Experimental Biology and Medicine

(1) Ammunium salts in toxic doses produced an acute pulmonary edema in the rat, guinea pig and cat. The cat was more refractory to this effect than the rat and guinea pig. The rabbit did not appear to be susceptible to ammonium lung edema. (2) While a number of routes of administration of ammonium chloride were found effective for the production of acute pulmonary edema, the gavage route (0.09-0.15 g per 100 g of body weight) was most dependable for the guinea pig, and the intraperitoneal route (0.04 g per 100 g of body weight) for the rat. (3) The ammonium ion was found to be the agent responsible for the lung edema. Many ammonium salts produced this effect. Acidosis was ruled out as the primary factor, because acidosis produced in other ways did not result in lung edema. (4) The syndrome of ammonium intoxication consisted chiefly of dyspnea. muscle fasciculations and convulsions, terminating in an early acute pulmunary edema. (5) Gross changes at autopsy were limited to the thoracic cavity. They consisted of pulmonary edema and congestion with variable degrees of hemorrhage and moderate dilatation of the right ventricle, right atrium, and entering venae cavae. The microscopic appearance of the lungs was one of edema, congestion and hemorrhage.

Severe respiratory and metabolic acidosis, accompanied by increases in plas lactate, phosphate and sodium concentrations, occur in rats following maximal electrically-induced seizures. Recovery is complete in 40 minutes. It is suggested that the profound chemical changes occurring during the seizure may contribute to the post-ictal depression.

This paper presents the application of the transducer tube to the detection and recording of movements of the type associated with the peripheral venous pulses. An adequate amplifier circuit is given and the usefulness of the device in other applications is suggested.

1. In order to test the extent of utilization of fat emulsions in parenteral feeding, palmitic acid labeled with C¹⁴ at its sixth carbon was injected intravenously, in the form of the triglyceride, into fasted rats.

2. From 36 to 59% of the administered C¹⁴ was expired as CO₂ in 24 hours.

3. Considerable amounts of the administered fatty acids were stored in adipose tissues throughout the body.

4. The availability of intravenously administered tripalmitin for metabolic purposes is further shown by the finding that as much as 78% of the radioactive fatty acids recovered from the liver and small intestine had been incorporated into phospholipids.

1. The preparation of a stable olive oil emulsion in which glycerol monostearate was employed as the emulsifying agent is described. 2. Observations on its use for intravenous feeding in dogs are recorded.

The 17-ketosteroids excreted into the urine by patients suffering from different types of poliomyelitis showed no significant variations from normal excretion levels.

Vitamin B₁₂ counteracts the growth retarding effect of thyroid powder when fed in conjunction with a diet devoid of animal protein. The vitamin is equally effective when administered by either the oral or the subcutaneous route.

After intravenous injection sucrose occurs in the spinal fluid in very low concentration. Even when hemorrhages into the central nervous system occur, the concentration does not approach that found in blood.

The compound 4-Amino-N¹⁰-methyl pteroylglutamic acid, has shown the ability to inhibit the growth of the transplantable mouse Sarcoma 180 when administered intraperitoneally in concentrations of 1.5 mg/kg each day for 7 days. At this dosage very few mice died from drug toxicity. The inhibition is most apparent when the compound is administered early in the development of the tumor.

Whole liver powder prolonged survival and counteracted the growth retardation of immature mice fed massive doses of desiccated thyroid, thyroxin or iodinated casein. The protective factor(s) was retained in the water-insoluble fraction of liver.

1. The alveolar O₂, CO₂ tension and R.Q., minute volumes and respiratory rates have been recorded continuously in animals and man under pentothal sodium anesthesia administered by single and intermittent injection.

2. When the alveolar gas concentrations are plotted with the aid of a CO₂-O₂ diagram a typical anesthesia pattern can be shown indicating the regions of depression, compensation and recovery.

