Experimental Biology and Medicine

1. Incidence of thymic leukemia in AK/Z mice injected as newborns with Gross leukemia virus(agent A) was 90% and the peak incidence of the disease occurred at 3-4 months of age. Incidence of leukemia in the controls was 73% with a peak occurrence at 8-12 months. 2. Thymuses from 52 sacrificed virus-injected AK/Z mice were examined at 13-72 days of age. No gross or microscopic abnormality was noted until about SO days, when multiple foci of medium to large lymphocytes appeared in the cortex. These foci rapidly became confluent and at about 70 days of age, the thymus was transformed into a lymphomatous tumor. 3. Bioassays of 22, 57-74 day old thymuses from virus-injected mice disclosed autonomous leukemic cells in 10. Correlation of microscopic and bioassay diagnosis of malignant transformation was somewhat below 100%. Some thymuses, which were judged to be leukemic “in situ”, were not transplantable. 4. Bioassays indicate the presence of virus in non-leukemic thymuses of virus-injected mice. 5. It is concluded that the pathogenesis of virus-induced thymic lymphoma is similar to that of “spontaneous” lymphoma in the high leukemic strain but occurs at an earlier age.

The effects of a series of steroids on the carbohydrate metabolism of the bird were studied using blood glucose and liver glycogen as endpoints. The highly active compounds in the hyperglycemic reaction were hydrocortisone and corticosterone and the active compounds in the liver glycogen test were the above two plus 11-dehydrocorti-costerone. Cortisone was inactive in both tests and 11-desoxycorticosterone acetate was tested only in the hyperglycemia reaction and was inactive. If hydrocortisone is assigned an activity of 100 in the glycogen test, then corticosterone shows an activity of 12.5 and 11-dehydrocorticosterone an activity of 1. In direct contrast to the mammal, cortisone is inactive in the bird. Testosterone appears to lower blood glucose but this apparently is a result of an increase in red blood cell number rather than an absolute drop in glucose present in the blood. Stilboestrol had no effect on blood glucose levels.

1. Influenza and Newcastle Disease Viruses are adsorbed to red blood cells and to platelets in a similar manner. Evidence is presented indicating that there exists similar virus receptors on the surface of the red blood cells and of the platelets. 2. Virus is adsorbed to platelets in the absence of cations as well as after its previous elution and after RDE treatment of platelets. Furthermore elution of the virus from platelets is much slower and less complete than that from red blood cells. These phenomena may be due to incorporation of virus particles into the platelets.

Guinea pigs infected intra-nasally with human(HA-1) and bovine(SF-4) strains of para-influenza 3 virus produced 4-fold or greater HI, N and CF antibodies to the homologous strain than to the heterologous strain. Children and cattle showed similar species-linked responses following infection with para-influenza 3 viruses. Human and bovine strains of the virus originating from various states and foreign countries and isolated in different years were shown to react in the same manner as the HA-1 and SF-4 prototype strains.

An increased antihypertensive action of a combination of reserpine and acetazolamide over that produced singly by either drug was demonstrated in metacorticoid hypertensive rats. Acetazolamide alone had a moderate antihypertensive action, and the enhanced reduction in blood pressure following co-treatment was an additive rather than a potentiated effect. The typical hypertensive left ventricular cardiac hypertrophy was significantly reduced in the metacorticoid rats receiving acetazolamide-reserpine.

1. Adult mice of the Z(C3H) strain have been made tolerant of skin homo-grafts of the(A X Z) F₁ hybrid strain by repeated intravenous and intraperitoneal injections of homologous spleen cells. 2. Repeated intraperitoneal injections of homologous spleen cells generally failed to induce a tolerant state, although 3/75 recipients accepted the homologous skin homotransplant.

1. Female mice of the C57B1 (Subline 1) strain capable of rejection of small male skin isografts regularly accepted large male skin isografts. 2. Large homologous skin grafts between genetically closely related strains were regularly rejected as were small skin homografts. 3. Large skin homografts between strains of mice characterized by strong histocompatibility differences regularly resulted in early death of the recipient. 4. Tolerance of C57B1(Subline 1) female mice to male skin isografts induced by spleen cell injection could be transferred by injection of spleen cells from tolerant donors to new females during the post-neonatal period. Attempts to transfer tolerance induced with a large skin graft were unsuccessful.

