Experimental Biology and Medicine

1. Mouse lung tissue possesses the capacity to oxidize several of the naturally occurring compounds which are capable of undergoing oxidative decomposition and giving rise to energy-yielding mechanisms. Under the limiting conditions of these exploratory experiments, the presence of a Type A, PR8 influenza virus infection in this tissue does not appear to alter, to a significant degree, these oxidative reactions. 2. Influenza infection appears to increase the capacity of host lung tissue to metabolize several compounds concerned in nucleic acid metabolism. Whether this phenomenon is indicative of cellular breakdown incidental to the viral infectious process or whether it represents an “active” degradation of specific molecules consequent to virus synthesis is still to be determined. 3. Xanthine oxidase appears to play a central role in the in vitro purine metabolism of mouse lung; the activity of this enzyme is increased in the infected tissue. The increment and decrement periods of virus proliferation roughtly parallel the increment and decrement periods of enzyme activity. In no case was a qualitative difference found between the xanthine oxidases of normal and virus infected lung tissue; the effects produced by the addition of metabolic inhibitors, the influence of methylene blue, and the end-products of the reactions were the same. The significance of these findings has been discussed.

A biologically active factor is present in crown gall tumor tissue extracts which when used in association with an auxin is capable of encouraging the very active proliferation of normal tobacco pith tissue. Neither the factor present in the tumor extract nor the auxin is by itself effective in stimulating the active division of the pith cells.

Dihydrouracil and β-ureidopro-pionic acid, the “uracil counterparts” of di-hydroorotic acid and ureidosuccinic acid, intermediates in the biosynthesis of orotic acidr are inactive in promoting growth of 8 pyrimidineless lactobacilli.

Diacetyl prevented the growth of all of a variety of microorganisms in a range of 200-1600 μ/ml. In quantitative studies with a single strain of E. coli, diacetyl exerted an inhibitory action at low concentrations (< 129 μg/ml) and lethal action at higher concentrations (> 129 μg/ml). It was demonstrated that diacetyl was utilized during growth of E. coli and enhanced final growth when the medium was deficient in glucose.

Administration of cortisone to rabbits caused hyperlipemia due chiefly to an increase of lipids other than cholesterol and phospholipid. Cholesterol-fed rabbits treated with cortisone developed severer degrees of hypercholesterolemia and hyperlipemia than rabbits on cholesterol alone. The relative proportion of cholesterol in the serum lipids of cholesterol-fed rabbits on cortisone was less than in the serum lipids of rabbits on cholesterol alone. Significantly less lipid was deposited in the arteries of the cortisone-treated, cholesterol-fed animals than in the cholesterol-fed controls. It is suggested that hyperlipemias in which the lipid fractions other than cholesterol undergo the greatest increase, are less likely to be associated with arterial lipid deposition than hyperlipemic states in which cholesterol is the major constituent.

1. Administration of large amounts of manganese to rats was associated with an increase in the concentration of copper in plasma and brain, a decrease in the urinary excretion of copper, a decrease in the concentration of copper in the kidneys, no alteration in the concentration of copper in the liver, and microcytic, hypochromic anemia. The total amount of copper in the body was not increased. 2. Administration of large amounts of copper was accompanied by an increase in total body copper and an increase in the concentration of copper in the plasma, urine, liver, and kidneys but not in the brain. Anemia did not occur. 3. Simultaneous administration of large amounts of both manganese and copper resulted in a marked increase in total body copper, an increase in the concentration of copper in the plasma, liver, kidneys and brain, and microcytic, hypochromic anemia. The total amount of copper in the body of these animals was twice as great as in rats given the same amount of supplemental copper alone. The concentration of copper (μg/100 g of body weight) was increased 5-fold. 4. It is suggested that manganese may form a complex with copper which makes the latter unavailable or that in some manner it blocks the action of copper-containing enzymes.

1. Insulin labeled with I¹³¹ was used to determine the effect of liver slices on the degradation of insulin. 2. The insulin-inactivating activity of slices of rat liver (insulinase) is associated with a degradation of I¹³¹ insulin. 3. The degradation of I¹³¹ insulin by liver slices follows first order kinetics and is related directly to the quantity of liver slices employed. 4. A non-protein fraction of liver (insulinase-inhibitor) which inhibits the action of insulinase also inhibits the degradation of I¹³¹ insulin by liver slices.