3. With intermittent injections of pentothal sodium this typical pattern is repeated.

4. The theoretical significance of this respiratory pattern and its utilization for analysis of quantitative changes in respiration in the study of anesthetic agents is discussed.

Using an infusion broth diluent containing 10 mg streptomycin and 2 mg tyrothrycin per ml, it was possible, by injection into the yolk sacs of 6-7-day-old embryonated eggs, to recover free from bacteria: psittacosis, influenza or mumps viruses from suspensions of fresh feces to which they had been added. The diluent had no apparent injurious effect on these viruses.

P-aminobenzoic acid was found to counteract the inhibitory action of sulfadiazine allowing for the recovery of psittacosis virus when the virus was suspended in materials containing the sulfonamide and injected into eggs. The injection of the p-aminobenzoic acid could be delayed up to 24 hours when injected in 1 mg amounts after a virus suspension containing 10 mg of sulfadiazine. In a similar series of experiments it was found that 15 mg cysteine hydrochloride would overcome the inhibitory action of l000 U penicillin on psittacosis virus when given as long as 24 hours after the virus suspension containing this antibiotic. These antagonistic compounds made it possible to recover psittacosis virus from materials containing large quantities of sulfadiazine or penicillin in spite of the fact that this strain of psittacosis virus is known to be susceptible to much smaller quantities of each of these therapeutic agents.

This technic was useful in the isolation of virus from the intestines of mice infected with psittacosis virus and may find application in the isolation of viruses from the gastrointestinal tract of other animals or man.

Lupulon, an antibiotic extracted from hop resins, was found to be effective against Gram-positive bacteria in vitro but inactive against Gram-negative organisms. The antibiotic had no demonstrable effect on a numlber of pathogenic and nonpathogenic molds and actinomycetes.

Lupulon displayed no activity in the presence of horse serum. In the absence of serum the antibiotic exhibited its greatest activity against M. tuberculosis H37Rv. This may have, been due to the fact that the tubercle bacillus was cultivated in a mineral medium with only an appreciable amount of interfering organic matter whereas the other organisms were grown, in a medium containing peptone. The addition of serum to both media completely inactivated the antibiotic.

Lupulon is slowly inactivated in the presence of air and more rapidly in the presence of serum. Because of its inactivation by serum, the antibiotic is not suitable for clinical administration.

The effect of autonomic blocking agents on sweat gland response to single shock excitation of the sympathetic chain was studied in cats by a quantitative and objective method. Dibenamine, an adrenolytic and sympatholytic agent, failed to block sweat secretion whereas atropine consistently produced complete and irreversible sudomotor paralysis. It is concluded that the sudomotor innervation in cat is entirely cholinergic and possesses no adrenergic component, as reported in man.

A method is described for the preparation of a very stable, desiccated, reduced streptolysin “O”. The material, when reconstituted with distilled water, is suitable for use in the determination of the antistreptolysin “O” titer of human serum. The availability of this material greatly simplifies this procedure since it is always immediately ready for use without the addition of the reducing agent. In addition, it may be shipped and stored conveniently since refrigeration is not required. Its production on a large scale or commercial basis would not prove difficult if a sufficient need for this material should arise.

A study was made on the effect of boiling on the liberation of amino acids by acid and enzymatic hydrolysis using microbiological assay methods.

Boiling up to 12 hours did not not affect the release by acid hydrolysis of α-amino nitrogen and of 7 essential amino acids studied.

Boiling for 15 minutes caused a slight increase in the release of α-amino nitrogen and amino acids by pancreatic digestion but boiling for 1 hour and longer up to 12 hours resulted in a marked increase. The increase in the enzymatic liberation of amino acids for periods of over one hour was about twice that liberated from raw soybean. Prolonged boiling up to 12 hours with definite browning did not result in a decrease in enzymatic liberation of amino acids from the “overcooked” soybean.

A colorimetric method is described for the determination of urethane in blood, which gives 99 to 111% recoveries in the range 4 to 44 mg % urethane, and a nonspecific “urethane” value of normal blood of 0.1-1.4 mg %.

