bluuebunny/crossref_metadata_2025 huggingface dataset:
PANMYELOPHTHISIS WITH HEMORRHAGIC MANIFESTATIONS IN RATS ON A NUTRITIONAL BASIS
Authors: György Paul , Goldblatt Harry , Miller Franklin R. , Fulton Robert P.
Published: June 2004

During the 12 months ending May, 1937, 72 rats were observed that manifested typical symptoms of panmyelophthisis. The disease may start as agranulocytosis, thrombocytopenia or pure red cell anemia, leading progressively, often rapidly, to aleukia hemorrhagica with its typical manifestations (epistaxis, melena, hematuria, purpura).

Blood examinations revealed correspondingly low white cell, red cell and platelet counts with very pronounced granulocytopenia (0 to 4 per cent). Bone marrow smears and histological findings were consistent with the diagnosis of panmyelophthisis.

Suprarenal hemorrhage was a frequent postmortem finding.

The pathogenesis of this experimental panmyelophthisis and this hemorrhagic diathesis is confined to special nutritional conditions. These diseases have been observed by us in rats kept on a diet deficient in vitamin B6, containing cane sugar and supplemented with vitamin B1 and crystalline natural or synthetic lactoflavin. Lack of vitamin B6, however, is not a necessary condition, since the disease was encountered in the majority of the animals after the specific deficiency disease which became apparent in rats kept on the B6 free diet was successfully treated with purified B6 preparations. Even in the untreated animals kept on the B6 deficient diet acrodynia was, as a rule, in distinct remission before symptoms of panmyelophthisis and hemorrhagic diathesis became manifest.

By means of the addition of Peters' eluate to the basal diet, panmyelophthisis could be prevented and, in animals where it was recognized in an early stage, cured. In view of these facts it is suggested that Peters' eluate contains a specific maturation factor for the primary blood-producing tissue, the reticulo-endothelium, a factor which, being different from lactoflavin, vitamin B6 and probably also from the so called filtrate factor, constitutes another distinct component of the vitamin B2 group.

Bacteriological studies brought forward no conclusive positive evidence for the infectious etiology of the experimental panmyelophthisis in our rats.

The possible relation of this new disease in rats to aleukia hemorrhagica and its partial manifestations in man, as well as to the so called Waterhouse-Friderichsen syndrome, is discussed.

Administration of amidopyrine, at least under the conditions chosen, failed to provoke panmyelophthisis in rats kept on the same diet as that given to rats in which the disease spontaneously developed.
STUDIES ON IMMUNITY IN A TYPE OF HUMAN ALLERGY (HAY FEVER): SEROLOGIC RESPONSE OF NON-SENSITIVE INDIVIDUALS TO POLLEN INJECTIONS
Authors: Cooke Robert A. , Loveless Mary , Stull Arthur
Published: June 2004

Large injections of ragweed pollen extract into normal non-sensitive volunteers did not produce a sensitization to ragweed.

Group 1 volunteers in whose skin many reactions were induced by injections of ragweed extract mixed with ragweed sensitive serum failed to show any serological changes. The theory that the immune substance found in the serum of treated ragweed sensitive cases was due to the reaction or to some substance created by it and not to the ragweed per se was not upheld.

On the contrary in group 2, volunteers who received larger amounts of ragweed but no sensitive serum, serological changes were induced resembling those previously observed to occur in ragweed sensitive patients after treatment. They were demonstrable by an inhibition of the immediate reaction and by interference with the neutralization of sensitive serum by its antigen. These serological changes are therefore independent of the specific reaction characteristic of this type of allergy.

The inhibiting factor was found to be related to the pseudoglobulin fraction of the serum and was shown to be specific.
INFLUENCE OF HOST FACTORS ON NEUROINVASIVENESS OF VESICULAR STOMATITIS VIRUS
Authors: Sabin Albert B. , Olitsky Peter K.
Published: June 2004

Peripheral inoculation of vesicular stomatitis virus is constantly followed by myelitis or encephalitis in young mice, but not in young (or old) guinea pigs. The cause of this variation was elucidated by investigating the fate of the virus after inoculation by a number of different routes.

Direct intracerebral injection of minimally infective amounts of virus was found to be equally fatal for young mice and young guinea pigs, indicating that the central nervous system as a whole was as easily injured by the virus in one species as in the other.

The events following nasal instillation of the virus varied in young and old guinea pigs. While there appeared to be a transitory multiplication of virus in the nasal mucosa of both young and old, the central nervous system was regularly invaded only in the young. In these, virus was first found only in the anterior rhinencephalon; later it spread to the piriform and hippocampal (olfactory regions) but not to the neopallial portions of the cortex, and the only other area to exhibit virus was the diencephalon (including the pars optica hypothalami), where its further progression was apparently arrested.

Absence of central nervous system disease following inoculation into sites supplied by spinal nerves (e.g. sciatic) was found to be due to inability of the virus to invade the nerves.

Since direct intrasciatic inoculation frequently led to a fatal ascending myelitis, it was evident that the central nervous system could be invaded along the spinal nerves, and that they did not constitute the main barrier. Furthermore, since multiplication of virus was demonstrated in tissues supplied by the spinal nerves, a process of elimination made it seem possible that the specialized, terminal nerve endings might be the structures which prevent the progression of the virus from the infected tissues to the axons and hence also to the central nervous system.

