies around the central fragment, and the cells disintegrate.

The enzymatic digests exert a marked effect on the morphological appearance of the cells and finally cause them to agglutinate. The extent of this effect is determined by the degree of hydrolysis of the digest, its concentration, and the length of time the cells are cultivated in it. The morphological appearance of the cells is also somewhat influenced by the nature of the plasma or serum used with the digest.

Digests having very little free amino nitrogen produce short, round, granular cells. Those more highly hydrolyzed produce large, long, slender forms.

An increase in the concentration of the digest in the medium causes a shortening and broadening of the cell and an increase in its granulations. Therefore, even a highly hydrolyzed digest may, if concentrated, give cells resembling those in a lower concentration of a less hydrolyzed one.

The digests have a cumulative effect on the cells, as the time of cultivation is extended. Therefore, cultivation for a long period in a dilute solution may give the same effect as a shorter time in a higher concentration.

A different effect is obtained if plasma is used with the digest than if serum is used, even when the plasma and serum are taken from the same animal. The monocytes cultivated in serum and digest are generally shorter, broader, and more granular than those cultivated in heparin plasma and digest. They also contain more fat and have a greater tendency to digest the clot.

Agglutination of the cells takes place more readily in highly hydrolyzed products than in those slightly hydrolyzed. It is hastened by increase in concentration of the digest in the medium. It occurs more readily at the periphery of the culture and sooner in serum and digest than in heparin plasma and digest.

Completely hydrolyzed proteins and mixtures of pure amino acids do not produce effects at all comparable to those of the enzymatic digests either in their effect on the rate of cell proliferation or their action on the morphology of the cell.

Arsenic pentoxide in dilutions from 1:20,000 to 1:80,000 is the only other agent known to bring about agglutinations of the monocytes when cultivated in vitro.

The early changes in the morphological appearance of the cell that are produced by these digests are reversible. When the digests are removed from the medium and the cells cultivated in plasma and Tyrode solution, they very gradually revert to their original form.
THE LYMPHATIC PARTICIPATION IN HUMAN CUTANEOUS PHENOMENA
Authors: Hudack Stephen S. , McMaster Philip D.
Published: June 2004

A technic is described for the demonstration of lymphatic capillaries in living skin and for their study. By means of vital dyes injected intradermally these vessels can be rendered plainly visible. They form an extraordinarily abundant anastomotic web. The least scratch, one which does not penetrate through the epidermis, gives rise to such conditions that lymphatic absorption readily takes place from the abraded surface; and so close-meshed is the lymphatic web that an intradermal injection with even the finest hypodermic needle tears some of the constituent vessels open with result that they undergo direct injection. In many individuals much of the fluid introduced at an ordinary intradermal injection, like that made in the clinic, spreads through the superficial lymphatic network, whereas in others it tends to enter the deeper lymphatics at once, the difference being due to merely physical factors determined by skin texture. Normal flow along the skin lymphatics is rapid even when the body is at rest, dye introduced into the skin of the resting forearm reaching the axilla within a few minutes. The observations make plain the fact that every intradermal injection is an intralymphatic one, often preponderantly such, while furthermore every local injection into the skin becomes within a few minutes a general one, so rapidly is the introduced material transported to the blood.

The normal permeability of the skin lymphatics of man is approximately the same as that of the mouse. Tests indicate that in both instances the lymphatic wall behaves like a semipermeable membrane. The permeability of the human lymphatic wall like that of the mouse is subject to rapid and great changes. A stroke on the skin with a blunt instrument to produce a wheal, causes the lymphatic capillaries to become so permeable temporarily that dyes pass through their walls as if practically no barrier existed, instead of being held back for a greater or less period. Slight inflammation due to heat, ultraviolet light or bacterial products has a similar effect. So, too, has histamine. When fluid pours rapidly into the tissue from the blood, as when a wheal is formed, the lymphatics are compressed and their efficiency as drainage channels is interfered with.

These facts are briefly discussed in their bearing upon skin phenomena in general. The lymphatics cannot be disregarded in considering such phenomena, in which it is plain that they have a large share.
ELECTROLYTE BALANCE STUDIES IN ADRENALECTOMIZED DOGS WITH PARTICULAR REFERENCE TO THE EXCRETION OF SODIUM
Authors: Loeb Robert F. , Atchley Dana W. , Benedict Ethel M. , Leland Jessica
Published: June 2004

1. Balance studies have been made on three dogs before and after adrenalectomy, performed in two stages.

2. It has been shown that the sodium concentration of the blood decreases in adrenalectomized dogs, as is true in patients suffering from Addison's disease and in cats experimentally adrenalectomized.

3. There are also decreases in the chloride and bicarbonate concentrations which together are approximately equivalent to the decrease in sodium.

4. An increase in the potassium concentration of the blood occurs after adrenalectomy, as reported in other studies. There is no obvious correlation of this change with changes in potassium balances.

5. The balance studies show a striking loss of sodium from the body during the development of adrenal insufficiency. This loss of Na results from an increased excretion of sodium in the urine and is not complicated by loss of base as a result of vomiting or diarrhea.