A part of the method may be directly used for the determination of ethyl alcohol.

The agglutination of sea urchin eggs and sperm by basic protein extracts of homologous and unrelated sperm (reported by Hultin, ^5,6) is confirmed. Experiments are cited which show that antifertilizin, another egg agglutinin obtainable from sperm, is not present in or identical with the egg agglutinating basic protein fraction of sea urchin sperm as Hultin claims. Thus two distinct epp agglutinins are obtainable from whole sperm. One of these, antifertilizin, is obtained by heating, freeze-thawing or pH 3 extraction (Frank,⁷ Tyler,^8,10); the other, a basic protein(s), is obtained by pH 1 extraction of sperm.

Repeated injections of small amounts of glycine (3 mg per kg body weight) appear to increase the action of subsequent injections of insulin for a prolonged period of time.

1. Changes in the gastric mucosa produced by continuous irritation are described.

2. The sequence of events following irritation is compared in colon, small bowel, and stomach.

3. The process of regeneration after superficial destruction of the mucosa is described and is offered as a possible simple explanation for the resistance of the stomach to auto-digestion.

4. The possible implication of this mechanism in the pathogenesis of gastric ulceration is suggested.

1. A saturated solution of DDT (estimated at 1 ppm) in spring water for Rana pipiens larvae and in distilled water for Fundulus heteroclitus larvae, was sufficiently toxic to produce morphological deformities of a similar nature, the most obvious of which was the sharply bent tail and the very much reduced neuro-muscular response to tactile stimulation.

2. The initial evidence of damage by DDT appeared after 7 days of treatment of Rana pipiens larvae (beginning at stage 11) and after hatching of Fundulus heteroclitus larvae (treatment beginning at stage 8). There was a considerable lag in the effect, due, in all probability, to the (fact that DDT is relatively insoluble and therefore difficult to assimilate by the larvae.

3. In addition to the bent tail, there was a gradual decrease in neuro-muscular responses as determined by the Detwiler racetrack method following tactile stimulation, in both Rana and Fundulus larvae. Ultimately the larvae responded with only muscular tremors.

4. The toxic symptoms were not manifest in Rana larvae if they were returned to the control medium after 6 days of subjection to the DDT or in Fundulus as late as 16 days in the medium if subjected at stage 8.

5. There was no effect of DDT on the growth rate of Fundulus larvae, but after 9 days of exposure of Rana larvae they show a definite inhibition of growth.

6. The older the larvae at the time of DUT exposure, the longer the period before the onset of deleterious symptoms.

Determinations of desoxypentose nucleic acid and pentose nucleic acid, pteroylglutamic acid (PGA), and conjugase have been made on the livers of chicks receiving 0, 5, 10, 20, 40, 80, 200, and 1000 pg of PGA per 100 g of diet and on controls receiving a commercial diet. Desoxypentose nucleic acid was found to be somewhat low in the livers of the negative control group of chicks but differences between all other groups uere of doubtful significance.

The liver conjugase levels of the various groups, whether determined at pH 4.5 or at pH 7.0, were found to be unrelated to the dietary intake of PGA and to the nucleic acid content of the livers.

The liver PGA freed by autolysis was approximately the same as that determinable after treatment with either chick pancreas conjugase or hog kidney conjugase. The levels of PGA found in the chick livers indicate that storage of excess vitamin did not take place until the dietary level exceeded 40 μg per 100 g.

The bearing that the findings have on the mode of action of dietary PGA in reducing liver xanthine oxidase is briefly discussed.

As a part of long-time experiments in this laboratory on riboflavin metabolism in human subjects on weighed diets of known riboflavin content, it was noted that with the daily administration of 10 mg of synthetic pteroylglutamic acid for 25 to 40 days there was a striking decrease in fecal riboflavin values as compared to basal periods.