Experiments were undertaken to determine male skin isograft survival in multiparous female mice of the C57B1(Subline 1) strain, as compared to virgin controls. No significant difference in male isograft acceptance was found in multiparous mice as compared to that in virgins.

Phases of enhanced resistance and susceptibility to Newcastle disease virus were induced in chick embryos by infection with E. coli. These effects were duplicated by treatment of embryos with E. coli endotoxin at appropriate times.

Six of 8 amino acids tested at concentrations of 10²-10³ M demonstrated significant inhibition of glucose uptake by adipose tissue. This inhibitory action was diminished as amino acid concentration was further decreased.

1. Smilagenin fed to lambs at levels of 2, 4, 8 and 24 g per ton of complete feed improved growth rate and feed efficiency. The most consistent results were obtained with 8 g per ton, or approximately 12 mg per lamb per day. Dressing per cent and carcass grade tended to be improved by addition of smilagenin. Ground Agave lecheguilla containing smilagenin in the saponin form appeared to be quantitatively similar to the free sapogenin; however higher levels of the isolated saponin depressed performance. Sarsasapogenin or hecogenin at 8 g per ton in separate tests exerted a growth effect comparable to that from smilagenin. Diosgenin and tigogenin were not beneficial under conditions tested. 2. In 2 trials, steers fed 20 mg of smilagenin daily showed weight gains similar to those of animals receiving 10 mg stilbestrol daily. In one trial, 100 mg of smilagenin was not as effective as 20 mg.

Heparin S³⁵ was extracted from the liver of dogs administered inorganic Na₂S³⁵O₄. Distribution of this heparin was determined in rats. The mast cells were found to take up injected heparin S³⁵, and radioactivity persisted in liver and spleen after virtual disappearance from plasma. Anticoagulant activity was found to parallel isotope activity of the plasma of dogs injected with heparin S³⁵. Urinary excretion in dogs accounted for only about 20% of the injected isotope at a time when plasma anticoagulant activity had returned to normal.

The activities of carbamyl phosphate synthetase, ornithine transcarbamylase and arginase have been found to be unchanged in regenerating liver of thyroidectomized rats. Complete thyroidectomy results in an impaired rate of liver regeneration. Daily injection of thyroxine during the regeneration period restores the capacity of the liver to regenerate.

Pre-treatment of mice with different preparations of zymosan modified the lethal effect of a subsequent endotoxin challenge, ranging from increased resistance to increased susceptibility, despite equivalent RES stimulation. Source and degree of heating in preparation for injection were determinants. Greater relative sensitivity to i.v. than to i.p. challenge was found regardless of the zymosan used. Protection was not attributable to endotoxin contamination or to stimulation of serum antibody titer to the challenge. Zymosan produced a monophasic fever in the rabbit, differing from the biphasic endotoxin fever, and did not elicit an acute leucopenia.

An infusion-withdrawal apparatus is described which eliminates the necessity for long cannulae between syringes and experimental animal and permits multiple infusion and withdrawal to be carried out simultaneously. Engineering plans are available from the senior author.

Rabbits have been placed in a low O₂ atmosphere for varying periods of time and plasma erythropoietin content determined after set intervals of hypoxia. EPF was found to rise significantly at 8 hours, reach peak levels at 24 and 48 hours, and return to normal at 72 hours.

A microbioassay for acetylcholine is described in which a solution containing acetylcholine is microperfused onto the endplate area of a chronically denervated skeletal muscle fiber. The endpoint, a brief tetanus, can be produced by application of as little as 0.15 μl of a solution which contains acetylcholine chloride at a concentration of 2.5 × 10^-8 moles/1.

Electrophoretic and immunologic studies on the partitions of the sera of laying hens and of cocks and egg yolk obtained by ultracentrifugation showed the presence of 2 specialized components, (a low density phospholipo-P-free protein and a phosphoprotein or a phosphoprotein complex) either in the serum of laying hens or in egg yolk, which were not found in the serum of cocks. Each component was capable of producing the specific antibody or antibodies. The specific antibody or antibodies to one specialized component could not be exhausted by absorption with the other component of the serum. Low density phospholipo-P-free protein, found in the top layer of the serum of laying hens, obtained by ultracentrifugation is almost identical with that found in the supernatant solution of egg yolk obtained by ultracentrifugation. This protein is a single antigenic substance as shown by the appearance of only one precipitin zone in the agar-antiserum gel. Phosphoprotein or phosphoprotein complex, found in the sediment of the serum of laying hens, is not identical with that found in the sediment of egg yolk, since the former is soluble in isotonic saline, while the latter is quite insoluble in isotonic saline. The pattern of precipitin reaction zone to the material in sediment of serum in agar-antiserum gel, which showed several zones, differed from that to the material in sediment of yolk.