6. Following adrenalectomy, both the total amount of sodium and its concentration in the urine are markedly increased. This increase in concentration of sodium occurs in spite of an augmented urine volume.

7. The behavior of the chloride ion following adrenalectomy parallels that of the sodium ion, but the loss is not equivalent.

8. During the period of accumulation of non-protein nitrogen in the blood, the rate of water excretion by the kidney is even greater than before removal of the adrenal glands.

9. The possibility of a regulatory effect of the adrenal glands upon sodium metabolism and renal function has been discussed.
INHERITED AND ACQUIRED FACTORS IN RESISTANCE TO INFECTION
Authors: Webster Leslie T.
Published: June 2004

1. A colony of inbred mice has been established free from inter-current infections and from the influence of extraneous variables detrimental to a study of their resistance to natural infection. A technique of measuring the resistance of mice to natural B. enteritidis mouse typhoid infection has been developed.

2. The Rockefeller Institute albino strain showed an average 37.4 per cent mortality to B. enteritidis mouse typhoid infection.

3. By breeding from progeny of mice dying early after exposure, lines approximately 85 per cent susceptible were obtained; by breeding from unexposed progeny of mice surviving infection, lines 15 per cent susceptible were obtained. Further selection within the most susceptible and most resistant lines did not alter their reaction; selection within the less susceptible and less resistant lines increased the sought factor. These rates remained approximately the same when the susceptibles received 1/100th and the resistants ten times the standard dose. The selected mice reacted consistently when exposed to spontaneous herd infection.

4. Several strains of mice, brother to sister inbred for special factors, did not differ materially in susceptibility. White-face and selected black-and-tan strains, however, proved 89.0 and 97 per cent susceptible.

5. White-face susceptibles mated with resistant Rockefeller Institute mice gave F1 progeny, 17.7 per cent susceptible. F1 mice back-crossed to susceptibles gave progeny 61.2 per cent susceptible and back-crossed with resistants gave progeny 26.3 per cent susceptible. F2 mice mated inter se gave progeny 34.2 per cent susceptible. The results indicate that resistance factors are dominant and not sex-linked.
PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES IN ITS RELATION TO BACTERIAL HYPERSENSITIVENESS
Authors: Shwartzman Gregory
Published: June 2004

The observations reported in this paper demonstrate that the intravascular interaction of bacterial and animal protein antigens with homologous antibodies at the site of a tissue made vulnerable by bacterial filtrates induces prompt severe hemorrhagic necrosis in this tissue. In the light of these observations there is offered an explanation of the mechanism underlying focal and skin bacterial hypersensitiveness.
THE HYPOPHYSEAL SUBSTANCE GIVING INCREASED GONADOTROPIC EFFECTS WHEN COMBINED WITH PROLAN
Authors: Evans Herbert M. , Simpson Miriam E. , Austin Paul R.
Published: June 2004

The increased gonadotropic effect obtained by combining prolan with hypophyseal extracts can be secured equally well by the use of preparations which contain high amounts of the growth or of the gonad-stimulating hormone.

In hypophyseal extracts containing the growth hormone, the synergistic effects do not parallel the content of growth-promoting substance.

Similarly, in hypophyseal extracts containing the gonad-stimulating hormone, the synergistic effects do not parallel the content in the gonadotropic factor.

The hypophyseal substance involved has been prepared sufficiently free of the growth and gonad-stimulating hormones to make it inadmissible to consider either of these substances as responsible for the reaction.
THE REACTION OF STANDARD BREEDS OF RABBITS TO EXPERIMENTAL SYPHILIS
Authors: Rosahn Paul D.
Published: June 2004

A comparative study was made of the character and severity of the infection produced by Tr. pallidum in groups of standard bred Havana, Dutch, English, Himalayan, and Rex rabbits. All known variables that might influence the course of the disease were common to the different breed groups.

On the basis of certain clinical data selected as criteria for the determination of variations in the response to syphilitic infection, it was found that the Havana and Dutch animals were resistant while the English, Himalayan, and Rex rabbits were susceptible.

From these results, it appears that breed, race, or family is a factor which significantly influences the response to infection with Tr. pallidum.
OBSERVATIONS ON THE IMMUNOLOGICAL RELATION OF POLIOMYELITIS TO LOUPING ILL
Authors: Schwentker F. F. , Rivers Thomas M. , Finkelstein M. H.
Published: June 2004

The results of the work presented in the present paper show that louping ill and poliomyelitis immunologically are not closely related. Although relatively few experiments were performed, the data obtained were sufficiently decisive for our purposes. Certainly nothing was found to indicate that one might be able to immunize human beings against poliomyelitis by the use of louping ill virus. In addition to the negative findings, a certain amount of useful information was also secured, namely, (1) monkeys can be solidly immunized against louping ill by intraperitoneal injections of virus and partially protected by intramuscular administrations of the active agent, (2) during the process of immunization no signs of involvement of the central nervous system are manifested, and (3) sera from monkeys immunized in the manner described contain antibodies capable of neutralizing the virus.
STUDIES ON INFLAMMATION
Authors: Menkin Valy
Published: June 2004

Trypan blue injected into an area of cutaneous inflammation induced by Staphylococcus aureus failed to drain readily to the tributary lymphatics when the dye was injected as early as 1 hour after the inoculation of the microorganisms.

