Experimental Biology and Medicine

Sodium oleate in a concentration of 90 γ of sodium oleate per ml of medium inhibits the growth of Streptobacillus moniliformis. This inhibitory effect was reversed by addition of adequate amounts of bovine serum. Animal lecithin in concentrations of 100 and 200 γ per ml of medium failed to neutralize the inhibitory effect of sodium oleate.

1. Alliin and L-cystine disulfoxide stimulated the growth of Leuconostoc mesenteroides but to a lesser degree than L-cystine. 2. Substitution of the sulfur hydrogen of L-cysteine by alkyl and alkene radicals did not produce any observable response. The sulfoxide of S-ethyl-L-cysteine was also inactive; however, S-propyl-L-cysteine sulfoxide was found to have a very slight activity. 3. The activity of alliin may be due to both the presence of the sulfoxide group and the unsaturation in the allyl radical.

About 400 6-month-old virgin female C3H mice were divided into two groups: one was maintained on a normal diet; the other on an anti-estrous diet of 10-15% Lithospermum. Eighteen months later the latter group had developed half as many spontaneous mammary tumors as the former; however, if the differential mortality observed throughout the experiment is taken into statistical account, the tumor incidence ratio for the total period is 3 for the control, 2 for the experimental group. This reduction in tumor incidence was possibly connected with the Lithospermum-diestrus, but inanition and differential survival factors remain to be more fully evaluated.

A study of the neuropathology of Teschen disease reveals it to be a diffuse encephalomyelitis with characteristic lesions both as to type and distribution. The lesions are, with minor exceptions, confined to the grey matter of the brain and cord. Their widespread distribution in the CNS, and particularly their striking density in the cerebellum serve to distinguish Teschen disease from poliomyelitis, although spinal cord lesions may be similar in the 2 diseases.

Chicks very deficient in vit B₁₂ grew as well when homocystine and betaine were added to a methionine-deficient diet as when a comparable amount of methionine was added. No evidence was obtained that vit B₁₂ increased the efficiency with which preformed methyl groups were tranferred to homocystine since the effects of vit B₁₂ were additive to those of methionine or its equivalents of homocystine plus labile methyl. It appears likely, however, that when the chick's diet lacks methyl groups vit B₁₂ is concerned in the synthesis of such groups and their combination with homocystine to form methionine. Formation of methionine by this procedure, however, is limited and insufficient to meet the needs of the chick.

1. Citrovorum factor in parenterally administered doses of 75 μg daily produced a remission in 2 patients with megaloblastic anemia of infancy. 2. Folic acid was effective in 2 cases of this syndrome at oral dose levels of 500 μg and 200 μg daily.

Aureomycin can replace vit. B₁₂ in the purified diet of the rat. A possible explanation for these findings must consider the influence of the antibiotic on intestinal synthesis in the rat. When the antibiotic activity is destroyed, the growth response is not observed.

Rats given ACTH for 3 to 10 days in doses sufficient to produce sustained eosinopenia when compardd with controls, showed: (1) no change in the blood glutathione; (2) decreased nonprotein sulf hydryl contents of the kidneys; (3) increased non-protein SH contents of the livers; (4) markedly decreased renal ascorbic acid; (5) no change in the ascorbic acid contents of the livers; and (6) no change in the protein sulfhydryl contents of the livers or kidneys.

In experiments in which monkey or human testicular cells in tissue culture were infected with poliomyelitis virus, Lansing and Yale-SK strains, proof was obtained that the virus in 3 passage series had been propagated. At the time this report was written it had been established for these 3 passage series that the minimal dilution factor based on tissue replacements ranged from 10^14.6 to 10¹⁸ and, when assessed by fluid replacement, from 10²⁹ to 10^36. The LD₅₀ of each strain of virus was determined on successive transfers, and the identity of each strain of virus was established by neutralization tests and histopathological findings in monkeys dead from the injection of tissue culture virus. Control experiments and other tests made known that propagation of poliomyelitis virus did not occur in the absence of viable testicular cells and that an extraneous virus was not inadvertently acquired during the course of these studies. It is plain that the results of the present investigation substantiate the observations of other workers that poliomyelitis virus can propagate in extraneural tissues. From these findings it is apparent that the assumption of an obligate neurotropism for poliomyelitis virus no longer is tenable. This observation and the demonstration regularly of the natural occurrence in poliomyelitis of virus in the oro-intestinal tract emphasize the need for a renewal of investigative studies of the factors that make possible invasion of the central nervous system to result in the overt and residual manifestations of poliomyelitis.