1. White Leghorn laying hens injected subcutaneously with aqueous adrenal cortical extract, showed leucopenia, absolute and relative lymphopenia and absolute and relative increase in granulocytes attributable mainly to heterophils. The effects were maximal at 3 hours and the blood picture returned to normal by the end of 24 hours.

2. New Hampshire Red non-laying pullets injected with ACE displayed similar changes with the exception of leucopenia which was masked by increase in polymorphonuclear cells.

3. ACE therapy produced no statistically significant increase in total serum protein or serum globulin levels. However, a trend toward increase in total serum protein, accompanied by lymphopenia, is indicated for the majority of the individual birds studied.

Hydroquinone in concentrations as low as 0.5% protected a thromboplastically active phospholipid preparation from being autoxidized for a period of at least 25 days. With this protection against autoxidation there was a protection against loss of thromboplastic activity.

1. The oxidation of the sulfur of isocysteine by the rat was studied with the aid of isocysteine containing S³⁵.

2. It was found that only a small amount of S³⁵ was excreted as sulfate in the urine within 24 hours after administration of the compound by stomach tube or by intraperitoneal injection. A much larger portion was excreted as organic sulfur. A very small fraction of the S³⁵ was recovered in the feces and intestinal contents of the rats.

3. The results of the present study are compared with those of an earlier investigation in which rabbits served as subjects.

The data here presented prove that chronic renal infections with leptospira in hamsters and dogs may be successfully cured with streptomycin. Although penicillin, as well as streptomycin, effectively influences the leptospiremia in experimental infections in guinea pigs, mice and hamsters, only streptomycin is capable of destroying the organisms found in the convoluted tubules.

Canine leptospirosis is usually treated after the parasite has already disappeared from the blood. Obviously, penicillin is of little value. Streptomycin in oil and wax in a daily dose of 40 mg per kilo given intramuscularly should be used in the treatment of acute and chronic canine leptospirosis. In fact, this antibiotic may be employed in the prevention of this destructive disease in dogs. It is recommended that the urine of all dogs intended for breeding be examined for leptospira, and when infection is found, the dogs should be treated for 3 to 5 days with streptomycin a few days before the act of breeding.

PGA when administered subcutaneously to normal mice in a single injection, produces after 24 hr an effective increase of the total weight and a decrease of the “alkaline” phosphatase of the kidneys. Normal values based on 54 mice are reported and compared with those obtained from 88 mice injected with graded doses of PGA (0.5 mg/kg to 500 mg/kg of body weight). The “alkaline” phosphatase was determined by a slight modification of the colorimetric method of King and Armstrong using disodium phenylphosphate as a substrate. The retention and precipitation of PGA in the renal tubuli, could be responsible for the increased weight and decreased phosphatase activity of the kidneys. Further experiments to determine the mechanism of action of PGA on kidney phosphatase are in progress and will be reported in the near future.

The use of benzene-ether extraction as a preliminary step in eventual purification of rabies vaccines has been made a more practical procedure by the demonstration that inactivation of the virus by heating in benzene results in a highly potent vaccine. Thus the necessity for preliminary ultraviolet irradiation has been eliminated.

A method has been presented for the removal from rabies vaccine of the factor which causes allergic encephalomyelitis. This factor is not removed by extraction with benzene and ether, but preliminary treatment of the vaccine with these solvents facilitates separation by subsequent treatment. The presence of calcium acetate prevents the loss of antigen when the vaccine is washed. It does not prevent removal of the encephalitic factor which appears to be water soluble. About one-half of the total nitrogen of the vaccine is removed by this washing process. The technic may be briefly summarized as follows:

1. A suspension of infected brain in water is dried from the frozen state.

2. The dried brain is extracted with benzene followed by ether (Live virus may be killed in this stage by heating in benzene).

3. After removal of the ether the dried brain is suspended in distilled water.

4. Sufficient solution of calcium acetate is added to make final concentration of M/10 calcium acetate, and the suspension is permitted to stand in the cold for an hour or two.