Trypan blue introduced into an area of cutaneous inflammation induced by Pneumococcus Type I was retained in situ when the dye was injected about 6 or more hours after the inoculation of the bacteria.

When an area of cutaneous inflammation was induced by the inoculation of a culture of Streptococcus hemolyticus, trypan blue injected into it drained readily to the tributary lymphatics for the first 30 hours following the onset of the inflammatory reaction. When the inflammation had lasted for 45 hours or longer, the dye was fixed in situ and failed in most instances to reach readily the tributary lymphatics.

The rapidity of fixation of the dye in the instances given would appear to depend on mechanical obstruction in the form of both a fibrinous network and thrombosed lymphatics or thrombosed lymphatics alone at the site of inflammation.

Inasmuch as staphylococci, pneumococci, and streptococci spread from the site of cutaneous inoculation primarily through lymphatic channels, the difference in the rapidity with which mechanical obstruction is set up in the areas inflamed by them will help to explain the differing invasive abilities of these pyogenic organisms.
STUDIES ON THE PREVENTION OF CHOLESTEROL ATHEROSCLEROSIS IN RABBITS
Authors: Turner Kenneth B.
Published: June 2004

1. Whole thyroid gland when administered simultaneously with cholesterol prevented the atheromatous changes produced by the latter in the aorta of rabbits in 17 of 19 animals.

2. In this series thyroxin was less effective, as atherosclerosis occurred in 8 of 11 rabbits.

3. Potassium iodide also exerted a strong protective action as aortic lesions were present in only 1 of a series of 12 rabbits fed cholesterol and potassium iodide concurrently.

4. The effectiveness of potassium iodide was not shared by potassium bromide or potassium chloride.

5. A relationship was noted between the level of the cholesterol in the blood and the development of atherosclerosis. In general, the aortic lesions accompanied a hypercholesterolemia.
STUDIES ON THE SUPRARENAL CORTEX
Authors: Harrop George A. , Soffer Louis J. , Ellsworth Read , Trescher John H.
Published: June 2004

A characteristic alteration in the electrolyte structure of the blood plasma of the suprarenalectomized dog occurs when injections of cortical extract are stopped. This alteration progresses during the course of the suprarenal insufficiency, parallel with the hemoconcentration and the loss in weight. When injections of cortical extract are resumed, the electrolyte structure returns to its original form, the alterations paralleling the dilution of the blood and the return of the body weight to its original level.

The hemoconcentration, with the resulting physiological changes which take place in the suprarenalectomized dog after the cessation of cortical extract injections, is associated with a loss of sodium and chloride, accompanied by their proper complement of body water, by way of the kidney. Since this effect is produced in the suprarenalectomized animal, well nourished and in excellent condition, solely by cessation of injections of the cortical hormone, and since the reverse process of repair of the electrolyte and water losses can be effected solely by resumption of extract injections, it follows that all of the observed phenomena are due to this cause, and to this alone. It can be concluded that one function of the cortical extract in the suprarenalectomized dog is that of participation in the regulation of the sodium and chloride metabolism, and consequently, of the balance and distribution of water. The loss of water, in the absence of the cortical hormone, is sustained partly by the blood plasma, but to a far greater extent by the interstitial body fluid. The available evidence points to the kidney as the locus of this regulatory function of the cortical hormone.
OBSERVATIONS ON ATTEMPTS TO PRODUCE ACUTE DISSEMINATED ENCEPHALOMYELITIS IN MONKEYS
Authors: Rivers Thomas M. , Sprunt D. H. , Berry G. P.
Published: June 2004

No evidence was found to support the idea that vaccine virus placed in the cisterna magna is capable of producing an acute disseminated encephalomyelitis with perivascular demyelination either in normal or in partially immune monkeys.

A testicular extract (Reynals' factor) did not induce vaccine virus to cause an acute disseminated encephalomyelitis in monkeys.

Repeated intramuscular injections of brain extracts and brain emulsions into eight monkeys were followed in two instances by an inflammatory reaction, accompanied by demyelination, in the central nervous system. The exact relation of the injections to the disease of the nervous system is not clear.

The combined action of vaccine virus and an emulsion of fresh rabbit brain did not lead to the production of an acute disseminated encephalomyelitis in monkeys that had received repeated intramuscular injections of emulsions and alcohol-ether extracts of normal rabbit brains.
THE ANTIGENIC RELATIONSHIP BETWEEN PROTEUS X-19 AND TYPHUS RICKETTSIAE
Authors: Castaneda M. Ruiz , Zia Samuel
Published: June 2004

1. The absorption of typhus sera (human or antityphus horse serum) with Proteus X-19 removes only the Proteus agglutinins, leaving the Rickettsia agglutinins intact.

2. The absorption of typhus sera with Mexican Rickettsiae removes the agglutinins for both the Rickettsia and Proteus X-19.