1. The daily oral administration of 10 μg aminopterin to weanling rats induced a severe aplasia in the bone marrow within 5 days. 2. The simultaneous injection of 150 μg leucovorin completely prevented the aminopterin toxicity. 3. Simultaneous injection of folacin was also effective in preventing toxic effects of aminopterin. Folacin was about 1/50th as active as leucovorin. 4. Ascorbic acid and/or vit. B₁₂ did not influence the effect of folacin, i.e., no augmentation of submaximum amounts of folacin by either ascorbic acid and/or vit. B₁₂ was observed.

Muscular exercise in human subjects produced no alteration in peripheral utilization of thyroid hormone as measured by concentration of circulating hormone and by rate of disappearance of injected radio-thyroxine.

Suture line leakage was not observed in a series of 10 dogs given large daily doses of ACTH following end to end anastomosis of the colon. The strength of the suture lines was not significantly altered by ACTH administration as compared with non-treated controls. No correlation was evident between the amount of ACTH given and the strength or gross appearance of the anastomoses.

A mixture of 2 strains of Type I poliomyelitis virus was adapted to the PRI strain of mice and to cotton rats. The virus could be propagated in certain sublines when either the intraspinal or intracerebral route of inoculation was used. The infectivity of different sublines for mice and cotton rats varied, but the cytopathic titer in tissue culture was of similar magnitude. The passages in PRI mice resulted in a subline completely avirulent for rhesus and cynomolgus monkeys.

Two human subjects who had no antibodies against Type I poliomyelitis virus were fed a mouse adapted Type I strain, and one human subject who had no antibodies against Types I and II was fed a mixture of mouse adapted Type I and Type II strains. None of the individuals showed clinical signs of illness as a result of ingestion of the virus. In the absence of viremia, all 3 excreted virus in the stools. Homologous neutralizing antibodies developed in the sera of each person. Virus passaged through the human intestinal tract maintained the very low pathogenicity for monkeys when injected intracerebrally.

1. Weanling rats were fed diets containing one of the following antioxidants: α-conidendrin, β-conidendrin, α-conidendrol, and β-conidendrol. The concentrations were, for the females, 0.125 and 1.0% of the diet; and for the males, 0.5 and 1.0% Body weight increase was normal, or approximately normal, during the first 220 days of the experiment, after which frequent weighings were discontinued. 2. Histological examination of the tissues after 420 days on the diets indicated essentially normal tissues, except for the following: In males receiving the higher concentration of β-conidendrol there was vacuolation (presumably fat) of the liver cells, without indication of severe injury. In several of the males receiving the higher concentration of the conidendrols, there were renal changes suggesting mild, old pyelonephritis. In males, several of the rats receiving the conidendrols had focal abnormalities in the pancreas. 3. There was no evidence of irritation to the skin or to the eye of rabbits, and skin sensitization was not developed in guinea pigs. It is concluded that there is at least a 100-fold margin of safety between the amount of conidendrol suggested for fat antioxidant and the amount ingested by rats eating the 1.0% level.

Passive transfer of delayed cutaneous hypersensitivity to 274-dinitro-chlorobenzene in guinea pigs has been accomplished with extracts of peritoneal exudative leucocytes disrupted by sonic vibration. Crude extracts of cells treated and subsequently centrifuged were effective as transfer media. Sedimented material was essentially ineffective.

Mice were exposed to cold (5°C) for periods of 15 minutes and 5 days and the effect on erythrocyte number, hemoglobin concentration and blood sugar level determined. The only significant change occurred in the blood sugar level during the short period of cold exposure. Statistically this change had a P value of <.001. Possible physiological changes are discussed.

Administration to intact rats of an extract, prepared from the plasma of phenylhydrazine-treated rabbits, results in significant increases in peripheral red cell counts, hemoglobin concentrations, reticulocyte percentages, hematocrit values, and in the concentrations of nucleated erythrocytes within the marrow. The extract exerts no significant influence upon the total and differential white cell numbers or the sedimentation rates and red cell fragility values. The factor may be related to, or identical with, the circulating “hemopoietine” hypothesized to be the humoral mediator of anoxia, the fundamental erythrocytogenic stimulus.