Short mechanical or electrical stimulation of the dog's ventricle, following the administration of acetylcholine and atropine, leads to the temporary appearance of parasystolic arrhythmias. The ectopic parasystolic center may form stimuli in groups.

In the present experiments, utilizing 1320 observations on the eyes of 44 rabbits, physostigmine, either topically or subcutaneously, did not alter the topical anesthetic activity of procaine. Subcutaneous administration of physostigmine or pilocarpine produced corneal anesthesia in the rabbit eye as measured by loss of corneal reflex. The role of cholinesterase inhibition in the penetration of non-surface anesthetics is discussed.

1. It was observed that a relaxin preparation extracted from swine ovaries contained a spreading factor which was inactivated by heating at 50°C for ten minutes. The inactivation of the spreading factor did not diminish the effectiveness of the relaxin preparation to cause pelvic relaxation. 2. The spreading factor extracted from the mammary glands of pregnant rats had no ability to cause pelvic relaxation in the amounts employed.

The administration of intermedin, prepared from hog pituitary glands, results in a decrease, after four weeks, of twenty per cent in the melanin content of the skin of Rana pipiens. Subsequently, there is a rapid increase, reaching levels 40% above normal after a total of 8 weeks.

1. A hitherto unidentified structure in the medulla oblongata is described. It is an essentially non-neural zone situated between the ala cinerea and the vestibular complex and is contiguous medially with the area postrema which overlies the ala cinerea. The zone consists largely of fibroblasts and cells resembling protoplasmic astrocytes and astroblasts which have an abundance of vascular feet abutting on a dense network of blood vessels. Numerous nerve endings found in this zone are observed to connect with a loose fiber bundle which passes towards the nucleus of the fasciculus solitarius. 2. Experimental studies made with the ablation technic have yielded evidence that this structure is the anatomical framework of the medullary chemoreceptor trigger mechanism for the emetic center. Destruction of this chemoreceptor trigger zone in cats makes the animals refractory to the emetic effect of the intravenously administered cardiac glycosides-lanatoside C, scillaren A and ouabain-in doses which are known to be effective in intact animals.

Studies by electron microscopy of the spinal cords of monkeys infected with poliomyelitis virus (Leon strain) showed rod-shaped, virus-like particles ranging in width from 12-15 mμ. These bodies could not be demonstrated in normal monkey cords.

The leukocyte response to bacterial pyrogen is superficially similar to that produced by ACTH. However, removal of the adrenals substantially modifies the response to ACTH in the dog, but is without effect on pyrogen induced leukocyte responses. It is concluded that pyrogen produces its characteristic changes in the W.B.C. count by mechanisms other than pituitary-adrenal discharge.

(1) The anti-tubercular activity of the thiosemicarbazone of nicotinaldehyde in the intravenous infection of mice with M. tuberculosis as described by Levaditi was confirmed. (2) The thiosemicarbazone of isonicotinaldehyde was found as active as the thiosemicarbazone of nicotinaldehyde and the effect of both compounds was comparable to that of Tibione. Picolinaldehyde thiosemicarbazone was ineffective. (3) The thiosemicarbazones of nicotinaldehyde and isonicotinaldehyde also were found appreciably active in the therapeutically more resistant bronchogenic type of tuberculosis of mice produced by intranasal infection. Under these experimental conditions the compounds appeared superior to Tibione.

It has been shown that thiopental, pentobarbital and amobarbital lower the phosphate : oxygen uptake ratio obtained in particulate tissue preparations from liver and brain respiring on a pyruvate substrate. This depression is obtained at concentrations of the drugs which have only a slight effect on the oxygen uptake of the preparations and which approximate those which are necessary in vivo to produce surgical anesthesia. It is postulated that such an uncoupling of phosphorylation from oxidation may be one of the ways in which barbiturates act to produce anesthesia.

The chemical composition of bovine spermatozoa has been determined. Data are presented including total N, total lipid, ash, and total phosphoru. Seventeen amino acids were determined by microbiological assays.