7 day old guinea pigs (or guinea pigs as a species) were thus found to possess much the same type of barriers to the progression of peripherally inoculated vesicular stomatitis virus as are acquired by mice at a considerably later age.

In a discussion of the present data, they have been correlated with known variations in neuroinvasiveness of other viruses and their bearing on the nature of inapparent or subclinical infections of the central nervous system has been considered.
SERUM SODIUM, POTASSIUM AND CHLORIDE AFTER SUPRARENALECTOMY IN CATS WITH DIABETES INSIPIDUS
Authors: Winter Charles A. , Gross E. G. , Ingram W. R.
Published: June 2004

The external symptoms of suprarenal insufficiency in cats with diabetes insipidus are the same as in those animals with only the suprarenals removed, except that the symptoms develop more rapidly in the former. The serum electrolyte changes, however, are different; there is no consistent or marked decrease in the concentration of sodium or chloride following suprarenalectomy in cats with diabetes insipidus, but there is the usual increase in the concentration of potassium. It is suggested that this indicates that changes in sodium are less characteristic of suprarenal insufficiency than are disturbances of potassium metabolism or distribution. A possible inter-relationship between the suprarenal cortex and the posterior lobe of the pituitary as salt-regulating mechanisms is discussed.
RESULTS OF THE INTRATRACHEAL INJECTION OF THE BORDET-GENGOU BACILLUS IN THE MONKEY AND RABBIT
Authors: Sprunt Douglas H. , Martin Donald S. , McDearman Sara
Published: June 2004

Experiments are reported which show that the virulent Bordet-Gengou bacillus can produce a significant lymphocytosis and an interstitial mononuclear pneumonia in both the monkey and the rabbit. Both of these reactions occur apparently as the result of a toxic material formed in vivo from the Bordet-Gengou bacillus and are not dependent on the multiplication of the organism itself.

It was also shown that the strictly avirulent form could also cause an interstitial mononuclear pneumonia but no lymphocytosis. This interstitial mononuclear pneumonia was thought to be the result of the foreign substance produced by the organism when it was in this stage. This was substantiated by the fact that this lesion could be produced both by living and dead organisms.
BLOOD PLASMA PROTEINS AS INFLUENCED BY INTRAVENOUS INJECTION OF GUM ACACIA
Authors: Heckel G. P. , Erickson C. C. , Yuile C. L. , Knutti R. E.
Published: June 2004

Lowered plasma protein concentration following single injections of gum acacia in the dog is due in some part to dilution, and in greater part to actual decrease in total circulating protein. The maximum decrease in the total circulating protein does not take place at the same time as the maximum decrease in concentration. Fluctuations in fibrinogen concentration are marked, and are not necessarily proportional to changes in plasma protein concentration. Plasma protein concentration returns to normal limits within 10 to 21 days after the injection, at which time total circulating protein and plasma volume are lower than normal. Loss of protein cannot be accounted for by increase in urinary nitrogen.

It is possible to maintain dogs at low levels of plasma protein concentration for several weeks by repeated injections of gum acacia solution. Anatomical changes following such a procedure in a normal dog are most conspicuous in the liver (Fig. A). These observations further implicate the liver as a source of plasma protein.

Two mechanisms for the diminution of plasma protein following gum injection are suggested. One of these is based on the possibility that the liver cells being engorged with gum acacia are not able to produce the necessary amount of plasma protein to supply the normal demand. The other possibility is that with the injection of the gum, since there is obviously a greatly increased amount of colloid in the blood, the more readily removable colloid, i.e. plasma protein, is taken out of the blood stream, in an attempt to return plasma volume and colloid osmotic pressure to the normal limits. It is probable that both of these mechanisms are involved.

Injection of gum acacia is suggested as a technique for further study of disturbed liver function.

It must be obvious that clinical use of gum acacia for intravenous injection is not without danger.
IMMUNOLOGICAL STUDIES OF A HEAT-STABLE SUBSTANCE ISOLATED FROM TISSUES INFECTED WITH VACCINE VIRUS
Authors: Parker Robert F.
Published: June 2004

We have shown that it is possible to obtain from extracts of vaccine virus-infected tissues a substance or substances, apparently protein, which are serologically active, and which are specifically related to vaccinal infection. The present investigation is concerned with a study of their immunological reactions. Their intraperitoneal injection in rabbits is followed by the appearance in the serum of these animals of antibodies directed specifically against them. The precipitating capacities of this serum are entirely removed after addition of appropriate quantities of heated vaccine virus extract, indicating that antibodies against only the heat-stable antigens have been produced. Further evidence of the specificity of the antibodies is gained from the reverse experiment, that is, absorption of a virus extract with the serum. We have shown that under suitable conditions the serum will remove S antigen specifically leaving the labile substances in solution. This would apparently indicate that they are serologically distinct although both are vaccinal products.