3. While normal or formalinized Rickettsiae are not agglutinated by anti-Proteus serum, these organisms—when formalinized and heated at 75°C.—become agglutinable by such serum.

4. The absorption of anti-Proteus serum with Mexican Rickettsiae removes agglutinins for formalinized and heated Rickettsiae but does not affect those for Proteus X-19.
THE FORM AND FUNCTION OF SYNOVIAL CELLS IN TISSUE CULTURES
Authors: Vaubel Ernst
Published: June 2004

A detailed description is given of the various forms assumed by synovial cells in tissue cultures under varying conditions. A discussion of correlation between different morphologic appearances and certain functions of the cells is deferred until the end of the next paper (17).
THE FORM AND FUNCTION OF SYNOVIAL CELLS IN TISSUE CULTURES
Authors: Vaubel Ernst
Published: June 2004

1. Synovial cultures are differentiated in tissue cultures from other tissues of mesenchymal origin by their type of growth and cell function.

2. In these respects they are more closely allied to chondroblasts and osteoblasts than to fibroblasts.

3. Synovial cells in tissue cultures develop marked globular cytoplasmic granulations that stain easily with neutral red and sometimes with toluidine blue; they show marked polymorphism with all transitions from round to spindle, polygonal and star shapes and eventually form an epithelial-like membrane, composed of cells with numerous syncytial bridges.

4. In cultures of typically growing synovial cells a mucin-like substance is elaborated. Typical growth and maximal mucin production is best maintained in media containing a minimum of growth-stimulating substances. Transformation of synovial cell growths into fibroblastic growth is accompanied by a loss of mucin production. Dying cells apparently do not produce mucin.

5. Amitotic cell division and the formation of macrophage-like cells were observed.

6. Marked tendency to liquefaction of the plasma about the growths was observed and attributed to the elaboration of a proteolytic ferment.

7. The specific designation "synovioblasts" is proposed for these cells.
THE RACES THAT CONSTITUTE THE GROUP OF COMMON FIBROBLASTS
Authors: Parker Raymond C.
Published: June 2004

1. Under appropriate conditions, fibroblasts are able to multiply in serum, at a slow rate, for very long periods.

2. The rate of multiplication of fibroblasts in a given sample of serum depends entirely upon the nature of the strain. Cell races endowed with a high residual growth energy multiply more rapidly in serum than those whose growth potencies are of a lower order.

3. Fibroblasts, in the beginning, multiply more abundantly in plain serum than in heparinized serum, and also more abundantly in heparinized serum than in herparinized plasma. Later, these differences become less pronounced.

4. The first effect of serum on fibroblasts is invariably injurious, the degree of injury differing according to the nature of the cell strain and the age of the animal from which the serum is derived. With the passage of time, however, the colonies undergo gradual improvement, both in the appearance of the component cells and in their rate of proliferation.

5. In media containing embryonic tissue juice, or other growth-activating substances, fibroblasts form colonies that are isomorphic and composed of isomorphic cells. In serum, fibroblasts form colonies of heteromorphic appearance. Each colony becomes composed of cells that differ from one another, to a more or less marked degree.
QUANTITATIVE STUDIES ON THE PRECIPITIN REACTION
Authors: Heidelberger Michael , Kendall Forrest E. , Soo Hoo Check M.
Published: June 2004

1. The preparation is described of a deep red protein dye, R-salt-azo-benzidine-azo-crystalline egg albumen, which contains no more than traces of protein with the original egg albumen specificity.

2. Based on previous publications of the writers, a quantitative method is given for the micro estimation of precipitin in the antisera to the dye. The method gives the actual weight of precipitin and may be applied to the determination of the maximum amount of precipitable antibody in any antiserum.

3. Data are given (1) on the influence of the period between the final injection and the bleeding on the precipitin content of rabbit antisera to the azo protein; (2) on the magnitude of the antibody response following the injection of multiple doses of the antigen varying within wide limits; (3) on the variations in the precipitin content of the sera of rabbits given successive courses of antigen injections; and (4) on the stability of antisera stored in the cold.

4. Four antisera were obtained in which over 100 times as much precipitin was recovered as the amount of antigen injected. This supplements the growing mass of evidence against the theory that specific antigen fragments are actually incorporated into the antibody molecule.
THE EFFECT OF PNEUMOCOCCUS AUTOLYSATES UPON PNEUMOCOCCUS DERMAL INFECTION IN THE RABBIT
Authors: Goodner Kenneth
Published: June 2004

In pneumococcus dermal infections in rabbits, the addition of pneumococcus autolysate to an infective inoculum favors the invasiveness of the particular strain employed, but does not alter the kind of virulence possessed by that strain.