Complete removal of the liver from dogs has been achieved by various methods( 1 - 3 ). The following new, one-stage method has given satisfactory results to the authors and can be executed without great difficulty. The abdomen having been widely opened, and the incision kept apart with a self retaining retractor, the gastro-hepatic omentum is cut, after the portal vein has been freed from all other structures. The portal vein is cut against the liver, introduced into a small metallic tube according to Queirolo's method( 4 ) and implanted sideways into the vena cava above the renal veins. The liver is then severed from the abdominal wall. When this is done, a strong thread is placed around the vena cava against the diaphragm in order to prevent the reflux of the blood from the heart. The flow of the blood to the liver has been previously stopped by 2 clamps placed one on the vena cava and the other on the portal vein upstream from the portal-cava fistula. Then a veinous graft which is to replace the intrahepatic part of the vena cava is put into position. The graft is the intra-thoracic part of the vena cava of another dog used in a previous operation; it has been kept at 0°C in Tyrode solution to which penicillin and a sulfamide have been added. After the vena cava of the dog has been cut transversely under the liver and against it, the inferior part of the graft is inserted into the caudal segment of the vein and fixed above the portal-cava fistula. The other end is introduced into the intra-hepatic part of the vena cava and pushed upwards until it finds its place between the top edge of the liver and the diaphragm.

1. The time required to excrete 50% of an ingested water load was increased in 3 protein-depleted dogs. 2. The glomerular filtration rate was reduced in all protein-depleted dogs. 3. The urinary suppression produced by pituitrin was increased in the protein-depleted dogs.

These studies indicate that alkalis, particularly sodium citrate and sodium lactate, may increase the conjugation of sulfamerazine and sulfadiazine with glucuronic acid and decrease conjugation with acetic acid in human subjects.

Carbon dioxide alone was a mosquito attractant in disease vector studies. Large numbers of female mosquitoes of several species were attracted into a trap baited with carbon dioxide. It consistently attracted more mosquitoes than calf or chicken baits. This chemotropism may be a major factor in controlling host selection by various species of mosquitoes.

The length of survival or function of homogenous kidney transplants is not improved by the administration of ACTH or cortisone.

When radioactive mercuric chloride is administered to animals rendered proteinuric by the administration of bovine albumin, less radiomercury is localized in the renal cortex than in that of the control animals. Diminished renal toxicity is associated with a diminished localization of radiomercury in the kidney.

Mice inoculated intranasally with a culture of H. pertussis developed lung infections from which more than half of the mice survived. The average time of death ranged from 16 to 23 days. They developed a high degree of sensitivity to histamine comparable to that induced by pertussis vaccine, but it was slower in developing and it persisted much longer. A high percentage of the mice that died from histamine shock showed gross lung lesions and H. pertussis was recovered from the lungs of the majority. Most of the mice that survived this infection were resistant to an intracerebral inoculation of H. pertussis.

1. The titratable SH content of hemoglobin was determined amperometrically in saline, and found to approximate 2 moles SH per mole of normal hemoglobin and 3 moles SH per mole of hemoglobin from patients with sickle cell anemia. 2. The SH content of hemoglobin from two patients with sickle cell trait was greater than that of normal hemoglobin and less than that of sickle cell anemia hemoglobin suggesting that a mixture of the two types of hemoglobin was present in these patients.

In these experiments, death was associated with bacteremia. When avirulent live bacteria were injected, the recovered organisms were either of the strain inoculated, or were apparently autogenous bacteria. However, when heat-killed bacteria were introduced, the recovered organisms were of autogenousorigin only. It is known that bacteremia, identified with normal bowel inhabitants, is often an integral part of the syndrome observed in animals dying from whole body irradiation. In this instance, however, bacteremia and death were induced in animals exposed to sublethal doses of irradiation and subsequently inoculated with live avirulent, or even dead organisms generically different from the bacteria normally present in the intestines of these animals. This observation may be of importance under conditions where irradiation is a factor and vaccination is indicated.

1. Autoradiograms of irregular surfaces of mollusc shells and curved surfaces of bone canbe made without difficulty by applying sheets of emulsion removed from Eastman Industrial X-ray Film, Type A. The emulsion is developed while on the object, facilitating the localization of radioactive areas, and maybe removed for densitometric measurements if desired. 2. Darkening of the emulsion may occur as a result of direct contact with sutures and certain definite regions of non-radioactive bone. Accordingly, in making autoradiograms by this method control exposures on non-radioactive bone are required to evaluate this effect.