Serum of animals injected with the S substance and containing antibodies against it in high titer is apparently capable of neutralizing minute amounts of active virus. The animals providing the serum are, however, without demonstrable resistance to vaccinia. The significance of the neutralizing activity of the serum is debatable because it is of a greatly different order of magnitude from that which follows infection with vaccinia.
BLOOD PLASMA PROTEIN REGENERATION AS INFLUENCED BY FASTING, INFECTION, AND DIET FACTORS
Authors: Madden S. C. , George W. E. , Waraich G. S. , Whipple H.
Published: June 2004

When blood plasma proteins are depleted by bleeding, with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal with normal appetite, no anemia and normal nitrogen metabolism. These dogs become test subjects by which various factors relating to plasma protein production may be tested.

The normal dog (10 to 13 kg.) has a substantial reserve store of plasma protein building material (10 to 60+ gm.) which requires 2 to 6 weeks plasmapheresis for its complete removal. After this period the dog will produce uniform amounts of plasma protein each week on a fixed basal diet.

Dogs previously depleted by plasmapheresis and then permitted to return to normal during a long rest period of many weeks, may show much higher reserve stores of protein building material in subsequent periods of plasma depletion (see Table 1).

Under uniform conditions of low protein diet intake when plasmapheresis is discontinued for 2 weeks the plasma protein building material is stored quantitatively in the body and can subsequently be recovered (Table 4) in the next 2 to 3 weeks of plasmapheresis.

Given complete depletion of plasma protein building reserve stores the dog can produce very little (2± gm. per week) plasma protein on a protein-free diet. This may be related to the wear and tear of body protein and conservation of these split products.

Abscesses produced in a depleted dog during a fast may cause some excess production of plasma protein which is probably related to products of tissue destruction conserved for protein anabolism.

Gelatin alone added to the basal diet causes very little plasma protein production but when supplemented by tryptophane gives a large protein output, while tryptophane alone is inert.
STUDIES ON EXPERIMENTAL HYPERTENSION
Authors: Goldblatt Harry
Published: June 2004

The production of the acute malignant phase of experimental hypertension has been accomplished in seventeen dogs.

The method used to produce this type of hypertension was the same as for the benign type (4), namely, constriction of the main renal arteries, or the equivalent, constriction of the aorta above the origin of both main renal arteries, but the constriction was especially severe.

The malignant phase in the animals was characterized by hypertension, terminal renal insufficiency and the development of petechiae and larger hemorrhages in many internal organs, especially the alimentary tract. These were due to dissecting hemorrhage through, or rupture of, the wall of severely hyalinized or necrotic arterioles, or rupture of capillaries. Hyalinization and necrosis of arterioles were more severe and more widespread in animals that had a period of benign hypertension before the onset of renal insufficiency. In animals with a previous long period of benign hypertension, thickening of the media also occurred in arterioles, with or without hyalinized intima.

Elevation of blood pressure (mechanical factor) and renal insufficiency (humoral factor) are at least two of the necessary conditions for the development of the necrotic arterioles and hemorrhages. Necrotic arterioles and hemorrhages have not yet been observed in animals that have had very high blood pressure for years without renal insufficiency, nor in animals with azotemia, due to removal of both kidneys, but without hypertension. Hyalinized retinal arterioles have been observed in dogs with persistent hypertension and with moderate or no disturbance of renal function. That ischemia is not the cause of the necrosis of the arterioles is shown by their absence from the ischemic kidneys of the dogs and their widespread presence in other organs that were not ischemic.

These experiments show that the necrotic arterioles and hemorrhages are secondary to and not the primary cause of the malignant phase of hypertension.
BLEEDING TENDENCY AND PROTHROMBIN DEFICIENCY IN BILIARY FISTULA DOGS: EFFECT OF FEEDING BILE AND VITAMIN K
Authors: Smith H. P. , Warner E. D. , Brinkhous K. M. , Seegers W. H.
Published: June 2004

In biliary fistula dogs the plasma prothrombin falls eventually to low levels and bleeding commonly occurs. Faulty absorption of vitamin K from the intestine in these animals is an important causative factor. Feeding bile permits absorption of the traces of this vitamin normally present in mixed diets, and as a result a slow rise in prothrombin level is observed. If a standard diet is supplemented with large amounts of vitamin K concentrate the prothrombin rise is rapid, provided bile or bile salt is supplied to aid in the absorption.

Variations in the rate of prothrombin depletion in biliary fistula dogs kept on constant diet indicate the existence of additional factors which require further study. Our experience indicates that vitamin A and vitamin D supplements do not correct the prothrombin deficiency in biliary fistula animals.
RENAL INSUFFICIENCY FOLLOWING TRYPSIN INJECTION INTO THE RENAL ARTERIES
Authors: Friedman M. , Katz L. N.
Published: June 2004

1. The injection of trypsin into both renal arteries of the dog was found to cause an acute necrosis of large sections of the kidney, an immediate excretory insufficiency, and a transient hypertension.

2. Dogs surviving the acute phase of the trypsin injection, developed a chronic renal excretory insufficiency with no hypertension, despite the severity and duration of the renal excretory insufficiency.

3. The application of a Goldblatt clamp to the renal artery of one of the two kidneys, previously injected with trypsin, led to a rise in blood pressure which returned at once to normal when the ischemic kidney was removed, even though the pre-existing renal excretory insufficiency was augmented. This experience demonstrated unequivocally that chronic renal excretory insufficiency and hypertension are not directly related.

