Experimental Biology and Medicine

Penicillin is shown to be of value in the protection of mice against experimental Erysipelothrix rhusiopathice infection.

Oral administration is successful in the treatment of mice even without any protective action from oil coating, or buffers, provided it is instituted within 24 hours after exposure. The use of penicillin in drinking water is found to be as effective as is its addition to the feed. Oral administration compares favorably with parenteral injection although larger amounts are required.

The increase in agglutination titer following immunization confirms the work of Witebsky 1 and Wiener. 2 In addition it has been shown that immunization with group specific substances increases the avidity, and that this increase roughly parallels the increase in agglutinin titer.

1. The turbidity produced by the growth of Lactobacillus arabinosus is greater in relation to acid production when the organisms are responding to suboptimal amounts of nicotinic acid than when they are responding to suboptimal amounts of biotin, pantothenic acid, or Z-tryptophane.

2. All the acid produced by the Lactobacillus arabinosus is lactic acid regardless of whether the bacteria are responding to nicotinic acid, biotin, or pantothenate.

Castration of hamsters caused a decrease in the number (25-30%) and in the size of erythrocytes. In animals castrated when young enough to have fewer cells than the number typical for castrates the count increased up to the castrate level. Splenectomy had the same effects as castration upon the number and size of red blood cells and no additional change occurred when castrated animals were splenectomized. Liver extract or iron citrate injected daily for three days restored a normal count and normal average corpuscular volume in all operated animals, castrates, splenectomized, and splenectomized castrates. Testosterone injected for a similar length of time was effective in castrates only and was ineffective in all splenectomized animals.

Rats maintained either from birth or from weaning on a pantothenic aciddeficient diet containing 64% casein grow more and survive longer than littermates maintained on a 24% casein-deficient diet under the same conditions. Several possible explanations for this sparing action are given.

Multiplication of Tetrahymena geleii was inhibited by 50 y of atabrine per ml. Resistance of the cells to atabrine was progressively decreased by the environmental changes occurring during growth of the culture and was strikingly decreased when the pH of the culture was increased.

Streptomycin exerts a protective therapeutic effect on the course of experimental murine pertussis as indicated by a significant reduction in the mortality rate and the disappearance of the organisms from the lungs of the surviving mice.

Numerous experiments have been performed to determine the effects of continuous electric currents passed through growing roots immersed in various aqueous media. In practically all, the electric field was oriented at right angles to the long axis of the root. Under such conditions a minimum of two diverse stimuli, viz., gravity and applied E.M.F., operate at right angles to one another, thus causing a complicated type of variable growth response. 1 , 2

To provide simpler experimental conditions, an electric current having parallel isopotential lines and appropriate current density must be passed up or down the polar axis of the root and must coincide with the orientation of the general axis of the inherent electric field of the root as well as that of gravity.

An apparatus was designed to comply with this requirement and to maintain the roots under normal conditions of growth except for the applied current. Three sets of roots were used in each experiment: (1) control roots, (2) roots through which an electric current was passed upward, and (3) roots in which the same current was passed downward. Since individual roots vary slightly with respect to the threshold of current density for reversible inhibition of growth and also in their rates of elongation, each experiment involved 3 or more duplicate sets of roots. Preliminary experiments led to a choice of a current giving an IR drop of 40 mV/mm, with the root immersed in tap water as the growing medium and the current passed upward through 25 mm of the apical end of the growing root. This gives complete inhibition of growth. The same current passed downward gives a very slight inhibition of growth, Fig. 1, or none at all. At 37.8 mV/mm, complete but reversible growth inhibition is obtained with acdending current.

Experiments have been made in normal human subjects which demonstrate that induced pain of short duration produces long lasting analgesic effects.

The stimulating action of ACTH on the adrenal cortex of hypophysectomized rats, as far as could be judged by adrenal weights and by morphology as seen in lipid stains, was the same in the absence of the medulla as in the intact adrenal.

A prompt and sustained hypertension was produced in 6 dogs by unilateral subtotal ligation of periadrenal blood vessels and tissue.

1. Varying degrees of shock can be produced in rats by subjecting them to various periods of trauma in Noble-Collip drums. The method appears to be suitable for use where graded and reproducible degrees of trauma are desired.

2. The percentages of survival were: for 5 minutes of tumbling, 100%; for 8 minutes, 65.6%; for 10 minutes, 71.4%; for 12 minutes, 47.2%; for 13 minutes, 9.5%; and for 15 minutes, 4.3%.

3. The Sprague-Dawley strain and a cancerresistant strain of rats were found to be less resistant to trauma of the Noble-Collip type than were rats used by other investigators.

4. Survival of previous hemorrhage did not increase resistance to Noble-Collip trauma, but appeared to decrease resistance to some extent.