1. The clearance of endogenous inorganic phosphate is relatively low in the newborn period. 2. The clearances of phosphate in older infants, children and adolescents approximate those of the adult. 3. The tubular reabsorption of phosphate was found to average 87.7% of the glomerular filtrate in children and adolescents. 4. The clearances of phosphate at all ages have a wide variation

Rat ACTH is a dose equivalent to 100 μg La-l-A per 100 g body weight, injected intravenously into rats, disappears rapidly from the circulating blood of intact and adrenalectomized rats. Five minutes after injection of the hormone into intact rats about 40% of the injected dose is present in extracellular fluid and 20% in the kidneys; after 15 minutes a negligible quantity is present in extracellular fluid and 15% in the kidneys. The adrenals have a relatively high concentration of the hormone although the concentration is lower than in the kidney. It is estimated that less than 1/500th and 1/2000th of the injected dose is present in the adrenals at 5 and 15 minutes after injection, respectively. Liver contains no detectable quantity of the injected ACTH either 5 or 15 minutes after injection of hormone. Injected ACTH could not be detected in the urine in these experiments.

Vit. B₁₂ injected at low levels increased the PGA stored in chick liver tissue. Higher levels of injected vit. B₁₂ suppressed the liver storage of PGA. Vit. B₁₂ administered orally, increased the level of both PGA and LCF as measured by chick liver storage.

Vit. B₁₂ injected at the level of 1 γ per day significantly inhibited the conversion of PGA to LCF in PGA-vit. B12 deficient chicks. This inhibition was overcome by the in vitro addition of ascorbic acid. The oral administration of vit. B₁₂ at the level of 1 γ per day significantly increased the conversion of PGA to LCF with or in the absence of ascorbic acid, in the PGA-vit. B₁₂ deficient chick.

The possible relationships and interactions of vit. B₁₂, PGA, LCF, and ascorbic acid have been discussed.

1. Results are presented from analyses of 147 samples of mature human milk from healthy mothers for nitrogen and 10 essential amino acids. The samples consisted of 18 collections from 5 women of all milk secreted in 24-hour periods and 129 collections from 56 women of milk secreted in periods of 4-8 hours. Mean values for concentrations of the amino acids in the 2 groups of samples agreed well. 2. Wide individual variations were found among successfully nursing women and at different intervals postpartum. Mean concentrations of nitrogen and the essential amino acids in 24-hour samples of colostrum, transitional, and mature milk showed a general lowering to the levels in mature milk as lactation was established and application of the Analysis of Variance to the data for 11 women, each of whom provided a sample during the same postpartum interval of mature milk production also indicated a gradual reduction in amino acid concentrations.

1. Chicken erythrocytes exposed to the toxins of Bacillus cereus undergo a change in the surface of the cells which eventually leads to hemolysis. 2. Rabbit erythrocytes similarly treated are much more slowly altered by the toxins, but eventually do show a “fragility” change. 3. There is no significant change in the total lipid, total cholesterol or free cholesterol content of the experimental cells. 4. The experimental cells hemolyze more rapidly in solutions of non-electrolytes. 5. There is an increase in “fragility” and in the size of the experimental cells. 6. The toxins have no effect on the rate of shrinking of cells placed in 1.25× Ringer Locke following previous equilibration in 0.6 M dvcerol in Ringer Locke.

1. An assay system is described for the direct measurement of the ability of heart preparations to couple esterification of phosphate with oxygen uptake. With this system a high efficiency of phosphorylation is obtained with normal rabbit heart tissue. 2. Heart tissue preparations from rabbits made dystrophic by lack of vit. E showed no decrease in the ability to carry out oxidative phosphorylation.

1. Pretreatment with nitrogen mustards failed to protect rats injected with nephrotoxic serum against the development of acute or chronic nephritis but did appear to modify certain early manifestations of the disease. 2. No consistent effect on the proteinuria of rats with chronic nephritis was produced by the administration of nitrogen mustards.

Circulin possesses high in vitro activity against several gram-negative plant pathogens.