4. The application of a Goldblatt clamp to the renal artery of one kidney and the simultaneous injection of trypsin into the other led to a hypertension. The later removal of the ischemic kidney led to a severe renal excretory insufficiency, at the same time the pre-existing hypertension disappeared. This indicated again that renal excretory insufficiency and renal ischemia produced different phenomena and that the former had no direct relation to hypertension.
STUDIES ON THE NASAL HISTOLOGY OF EPIDEMIC INFLUENZA VIRUS INFECTION IN THE FERRET
Authors: Francis Thomas , Stuart-Harris C. H.
Published: June 2004

A study of the respiratory mucous membrane was made in the turbinates of ferrets which had received repeated inoculations of influenza virus. There was no evidence that persistent immunity is related to the presence of a structural modification of the respiratory epithelium. In fact, the respiratory epithelium in fully immune animals differs histologically only in minor respects from that of the normal, untreated ferret. On the other hand, a functional difference exists between the normal and the previously infected animals as evidenced by a marked acceleration of the repair process in the latter.

Serological studies at the time of reinfection, 4 months or more after the previous attack, indicate that a relation exists between the height of antibody titer and resistance. The degree of immunity is probably a product of serological immunity and the rate of tissue repair.

The implications of these studies to the problem of influenza in man are discussed.
NUTRITIONAL CYTOPENIA (VITAMIN M DEFICIENCY) IN THE MONKEY
Authors: Langston William C. , Darby William J. , Shukers Carroll F. , Day Paul L.
Published: June 2004

Young rhesus monkeys (Macaca mulatta) were given a diet containing casein, polished rice, whole wheat, salt mixture, sodium chloride, cod liver oil, and ascorbic acid. They developed a syndrome characterized by anemia, leukopenia, and loss of weight. Ulceration of the gums and diarrhea were common, and death occurred between the 26th and 100th day. 4 monkeys were given the deficient diet supplemented with 1 mg. of riboflavin daily, and these developed the characteristic signs and died. in periods of time similar to the survival of monkeys receiving the deficient diet alone. Nicotinic acid, either alone or in combination with riboflavin and thiamin chloride, failed to alter appreciably the course of the deficiency manifestations. Thus, it is evident that this nutritional cytopenia is not the result of a deficiency of vitamin B, riboflavin, or nicotinic acid.

The deficient diet supplemented with either 10 gm. of dried brewers' yeast or 2 gm. of liver extract (Cohn fraction G) daily supported good growth, permitted normal body development, and maintained a normal blood picture over long periods. It is obvious that yeast and liver extract contain a substance essential to the nutrition of the monkey which is not identical with any of those factors of the vitamin B complex that have been chemically identified. We have proposed the term vitamin M for this factor which prevents nutritional cytopenia in the monkey.
PHYSIOLOGICAL CONDITIONS EXISTING IN CONNECTIVE TISSUE
Authors: McMaster Philip D. , Parsons Robert J.
Published: June 2004

The interstitial movement of several dyes of widely different chemical constitution and diffusibility, in the connective tissues of the mouse ear, has been observed at high magnification. Dye extension seems to be conditioned by the form and structure of the connective tissue fibers. After escaping from the lymphatics of the ears of living mice, each dye appeared first in the tissues as bristly projections of color. These bent and twisted when pressed upon by a micro probe but sprang back into place when the pressure was removed. The present work and the preceding have shown that the lines of color are formed by dye along or between connective tissue fibers.

Intermittent external pressure applied to the tissue, squeezes and bends the fibers together and greatly increases the spread of dye along them. The connective tissue fibers assume an important role in the spread of substances through tissues subjected to pressure changes.

The experiments have given evidence of the existence of a tissue matrix in the organ but none of the presence of free interstitial fluid. In tissue subjected to irritant stimuli and in frankly edematous tissue, free fluid is readily demonstrated. When it is present the method of extension of dye is completely changed. Dye appears in the tissues as a diffusely colored cloud which can be freely moved by pressure with a micro probe.

The bearing of this evidence upon the condition of interstitial fluid and the nature of the interstitial spaces is discussed.
NEPHRITIS AND ITS INFLUENCE UPON HEMOGLOBIN PRODUCTION IN EXPERIMENTAL ANEMIA
Authors: Whipple G. H. , Robscheit-Robbins F. S.
Published: June 2004

Spontaneous glomerulonephritis develops not infrequently (11 per cent incidence) in the anemia colony. The course of the nephritis is insidious and usually extends over several years but ends in uremia, often with terminal bronchopneumonia.

Hemoglobin production in these standard anemic dogs is well established as related to various standard food factors. These tests are summarized in the tables above to show the changes that appear year by year in the life of each dog.

Nephritis causes little or no change in hemoglobin production in anemic dogs in the early stages of the disease. In the late stages of nephritis there may be no change or moderate changes in hemoglobin production in these anemic dogs. The average is 70 per cent of normal hemoglobin production in advanced nephritis.