The dose-response relationships which describe the effects of small amounts of vasopressin on femoral arterial pressure and flow have been presented. The IA and IV routes of administration were examined in 5 experiments on anesthetized dogs. The decrease in flow following IA administration and the secondary decrease in flow following IV administration have been attributed to vasoconstriction in the vascular bed supplied by the femoral artery. The primary increase in flow following IV administration has been discussed in terms of elevation of central arterial pressure and reflex vasomotor activity. It is postulated that sub-maximal antidiuretic amounts of exogenous vasopressin are vasoactive.

Biological decay curves of Na²² excretion showed good correlation with urinary sodium excretion during alteration of sodium excretion by sodium chloride, DCA and hydrochlorothiazide over periods of 3 to 7 days. During these short intervals, biological decay curves of serum radioactivity and serum specific activity were too variable to allow correlation with urinary sodium excretion. Daily total exchangeable sodium shows a progressive rise and cannot be used to reflect acute changes in sodium balance.

A striking depression in rate of flow of the nasal mucous blanket was observed in 4 water-deprived herring gulls, in contrast to 10 normally hydrated gulls. The observation was repeated in a series of 20 water-deprived and 10 normally hydrated chickens. In both species normal mean rate of flow was about 10 mm/minute. Two gulls and 2 chickens that were deprived then rehydrated showed a normal rate of motion of the blanket. Anchoring of the mucous sheet to the mucosal surface by fine strands of mucus was seen in whole mounts and histological sections of conchae of dehydrated baby chicks.

Uteri of ovariectomized immature mice did not show subnormal growth. No increase in uterine sensitivity to estrogen was observed at about the age of expected puberty in comparison to those of ovariectomized immature rats.

Rabbit anti-rat kidney sera, in a prescribed dosage, injected intravenously into pregnant rats on the 8th day of gestation. resulted in severe congenital malformations in 100% of the fetuses. Larger doses caused complete fetal resorption. These antisera may produce teratogenesis by interfering with placental function.

The incorporation of glycine-U-C¹⁴, glutamic acid-U-C¹⁴, glutamine-U-C¹⁴, cystine-S³⁵ and glutathione-S³⁵ into the major mercaptide conjugate of sulfobromophthalein (BSP) was studied in bile from isolated perfused rat liver. Incorporation of label from each of the amino acids was demonstrable in the purified metabolite obtained after 3 serial chromatographic steps, whereas control fractions were negative. Acid hydrolysis of the metabolite and subsequent paper chromatography revealed that the amino acids had been incorporated intact, that 3 M of amino nitrogen were released for each M of BSP, and that glycine and glutamic acid were in equimolar ratio (cysteine was degraded during hydrolysis and could not be quantitatively recovered). High concentrations of cysteine in the perfusate did not compete with glutathione for the synthesis of BSP mercaptide. It was concluded that BSP is secreted into bile, at least in part, as a mercaptide conjugate with glutathione.

A number of urea derivatives added at low concentrations to plasma before or after clotting induce spontaneous dissolution of human plasma clots. They also considerably enhance the activity of urokinase. Ethyl urethan was the most active compound of the group. Bovine fibrin clots are dissolved by ethyl urethan only in presence of human plasma.

Data have been presented confirming experimental production of phenylketonuria in rats. Supplementation of the diet with both phenylalanine and tyrosine resulted in a marked increase of phenylpyruvate excretion in urine and of phenylalanine level in plasma. Supplementation with 2.5% DL-phenylalanine alone showed a much less marked effect. The rise of phenylpyruvate coincided with a decrease of 5-hydroxyindole-acetic acid in the urine. Similarly, the increase of phenylalanine in the plasma coincided with a decrease of 5-hydroxytrypta-mine in the plasma. This indicates that the disturbance of 5-hydroxyindole metabolism in phenylketonuria is secondary to the increase in phenylalanine. The possible significance of these phenomena in the etiology of mental deficiency and phenylketonuria has been discussed.