5. The calcium acetate solution is removed by centrifugation or filtration and the sediment is resuspended in distilled water to the original volume with agitation (clumps of sediment must be broken up).

6. The distilled water is removed by centrifugation or filtration.

7. The sediment is resuspended in distilled water or saline and homogenized. This is the washed vaccine.

The bacteriostatic effect of p-aminosalicylic acid is antagonized by high concentrations of salicylic acid. This effect of salicylate is highly specific and not shared by related compounds. Pantothenic acid does not inhibit the tuberculostatic effect of salicylate.

1. Aureomycin is highly effective against many strains of gram-negative bacilli in vitro, including many which were found to be resistant to sulfonamides, penicillin, and streptomycin. The sensitivity of various strains of a given species, however, varies greatly.

2. Clinical trial in 10 patients with urinary infections which were refractory to previous treatment with other antibiotics, resulted in a clinical cure of all ten patients. Bacteriologically eight patients were cured, and 2 were markedly improved.

A new quaternary amine, 2,6, dimethyl, diethyl piperidinium bromide, described as a ganglionic blocking agent,⁴ has an inhibitory or blocking action upon functions mediated by the sympathetic and para-sympathetic divisions of the autonomic nervous system. In dog and in man it reduces blood pressure and prevents several vasomotor reflexes, but does not prevent the vaso-pressor action of epinephrine. It causes a reduction of tone of the stomach and small intestine and abolishes their motor activity, reduces gastric acidity, and causes pupillary dilatation, loss of accommodation, and dryness of mucous membranes. Urecholine causes a reversal of effect on gastric motility. Neostigmine apparently causes a reversal of all effects of the drug.

1. The differential sheep cell agglutination test of Rose and his associates was performed with serum specimens from 42 individuals with rheumatoid arthritis. Serum from 17 of these patients showed differential agglutination titers of 16 or greater. In 24 active cases of mild and moderate severity and in one inactive case of long duration a differential agglutination titer of less than 16 was obtained.

2. Sera from 88 individuals with a variety of other conditions and from 18 presumably normal persons tested in the same manner showed differential agglutination titers less than 16.

3. Although differential agglutination titers less than 16 were observed in more than half the cases of active rheumatoid arthritis, the test appears to reflect the clinical severity of the disease.

4. These data partially confirm the observations of Rose and his associates but indicate that the differential sheep cell agglutination test is of limited value as an aid in the diagnosis of active rheumatoid arthritis of mild severity.

A variety of tests were made to determine if superabundant amounts of essential nutrients or optimal amounts of these nutrients from different sources would alter the initiation and development of carious lesions in caries-susceptible cotton rats after tooth development was almost complete. Negative results were obtained in all cases indicating that initiation and development of carious lesions in teeth formed before the beginning of the experimental period were not influenced by additional amounts of the known nutrients tested.

The ration described by Keyes for production of carious lesions in hamsters resulted in very poor growth and a low rate of initiation and development of carious lesions in the cotton rat. A supplement of 8% dried brewer's yeast to the purified ration produced good growth and permitted a slight reduction in the dental caries experience of cotton rats.

1. Furacin exerts a bacteriostatic and bactericidal action on virulent human tubercle bacilli in vitro. In a concentration of 1:20,000 (5 mg %) it prevented growth for 22 days in 4 different types of fluid media. A concentration of 1 : 5000 (20 mg% 0) was required for bactericidal effect.

2. Resistance to Furacin was not evident after many transfers of the H37 Rv culture in drug-containing medium.

3. The combination of Furacin and streptomycin in Tween-albumin liquid medium delayed, but did not prevent, the development of streptomycin-resistance by the H37 Rv tubercle bacillus.

4. Furacin, in the maximum tolerated dose of about 35 mg per kg daily for 64 days, did not appreciably affect the course of tuber-culosis produced in guinea pigs by the human type H37 Rv culture.