It seems unlikely that this degree of impairment of hemoglobin production in nephritis would result in spontaneous anemia in the dog.
THE SOLUBLE MALARIAL ANTIGEN IN THE SERUM OF MONKEYS INFECTED WITH PLASMODIUM KNOWLESI
Authors: Eaton Monroe D.
Published: June 2004

A soluble malarial antigen which fixes complement with immune serum is found in the serum of monkeys infected with Plasmodium knowlesi.

The amount of antigen in the serum is related to the parasite count during the acute phase of the infection. The antigen is not excreted in the urine.

Intravenous injection into normal monkeys of serum containing the antigen stimulates the production of specific complement-fixing antibodies which react with antigens extracted from parasitized cells, as well as with the antigen present in serum obtained during the acute phase of infection.

Monkeys immunized with serum antigen apparently possess very little or no immunity to infection.

The soluble malarial antigen is labile to acids and alkalies, is not destroyed by a temperature of 56°C., and is precipitated, for the most part, in the albumin fraction of the serum by ammonium sulfate.
EFFECT OF PREGNANCY UPON THE IMMUNITY OF MICE VACCINATED AGAINST ST. LOUIS ENCEPHALITIS VIRUS
Authors: Hodes Horace L.
Published: June 2004

1. Virgin and pregnant Swiss mice are equally susceptible to intracerebral inoculation of St. Louis encephalitis virus.

2. Following subcutaneous vaccination with the St. Louis virus, the great majority of virgin Swiss mice become immune to subsequent intracerebral injection of 10,000 M.L.D. of the virus.

3. The majority of mice vaccinated during pregnancy do not become immune to even as little as 500 intracerebral M.L.D. of the virus. The depression of the ability to acquire immunity against the virus is most marked when the vaccination is carried out late in pregnancy, but it is also demonstrable when the mice are vaccinated early in the gestation period and during the first 2 weeks postpartum. At 7 weeks postpartum the response to vaccination is more nearly like that of virgin mice.

4. Pregnancy not only interferes with the development of acquired immunity but it also diminishes a previously established immunity.

5. Offspring of the mice vaccinated during pregnancy are not immune to 100 M.L.D. of virus.
ARTIFICIAL MAINTENANCE MEDIA FOR CELL AND ORGAN CULTIVATION
Authors: Baker Lillian E. , Carrel Alexis
Published: June 2004

Experiments have been described in which organs cultivated in the Lindbergh apparatus have been kept alive in artificial media for periods ranging from 3 days to 3 weeks, with life continuing in portions of some glands for from 35 to 62 days. The media used varied in composition from very simple and inexpensive ones in which some serum was used to a rather complex medium containing only that negligible amount of serum that is necessary as a solvent for vitamin A. The experiments performed demonstrate that artificial media can be used for organ cultivation, thus making it possible to study the behavior of human organs; to control the composition of the media at will; and to reduce the cost of experimentation.
ENCEPHALOPATHY FOLLOWING INJECTIONS OF BONE MARROW EXTRACT
Authors: King Lester S.
Published: June 2004

Monkey bone marrow extract when injected intracerebrally into guinea pigs or rabbits produces a distinctive encephalopathy. The Purkinje cells are severely affected, especially those at the periphery of the cerebellum. Nuclear alterations first appear, with well marked intranuclear acidophilic inclusion bodies. Similar inclusions appear at a little later stage in the ectodermal glia. The affected cells later become necrotic and usually disappear. The reaction is essentially glial and non-inflammatory, and hence is called encephalopathy rather than encephalitis.

A hyaline necrosis of cerebral blood vessels, especially at the base of the brain, is described. Small areas of softening may appear in the cerebellum as a result, but this is considered a secondary process, independent of the Purkinje cell loss. There may also inconstantly be found a loss of cerebellar granule cells and a selective necrosis of the hippocampal pyramidal cells. Secondary and reparative reactions are described.

Similar changes are produced by extracts of lymph nodes from Hodgkin's disease, and by leucocytic cream of human blood.

A tentative explanation of the pathogenesis is suggested, and similarities to certain virus diseases are pointed out.
CHARACTERISTICS OF A STRAIN OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS ENCOUNTERED AS A CONTAMINANT IN TISSUE CULTURES OF RABIES VIRUS
Authors: Casals-Ariet J. , Webster L. T.
Published: June 2004

A strain of lymphocytic choriomeningitis virus has been encountered, which grows readily in mouse embryo, serum, Tyrode culture media. Its origin is not definitely known but appears to be either the mouse brain tissue or, more probably, the monkey serum.

This strain gives clear cut results on filtration tests through Elford membranes, establishing the size of the virus, according to formula, as 33 to 50 mµ.

The strain shows a high and uniform virulence in W-Swiss mice. This appears to be due in part, at least, to the age and strain of mice employed for passage and titration.

The strain has been found to be more virulent in young than in old mice, especially following intraperitoneal inoculation.