2-deoxyglucose(2-DG) causes marked release of adrenaline from the adrenal medulla in the intact rat but not after adrenal denervation. The adrenaline released is to a great extent responsible for the hyperglycemia appearing after 2-DG, but other factors might also be involved. The inability of 2-DG to cause increased adrenaline secretion after denervation of the adrenal glands points to its action via a centrally located receptor mechanism regulating adrenaline secretion; this center seems not to be sensitive to the blood glucose level as such.

A new method for portal venography by retrograde hepatic vein flushing was described. Application for the study of human cases is in progress.

The susceptibility of primary feline renal cell cultures to 24 viruses is reported. Of these, infectious bovine rhinotracheitis, vesicular stomatitis, equine abortion, vaccinia, herpes, Sendai, ECHO 10, and adenovirus 4 were shown to produce marked cytopathic effects with multiplication. Canine hepatitis virus, Coxsackie B-l through B-5, adeno 3 and 7, and parainfluenza III(SF-4) were cytopathogenic for one or more passages but did not multiply. The polio-viruses, Newcastle disease, ECHO 4, and Coxsackie A-9 had no cytopathogenic effect on the cell, and there was no evidence of viral multiplication.

The acid hematein lipoprotein staining was used on non-neoplastic and neoplastic human uterine biopsy specimens. Epithelioma cells are conspicuously unstained, while epithelial cells and other tissue cells show a positive reaction.

1. Mouse plasma lipid and lipoprotein fatty acids were evaluated by gas chromatography. 2. The plasma cholesteryl ester fraction contained a high percentage of polyunsaturated acids, linoleic (50.1%) and arachidonic (29.9%). 3. Mouse fatty acid data were compared with human values. 4. Concentration of albumin-bound NEFA in mouse plasma was found to be significantly higher than normally present in humans.

These in vitro experiments show that both magnesium and calcium in muscle can contribute to the buffering of pH. In low pH solutions there is a decrease in both calcium and magnesium, and in high pH solutions there is an increase in both calcium and magnesium in muscle.

Tissue resistance to peptic digestion is decreased significantly by pitressin and nitroglycerin and by large doses of hydrocortisone. Reserpine, pitressin and nitroglycerin produced decreased esophageal blood flow. These experiments suggest definitely that decrease in blood flow abets the ulcer diathesis.

Rigidly controlled experiments on middle-aged men subsisting on diets of natural foods with and without supplements of 15 g daily of either cellulose(fiber) or pectin failed to show any significant effect on serum cholesterol concentration from the cellulose but they did consistently show an effect from the pectin. The pectin effect was apparent in 3 weeks and amounted to an average fall of about 5% below the level on the same diet without pectin supplement. It is suggested that the amounts of cellulose and pectin used correspond to the upper levels of these substances provided in natural human diets.

1. Intraocular ovarian isotransplants in ovariectomized lactating BALB/c mice showed little growth and developed only vesicular follicles in the first part of the lactation interval. The first vaginal estrus occurred between 17 and 21 days after parturition, followed by abrupt appearance of pink or red corpora lutea. 2. These atypical corpora persisted from 5 to 8 days, concurrently with vaginal diestrus. They then became white and a second vaginal estrus occurred, unaccompanied by red corpora. Transplants showed considerable growth between the first and second estrus. 3. Similar transplants in ovariectomized virgin females developed vesicular follicles and corpora lutea from the 10th day onwards, with more or less normal estrus cycles. Corpora were typically white. Growth of transplants was moderate but continuous. 4. It is suggested that red corpora lutea indicate the action of LTH; and that pituitary release of LH, but not of FSH, is inhibited over most of the lactation interval.

Evidence has been presented to show that concentrated measles virus in presence of monkey red blood cells will demonstrate the phenomenon of hemagglutination. Baboon kidney propagated measles virus yielded higher levels of hemagglutinin than measles virus grown in other primate tissue. Chick tissue propagated measles virus did not demonstrate hemagglutination. Specific inhibition of hemagglutination was demonstrated by rabbit and guinea pig antisera prepared against measles virus in our laboratory and in another laboratory, by naturally occurring simian measles antisera, by human gamma globulin and by human convalescent measles antisera. Inhibition was not observed when measles CF negative simian sera, measles acute human sera and a number of viral antisera were tested.