1. The effects of both slow and relatively rapid infusion of modified human globin in 6 human subjects without renal disease were studied. No untoward effects of the infusion were noted. 2. No significant increase in urine flow over control flows was noted. There was no change in the clearances of PAH during the globin infusion as compared with the control levels. There was a slight increase in the rate of excretion of sodium during the globin infusion as compared with control levels in 2 of the 6 patients. 3. No alteration in sedimentation rate and agglutinability of red blood cells was noted as a result of the infusion of globin.

1. Four rabbits were given equal amounts of concentrated rabbit antipneumococcal globulin solution. Two of the rabbits were pretreated with cortisone and continued to receive the hormone. During the subsequent ten days, no difference was observed from the controls in the rate of disappearance of the “labeled” protein from the circulation. 2. Factors concerned with the interpretation of the data are discussed with reference to the effect of cortisone on protein metabolism.

1. The blood-group-specific substances present in meconium from a series of 53 infants were found to correspond to the blood type of the baby and its ability to secrete blood group material in its saliva in all except 2 cases in which O activity was demonstrated in the meconium but could not be found in the saliva. 2. The meconiums of blood groups A and B were more active than those of groups AB or O. 3. No M or N activity could be demonstrated in meconium. 4. The blood-group-specific substances in amniotic fluid corresponded with the blood type of the baby and not that of the mother.

1. It is possible to obtain electrograms on the isolated perfused dog's ventricular septum, and these show a reproducible pattern. 2. The records indicate that the excitatory process in these experiments traveled in a complicated fashion and the pattern varied somewhat from animal to animal. In some of the experiments the excitatory pathways varied over a period of time. As a basic rule, the left side of the septum was found to be activated early and the upper right side late. 3. The apparent absence of septal electromotive forces in electrocardiograms recorded by usual clinical methods, which has been explained by neutralization of potentials spreading inward from each side, is not supported by these preliminary observations on the isolated septum.

It is impossible at present to distinguish epidemic keratoconjunctivitis virus from St. Louis encephalitis virus by means of the intracerebral neutralization test in mice. The sera from convalescent epidemic keratoconjunctivitis animals and from convalescent or hyperimmune St. Louis encephalitis animals neutralized epidemic keratoconjunctivitis and St. Louis encephalitis viruses to an equal extent. No differences could be elicited by performing neutralization tests with the keratoconjunctivitis virus that had been through 3 successive rabbit passages. Neutralization tests in which serum dilutions were used against a constant amount of virus also failed to show any differences between the 2 viruses. Considerable cross-neutralization was obtained with the related Japanese B and West Nile viruses. Infectivity tests in animals revealed that rabbits and guinea pigs were susceptible to intracerebral inoculation with keratoconjunctivitis virus but not to St. Louis virus.

Evidence has been presented which confirms Ruchman's observations that the viruses of St. Louis encephalitis and epidemic keratoconjunctivitis are closely related. The importance of careful study of current outbreaks of epidemic keratoconjunctivitis as a means of assessing the significance of these findings is stressed.

A filterable neurotropic virus was isolated from mice inoculated intracerebrally with a mixed lot of mosquitoes captured in western Uganda. The agent is believed to be hitherto unknown and has been named Ntaya virus in respect of the locality in which the mosquitoes were caught. Certain of its pathogenic and immunological properties are discussed.

1. The erythrocytes of 5 normal premature infants and of 9 with retrolental fibroplasia have been examined for a deficiency of vit. E by the hemolysis test of Rose and György. The red blood cells from all of the infants were resistant to hemolysis by dialuric acid. 2. We have confirmed the validity of the hemolysis test for a deficiency of tocopherol in the rat.

1. Adult mice, ordinarily insusceptible to Coxsackie virus infection, may be lethally infected if preliminarily administered cortisone. 2. Multiplication, serial passage, and specific neutralization of Coxsackie virus in adult mice have been demonstrated. 3. Recovery of Coxsackie virus from a human source has been accomplished in adult mice.

Treatment of pantethine with sodium sulfide, cysteine, glutathione, β-mercaptoethylamine, or several other thiols followed, in some cases, by oxidation with iodine resulted in formation of a series of new compounds with growth-promoting activity for Lactobacillus helveticus 80. These compounds appear to be mixed disulfides. The natural occurrence of similar mixed disulfides formed from pantetheine and other naturally occurring thiols may explain in part the presence of several chromatographically distinct forms of LBF in natural materials.