5. Adrenal enucleation decreased the resistance of rats to Noble-Collip trauma although regeneration of cortical tissue had been sufficient to support normal growth and to maintain the rats in a healthy state.

6. Protection to the abdomen and taping of the paws gave only limited protection to the rats of the Sprague-Dawley strain subjected to Noble-Collip shock.

Rats of a pure inbred line treated with embryo skin of the same strain failed to produce a resistant state to grafts of a tumor autogenous to the strain.

1. A method for producing tourniquet shock in rats is described. The method yields graded and reproducible results.

2. The percentage survival of rats to tourniquet shock was progressively decreased as the time of tourniquet application was increased. Following 3% hours of tourniquets 100% of the rats survived, while after 4 hours of tourniquets only 3% survived.

3. Rats which had tourniquets applied for 4 hours with periods of release for 1 to 6 hours, followed by a second application of tourniquets, showed 100% in contrast to 3% survival for those without replacement, while 87.5% survived when the tourniquets were replaced after 7 hours.

4. The degree of hemoconcentration developing in rats in tourniquet shock was approximated by hemoglobin determinations. Increases in hemoglobin ranged between 27 and 52%.

Impairment in ability to inactivate estrone accompanies dietary hepatic injury and can be rectified by the addition of lipotropic factors such as methionine or protein digests.

Fivefold increase of the basal vitamin B supplements was ineffective.

Under the conditions described, the toxicity of untreated yolk suspensions and the antigenicity of typhus vaccines prepared from embryos harvested on consecutive days rose together with the complement-fixing activity of the same antigens.

High concentrations of nicotinamide exert a synergistic effect upon penicillin inhibition of Staphylococcus aureus. Nicotinic acid was inactive in this respect. No evidence for a reaction between nicotinamide and penicillin could be found. Although the effect of nicotinamide appeared to be general for the 3 strains of staphylococcus tested, no effect could be demonstrated upon either Streptococcus pyogenes or E. coli.

Penicillin-fastness developed most rapidly in gonococci under conditions which permitted the greatest number of viable microorganisms to be transferred to a higher concentration of penicillin at each transfer. One strain of gonococcus acquired the ability to prow on media containing 21 units per ml. So appreciable increase in penicillin tolerance resulted from repeated exposure to bacteriostatic concentrations of penicillin.

The antibody response of swine to formolized swine influenza virus adsorbed on alum is essentially the same as that to the vaccine dispersed in saline solution. The chief influence of the alum is a brief delay in the peak response. The higher concentrations of alum lessen the primary antibody response, but the subsequent antibody levels and the rates of diminution in titers are nearly identical with the two sorts of vaccine.

The in vitro inhibition of 412 cultures of Salmonella by streptomycin was studied. All of the recognized types in the genus were included in the work. Of the commonly occurring types, S. paratyphi A and S. typhi were the most sensitive while S. pullorurn and S. enteritidis were somewhat less susceptible. The remainder of the types which are found frequently were more resistant. The majority of the types required 2 to 4 times as much streptomycin to inhibit growth as did E. coli W. Different cultures of the same type often varied widely in their susceptibility to streptomycin.

Several different preparations of streptomycin were tested on cultures of rabbit's spleen and were found to have a uniformly low toxicity for wandering cells and fibroblasts. Streptothricin had a relatively low cytotoxicity for leukocytes and macrophages but showed a fairly high cytotoxicity for fibroblasts.

Some specimens of larval Eustrongylides ignotus could be maintained for 4 years in vitro. The worms survived for long periods in media showing a pronounced partial lack of oxygen, but they did not tolerate complete absence of oxygen for very long periods. Anaerobically kept worms seemed not to feed but they consumed from their body reserve about three times as much glycogen as worms starving under aerobic conditions.

The physiological effects of A-V fistula have long been the subject of extensive experimental investigation. Added impetus has been given to this work by successive wars. The existence of such effects as the Nicoladoni-Branham phenomenon, increased pulse pressure, decreased diastolic pressure, and the relationship of these changes to the size and location of the fistula, have been definitely established. On the other hand, another group of physiological effects or the explanation thereof, such as increased cardiac output, 1 , 2 , 3 increased blood volume, and increased pressure in the large veins proximal to the fistula, 4 , 5 have been matters of considerable controversy. Finally there are some effects which have been studied incompletely or not at all. The present investigation was undertaken to determine the effect of A-V fistula, first, on femoral and jugular circulation times and the relationship between the two, and second, on auricular pressures.