1. Maximum growth of the lobule-alveolar system of mammary gland, as measured by total DNA, in ovariectomized female and estrogen-primed male mice(to develop duct system) was observed when 1 μg estradiol benzoate and 3 mg progesterone were administered daily for 19 days.(2) Maximum total DNA experimentally stimulated in female mice, on an equal weight basis, was only 57.6% of the DNA observed in normal mice pregnant 18 days.(3) Corresponding value for males was 48.3%.(4) These data suggest that a hormone of placental origin may be involved in mammary gland growth other than ovarian hormones.(5) On an equal body weight and gland basis, the mammary glands of mice at end of pregnancy contain approximately 150% as much DNA as do rats.

Mice were vaccinated by repeated subcutaneous inoculations of living, merthiolate-killed, or sonically-ruptured cells of C. albicans and were then challenged intravenously with 10⁴ or 10⁵ viable particles of a homologous strain. Although not all of the vaccinated mice survived challenge, a significant degree of resistance was conferred since fewer deaths occurred among vaccinated animals.

1. Runt disease in adult mice of the Z(C3H) strain made previously tolerant of A tissue by antigenic exposure at birth was obtained by injecting these animals intravenously with large numbers of immunological competent spleen cells taken from A strain donors. 2. The main pathological findings in these animals were: a) marked body weight loss; b) Splenomegally and c) Atrophy of lymphoid tissue followed by death.

Others have observed the stimulation produced by glucose(8), insulin(9) and electron acceptors(6,10) on lipogenesis in various tissues under oxygen. The present data show that a combination of these materials enhanced the anaerobic conversion of acetate to squalene in pieces of rat skin. The amount of activity incorporated(1620 cpm/g skin) was sufficient to serve as labeled squalene for subsequent conversions of squalene into sterol precursors or the sterols themselves.

In contrast to human skin, rat skin contains relatively little squalene(11), and most of the activity incorporated into the unsaponified fraction of rat skin under oxygen is associated with the sterols rather than with squalene. Aerobic incubation of human skin with acetate, on the other hand, yields substantial amounts of labeled squalene(5,12). Presumably, the yield of labeled squalene by human skin could be increased by an anaerobic incubation in fortified buffers like those used in the present study.

Summary. 1. Rat skin incubated anaerobically accumulated labeled squalene from acetate and only negligible amounts of labeled sterols. Incorporation of acetate into squalene was enhanced markedly by the presence of glucose in the medium. 2. Insulin, ferricyanide and methylene blue enhanced squalene synthesis in vitro in presence of glucose. Increasing amounts of insulin or ferricyanide produced regular increases in squalene synthesis until a plateau was reached; methylene blue on the other hand showed a sharp maximum at 10^-3M, with a decline at higher concentrations. 3. Skin containing labeled squalene accumulated labeled sterol on subsequent incubation under oxygen.

Acute reserpine treatment of guinea pigs, rats and human patients resulted in activation of the pituitary-adrenal cortex axis demonstrated by hypertrophy of adrenals, adrenal ascorbic acid depletion and higher 17-KS and 17-OHCS levels. These changes disappeared during chronic treatment. It is hence suggested that reserpine through its transistory stimulating effect on the pituitary-adrenal cortex axis acts as a non-specific stimulus, which loses its effect on chronic administration.

Multiplication of measles virus has been demonstrated in suspensions of human and simian blood leucocytes. Under the experimental conditions employed the virus failed to multiply in canine, rabbit, guinea pig, mouse and chicken blood leucocytes. Evidence is presented which indicates that multiplication takes place in mononuclear cells.

Erythropoietin of human urinary origin was injected into groups of rats of various ages, after which both measurements of total circulating red cell volume and Fe⁵⁹ red cell incorporation were made. Total red cell volume of young rats throughout the period of neonatal anemia did not increase in response to administration of erythropoietin, whereas it did increase in all older groups. According to this assay, the rat most sensitive to erythropoietin was the oldest rat studied. Using the Fe³⁹ red cell incorporation assay, no increase in erythropoiesis was observed in normal young rats(14 days of age) following erythropoietin administration. However, when erythropoiesis was depressed in young rats by hypertransfusion. red cell uptake of Fe⁵⁹ was greatly reduced. When such hypertransfused rats were injected with erythropoietin, red cell incorporation of Fe⁵⁹ was significantly increased.