Two series of 36 and 24 guinea pigs were studied. Cortisone was given to a third of the animals, ACTH to a third and the remaining third served as controls. The administration of the hormones, in moderate or large doses, was started before giving the sensitizing injections of egg white, and was continued while they were being given and for varying periods after their completion. N treatment had any effect on the severity of anaphylactic reactions induced by the subsequent intravenous injection of the antigen. Used in adequate amounts, both hormones produced pronounced and sustained reductions in the number of circulating eosinophils in the blood of male and nonpregnant female guinea pigs.

1. Oral or intramuscular administration of large amounts of vit. B₁₂ was without effect on the blood of healthy adults and children. In particular, an eosinophilia was not observed. 2. Neither allergic nor toxic symptoms were noted during or after therapy. 3. It is concluded that vit. B₁₂ is not the eosinophilic factor present in raw calves liver.

It was not possible to confirm the antigoitrogenic effect of vit. B₁₂ in thiourracil-fed rats.

1. Normal dogs excrete less than 1 mg neutral 17-ketosteroids per day. 2. No sex difference exists in the urinary ketosteroid excretion of dogs. 3. Administration of ACTH to dogs does not result in increased excretion of ketosteroids.

A study of chick embryo and horse placental tissue, when cultivated in tissue culture with H. capsulatum by the cover-glass method, has revealed that fibroblasts or fibroblast-like cells of the outgrowth contain yeast cells of this organism in the cytoplasm. It is of interest to note that sections of infected tissues from systemic histoplasmosis rarely, if ever, show yeast cells in fibroblasts. Whether or not these intracellular yeasts can continue to multiply within the fibroblast, or are ultimately destroyed, remains to be determined. Similarly, whether or not the fibroblast which contains yeast cells can divide further, or undergoes degeneration, is not yet known. An explanation for the unique type of colconial morphology of H. capsulatum seen in the cover-glass cultures, cannot be given at this time. This phenomenon is not dependent upon the presence of living tissues, since the sac-like type of colonies were observed in the controls which lacked tissue fragments. Of possible significance is the fact that this type of colony occurred only when the inoculated yeast cells were fixed in situ and surrounded by clotted plasma; in the supernatant of the flask cultures, only free, individual yeast cells were seen. Further work is in progress in an attempt to clarify tshese problems.

1. ACTH and Cortisone, in doses sufficient to alter the adrenal glands and depress the level of circulating eosinophils, failed to influence the repair of wounds in normal and in scorbutic guinea pigs. 2. It is suggested, therefore, that the connective tissue of the guinea pig may respond to adrenal hormone, if at all, less readily than that of other species studied. 3. The specificity of the “anti-scorbutic” action of Cortisone and of ACTH is questioned. 4. The adrenal response of scorbutic guinea pigs to ACTH? in the virtual absence of adrenal vit. C, suggests that ascorbic acid is not essential for the secretion of adrenal hormone. 5. The relationship of ascorbic acid to the metabolism of the adrenal cortex remains obscure.

Studies on dogs show that successful ligation and division of the pancreatic ducts inhibits the visualization of the gallbladder by cholecystographic media whether administered orally or intravenously. Failure of visualization appears to be due to the development of physiological stasis of the vis-cus. The experiments demonstrate a close relationship of the two organs and suggest that the pancreas may control the tone of the gallbladder

The oral administration of aureomycin or terramycin to man results in an extremely low concentration of fecal urobilinogen; a change which occurs during the first 48 to 72 hours of drug therapy, concurrently with other modifications in the character of the intestinal contents. Normal concentrations of urobilinogen may not be restored for so long as six or seven days following the discontinuance of drug administration. The depression of urobilinogen formation is probably the result of alterations in the flora of the intestine, which have not yet been completely defined. A case of hemolytic anemia is reported in which strikingly low fecal and urinary urobilinogen concentrations were observed while the patient was receiving aureomycin.

1. A new antibiotic, fumagillin (“Antibiotic H-3”), was found to be effective in vitro against E. histolytica at concentrations of 1:10,000,000 to 1: 15,000,000. 2. Preliminary in vivo studies on monkeys naturally infected with E. histolytica indicated that fumagillin possesses considerable amebacidal activity. Further investigations are necessary to evaluate this drug more completely.