1. Sixteen diabetic patients exhibiting local skin reactions to insulin as nodules with or without erythema or stinging were tested intradermally with various insulin products, beef and pork protein. 2. Sixteen nondiabetics not using insulin were similarly tested with the same substances. 3. Passive transfer tests with the sera of 5 patients manifesting local reactions to insulin were performed. 4. Skin reactions noted in patients exhibiting local reactions to insulin were no different from those obtained in the control group of nondiabetics, non-users of insulin. 5. The Prausnitz-Küstner passive transfer phenomenon was absent in all 5 instances. 6. It is concluded that local nodules with or without stinging or erythema observed in patients receiving insulin therapy are not due to any antigen-antibody mechanism.

1. Stock strains of Ducrey's bacillus obtained from various sources have been found to conform to classical and current descriptions of H. ducreyi. 2. Comparison of stock “R” strains with freshly isolated anaerobic cultures, indicates that the “S” form of this species has not been previously recognized. 3. Our experiments indicated that blood is not required for growth of the “S” form and that its use leads to rather rapid production of the classical “R” variant currently classified as H. ducreyi.

Two days after hypophysectomy, the pyridoxine-deficient rat treated with ACTH had the same amount of adrenal ascorbic acid depletion and adrenal weight increase as did the pair weighed and ad libitum controls but like these controls no decrease in adrenal cholesterol. When intact animals were subjected to hypoxia, however, the pyridoxine-deficient group, although able to maintain adrenal weights and adrenal ascorbic acid content as did the pair weighed and ad libitum groups, clearly failed to show the adrenal cholesterol depletion characteristic of the latter groups. The depletion of adrenal cholesterol is apparently not controlled by the same mechanism involved in adrenal hypertrophy and adrenal ascorbic acid depletion.

1. Single doses of radioactive phosphorus, administered internally to rats in amounts of from 1 to 3.5 μc/gram body weight, proved carcinogenic. Two types of malignant neoplasms were produced, i.e., osteogenic sarcoma and carcinoma of the face.

2. The incidence of neoplasms ranged from 22 to 50%. The latent period of tumor development was lengthened with smaller doses of P³².

3. Amounts of P³² less than 1 μc/gram body weight failed to induce neoplasms.

Studies were made to determine the specificity of the chemical inhibition of division of Escherichia coli and to determine the relationship of division inhibition to important biochemical metabolites. It was found that the cell-division process of E. coli could be specifically inhibited, without an accompanying inhibition of culture growth, by diazouracil and by other diazonium compounds, and it is suggested that the diazo group on the compounds is responsible for the inhibition. The inhibition of division by diazouracil was antagonized by tyrosine, and it was shown that the antagonism can not be attributed to a destruction of the inhibitor by tyrosine. Other amino acids, intermediate in the glycolytic and tricarboxylic acid cycles, and energy-rich phosphorus compounds were incapable of antagonizing diazouracil-inhibited cultures.

1. Exclusion of the antrum from continuity with the residual gastric pouch is the chief ulcerogenic factor in the Sauvage operation in which the antrum is anastomosed to the esophagus (Group II dogs). 2. Stomal peptic ulcer was not observed in vagally innervated total gastric pouches when the antrum remained in contact with the residual gastric pouch (Group I dogs). 3. Augmentation of the secretion of acid from an isolated Heidenhain pouch attends antral migration or exclusion (Group II dogs). Diminution of secretion from such a pouch was observed when the vagally innervated entire stomach, with the antrum in its normal position, was attached to the side of the duodenum as a blind pouch (Group I dogs).

The findings just summarized support the presumption that this group of agents is composed of representatives of the viral species responsible for measles.

Eight agents exhibiting the properties of viruses have been isolated in cultures of human or simian renal cells from the blood or throat washings of five cases of typical measles. Multiplication of the agents in vitro is accompanied by characteristic changes in the cells. Primarily these changes consist in the formation of syncytial giant cells wherein the chromatin assumes a marginal position and is replaced centrally by an acidophilic substance of unknown nature. The cytopathogenic effect of at least one of the agents is inhibited by convalescent phase measles sera from other patients with measles. Antigen appears during cultivation in vitro of the measles agents that reacts specifically in complement fixation tests with convalescent phase measles sera.