Finally, the strain, when given as a vaccine intraperitoneally in amounts as small as 160 intracerebral lethal doses, induces an immunity against subsequent intracerebral inoculations of as much as 10,000 lethal doses.
PASSIVE IMMUNITY IN AVIAN MALARIA
Authors: Manwell Reginald D. , Goldstein Frederick
Published: June 2004

The effect of therapy with immune serum has been studied in thirty-two cases of Plasmodium circumflexum infection, all of them produced by blood inoculation. Eighteen of these cases never showed parasites, and seven others developed infections which were definitely milder than those of the controls. The therapeutic serum was in all cases obtained from chronic cases which had previously been superinfected to raise the immune titre. It seems justifiable to conclude that:

1. Passive immunity can be conferred in avian malaria, at least when caused by Plasmodium circumflexum just as it can be in certain types of monkey malaria, and perhaps in human malaria as well.

2. Whatever the nature of the protective substances present in the serum of chronic cases may be, they are present in very low concentration. Their concentration can be raised by superinfection, however. These substances may be strain-specific or species-specific, but the results of these experiments do not give any clear-cut answer to this question.

3. Serum therapy previous to infection seems to be more effective than when given afterward.

4. The administration of normal serum or even of physiological saline in a dosage comparable to that employed with the immune serum used in these experiments produced similar macroscopic changes in the size of the spleen.

5. Agglutination of cells parasitized by Plasmodium circumflexurn when mixed with immune serum was observed.
CANCERS DERIVING FROM THE VIRUS PAPILLOMAS OF WILD RABBITS UNDER NATURAL CONDITIONS
Authors: Kidd John G. , Rous Peyton
Published: June 2004

The naturally occurring virus papillomas of western cottontail rabbits become malignant occasionally. The cancers derive from the papilloma cells, that is to say from elements already rendered neoplastic by the virus and still infected therewith. Papillomas produced with the virus in jack rabbits and snowshoe rabbits become cancerous in the same way but much more frequently, as is the case in domestic rabbits also. To all three species the virus is foreign. The character of the cancers of the wild rabbits is described and the relation of the virus to them discussed on the basis of experimental findings. The facts support the view that the cancers result from virus variation, this in many instances being but slight.
STUDIES ON EPIDEMIC INFLUENZA VIRUS
Authors: Lennette Edwin H. , Horsfall Frank L.
Published: June 2004

Evidence is presented which indicates that influenza virus elaborates a soluble antigen. The antigen is considerably smaller than the virus and can be separated from it, but the virus has not been washed free of antigen. The properties of the antigen suggest that it is an unstable protein of relatively large size.
STUDIES ON THE RENAL ARTERIAL BLOOD PRESSURE AND THE METABOLISM OF KIDNEY TISSUE IN EXPERIMENTAL HYPERTENSION
Authors: Mason M. F. , Robinson C. S. , Blalock Alfred
Published: June 2004

1. In the hypertension which accompanies constriction of the renal arteries, there is no constant relationship between the height of the general systemic arterial pressure and the pressure in the renal artery distal to the point of constriction. The hypertension may persist even though the renal arterial pressure returns to or almost to the control level.

2. Studies on the renal blood flow and oxygen consumption following subtotal nephrectomy were abandoned because of inability to produce hypertension in dogs by this method. It is suggested that the mechanism of the hypertension following renal arterial constriction (dogs) and that following subtotal nephrectomy (rats) may not be the same in the two instances.

3. Studies on isolated renal cortical tissue of dogs and of rabbits following renal arterial constriction and subtotal nephrectomy showed that there is not necessarily a diminution in the capacity of the tissues of hypertensive animals to use oxygen.
THE VASOCONSTRICTOR ACTION OF PLASMA FROM HYPERTENSIVE PATIENTS AND DOGS
Authors: Page Irvine H.
Published: June 2004

1. Plasma from the renal vein, femoral artery or vein of normal dogs and plasma from the femoral artery, femoral and antecubital veins of man cause little or no vasoconstriction when added in small amounts to blood from a bilaterally nephrectomized dog used as perfusing medium in an isolated rabbit's ear.

2. Plasma from the femoral vessels and antecubital vein of patients with essential hypertension, malignant hypertension, and chronic nephritic hypertension causes marked vasoconstriction under the same circumstances. The plasma of dogs made hypertensive either by constriction of the parenchyma by the scar of silk perinephritis or by constriction of the renal artery by a clamp also causes pronounced vasoconstriction.

3. Plasma from the renal vein of normal dogs produces little or no vasoconstriction, but that of hypertensive dogs elicits vasoconstriction but usually not so marked as that elicited by plasma collected from peripheral vessels. A sample of renal venous plasma from one hypertensive patient caused severe vasoconstriction, not quite so intense as that produced by the peripheral vein plasma.

4. Since renin is liberated into the renal vein in large amounts in hypertensive dogs and reacts with renin-activator to produce angiotonin and since the conditions of the experiment are such as to enhance greatly the sensitivity of the ear preparation to angiotonin, it is believed that the vasoconstriction is the result of the presence of angiotonin in the peripheral blood.

5. Since vasoconstriction occurs under the same experimental conditions with plasma from both hypertensive patients and dogs, this is considered cogent evidence in favor of the view that the chemical mediator of both is similar and is possibly angiotonin.