The subcutaneous injection of epinephrine solution containing sodium bisulfite as an antioxidant produced a more rapid and higher rise in systolic blood pressure than did the same amount of epinephrine in a solution containing sodium hypophosphite as a preservative. Small doses of rutin given intravenously immediately before the epinephrine did not significantly alter the “bnisulfite effect” nor did the rutin influence the effect of epinephrine.

The action of ascorbic acid on the leukocyte response of normal (shamadrenalectomized) and adrenalectomized rats was investigated. The data indicate that, of all the leukocytes studied, only the eosinophils are related to the action of ascorbic acid. The vitamin alters the eosinopenia of stress in intact rats, and delays the eosinophilia characteristic of stress in adrenalectomized rats.

1. A continuously recording counter adapted to the scanning of radio chromatograms has been described. 2. This method has been applied to a chromatographic method of demonstrating and measuring the reaction between radioactive iodine labelled bovine serum albumin and its antiserum. 3. Preliminary experiments have shown a reasonable agreement between the zone of maximum antigen fixation obtained by a chromatographic method and the zone of maximum precipitation obtained by the precipitin method. 4. The method appears to have useful possibilities in characterizing soluble antigen-antibody complexes as well as other protein-protein interactions. 5. It has been demonstrated that normal sera have the property of permitting a homogeneous movement of the labelled bovine serum albumin whereas the buffered solutions thus far tried have resulted in streaking of the albumin.

A chlorguanide-resistant strain of Plasmodium gallinaceum was cross-resistant to 2,4-diamino-6,7-diphenylpteridine. The same chlorguanide-resistant strain was not cross-resistant to 2,4-diamino-5-(p-chlorophenoxy)-6-methylpyrimidine. Chlorguanide and 2,4-diamino-5-(p-chlorophenoxy)-6-methylpyrimidine were not synergistic in their antimalarial activity.

The chemotherapeutic effect of a certain napthoquinonimine (compound Ro 2-3532/1) was studied on the peripheral infection of mice with Col-SK virus, F virus and EMC virus. It was found that a well tolerated single dose of 5 mg of the drug, administered intraperitoneally, was sufficient to protect a high percentage of the mice against infection with multiple paralytic doses of Col-SK or F virus injected simultaneously by the same route. Experiments in which the virus was injected intraperitoneally but the drug subcutaneously showed likewise a definite degree of protection though inferior to that observed when both were given by the same route. Significant protection could also be obtained up to and including 1 hour after intraperitoneal infection with small doses of virus. Experiments in which the drug was tested for its chemotherapeutic action against EMC virus showed only a minimum degree of protection considered to be insignificant. Some attempts were made to analyze the probable mode of action of the drug on Col-SK virus. It is concluded that protection occurs not because of cell-receptor blockade but that the virus is rendered non-infectious by some form of direct interaction between virus and drug.

(1) The group of 2-hydroxy-1,4-naphthoquinonimines contains compounds which show activity against infections with Col SK and MM virus in mice. The effect of one member of this class of compounds, designated Ro 2-3532/1 is described in detail. (2) A single intra-abdominal injection of the new compound (500 mg/kg), administered shortly after an intra-abdominal infection with 10-20 LD₅₀ of Col SK virus prevented the death of approximately 80% of the animals. A single subcutaneous injection of the substance under similar experimental conditions protected about 50% of the animals. Surviving mice were fully susceptible to reinfection with Col SK virus. (3) The effect of the intra-abdominal administration of Ro 2-3532/1 was dependent on the dose of the compound, on the time of treatment and on the infective dose of the virus. (4) Successful treatment by either the intra-abdominal or subcutaneous route was only observed in intra-abdominally infected mice. Infections induced by intracerebral, intramuscular, subcutaneous or plantar injections of the virus did not respond to the treatment with Ro 2-3532/1.

A method is described for partial hepatectomy in the rat which is applicable to animals with fatty livers. It was found that in rats with enlarged livers, due to fatty infiltration, the relation of the weights of the various lobes to one another and to the total liver weight was similar to that in normal rats. Apparently, the individual lobes maintain their relationship in spite of fatty infiltration.