1. The rates of absorption of D(-), L (+), and DL-alanine from the gastrointestinal tract of white rats were found to be 85, 110, and 112 mg/100 g of body weight/ hour, respectively. All 3 were approximately equal in their ability to form liver glycogen, maximum values were obtained 6 hours after administration. Cortisone administration had no effect upon the rate of alanine absorption. 2. When DL-alanine was fed to rats at the same time as 5 or 2.5 mg of cortisone was injected no increase in liver glycogen was obtained over the sum of the amounts formed when each of the substances was given separately. When DL-alanine and cortisone was administered so that the peak of glycogen formation for each compound was reached at the same time then there was a significant increase in glycogen formation over the sum of the independent actions of the 2 compounds.

Data are submitted concerning the changes in cardiac output, systolic output, pulmonary ventilation, oxygen consumption, and oxygen content of the mixed venous blood of the right heart following intravenous administration in anesthetized dogs, of 2 radioprotectors, cysteine and cysteamine. 1. Cysteamine (= β-mer-captoethylamine = Becaptan Labaz), for doses of 10-40 mg/kg, generally increases the cardiac output and the systolic output from 10 to 75% of control values. Heart rate and femoral blood pressure are unaffected. No significant change is noted in the oxygen content of the mixed venous blood. 2. The effects of cysteine are as follows: a) For doses of 20-80 mg/kg, the cardiac and systolic outputs do not change significantly; blood pressure, heart rate, and oxygen blood content remain at control values, b) Doses of 320 mg/kg in 2 of 3 dogs induce a large decrease in both cardiac output and stroke volume. In all cases, the oxygen content of the mixed venous blood is reduced, most conspicuously 5 minutes after the injection. 3. Equiprotective doses of cysteamine do not decrease the oxygen content of the mixed venous blood. 4. It is concluded: a) that the remarkable protection afforded against X-rays by β-mercaptoethylamine is not due to tissular anoxia, b) that the temporary anoxia produced by large doses of cysteine can explain only partially the radioprotective action of the substance.

Chlorpromazine- (dime thylamino-1-n propyl-3) - N - (2-chloro) - phenothiazine HCl in doses of 10 mg/kg injected subcutaneously protected dogs against vomiting after 800 r x-radiation. Injections of 5 mg/kg were ineffective as were 10 mg/kg prepared from solutions allowed to stand for 2 hours at room temperature before injection. Cysteinamine (200 mg intravenously) had no or questionable protection whether given before, during, or after radiation. Increased survival time was noted with both chlorpromazine and cysteinamine. The mechanism of protection is discussed.

Soybean sterols inhibit the increase in blood cholesterol of rats receiving a diet containing 2% cholesterol and 1% sodium taurocholate. The degree of inhibition increased as the soybean sterol concentration of the diet was increased. It was also observed that pancreatic cholesterol esterase catalyzes the esterification of soybean sterols albeit at a slower rate than with cholesterol. Bile salts and a fatty acid source are required for their esterification. The mechanism of action of soybean sterols in inhibiting cholesterol absorption is discussed.

Heparin causes a clearing of the lipemic serum of normal and, less, of depancreatized dogs. In normal animals with alimentary hyperlipemia, this clearing is associated with a decrease in the lipid content of the slow-moving lipoprotein fractions, while in the diabetic lipemic dogs, the outstanding change is the appearance of, or sharp increase in, the amount of a fraction “F” migrating faster than albumin and containing large quantities of lipids. The possible significance of these results is discussed.

In the course of studies on the comparative biochemistry of cholesterol metabolism, it became necessary to isolate conjugated bile acids from the bile of several species of animals. Published procedures are based on the use of either single-stage extraction or counter-current distribution(1). The former method does not readily yield a pure product, while the latter requires elaborate equipment. In this communication, a simple adsorption technic for the rapid isolation of the compounds is presented.

Method. The sample of bile is mixed with 20 volumes of absolute ethanol, and the precipitated salts and proteins are removed by nitration. The filtrate and washings are evaporated to dryness in vacuo, with temperature kept below 40°. The brown, gummy residue is taken up in a small volume of methanol, the solution filtered if necessary and applied to an alumina column. (The amount of alumina should be at least 60 times that of the residue.) The column is washed with methanol, and the methanol is collected in fractions. The bile pigments are completely retained on the top of the column, while bile acids, neutral steroids, and fats wash through rapidly. Occasionally the retention of bile pigments is not complete, and when this occurs, larger quantities of alumina in a wide column of high flow rate should be used. The first fraction collected often has a yellow tinge which, however, does not interfere with the subsequent steps. Each fraction is evaporated to a small volume, and excess anhydrous ether is added. The conjugated bile acids precipitate out as a white, flocculent powder, while the neutral steroids, fats, phospholipids, and unconjugated bile acids (if present) remain in solution. (Failure to employ anhydrous ether may result in a gummy, hygroscopic precipitate of bile acids.)