1. Rats fed diets containing the incompletely digested carbohydrates, lactose, cellobiose and raw potato starch, excreted larger amounts of organic acids and had a lower content of body fat than rats fed glucose, sucrose or galactose. 2. The predominant urinary organic acids were identified by silica gel chromatography as citric, αketoglutaric, fumaric and succinic acids. 3. Organic acid excretion could be increased by increasing the amount of dietary salt mixture or by adding CaCO₃ but not CaCl₂ to the diet. 4. This latter finding, in conjunction with the results of urinary analysis of ionic constituents, indicated that the increased excretion of organic acid is not a consequence of an altered metabolism that decreases body fat deposition but is a renal acid-base mechanism for neutralization of increased urinary calcium, an increase resulting from the enhancement of gastrointestinal absorption of calcium by incompletely digested carbohydrates.

A moderate increase in serum leucinamidase activity occurred in colostrumdeprived pathogen-free pigs experimentally infected with swine influenza virus. Activity also increased during migration of Ascaris suum larvae through the liver and again when the larvae reached the lungs. Greatest leucinamidase activity was stimulated when influenza virus was provoked from its latent lungworm state by migrating A. suum larvae.

The influence of small oral doses of hydrocortisone analogs on serum and urine 17-hydroxycorticosteroids was studied in 281 human subjects. With the exception of medrol, the drugs produced changes in 17-OHCS which tended to be parallel in serum and urine. The drugs differed greatly in response produced.

Young male rats that differed in body weight by only about 20% had significant(p ≦ .05) metabolic differences during a 3-day fast. These included calcium, phosphate, urea, creatinine, the Na/K, Mg Ca, Ca/PO₄ and uric acid/creatinine ratios. There was an almost 10-fold difference in their respective growth rates, however, which undoubtedly contributed to the differences. These group differences tended to disappear in almost all variables as the fast progressed. The various ratios proved to be quite sensitive to the group differences.

Hemoglobinuria and hemoglobinemia in ewes followed intravenous injection of disrupted L. pomona cells. Hemolysis occurred only in presence of antibody. It is postulated that the hemolytic effect is due to interaction of a cellular component, antibody and red blood cells.

1. Whole body gamma irradiation in the rat produced significant whole blood cholinesterase depression on the tenth day at a dosage level of 75 r. 2. The levels tested when plotted and extrapolated indicated threshold changes in cholinesterase activity would be in the vicinity of 20 to 30 r. 3. AET alone, while producing some mild cholinesterase depression, failed to protect whole blood cholinesterase activity from the effects of gamma irradiation at the levels of agent and irradiation tested.

Experiments were conducted to determine the effects of source of dietary carbohydrate on survival time of mice exposed to multiple sublethal doses of total body x-irradiation. Findings indicate that average survival time of x-irradiated mice was significantly longer on a glucose-containing diet than on rations containing sucrose, dextrin or cornstarch as the source of dietary carbohydrate.

A colorimetric method for estimation of glucose-6-phosphate dehydrogenase activity of erythrocytic hemolysates is described. The method reported employs phenazine methosulfate as an electron carrier between TPNH formed in the reaction and dichloroindophenol. Rate of reduction of the latter compound is followed spectrophotometrically. The method gives turnover rates comparable to those obtained with the ultraviolet spectrophotometric method and is more sensitive than the latter. The assay utilizes a standard spectrophotometer or photoelectric colorimeter and is independent of diaphorase activity. The method should be readily adaptable to visual estimation of glucoses-phosphate dehydrogenase of erythrocytes.

Some physical properties and kinetics of the action of the inhibitor of lactic dehydrogenase of M. phlei, present in spleen and lungs of mice and on the surface of M. tuberculosis H37Rv grown in vivo have been studied. The inhibitor was identified as DPNase.

The use of a feeder layer of x-irradiated or non-irradiated primary human amnion monolayers in cultivation of leukemic and normal human bone marrow aspirates results in establishment of primary, human fibroblastic cell cultures. Comparison of normal and leukemic cultures failed to reveal differences in morphology, type of degeneration, rate of metabolism or viral susceptibility. A cytopathogenic agent was not recovered from leukemic aspirates and use of the fluorescent antibody technic failed to reveal a specific antigen capable of reacting with leukemic sera in leukemic bone marrow cell cultures. Cultures of cells from both leukemic and normal bone marrow supported multiplication of polio, herpes simplex and measles virus. Normal marrow cell cultures supported multiplication of Sindbis and influenza A virus, but not of an egg adapted strain of mumps virus. The reproducible cultivation of cells obtained from human bone marrow provides an accessible source of primary human fibroblastic cell culture that may prove useful in both microbiological and hematological experimentation.