Method. Thirty observations were made on 5 dogs. The animals were anesthetized with nembutal intravenously, 1 grain per 5 lb of body weight. The right femoral artery and vein, and right jugular vein were exposed under rigid aseptic conditions. Right femoral arterio-venous fistulae were made in the manner described by Holman. 4 Femoral and jugular circulation times, using the cyanide method described by Robb and Weiss, 6 were determined before and after the fistula was made. All injections into the femoral vein were made at a point just proximal to the site of the fistulous opening into the vein. The injections into the jugular vein were made at a point midway between the lower edge of thyroid cartilage and sternum. Next, auricular pressures were determined with the fistula open and closed. A No. 10 French catheter, with tip cut off, was introduced into the right auricle by way of the right jugular vein according to the method of Richards et al. 7 Heparin was added to the saline in the catheter to prevent clotting.

The protein of sunflower seed is a complete single source of amino acids for the growth of the young chick, when fed to provide 20% protein in the diet.

A method of preparation of thermost able thromboplastin from human placenta and of thermolabile but reactivable thromboplastin from chicken brain is described. The properties and differences of these preparations are discussed. Human placenta thromboplastin is not inactivated by heating at 98°C for 5 minutes. Chicken brain thromboplastin is inactivated by the heat treatment but is subsequently reactivated when it is stored at 44°C. The different activities of heated and unheated placenta and chicken brain thromboplastin on stored oxalated human plasma and native chicken plasma are explained by the assumption that thromboplastin is composed of two factors, one of them thermostable and the second thermolabile. Clinical, surgical, and research applications of thermostable preparations of thromboplastin are discussed.

A cage for the proper management of mice during nitrogen balance studies is described. The arrangement eliminates spillage of food, fouling by excreta, loss of ammonia, and other sources of error.

From the results reported it would seem that the presence of autoantibodies to human heart has been demonstrated in 75% of a group of patients with acute rheumatic fever.

The disturbance in neuromuscular transmission caused by sectioning of the tendon disappears when the tendon is spontaneously re-established.

Neostigmine (prostigmin) does not stimulate the denervated iris muscle of the cat. It causes miosis only when some or all of the ciliary (parasympathetic) ganglion cells are intact or when the postganglionic fibers are stimulated.

Guinea pigs exposed to simulated altitudes of 23,000 and 30,000 feet 6 hours a day and 6 days per week became fully acclimatized after 200 hours, as shown by maximal increase in the values for red corpuscles, hemoglobin, and hematocrit. Reticulocytosis and enlargement of the spleen were also demonstrated.

The intestinal extract used in this study apparently was not effective in preventing gizzard erosion in chicks.

Several agents were tested for protective action against carbon tetrachloride injury of the liver in rats. Marked protection was obtained with sodium thioglycollate, appreciable protection with glutathione, moderate protection with sodium thiomalate, and slight protection with cystein—all sulphydryl compounds. Sodium glycollate and sodium malate afforded protection comparable to their sulphydryl homologues. Methionine, and choline plus cystine did not afford protection. Other non-sulphydryl compounds, i.e., sodium thiosulphate, aspartic acid, glutamic acid, choline, and sodium acetate afforded no protection.

A protective action against carbon tetrachloride injury of the liver in rats is not as closely related to the presence of -SH in the test agent as previously was observed for the protective action of certain compounds against hepatic injury by chloroform in the dog.

A comparison of the blood pressure rises in the electronarcotised and test animals during electronarcosis and after the injection of 10^-5 g adrenaline (Fig. 3 I and II) shows that the rise during electronarcosis (after elimination of the vagus effect) can be explained only for a small part by hormonal mechanisms. It must be mainly a nervous phenomenon.

The considerable drop in pressure, which occurs when the high initial current is reduced, may be due to a period of decreased responsiveness of the sympathetic system after the strong stimulation. Normal stimuli and those set up by the lower maintenance current would then be unable to maintain the high or even the normal blood pressure. This is supported by the observation that, when electronarcosis is repeated at intervals of 10 minutes, this drop tends to become more marked.

The second maximum in blood pressure (Fig. 1) may be caused by impulses produced in the sympathetic by the smaller maintenance current, after this system has recovered from the effects of the high initial current.

Hair fat of adults contains free saturated aliphatic fatty acids which inhibit the growth of M. audouini in concentrations of 0.0002 to 0.001%. Preliminary chemical analyses of the still impure fractions, molecular weight estimations, and the range of fungistatic activity indicate that the fraction contains saturated aliphatic fatty acids between C₇ and C₁₁.

Graying of the hair results in black rats fed a vitamin B-complex-free diet, supplemented with thiamine, riboflavin, and pyridoxine. New hair growing in after the ablation of both adrenal glands in rats kept on such a deficient diet is again well pigmented. To determine whether the increased pigmentation was due to the lack of the medullary or cortical portion of the adrenal, the adrenals were transplanted into the kidneys. The medullary portion of the adrenal degenerated, the cortex persisted, and poorly pigmented hair grew on the animals. Thus the lack of the cortex was related to the increased pigmentation following adrenalectomy.