It has been observed that the reproductive mechanism of A. fischerii is more sensitive to x-irradiation at all measured dosage levels than is the luminescent system of this organism. These findings indicate that cells sterilized by x-irradiation are capable of metabolic activity for a measurable length of time after exposure.

1. Data are presented showing that the MEF1 (Type 2) baby mouse adapted strain of poliomyelitis virus can be lyophilized with little loss of infectious activity. The same appears to be true of the Leon (Type 3) mouse adapted strain. 2. Heating the dry MEF1 virus indicates that, although part of the viral population appears to be relatively heat labile, a measurable proportion of the virus particles is quite resistant to heat. 3. The epidemiological implications of the possible presence of dry poliomyelitis virus in nature are discussed.

The particles of the MEF1 poliomyelitis virus, grown in monkey-kidney tissue culture, and subsequently purified by chemical and physical means, are spherical in shape and highly uniform in diameter. The diameter of individual particles, prepared by normal air-drying from a 0.1 M ammonium acetate suspension, is found to be 31 mμ. The diameter of particles packed in a crystalline array, or frozen-dried from a 0.1 M ammonium bicarbonate suspension, is found to be 21 mμ. It is believed that the latter diameter is the more significant and reliable figure.

A new sensitive and objective method for the turbidimetric assay of tyrosinase activity in frozen skin sections is described. The procedure involves the dispersion of both melanin and skin and hair keratin, from previously incubated sections, in hot molar Na₂S and KOH. Turbidimetric readings are then obtained on the absolute scale of the Klett-Summerson photoelectric colorimeter. This method is immediately useful for determining order of effect, and, if sufficiently improved, might also be useful for comparing amounts of naturally occurring pigment in different skin and hair samples.

The anticoagulant effects of a sulfated polysaccharide, the sodium salt of the sulfuric acid ester of chitin, have been described. It has an in vivo potency 1/4 to 1/5 that of heparin activity. Duration of action and toxicity are both directly related to average molecular weight. The occurrence of toxic side reactions in the dog are similar to some of those reported in the human for another sulfated polysaccharide. Limitations of potential clinical usefulness are discussed.

The nucleic acid content per cell of chick livers was found to be unaltered as a consequence of infection with herpes virus. The distribution of the nucleic acid between ribosenucleic acid and deoxyribonucleic acid is the same in normal and infected tissues. The intracellular distribution of nucleic acids was determined and the data suggest a remarkable stability of the nucleus of the infected cell. Within the extent of the investigation, the nucleic acid pattern of the Ehrlich ascites tumor after infection with influenza virus was found to parallel that of the herpetic liver cell.

1. In the adult castrate rat, oil injections of 19-nortestosterone cyclopentylpropionate produced decreases in urinary N excretion comparable with those obtained with testosterone propionate. 2. This compound caused greater retention of N than was observed with parenteral administration of methylandrostenediol or androstanolone when given at 1/8 the dose of the 2 latter compounds. 3. 19-nor testosterone cyclopentylpropionate in a single injection of 2 mg produced retention of N lasting several days; unesterified nortestosterone, similarly given, did not result in significant N retention.

1. As long as the diet was ingested the addition of 3% aluminum hydroxide gel did not prevent hypercholesterolemia or atheromatosis in cholesterol-fed chicks. Neither did such a diet result in inanition or paralysis. 2. Normal cholesterol values, inanition, and paralysis developed with rejection of the diet. The stress of inanition did not produce hypercholesterolemia in chicks. 3. Neither cortisone acetate nor boric acid influenced the development of arterial lesions, although the latter had some effect on lipid deposition.

Using a previously described spot-spray technic, more than 400 simple, aromatic compounds were investigated as inhibitors of tyrosinase. 4-Chlororesorcinol inhibited melanin formation from tyrosine, DOPA or epinephrine at a concentration of 10^-9; it was thus 20,000 times more potent than resorcinol.