Using typhoid vaccine, soluble typhoid bacillus antigen, and specific agglutinin as a model antigen-antibody system, it has been possible to demonstrate the occurrence of specific antibody in human vaginal mucus as a consequence of active immunization. Vaginal antibody was produced in response to either parenteral or locally applied antigen and the response to the latter kind of antigenic stimulus was superior to that of the former. Vaginal agglutinin appeared earlier than serum antibody, reached a peak slightly sooner, and disappeared in 7-8 weeks though serum antibody persisted, often in relatively high titer. Vaginal antibody response to primary and secondary inoculation appeared to be substantially the same, and was not affected by menstruation or intervening pregnancy.

SLE patients do not possess higher levels of blood group isoagglutinins, Proteus OX-2 agglutinins or antistreptolysin O than other patients or normal individuals. The immunological hyperreactivity of these patients may be restricted, therefore, to circulating autoantibodies and possibly to the delayed or cellular hypersensitivity reaction.

Neurohypophyses of 7 cats were stained for AChE activity by AThCh method. In the infundibular stalk, fibers showed light staining, whereas fibers, their vesicular swellings, and terminations showed moderate staining in the infundibular process of the posterior lobe. No significant AChE activity was noted in the anterior or intermediate lobe. Thus, in conjunction with findings of an earlier study (7), neurons of the hypothalamico-neurohypophyseal tract appear to contain light to moderate concentrations of AChE throughout their full lengths. These findings are consistent with previous proposals (7,8) that liberation of endocrine secretions of the neurohypophysis is controlled by liberation of ACh from the same terminals.

Canine gastric secretions—both fluid acid and viscous non-acid—and hexosamine-rich fractions derived therefrom, were assayed for blood group substance activity in canine and in human test systems. None of the specimens tested was active in the canine test systems, but all exhibited A and H activity in the human test systems; no human B activity was detected. Hexosamine-rich fractions obtained by peptic digestion and phenol extraction of canine gastric secretion were largely of the neutral mucoid type, and were active in human A and H systems at the microgram level.

1-(1-phenylcyclohexyl) piperidine · HC1 was found to be a very effective agent in suppression of audiogenic seizures in mice. It was approximately 7 times more potent than Dilantin and phenobarbital and 25 times more potent than barbital. PCP was likewise the most active anticonvulsant in electrically induced tonic extensor seizures. Like Dilantin, on the other hand, PCP was devoid of any anti-clonic seizure activity in pentylenetetrazol-induced convulsions. A comparison was also made of the anticonvulsant effects of Dilantin, phenobarbital and barbital in audiogenic, pentylenetetrazol and electrically induced convulsions.

1. At a constant level of dietary vit. A, as the dietary protein was increased, vit. A content of the liver and blood serum of the chick decreased. Also in chicks receiving purified diets containing marginal amounts of vit. A and high protein levels. symptoms of vit. A deficiency occurred sooner and mortality was increased as compared to chicks fed diets containing moderate or low amounts of protein. 2. The decreased vit. A liver storage, resulting when the dietary protein was increased, could not be correlated with changes in liver lipids, nor vit. C blood levels. 3. The ataxia, mortality and other symptoms in young vit. A-deficient chicks was neither preceded nor necessarily accompanied by an increased blood uric acid level. A high protein diet produces high blood uric acid levels regardless of amount of vit. A in the diet. 4. Regardless of dietary vit. A level, the tibia bone ash of the chicks fed the high protein diets decreased as compared to that of chicks receiving a moderate level of protein in the diet.

Intracellular concentration and total amount of potassium in isolated guinea pig ventricle strips in the presence of both therapeutic and toxic concentrations of ouabain have been investigated. A concentration of the drug which produced an increase in the force of contraction without evidence of toxicity did not alter either intracellular concentration or total amount of this ion in the heart. A toxic concentration of ouabain which produced automaticity and a marked increase in the resting tension, followed by decline in force of contraction to zero, caused a mean decrease of 21% in intracellular potassium concentration.

Fasting plasma FFA concentrations were determined in 34 subjects with cirrhosis and 28 without cirrhosis.