6. A method is presented which is believed will distinguish between plasma from patients with normal blood pressure and that from those with hypertension, and between plasma from normal dogs and that from dogs with experimental renal hypertension.
THE TISSUE SPECIFICITY OF BRAIN AND MEDULLATED NERVES AS SHOWN BY PASSIVE ANAPHYLAXIS IN GUINEA PIGS
Authors: Bailey G. Howard , Gardner Raymond E.
Published: June 2004

Prolonged immunization of rabbits with a sedimented, heat-killed vaccine of Pasteurella boviseptica grown in an infusion broth prepared from rat brain resulted in the production of antisera containing antibodies for the broth as well as for the bacteria. When guinea pigs were prepared by intra-abdominal injection with such antisera and tested 24 hours later by intravenous injection with autoclaved extracts of different organs and tumors of rats, they were found to be passively sensitized, so that severe or fatal anaphylaxis was obtained with extracts of brain and carcinoma 256,—a transplantable tumor of the rat which originated in the mammary gland,—and very slight or negative reactions with extracts of other tissues. The brain antigen was found to be organ-specific but not species-specific. It was present in the white matter of the central nervous system and in sciatic nerve, but was almost completely absent from the brains of fetal and newly born rats and rabbits. It was absent from the brain of the fetal guinea pig but was present very soon after birth. The amount of the specific brain antigen seemed to be dependent upon the length of the period of gestation, the stage of development of the animal at birth, and the degree of myelinization of the central nervous system. The anaphylactogen of brain broth was soluble in water and insoluble in strong ethyl alcohol. It was thermostable in neutral and slightly acid solutions but more or less thermolabile on the alkaline side of neutrality.
CONSTITUENTS OF ELEMENTARY BODIES OF VACCINIA
Authors: Hoagland Charles L. , Ward S. M. , Smadel Joseph E. , Rivers Thomas M.
Published: June 2004

The effects of a number of crystalline and highly purified enzymes on elementary bodies of vaccinia are reported. These effects have been followed by determination of amino nitrogen, staining reaction, and studies of infectivity.

Pepsin, at a pH which inactivates the virus, results in its solution and rapid release of amino nitrogen.

Crystalline trypsin, chymotrypsin, carboxypeptidase, and ribonuclease are without appreciable effect on the virus.

Papain within a short time produces profound alteration in the staining reaction of the elementary body with release of amino nitrogen accompanied by complete inactivation of the virus. This reaction is not shared by crystalline ficin, another plant papain, or by cathepsin, an intracellular proteinase analogous to plant papains but of animal origin.
STUDIES OF THE TRANSMISSIBLE AGENT OF THE ROUS CHICKEN SARCOMA I
Authors: Shemin David , Sproul E. E. , Jobling James W.
Published: June 2004

The viscosity of Rous sarcoma extracts can be reduced with a polysaccharide enzyme isolated from pneumococcus or testis without destruction of the active agent and thus more concentrated active filtrates can be obtained.

The active agent can be precipitated with basic proteins.

The basic protein can be separated from the components originally coming from the tumor filtrate by electrophoresis.
THE ETIOLOGY OF HYPERTENSION DUE TO COMPLETE RENAL ISCHEMIA
Authors: Prinzmetal Myron , Lewis Harvey A. , Leo Sidney D.
Published: June 2004

1. Perfusates of totally ischemic kidneys of cats contain a pressor substance which is not present in the perfusates of normal kidneys, ischemic hind limbs, or ischemic gravid uteri.

2. The pressor material in ischemic renal perfusates originates directly in the kidney as a result of complete ischemia.

3. The pressor principle contained in ischemic renal perfusates is the cause of the hypertension which follows the reestablishment of circulation in completely ischemic kidneys, since perfusates of unreleased completely ischemic kidneys contain more pressor material than perfusates of released ischemic kidneys of the same animal.

4. The pressor principle in ischemic renal perfusates is presumed to be renin for the following reasons, (a) Both substances are destroyed by boiling, (b) Both substances induce tachyphylaxis. (c) The configuration of both pressor curves is identical, (d) The pressor action of both is not reversed by 933F, proving they are not epinephrine-like substances. (e) When incubated with plasma, both form a heat-stable pressor substance. (f) The pressor effect of both is uninfluenced by a previous injection of cocaine, (g) Unreleased, completely ischemic kidneys yield more pressor material on extraction than do released ischemic kidneys of the same animal.

5. The perfusates of blood-free ischemic kidneys contain more renin than those of blood-filled ischemic kidneys.

6. A method is described by which the power of various substances to inhibit or enhance the production of renin in the ischemic kidney may be tested.

7. A small amount of the heat-stable pressor substance, presumably angiotonin or hypertensin, is formed by the reaction of the pressor material (renin) and plasma in the vessels of the kidney during the period of complete ischemia.
INTERMITTENT TAKE-UP OF FLUID FROM THE CUTANEOUS TISSUE
Authors: McMaster Philip D.
Published: June 2004

Methods have been devised to bring microscopic amounts of fluid into contact with cutaneous connective tissue, under pressure or without pressure, in such a manner that it enters neither blood capillaries nor lymphatics directly. The take-up of fluid brought into contact with the tissues in this way has been measured and its characteristics studied. Elaborate control tests, here described and discussed, have indicated the possible errors in the employment of these methods.