In mice under 18 days of age, encephalitis and death invariably follow intraperitoneal injection of large doses of neurotropic-WS influenza virus. Older mice show varying degrees of resistance to infection. In general, decreased susceptibility is characterized by longer incubation periods and high proportion of survivors. The virus titer in infant mouse brain rises more rapidly and attains a higher level than in adult mouse brain. In addition, the degree of susceptibility may also be a function of the number of virus particles actually reaching the brain after intraperitoneal injection.

The existence in blood of an enzyme in relatively large amount, that accomplishes the hydrolysis of biocytin (∊-N-biotinyl-L-lysine) tentatively termed biocytinase has been pointed out. The enzyme has a pH optimum at 6.0-6.7 and requires for optimum effect the presence of an appropriate sulfhydryl compound.

Concentrations of steroids in arterial and venous blood of the adrenal have been determined. Those steroids whose concentrations in the blood are increased by passage through the gland are considered to be adrenal secretory products. Three steroids are consistently of adrenal origin: 17-hydrox-ycorticosterone, Fraction 8, and corticoster-one. In 2 of 3 experiments 11-desoxy-17-hy-droxycorticosterone was contributed to the blood by the adrenal gland. A steroid less polar than corticosterone (Fraction 13) also appeared to be an adrenal secretory product in 2 of 3 experiments. Five substances (Fractions 2, 5, 77 9, and 10) are clearly not secreted by the adrenal gland, since they were found in the same concentrations in arterial blood as in adrenal venous blood. The status of 4 substances (Fractions 1, 3, 4, and 14) as adrenal secretory products has not been established. 17-Hydroxycorticosterone and corticosterone, when added to arterial blood, are recovered without substantial alteration in the pattern of steroids present in such blood.

Periods of anoxia ranging from 1 to 20 minutes were induced in unborn rats by preventing the initiation of respiration before removing the full term fetuses from the uterus. Beginning at 65 days of age, the experimental and control animals were tested on the Hebb-Williams closed maze. In a series of 12 standardized tests the experimental rats made more errors than the controls (p = .06). The inferiority of anoxic animals was most marked in the final set of 6 tests during which they were significantly inferior to the control group (p = .04). Control rats displayed progressive improvement in performance in successive maze problems, but no such improvement was evident in the records of experimental cases. It appears that oxygen deprivation at the time of birth tends to reduce the rat's ability to transfer prior learning to new situations. Within the experimental group, however, there was no relationship between the duration of the anoxic period and the extent of deterioration in maze performance with respect to either total scores or improvement in successive tests.

Lysis by phage of germinating spores of Streptomyces griseus has been observed and photographed under the phase microscope, bright phase-contrast. The time required for complete lysis of a young hyphal cell is about 15 minutes.

1. Intraperitoneal injections of carbon tetrachloride in rats fed a dl-tryptophane supplemented nicotinic acid-deficient diet lowered urinary excretion of nicotinic acid, quinolinic acid and N-MN. 2. Liver homogenates of normal rats converted tryptophane to quinolinic acid more efficiently than that of carbon tetrachloride-treated rats. 3. It is suggested that liver is the principal site of synthesis of nicotinic acid and quinolinic acid from tryptophane.

1. A study of the beginning and development of the EEG in 73 chick embryos is made. 2. “Spontaneous” electrical activity and that produced by strychnine appear simultaneously on the 13th day. 3. “Spontaneous” activity undergoes changes during the course of embryonic development. The “early” rhythm appearing on the 13 th day gradually increases in frequency and voltage and becomes more constant. On the 16th day the high voltage “late” rhythm appears, becoming more constant on subsequent days. 4. Strychnine causes the appearance of spikes, which are generally biphasic, and increases the amplitude, frequency and constancy of the “spontaneous” activity in most experiments. 5. With development of the embryo, the strychnine spikes become of shorter duration and higher voltage, pointing to a better synchronization of the neurones. Frequency increases and spikes begin to appear earlier as the embryo grows. 6. From the 14th day spike discharges are to be seen in the embryonic brain, similar to the epileptic discharges produced in man and animals by certain agents like anoxia, strychnine, metrazol, and drying. 7. The bioelectric development is compared with the histological, cytological, and biochemical development of the brain, and with the physiological activity of the embryo.