1. The addition of 10.5% or 21.7% carbon dioxide to oxygen does not improve the altitude ceiling of mice.

2. Mice taken to altitude in 100% oxygen, with continuous ascent from 30,000 feet at a rate of about 6,000 feet per minute, collapse at a lower ceiling than mice which ascend from 40,000 feet in 2,000-foot steps with 5-minute stops at each stage.

3. In experiments on human subjects no favorable physiological effects were observed when 10% CO₂ was added to the inspired oxygen at 40,000 ft.

1. A simplified procedure for the indirect complement-fixation test is described.

2. The serums of 59 Newcastle disease immune chickens were tested by the simplified indirect complement-fixation and by the hem-agglutination-inhibition tests.

3. Good general agreement was observed between the titers obtained by the two methods.

A simplified procedure for the preparation of salmin and clupein is described. The amino acid content of clupein as well as salmin has been estimated.

There is reason to believe that when asphyxiation is prevented electronarcosis causes only small increases of the level of adrenalin-like compounds in blood. It had been found previously¹¹ when one of two rabbits connected by a double carotid-jugular anastomosis was given an asphyxia-free electronarcosis, that the blood pressure in the other showed a slight increase. This was believed to be dlue to a release of adrenalin. which in the present experiments may cause the slight rise in the level of “adrenalin-like” compounds during asphyxia-free electro-narcosis. It seems likely that the much larger increase of these compounds which is always present in animals subjected to electro-narcosis without further precautions, is caused by asphyxiation.

Kobro¹² did not observe any effect of respiratory impairment (letting the animal breathe through a tightly woven cloth) on the adrenalin level. The impairment employed in the present experiments, though of shorter duration, was more severe (clamping of the trachea), which may account for the difference in the results obtained.

Marked weight gains were produced in stock albino mice by single injections of goldthioglucose. Analysis of total body lipids, protein, water, and ash showed these weight gains to be primarily due to an increase in adipose tissue. This obesity occurred in approximately one-third of the survivors of sublethal doses of goldthioglucose. Except for centrolubular fatty infiltration of the liver in obese animals, no-anatomic lesions were found in the organs examined.

1. Large doses of aminophyl-line, administered intravenously to dogs, produced a transient elevation in prothrombin activity, followed by a late hypoprothrombinemia with return to normal in about 2 to 3 weeks. Simultaneously, a more marked and persistent rise in Ac-globulin activity occurred. Small doses of 6 mg/kg body wt were without significant effect.

2. No correlation could be found between the Lee-White whole blood clotting time and variations in prothrombin and Ac-globulin activity.

1. Under the stated experimental conditions Adrenoxyl does not influence (a) the speed of the coagulation process, and, (b) the vasomotor response.

2. The method of bleeding time determination in the experimental animal in our hands does not give conclusive results, therefore we are unable to confirm or deny the findings of Roskam and associates.

1. Under conditions very favorable for intravenous injection, the “Hypospray” has lodged as much as 97% of the total available drug in the vein, even when administered through the skin and subcutaneous tissues.

2. Large veins are easier to hit than small veins and retain a larger amount of the jet-injected material.

3. The probability of unintentionally penetrating a major vessel with the jet is small but the risk is always present.

4. Jet discharges should not be made in the neighborhood of large vessels unless the drug to be injected is safe for intravenous administration.

5. The jet may produce macroscopically visible damage to a vessel.

Syngenesiotransplants of ovaries made at one month of age caused mammary cancer in 5% of castrate male mice of strain A. The tumor incidence rose to 32.5%, if anterior hypophyses were grafted together with ovaries. Transplantation of anterior hypophyses alone failed to produce breast cancer. No mammary tumors occurred in castrates into which ovaries, anterior hypo- physes alone or anterior hypophyses in combination with ovaries were grafted at 7 months of age. Thus in male mice, an age factor which is independent of the testicle operates in the production of breast cancer by ovarian and anterior hypophyseal grafts.