Autolysates exhibiting this enhancing property also induce purpura in mice and inhibit the coagulation of rabbit blood. The relation of these properties to the infectivity of Pneumococcus and the possible role of bacterial autolysis in natural infection are discussed.
THE EVALUATION OF ACTIVE RESISTANCE TO PNEUMOCOCCUS INFECTION IN RABBITS
Authors: Goodner Kenneth , Stillman Ernest G.
Published: June 2004

The dermal pneumococcus infection has been employed to determine the active resistance of rabbits against infection, and an evaluating scale of the gradient of resistance has been established. The significance of the various degrees of resistance has been discussed, and the possible general inferences of the findings indicated.
RESISTANCE TO PNEUMOCOCCUS INFECTION IN RABBITS FOLLOWING IMMUNIZING INJECTIONS OF HEAT-KILLED PNEUMOCOCCUS SUSPENSIONS
Authors: Stillman Ernest G. , Goodner Kenneth
Published: June 2004

The degree and duration of the active resistance against pneumococcus infection have been determined in rabbits which received intravenous injections of a heat-killed suspension of pneumococci of the three principal types. The resistance induced by the immunization procedure varied in degree and in duration with each type of Pneumococcus.
A STUDY OF THE THERAPEUTIC MECHANISM OF ANTI-PNEUMOCOCCIC SERUM ON THE EXPERIMENTAL DERMAL PNEUMOCOCCUS INFECTION IN RABBITS
Authors: Gelarie Arnold J. , Sabin Albert B.
Published: June 2004

The purpose of the present investigation was to determine whether or not non-specific agents were capable of exerting any influence on the response of pneumococcus-infected animals to specific serum therapy. It has been demonstrated in these experiments that whereas gold (empirically chosen) by itself had very little effect either on the course or the outcome of the experimental pneumococcus infection, it is nevertheless capable of exerting a definite and marked beneficial effect in rabbits treated with a subeffective dose of the specific antiserum. Of the rabbits treated with the subeffective dose of serum alone, 71 per cent died and only 29 per cent survived; the additional administration of gold reversed this death-survival ratio with the result that of a large group of rabbits which received the combined therapy, 77 per cent survived and only 23 per cent died.
STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL
Authors: Nelson John B.
Published: June 2004

Three types of an uncomplicated fowl coryza, differing in the onset and duration of symptoms, developed after the intranasal injection into normal birds of exudate from natural cases. Protection tests were carried out with 2 of the types in an attempt to explain why the "bacillary" disease regularly ran a shorter course than the "exudate" disease. Reciprocal protection was demonstrated in one case, but in the other the birds which had recovered from the "bacillary" disease were susceptible to reinfection with exudate. There was no indication, however, that a second infectious agent was present in the exudate, and the failure to cross-immunize was ascribed, rather, to a reduction in the immunizing properties of the specific bacillus induced by artificial cultivation.

It was also noted that the coryzas produced by exudate and bacilli, respectively, could be transmitted from infected birds to normal ones by direct contact. In both cases 1 bird out of 5 failed to contract coryza on exposure. These 2 birds were later injected with the respective agents to which they had been exposed and found to be resistant.
STUDIES ON MENINGOCOCCUS INFECTION
Authors: Rake Geoffrey , Scherp Henry W.
Published: June 2004

Two group-specific substances, one a polysaccharide and the other a protein, have been isolated from the meningococcus and their serological properties are described. A discussion of these substances, together with the type-specific fraction, is given, and a relationship of these substances to certain serological phenomena is suggested.
STUDIES ON MENINGOCOCCUS INFECTION
Authors: Rake Geoffrey
Published: June 2004

Precipitin tests, carried out on the cerebrospinal fluid from cases of meningococcal meningitis with monovalent sera, demonstrate the presence in that fluid of type-specific precipitinogens of the meningococcus. Negative results are secured when the spinal fluid is obtained after the commencement of intrathecal serum treatment and also occasionally when the numbers of infecting organisms are very small. The reaction offers an easy and rapid method of ascertaining to which type of meningococcus a particular case of meningitis is due, and facilitates the immediate use of monovalent therapeutic antimeningococcal serum. Typing by means of the precipitin reaction can be confirmed by agglutination of the strain of organism responsible for the infection, if such strain be isolated. Confirmation by means of agglutination has been possible in all the cases discussed in this report. Spinal fluids from other diseases of the meninges and central nervous system fail to give any precipitin reaction with the monovalent sera.
EXPERIMENTAL AND STATISTICAL EVIDENCE OF THE PARTICULATE NATURE OF THE BACTERIOPHAGE
Authors: Feemster Roy F. , Wells W. F.
Published: June 2004

Experimental evidence is brought forward to show that the bacteriophage obeys very closely the laws of chance distribution of particles in suspension.
SOME OBSERVATIONS ON THE SPECIFICITY OF BACTERIAL ALLERGY TO CERTAIN OF THE NEISSERIAE
Authors: Miller C. Phillip , Castles Ruth
Published: June 2004

By means of the reaction to intracutaneous inoculation with bacterial suspensions in amounts of 0.2 cc., bacterial allergy was demonstrated in rabbits into which had been implanted agar foci containing either gonococci, meningococci, M. catarrhalis, or Bact. lepisepticum. The criterion of hypersensitiveness was the relative size and intensity of reaction evoked by an identical dose in "agar focus" and control rabbits. Rabbits sensitized to gonococci or meningococci usually reacted indistinguishably to either of these organisms, but were less allergic to M. catarrhalis. Similarly, animals sensitized to M. catarrhalis gave moderate but not maximal responses to the two former organisms. Cross-reactions did not occur between Bact. lepisepticum and any of the three Neisseriae. Animals sensitized to the four organisms mentioned reacted no more intensely than did controls to hemolytic streptococci, staphylococci, and rough pneumococci.