1. Heparin was found to inhibit in vitro the agglutination of red blood cells in 3 consecutive cases of idiopathic acquired hemolytic anemia. 2. Following incubation of patients cells with heparin, the auto-agglutination disappeared. The Coombs reaction also became negative while the anticoagulant activity of heparin greatly diminished. The heparin tolerance, tested in the first 2 cases, was abnormally high. 3. No interaction in vitro was observed between heparin and iso-agglutinins. 4. The possible mechanism, specificity and clinical value of the reaction is discussed, and certain implications with respect to the clotting mechanism are pointed out.

Use of the anthrone reagent offers a sensitive and accurate method that can be applied for the estimation of microquantities of inulin. Steps are given to prevent interference by glucose through the means of controlling the temperature of reaction. Boiling in alkali cannot be used to eliminate glucose because of an irregular distribution between blood and urine of the alkali labile fraction of inulin.

Blood cell counts were compared in samples drawn simultaneously from the aorta, right ventricle, superior vena cava, caudal vena cava, hepatic vein, and/or peripheral veins in dogs. The study was done on normal and splenectomized dogs, either un-anesthetized or anesthetized with pentobarbital. No differences in erythrocyte or leukocyte distributions were demonstrated as a result of anesthetization or splenectomy. The erythrocyte and leukocyte counts were the same in arterial and venous blood samples and in venous samples from different major vessels. Some factors are discussed which may be responsible for apparently contradictory reports concerning cell count distribution in circulating blood.

1. Cortisone, when administered during the first few days after transplantation of carcinoma 755 in C57 mice, has a profound inhibitory effect on growth of the tumor but the tumor remains viable. 2. These effects of cortisone appear to be due to the change in the environment and to the delay in new blood vessel formation about the tumor transplant.

1. Accumulation of At²¹¹ by thyroid gland in patients suffering from various disorders of that organ has been demonstrated. 2. Accumulation of At²¹¹ by thyroid glands of these patients appears to be relatively higher than has been observed in experiments employing rats. 3. There may be a correlation between the uptake of At211 and stable iodine in thyroid tissue. 4. One patient with papillary adenocarcinoma showed no discernible accumulation of At²¹¹ in metastases present in cervical lymph nodes.

A study has been made of the accumulation of I¹³¹ and At²¹¹ in normal and propyl thiouracil-treated rats. A very marked enhancement of the accumulation of At²¹¹ in the thyriod gland has been observed following administration of propyl thiouracil. This is in contrast to the diminution of the uptake of I¹³¹ by the thyroid glands of the rats receiving propyl thiouracil.

Labeled fuadin prepared from neutron irradiated antimony trioxide has been used in a study of the localization of antimony in the red cell fraction of rat blood. The results are consistent with the hypothesis that the antimony is attached to the globin portion of hemoglobin.

A polysaccharide preparation derived from autoclaved cells of Candida albicans or saline washings of unheated cells has been shown by quantitative immunogolic methods to contain a common antigen shared with Saccharomyces cerevisiae and a type-specific Candida polysaccharide antigen. Antiserum obtained from rabbits immunized with heat-killed Candida albicans or Saccharomyces cerevisiae contains considerably more antibody reacting to the common antigen than to the type-specific antigen.

White rats, originating from the Wistar strain, did not become obese following injections of gold thioglucose under experimental conditions that have resulted in obesity in 4 strains of mice studied. It is possible that genetic factors influence the capacity to develop obesity after injection of gold thioglucose.

An apparatus is described for infusion of small volumes of test solutions directly into tissues and organs. In more than 3000 successful infusions of the early regenerating limb of salamanders, volumes of 0.001 cc per hour have been introduced for periods of 5 or more hours. The apparatus consists of an advancing bar which is driven forward by a screw shaft attached to a clock motor. The advancing bar presses against the plungers of small syringes forcing fluid into fine polyethylene tubing and thence through a glass capillary needle into the tissues.

Three rodent-adapted strains of poliomyelitis virus, all belonging to the same immunologic type, were found to differ in their thermostability; these were, in decreasing order of resistance, Y-SK, MEF1, and Lansing. The differences between these strains became evident only when they were suspended in cream or ice cream before being heated. All three strains suspended in water were inactivated by heating at 71.1 °C for 15 seconds. When heated in cream the viruses withstood 79.5°C for 15 seconds and in ice cream they withstood 82.2°C for 25 seconds, with Y-SK resisting inactivation to the greatest extent.