The lactogenic and gonado-trophic hormone content of pituitaries of intact and ovariectomized rats was determined after full, 3/4, 1/2, 1/4 and no-feed regimes. The full or partially-fed groups were sacrificed at the end of 14 days and the unfed group at the end of 7 days. Pituitary lactogen content was reduced in the intact and ovariectomized rats on the 1/2, 1/4 and no-feed regimes below that of the 3/4 and full-fed controls. No change occurred in the gonadotrophin content of the pituitaries of either the intact or ovariectomized rats, regardless of the level of feed intake. In the intact but not in the ovariectomized rats, restricted feed intake caused a marked reduction in the weights of the pituitary, thyroid and adrenals, except that on the no-feed regime adrenal weight was increased in both groups.

The assay of secretin and CCK concentrates are affected by cannulation of the pancreatic duct and the gall bladder, respectively. The ratio of dosages of a vasodilatin-free standard concentrate (SI) to the test fraction yielding the same number of drops of pancreatic juice in a 10-minute interval is determined, and the value is taken as the secretin unitage contained in 1 mg of test fraction. Similarly, the dosage ratio of this standard to the unknown giving the same gall bladder contraction is equated to the units of CCK per mg of unknown. Good reproducibility is obtained in a large number of dogs.

The dose-response curves for CCK and their significance are discussed.

A number of compounds have been found which will replace CO₂, necessary for the anaerobic metabolism of Escherichia coli and Aerobacter aerogenes. The C₅ compounds appear to replace CO₂ more effectively than other compounds tested with the exception of oxalacetic acid and citric acid, the latter in the case of A. aerogenes only. The fact that oxalacetic by-passes the CO₂ requirement to such an extent indicates that this acid may function as the chief substrate for protein synthesis under anaerobic conditions.

Magnesium ion has been found to be essential for the hyaluronidase inhibitor activity of human blood under the conditions of the in vitro assay. The minimum amount of magnesium required for expression of maximum activity has been determined for the as-say method employed in these laboratories.

Under the circumstances which have been described, Darvisul revealed neither prophylactic nor therapeutic value in mice infected with the MM virus, the Lansing strain of poliomyelitis virus or Theiler's virus of mouse encephalomyelitis (TO).

Phenosulfazole (Darvisul) showed no beneficial effect in the treatment of mice infected with the Columbia SK virus and other neurotropic viruses, including a rodent adapted strain of poliomyelitis (MEF-1 strain). The lack of therapeutic effectiveness of the drug was also observed in monkeys infected intranasally with the Brunhilde strain of poliomyelitis virus. In other viral and rickettsia1 infections of mice and of developing chick embryos treatment with pheno-sulfazole was of no therapeutic value, with the possible exception of psittacosis in which a slight inhibition of growth in the developing chick embryos was observed. However, even in the latter case the effectiveness of phenosulfazole therapy was of much lower magnitude than that observed with other sulfonamides,^4-6 or antibiotics.⁷

Phenosulfazole (Darvisul) has been reported by Sanders, Subba Row, and Alexander¹ as having a therapeutic effect in mice infected with “a mouse virus isolated in 1940.”

Darvisul, N-(2-thiazolyl) -phenol sulfona-mide, or phenosulfazole was reported by Sanders, Subba Row, and Alexander¹ to be effective against as many as 100 LD₅₀ of a mouse virus, SK, when administration was begun 24 hours after intraperitoneal infection.

1. Thyroid filters preferentially and accumulates thiocyanates as well as all the elements of the seventh periodic group that have been studied, viz., Cl, Br, I, Mn, At.

2. All halides and thiocyanates when administered in relatively large amounts compared with iodine wash inorganic iodide from the body and prevent new supplies of iodine from being received by the thyroid, thus producing thyroid hyperplasia and goiter. It is suggested that these ions exert, at least in part, a mass action-like effect.