Locke's or Tyrode's solutions brought into contact with the cutaneous tissues, by the method described and at atmospheric pressure, pass into the tissue intermittently. Forced into the skin by pressures of 1.0 to 2.0 cm. of water the take-up is still intermittent in character. From this it follows that either the absorption of interstitial fluid from localized regions is periodic or the movements of interstitial fluid are influenced by intermittent physiological changes.
THE EXPERIMENTAL DISCLOSURE OF LATENT NEOPLASTIC CHANGES IN TARRED SKIN
Authors: MacKenzie Ian , Rous Peyton
Published: June 2004

A carcinogenic tar applied to rabbit skin renders many more epidermal cells neoplastic than ever declare themselves by forming tumors. They may be present in large numbers and persist for a considerable time after brief tarring, yet give rise to no growths unless encouraged. The stimulus of wound healing will suffice to make some of them multiply and form tumors.

No evidence has been obtained, in experiments specifically directed to the point, that the cells which tar renders neoplastic respond in this way because they are possessed of peculiarities not shared by the rest of the normal epithelium.

The fact that non-specific stimulation (as e.g. wound healing) may act as the deciding influence in tumor formation brings out the need for a sharp distinction between the forces which induce neoplastic change and those which determine, or prevent, its realization in terms of a tumor. The distinction is vital to the appraisal of the many carcinogenic substances worked with nowadays.

The ability of tumor cells to lie latent for long periods and respond to non-carcinogenic stimulation by multiplying into growths provides an explanation of those clinical instances in which cancer appears rapidly after acute injury to tissue that had seemed normal.
THE INTERACTION OF HOST AND BACTERIUM IN THE DEVELOPMENT OF COMMUNICABILITY BY STREPTOCOCCUS HAEMOLYTICUS
Authors: Coburn Alvin F. , Pauli Ruth H.
Published: June 2004

An epidemic of infections due to group A Streptococcus haemolyticus type 12 originated in an infant with bronchiectasis, and involved children and nurses. Some of the children spread contagion; the nurses did not spread contagion. The children who spread contagion had few or no recognizable type 12 organisms in their throats; most of the nurses had type 12 predominant in their throat flora.

Two children who spread contagion had non-hemolytic streptococci in their throat flora, which became hemolytic on cultivation and proved to be type 12. Four children had in their throat flora hemolytic type 12 streptococci which became non-hemolytic when grown in fluid media containing serum. These infants appeared to act as disseminating hosts in which the pathogen developed communicability and at the same time became morphologically and physiologically labile.

The labile streptococci gave rise to atypical forms whose requirements for rapid reproduction (as tested in vitro) were similar to those existing in the human host.

The hypothesis presented is that the genesis of communicability depends on the coexistence of two conditions: a transmitting host lacking in restraining influences, permitting the acquisition of physiological lability by the microorganism; and the development of adaptive mechanisms in the bacterial cell, facilitating survival under atmospheric conditions and subsequent colonization in the environment of human tissues.
THE QUANTITY OF IRRADIATED NON-VIRULENT RABIES VIRUS REQUIRED TO IMMUNIZE MICE AND DOGS
Authors: Webster L. T. , Casals J.
Published: June 2004

In the experiments described above, we found with respect to tissue culture rabies virus that 1 cc., which contains approximately 50,000 mouse intracerebral lethal doses, properly irradiated, was required to immunize a mouse; 500 cc., which contain 25,000,000 doses, were required to immunize a 20 pound beagle dog.

Tissue culture virus concentrated ten times proved capable of immunizing mice in a dose one-tenth as large as that required for unconcentrated culture virus.

Brain virus suspensions were centrifuged so as to remove a large part of the tissue particles without striking loss in the virulence of the supernatant. The centrifuged supernatants of 1 to 5 per cent brain virus suspensions were irradiated so as to destroy virulence and yet retain immunizing potency.

Irradiated supernatants of mouse brain virus proved capable of immunizing mice as well as or better than similar supernatants treated with chloroform.

0.1 cc. of a 1 per cent irradiated dog brain virus containing approximately 50,000 mouse intracerebral lethal doses immunized mice effectively.
THE PRODUCTION OF BACTERICIDAL SUBSTANCES BY AEROBIC SPORULATING BACILLI
Authors: Dubos René J. , Hotchkiss Rollin D.
Published: June 2004

Several species of aerobic sporulating bacilli recently isolated from soil, sewage, manure, and cheese, as well as authentic strains obtained from type culture collections, have been found to exhibit antagonistic activity against unrelated microorganisms.

Cultures of these aerobic sporulating bacilli yield an alcohol-soluble, water-insoluble fraction,—tyrothricin,—which is bactericidal for most Gram-positive and Gram-negative microbial species.

Two different crystalline products have been separated from tyrothricin. One, which may be called tyrocidine, is bactericidal in vitro for both Gram-positive and Gram-negative species; the other substance, gramicidin, is effective only against Gram-positive microorganisms. In general, tyrocidine behaves like a protoplasmic poison and like other antiseptics, loses much of its activity in the presence of animal tissues. Gramicidin on the contrary exerts a much more subtle physiological effect on the susceptible bacterial cells and, when applied locally at the site of the infection, retains in vivo a striking activity against Gram-positive microorganisms.