The hypersensitive state was found to begin early in the 2nd week and to end usually by the 4th week, being at its height in most instances on the 10th to 12th days. The number of organisms contained in the agar focus determined the success of the sensitization only to this extent, that very small and very large inocula failed to evoke the allergic state.

Rabbits immunized by intravenous injection of live organisms developed cutaneous reactions indistinguishable from those in controls.

The "secondary rise" of Andrewes, Derick, and Swift was rarely observed.
FURTHER STUDIES ON THE INFLUENCE OF TESTICLE EXTRACT UPON THE EFFECT OF TOXINS, BACTERIA, AND VIRUSES, AND ON THE SHWARTZMAN AND ARTHUS PHENOMENA
Authors: Duran-Reynals F.
Published: June 2004

The lesions produced by the Shwartzman and Arthus phenomena, as well as those produced by bacterial toxin and foreign sera in the normal rabbit, are spread by testicle extract over a larger area than would normally take place. With this spreading of the lesions there is a definite reduction in their intensity.

Lesions produced by invasive strains of staphylococcus at high dilutions or non-invasive staphylococci at moderate dilutions are definitely lessened in severity or even suppressed by the spreading action of testicle extract. Virus lesions are consistently enhanced by the spreading factor regardless of the dilution.
INTRANASAL VIRULENCE OF PNEUMOCOCCI FOR MICE
Authors: Webster Leslie T. , Clow Anna D.
Published: June 2004

1. Smooth colony pneumococci fresh from human beings, instilled in small doses into the nasal passages of special mice raised under standard conditions, brought about a characteristic infection and this spread to healthy contacts inciting in them the carrier state or fatal infection.

2. Differences in individual host response to the same dose of a given culture ranged from a complete refractory or nasopharyngeal carrier state, or a local cervical lymphadenitis, to fatal lobular or lobar pneumonias with or without pleurisy, empyema, and pericarditis, and acute fatal septicemia.

3. Pneumococci exhibited consistent individual strain differences with respect to ability to infect, when instilled intranasally into mice, and also differences in the spread to contacts. Degree of intranasal virulence paralleled demonstrable ability to spread to contacts.

4. Degree of intranasal virulence of strains did not parallel intraperitoneal virulence in 50 per cent of strains—high intranasal was accompanied by either high or moderate intraperitoneal virulence, and low intranasal by high, moderate, or low intraperitoneal virulence.

5. Type III strains were of relatively high intranasal and intraperitoneal virulences; Type II strains mostly low in intranasal but high or moderate in intraperitoneal virulence; Type I strains all low in intranasal but either high or moderate in intraperitoneal virulence. Most strains of other types were low both in intranasal and intraperitoneal virulences.

6. The intranasal virulence of pneumococci was not enhanced by animal passage. Nasal passage reduced the intranasal virulence to zero but did not affect intraperitoneal virulence, colony form, and agglutinative specificity. Passage by the intraperitoneal method maintained the characteristic level of intranasal virulence for a period, increased intraperitoneal virulence in some instances, but did not affect colony form or agglutinative properties.
NEUTRALIZING ANTIBODIES IN ABORTIVE POLIOMYELITIS
Authors: Trask James D. , Paul John R.
Published: June 2004

The neutralizing antibody content for poliomyelitis virus has been tested with both a human and a passage strain of the virus in serial samples of sera from five mild cases of abortive poliomyelitis, and an increase in this antibody content has been demonstrated in convalescent samples obtained within 4 weeks of the acute illness.
FURTHER STUDIES ON THE HYPOPHYSEAL SUBSTANCE GIVING INCREASED GONADOTROPIC EFFECTS WHEN COMBINED WITH PROLAN
Authors: Evans Herbert M. , Simpson Miriam E. , Austin Paul R.
Published: June 2004

The hypophyseal substance—the synergic factor—which gives increased gonadotropic effects when combined with prolan has been shown to itself possess a definite though slight gonadotropic activity. It produces transitory follicular enlargement within 24–48 hours, which, however, regresses at once on cessation of treatment so that by the end of the 4th day the ovary again approximates its infantile weight.

The synergic principle indeed provokes only moderate ovarian development when administered in 100 times the dose necessary to demonstrate the activation phenomenon.

By means of isoelectric precipitation or by means of tryptic and ereptic digestion, fractions containing the synergic principle were freed of many contaminants, in particular of the antagonistic factor.

The synergic principle has been shown to be unaffected by digestion with trypsin or trypsin followed by a short digestion with erepsin, but the action of pepsin inactivated the material.

A preparation of the active substance has been obtained which is potent in a total dose of 27 gamma.
THE RECOGNITION AND COMPARISON OF PROLAN AND PROLAN-LIKE SUBSTANCES
Authors: Evans Herbert M. , Simpson Miriam E. , Austin Paul R.
Published: June 2004

The synergism phenomenon has made possible the recognition of substances, which we have called "prolan-like," in a wide variety of conditions. Indeed, it has been possible to demonstrate a prolan-like material in the urine of normal men.