A standardized method for the measurement of clotting time on surfaces of different materials has been described. Several glass, plastic, and stainless steel surfaces, and surface coating agents, were studied for their comparative effects on the clotting of whole human blood. The results may provide an indication, with regard to clotting, of the suitability of these materials for use in the construction of blood systems and vascular prostheses.

1. On the basis of heat stability studies, the clotting properties of brain tissue extracts are due to 2 components: a) a throm-bokinase, which has the ability to convert prothrombin directly to thrombin, and b) a thromboplastin, which is an accessory factor and must react first with another plasma factor, such as proconvertin, before it is capable of converting prothrombin to thrombin. 2. The indirect effect of thromboplastin must be distinguished from the direct action of thrombokinase on prothrombin if the mode of action of so-called “thromboplastin” brain tissue extracts is to be understood.

1. The serum protein-bound carbohydrates and the serum protein fractions were studied in diabetic patients with retinitis proliferans. The serum protein-bound carbohydrates were found to be present in a higher concentration than in non-diabetes. By the method of paper electrophoresis, a definite decrease in the values for the albumin + α₁-globulin fraction and an increase in the α₂-globulin fraction was also found in all of the diabetics, although only those with both retinitis proliferans and proteinuria showed a decrease in the total protein. In the β-globulins no essential change was seen. In the group showing both retinitis proliferans and nephropathy, the γ-globulin concentration tended to be lower than in the group with retinitis proliferans alone, but none of the groups had values distinctly different from those of non-diabetics. 2. It is concluded that disturbances in the protein pattern exist which particularly involve the albumin and α₂-globulin fractions at a stage in the development of the diabetic vascular lesions where the changes cannot be accounted for by loss of protein in the urine.

Ability of the albino rat to adapt to stress of light restraint was investigated. Rats were able to adapt to the stress of restraint (for one week) in a cylinder of wire mesh so that they did not become hypothermic when exposed to the stress in the cold. The possible roles of emotional adaptation and adrenal cortical activity in producing the increased resistance to these stresses are discussed.

Both hypothermia and restraint were independently capable of decreasing the concentration of liver NPSH. When these stresses were applied simultaneously, the effect of the two stresses was approximately additive. No significant change of NPSH was observed in the muscle and kidney. The possibility that the more immediate cause of the drop in concentration of liver NPSH was activation of the sympathoadrenal mechanism is discussed.

Testosterone propionate after an initial latent period of 3 days causes a decrease in the urinary nitrogen excretion associated with an increased weight gain in the thyroidectomized rat fed a constant intake. Escape during continued treatment, and a “rebound” after the cessation of treatment occurs in the thyroidectomized rat just as it does in the normal, castrated or adrenalectomized rat.

A specific and sensitive method for the measurement of cinchophen in biological fluids and tissues is described. Cinchophen is essentially completely absorbed from the gastrointestinal tract. The drug is almost entirely metabolized in man, only about 2% being excreted in the urine. The rate of biotransformation of cinchophen is fairly uniform, among a number of subjects the average half-life being 4 hours. Cinchophen is localized in most organ tissues. The drug is largely distributed in extracellular fluid and at low concentrations is highly bound to plasma proteins.

Eosinophil counts were made on tail blood obtained at two times of day from male Line 3 Black rats kept under standardized circumstances and subjected either to splenectomy or to a sham-operation. Eosinophilia was seen to develop during the first few months after operation and to regress during the fourth month after operation. Irrespective of the degree of eosinophilia, the mean eosinophil counts of the groups of rats studied were higher by day than by night. In the strain of rats studied, the presence of the spleen is not essential for the maintenance of the eosinophil rhythm.

1. Results of cross agglutination-lysis and cross agglutinin-absorption studies indicate that the etiologic agent of Fort Bragg Fever is closely related to the other members of the leptospiral serogroup autumnalis. 2. Agglutinin-absorption studies with all members of the serogroup autumnalis reveal that the agglutinins responsible for strain specificity are not completely removed when absorbed with any of the other strains. 3. Classification of these leptospiral strains on the basis of a modified adoption of Wolff's scheme(5) designates autumnalis Akiyami A as the “incomplete” biotype of the Fort Bragg isolate and discloses L. autumnalis A Rach-mat, in addition to L. bangkinang, as a heterologous serotype member of the autumnalis group. 4. The Fort Bragg isolate is therefore designated as L. autumnalis, Fort Bragg.