3. It is further suggested that similarity in arrangement of electrons in the outer shell of the elements of the seventh periodic group enables the thyroid to differentiate between them and other elements.

The water content of the uterus and oviducts of adult rats during the period of proestrus and the end of sexual receptivity has tbeen determined. There is a significant decrease in the water content of the uterine tissue during the period of heat. No significant decrease was found in the water content of the oviducts examined during this same period.

These results fail to indicate any rise in fecal agglutinin titer prior to the appearance of blood serum agglutinins. In this respect and also in regard to the irregularity of antibody appearance in the feces of human subjects following T. A. B. vaccination our results differ from the regular and rapid appearance of coproantibody reported to follow cholera vaccination.

A concentration of 10⁻⁵ M: Zn⁺⁺ failed to affect the serum alkaline phosphatase activity in individuals either with or without cancer. These results are not in agreement with the findings of Roche et al. ^1,2 that this concentration of Zn++ activates the serum alkaline phosphatase activity of individuals without cancer and inhibits this activity in patients with cancer. Concentrations of 10⁻⁴ and 10⁻³ M decreased the serum alkaline phosphatase activity, but the extent of these decreases was the same in patients with and without malignancy.

Chick embryos killed by prolonged storage at room temperature or 4°C are capable of supporting the multiplication of influenza virus upon prolonged incubation at 35°C.

The growth of weanling white rats was stimulated by inclusion of vitamin B₁₂ or of whole dried liver in the diet. Rats which received no B₁₂ or liver grew poorly and showed little or no liver basophilia, whereas those which received B₁₂ or liver grew well and showed considerable cytoplasmic basophilia in their liver cells.

1. A hemorrhagic syndrome in dogs was produced by total body irradiation (450 r). Manifestations consisted of multiple areas of hemorrhage in the pulmonary, gastrointestinal, and urinary systems, anemia, leucopenia, thrombocytopenia, prolongation of clot retraction, and hypothrom-boplastinemia.

Intravenously-administered Rose Bengal can be visualized by fluorescence microscopy in the livers of rabbits and humans. The fluorescence is Seen in hepatic polygonal cells, but not in Kupffer cells. It is suggested that the polygonal cells of the normal liver are responsible for the storage of Rose Bengal, and by analogy, Bromsulfalein

The incorporation of 1,000 μg quantities of 5-nitro-2-fural-dehyde-2-β-hydroxyethyl semicarbazone and 5-nitro-2-furaldehyde-2-β-methyl semicarba-zone in paraffin blocks used as salivary stimulants completely prevented acid production in 38 of the 42 saliva samples obtained from caries active individuals. A significant partial reduction in acid formation occurred in the remaining 4 cases. The findings indicate that 5-nitro-2-furaldehyde-2-β-hydroxyethyl semicarbazone and 5-nitro-2-furaldehyde-2-β-methyl semicarbazone are not rapidly destroyed or absorbed by the tissues and fluids of the oral cavity.

Streptomycin incorporated into a synthetic liquid medium enhanced the growth of laboratory strains of S. schenckii, C. immitis, P. verrucosa, T. mentagrophytes, and H. capsulatum which had not been previously exposed to this antibiotic.

1. A study has been made of the level of phosphoprotein phosphatase activity in placentas, whole embryos, and whole young growing rats of various ages.

2. The total phosphoprotein phosphatase activity of the placenta and of the embryo and young rats continually rises. The activity was followed in placenta and embryo from thirteen days post-conception to parturition, and in young rats to 28 days of age.

3. The activity per gram of body weight rises slowly in early embryos, rapidly in the period immediately preceding and following parturition, and remains essentially constant during the age period of 12 to 28 days.

4. The activity per gram of placenta decreases from the 14th to the 20th day after conception, then rises again just before parturition. The preliminary decrease is due to the rate of weight gain of the placenta being greater than the rate of gain of total placenta phosphoprotein phosphatase; the reversal of direction of the curve is due to continued enzyme increase while the placenta gains essentially no further weight.