The method has shown a wide distribution of prolan-like substances in sera and urines of non-primates without demonstrating, however, significant difference in the reactions secured from pregnant as contrasted with non-pregnant states, or in males as contrasted with females.

The synergism phenomenon with pregnancy prolan can also be shown in the increased development of the seminal vesicles of immature male rats. However, such males cannot be advantageously employed in the detection of prolan-like gonadotropic substances occurring in the blood and urine in conditions other than pregnancy, for the prolan-like substances usually do not effect appreciable development of the seminal vesicles.
CONCENTRATION OF THE GONADOTROPIC HORMONE IN PREGNANT MARE'S SERUM
Authors: Evans Herbert M. , Gustus Edwin L. , Simpson Miriam E.
Published: June 2004

The gonadotropic hormone of the blood of the pregnant mare has been greatly concentrated by adsorption on active aluminum hydroxide followed by elution. The preparations so obtained gave demonstrable gonadotropic effects within 100 hours in 21 day old female mice following three subcutaneous injections of 0.001 mg. in 1 cc. of physiological saline.

As is well known, other gonadotropic substances do not cause conspicuous development of the male gonads but injections of comparatively large doses of these preparations into immature male rats caused marked development of the testes, which in 10 days were trebled in weight. An astonishing increase in the weight of the seminal vesicles resulted, for these organs were approximately 75 times heavier than in controls.
AN IMMUNOLOGICAL STUDY OF NATIVE, DENATURED, AND REVERSED SERUM ALBUMIN
Authors: Miller Benjamin F.
Published: June 2004

Native and reversed horse serum albumin are indistinguishable when tested immunologically by means of the precipitin reaction.
FURTHER OBSERVATIONS ON THE CULTIVATION OF VACCINE VIRUS FOR JENNERIAN PROPHYLAXIS IN MAN
Authors: Rivers Thomas M. , Ward S. M.
Published: June 2004

A dermal strain of vaccine virus has been passed through 99 successive culture passages. This procedure led to a diminution in the pathogenicity of the active agent for the rabbit. By repeated testicular passages in rabbits, however, the virus regained its pathogenicity for that host. New cultures were initiated with the revived virus. A culture strain of virus that has been twice revived in this manner has remained fairly stable for the rabbit through 60 culture passages and it produces mild, yet effective vaccinal reactions in man.

Virus in early cultures was not attenuated for man, but later cultures of the original strain and cultures of the 2nd and 3rd revived strains produced mild reactions without fever and discomfort to the patients. Intradermal vaccinations with the culture virus are safe and satisfactory.

With the culture virus 118 infants and children have been inoculated and in 100 of them a positive reaction occurred. The culture virus produced a refractory state to a standard dermal strain of calf lymph and vice versa.

Culture virus stored in 50 per cent neutral glycerol at –10°C. or at +3°C. maintained a considerable amount of its activity for at least 1 year. Desiccated culture virus sealed in tubes maintained some of its activity when stored at 37°C. for 5 weeks.

Fresh cultures can be initiated without difficulty from desiccated virus or from virus that has been stored with or without glycerol.
CONCERNING THE RELATIVE RESPONSE TO BLOOD GAINS AND BLOOD LOSSES; AND HABITUATION TO AN EXCESS OF BLOOD PIGMENT
Authors: Dick Macdonald
Published: June 2004

The effects of very gradually increasing or diminishing the amount of circulating hemoglobin have been studied in rabbits. Contrary to expectation it was found that when the pigment was increased by the injection of a small quantity of compatible blood every day during some weeks the erythropoietic tissue did not lessen its activities. The hemoglobin percentage mounted gradually yet considerably when even as little as 1/100 of the amount of blood initially possessed by the animal was injected each day; and the figure it finally attained must in some instances at least have been expressive of a superabundance. To this superabundance the animal itself evidently contributed through its persisting erythropoietic activity.

The results were very different when rabbits were bled daily to the same small amount that was injected into their fellows. The marrow became abnormally active, and this activity continued undiminished throughout the long period of the bleedings. The organism is evidently far more susceptible to blood losses than to blood gains, a fact which is scarcely surprising when one considers that throughout its differentiation as a going concern it has had to cope with exigencies of the first sort only.

Rabbits in which the hemoglobin is very gradually increased by the injection of strange blood become so accustomed to the abundance of pigment that even a slight falling off causes the erythropoietic tissue to become abnormally active to maintain the new status quo. Good reasons exist for referring the habituation thus manifested to readjustments in the functioning of the physiological mechanisms which mediate between oxygen demand and erythropoietic response. Too little recognition has been given to the rôle of these mechanisms in such relation. No evidence was obtained of any effective readjustment to protect the erythropoietic tissue from the stimulus of daily small blood losses.
CHEMOIMMUNOLOGICAL STUDIES ON THE SOLUBLE SPECIFIC SUBSTANCE OF PNEUMOCOCCUS
Authors: Avery Oswald T. , Goebel Walther F.
Published: June 2004

The soluble specific substance of Pneumococcus Type I has been chemically isolated from the bacterial cells and from autolyzed cultures as an acetyl polysaccharide.