Mean fasting FFA concentrations were elevated in subjects with cirrhosis and this was most marked in those subjects with acute hepatic failure or hepatic coma. The increased FFA concentrations were not accompanied by a rise in blood ketone concentrations.

Diffuse fatty infiltration of all liver lobes was found in cats given carbon tetrachloride intramuscularly. A statistically significant reduction in degree of fatty infiltration was found when the cats were also given injections of a protein-free aqueous fraction of liver. The nature of the lipotropic action is unknown.

The cytopathology of ECHO 22 and 23 was compared with other enteroviruses and found to be distinctive. The important differentiating features appeared in the nucleus. An eventual disappearance of the nucleolus and nuclear chromatin and a thickening and increase in staining intensity of the nuclear membrane resulted in appearance of an 'empty' nucleus. Seven isolates of ECHO 22 were found to have similar cytopathic changes. It is suggested that detailed study of the cytopathic effect of viruses in tissue culture may play an important role in relating new agents to the enterovirus group.

Determinations of calcium ion activities by potentiometric measurements using permselective sulfonated polystyrenecollodion membranes indicate that calcium is not very strongly bound by Bence-Jones protein. It is concluded that bone destruction frequently associated with plasma cell proliferation in patients who have multiple myeloma cannot be due to a direct chemical interaction of bone calcium with the Bence-Jones proteins.

A single injection of 0.5 ml of phenolized tularemia vaccine elicited detectable agglutinating antibodies in 67 of 162(41.4%) patients with hematologic disorders as compared to 45 of 48(93.7%) in normal controls. Particularly significant was the lack of response in 23 of 25 chronic lymphatic leukemia and in 37 of 57 lymphoma patients. In the latter group only 5 of 27 females as compared to 15 of 30 males exhibited antibodies.

The approximate LD₅₀ values of dimethylamino-hexose-reductone and morpholino-hexose-reductone injected intraperitoneally in mice were 300 and 850 mg/kg respectively. Oral LD₅₀ values of anhydrodimethylamino-hexose-reductone, dimethylamino-hexose-reductone, and anhydro-piperidino-hexose-reductone in mice were 300, 400, and 900 mg/kg respectively, while for the morpholino and piperidino-hexose-reductones they were greater than 1200 mg/kg. Single intraperitoneal injections and single oral doses of dimethylamino-hexose-reductone in both mice and rats, as well as long-term feeding of dimethylamino and piperidino-hexose-reductones in rats produced typical symptoms of hyperexcitability, elevation and nodding of the head, and whirling.

Colchicine in doses of 1.6, 3.2 and 6.4 mg/kg increases urinary taurine excretion in rats, but doses of 6.4 mg/kg are less effective than the two lower doses. Preformed tissue taurine does not appear to be the source of the extra urinary taurine excreted after colchicine administration.

Localization of antibodies in lungs was examined by fluorescent antibody technic after injection of rabbit anti-rat lung and anti-rat kidney serum into rats. Although both sera gave positive staining in lungs, anti-lung serum contained significantly higher amount of lung localizing antibodies than anti-kidney serum. The localizing components in both sera seemed to be fixed in the same region of alveolar walls.

Using an in vitro gut sac technic, active transport of calcium through the intestinal wall of the rat has been demonstrated. In the presence of physiologic amounts of Vit. D, active calcium transport is confined to the upper portion of the small intestine. In this area, large amounts of Vit. D increase, and cortisone decreases, calcium transport. In the jejunal and ileal areas, active transport occurs only when large amounts of Vit. D are present, and this transport is not reduced by cortisone.

Association of C14-labelled hydrocortisone with herpes virus-infected HeLa cells appeared nonspecific in that equal amounts of steroid were taken up at both 37°C and 4°C by noninfected as well as infected cells. The action of steroid on the cells resulted in a slight decrease in glucose uptake and a proportionally greater decrease in glucose stored. When steroid-treated cells were infected with virus, there was an increased uptake of glucose over that of virus-infected controls, and more glucose stored than in control cells treated with hydrocortisone suggesting that the action of steroid results in a partial return of stressed cells to more normal physiologic function.

Antivirus rabbit serum is shown to block 80% or more of the adsorption of vaccinia virus to susceptible L cells. Data supporting these conclusions are provided by direct virus particle counts with the electron microscope.