So far as could be determined by the methods employed, the acetyl polysaccharide in highly purified form absorbs from Type I antipneumococcus serum all demonstrable type-specific precipitins, agglutinins and protective antibodies.

Mice injected intraperitoneally with minute quantities of the acetyl polysaccharide develop active immunity to subsequent infection with Pneumococcus Type I. The immunity thus induced is type-specific. In several instances purpura has been observed in mice following the injection of larger amounts of the acetyl polysaccharide.

Under the experimental conditions of this study, no type-specific precipitins, agglutinins or protective antibodies were demonstrable in the serum of rabbits following repeated intravenous injections of the Type I acetyl polysaccharide. The treated rabbits were not immune to subsequent infection with Pnemnococcus Type I.

The acetyl polysaccharide is readily converted into its deacetylated derivative by treatment with dilute alkali.

The chemical and immunological properties of the deacetylated polysaccharide are identical with those of the soluble specific substance in the chemical form in which it was originally isolated; the deacetylated form of the specific carbohydrate is non-antigenic, does not produce purpura in mice, and only incompletely absorbs the type-specific antibodies from Type I antipneumococcus serum.

The immunological significance of the acetyl polysaccharide and its possible relationship to the specific substances isolated from Pneumococcus Type I by other workers are discussed.
AN INVESTIGATION OF THE ETIOLOGY OF MUMPS
Authors: Johnson Claud D. , Goodpasture Ernest W.
Published: June 2004

1. From four out of six specimens of saliva from six cases of mumps in the early stages of the disease, a filterable cytotropic virus has been obtained which induces in M. rhesus monkeys, following inoculation of the parotid glands through Stensen's duct, an acute, non-suppurative parotitis analogous to mumps.

2. This virus has not been found in normal saliva, nor does it correspond to any known virus with which we are familiar.

3. The virus is free of demonstrable microorganisms including spirochetes.

4. It is judged that this virus is the causative agent of mumps.
STUDIES ON THE NERVOUS SYSTEM IN DEFICIENCY DISEASES
Authors: Zimmerman H. M. , Burack Ethel
Published: June 2004

Adult dogs maintained on an artificial, balanced ration adequate in all dietary essentials as far as is known except water-soluble, heat-stable vitamin B2 (G) developed, after a sufficient time, a slowly progressive disease characterized by loss of weight, persistent vomiting and diarrhea, and marked muscular weakness, which ended fatally in from 200 to over 300 days.

The clinical features of this condition, as pointed out in the discussion, are quite different from those characterizing the canine disease known as black tongue.

The anatomic changes in this condition consist of marked demyelination of the peripheral nerves, including the vagus; degeneration of the medullary sheaths and replacement by gliosis of the posterior columns of the spinal cord, particularly the fasciculi graciles; degeneration of the medullary sheaths of the posterior and less often of the anterior nerve roots of the cord; occasionally slight degenerative changes in most of the other fiber tracts of the cord.

Attention is called to the fact that degenerative lesions in the central nervous system similar or identical with these have frequently been described in pellagra in man.
NUTRITIONAL MYOPATHY IN DUCKLINGS
Authors: Pappenheimer Alwin M. , Goettsch Marianne ,   With the Assistance of Anna Alexieff
Published: June 2004

Ducklings fed on a diet of skimmed milk powder, casein, corn-starch, lard, cod liver oil, yeast, salts and paper pulp rapidly develop a disease characterized by extreme and progressive myasthenia, ending in death within a few days.

Pathological changes are found in the skeletal muscles. These show widespread hyaline necrosis of fibers, with edema and cellular reaction. The brain and other parts of the central nervous system are not affected, and no significant alterations are found in other viscera or tissues. The creatine content of the muscles is reduced in proportion to the muscle injury. Controls on a natural food diet remain free from the disease.
AN INVESTIGATION INTO THE SIGNIFICANCE OF HORMONAL FACTORS IN EXPERIMENTAL POLIOMYELITIS
Authors: Jungeblut Claus W. , Engle Earl T.
Published: June 2004

1. Adult rhesus monkeys possess frequently a greater resistance to experimental infection with poliomyelitis virus than young monkeys as indicated by the prolongation of the incubation period and the content of feeble neutralizing substances in the normal serum.

2. Virucidal substances can be demonstrated in the normal serum of subadult chimpanzees.

3. Immature monkeys prepared with glandular anterior pituitary hormones and anterior pituitary-like principles from the urine of pregnant women are protected only in exceptional instances against intracerebral infection with poliomyelitis virus. However, the serum of such prepared animals frequently acquires the property of inactivating the virus in vitro.

4. Active immunization with live poliomyelitis virus renders the immunized monkeys resistant to intracerebral infection in a higher percentage of the cases than does preparation with hormone.

5. The relative merits of non-specific enhancement of resistance and of specifically acquired immunity are discussed in their relation to the probable mechanism of resistance to poliomyelitis in man.