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13209373 | Prevention of suicide. | Suicide is the ninth major cause of death in the nation. California, according to the prehensive figures (1949), ranks about 50 per cent above the national average. Yet the importance of suicide as a cause of death is gravely underestimated. At hospitals and other agencies only emergency treatment is given before discharge of persons who attempt suicide, although it is known that many will repeat the attempt. Rarely is psychiatric evaluation carried out or definitive treatment prescribed. Suicidal symptoms are often ignored in other cases. Physicians have a responsibility, as in any disorder, to recognize signs and symptoms of impending suicide and to use all means of prevention. Prevention could be forwarded by the education of physicians and laymen in detecting early signs of depression, in recognizing accident proneness, and in insisting upon legal control of use of barbiturates, mon means of suicide. Lay associations should encourage individuals with suicidal impulses to go to psychiatric clinics for help. Police should learn how to deal with suicidal attempts, and hospitals should include psychiatric examination and advice as to treatment of all such persons. Suicidal attempts should be registered and reported to public health officers in the same way as are other dangerous diseases. More research should be done on case records of these patients, in order to better understand motivations and means of prevention. |
13209374 | Ammoidin (xanthotoxin) in the treatment of vitiligo. | Eighteen patients with vitiligo were treated with two crystalline substances, xanthotoxin (Ammoidin) and imperatorin (Ammidin) from the plant Ammi majus. Four patients improved more than 50 per cent. One plete cure, but depigmentation recurred after a few months. Six patients had moderate improvement (less than 50 per cent), three had slight repigmentation, and in five cases there was no improvement. These results are similar to those reported by other investigators.Pronounced local inflammatory reactions are to be expected after exposure to ultraviolet light in nearly all patients treated with xanthotoxin. In one case prolonged sensitivity to sunlight, manifest by vesiculating dermatitis, occurred. |
13209376 | Epidemicity of poliomyelitis; possible role of seasonal variation in food quality. | Seasonal variations occur in the phosphate, phospholipid and protein content of foods. The lower content occurs in the dry season. This is most often in the summer and fall months, which is the usual time of year for epidemics of poliomyelitis. Question is raised as to whether epidemics of poliomyelitis are a consequence of the host-virus balance being shifted in favor of the virus during this season because of the lower nourishing power of mon to the daily diet. |
13209377 | Rauwolfia serpentina; prolonged use in elderly hypertensive patients. | In a group of older, arteriosclerotic hypertensive patients treated with an extract of Rauwolfia over a long period, a mild hypotensive effect was noted after weeks, or occasionally months, of therapy. No dramatic responses were seen, but the so-called "tranquilizing" effect was readily apparent and was appreciated by the patients. Side effects were usually relatively minor, were transient and rarely necessitated stopping the drug. |
13211905 | The effect of egg yolk in diets on anaphylactic arthritis (passive Arthus phenomenon) in the guinea pig. | WHOLE EGG YOLK INCORPORATED AS A SUPPLEMENT IN THE DIET OF BABY GUINEA PIGS AFFORDED PROTECTION AGAINST ANAPHYLACTIC ARTHRITIS AS DETERMINED: (a) by measurement of joint swelling; (b) by the rise in serum level of some substance which reacts with diphenylamine; (c) by histologic examination. The active material in egg yolk was shown to be in the alcohol-soluble fraction. Attempts to identify the active material with any known lipid have to date been unsuccessful. In the screening of lipid substances for protection against anaphylactic arthritis, it is shown that the weanling guinea pig is suitable, that a 3 week period is adequate, and that the test substance can be administered satisfactorily in the diet. |
13211906 | Growth characteristics of poliomyelitis virus in HeLa cell cultures; lack of parallelism in cellular injury and virus increase. | A detailed study of the cytological changes which are induced in HeLa cells by the Saukett strain of Type III poliomyelitis virus has been made. The observations were of cultures in which a single sequence of infection was induced. The cytological changes were examined in relation to the growth curve of the virus in the same type of culture. This curve showed a latent period of 4 to 5 hours, followed by a gradual release of virus over an interval of 6 to 7 hours. Changes in the staining character of the cells occurred before the major portion of the viral yield appeared. The infected cells exhibited a striking cytopathology with increased basophilia, nuclear pyknosis, and basophilic cytoplasmic granules. Individual cells showed characteristic differences in the rate at which the cytopathology progresses. The multiplication of the virus in HeLa cells was inhibited by fluorophenylalanine. The inhibitory effectiveness of the antimetabolite was related to the age of the infection. It apparently inhibits only an early stage of viral development. The inhibition pletely reversed by phenylalanine if the amino acid is added within 6 hours, not later, after the induction of virostasis. The data are interpreted in terms of the rate at which the ability of the infected cell to support viral synthesis was lost. Flurophenylalanine also inhibited the multiplication of HeLa cells; however, the effect upon the uninfected cell was reversible after 3 days, as indicated by viability after such treatment. While the fluoro pletely inhibited viral multiplication, it did not prevent the cytopathogenic effect of the virus. In the presence of fluorophenylalanine, the disintegration of an infected cell proceeded at what appeared to be the ordinary rate, without any increase of the infectious agent. Experimentally the processes leading to viral increase and to cellular injury have been shown to possess a significant degree of autonomy. |
13211907 | A study of the chemical nature of components of bovine white matter effective in producing allergic encephalomyelitis in the rabbit. | Fractions of bovine white matter, prepared by the methods of Folch and Lees, were studied for position and for their ability to produce experimental allergic encephalomyelitis in rabbits. Evaluation of the disease and of the lesions in animals injected with the more active fractions at several dose levels parison of the antigenic activity of these materials. When tissue was fractionated by the methods of Folch and Lees, antigenic activity was found in the chloroform-methanol extract but not in the denatured tissue residue. This activity was traced to proteolipides A and B and to the lower phase, more specifically the ether-soluble fraction of the lower phase. Proteolipide C was inactive. Correlation of the chemistry of fractions with their antigenic activity suggested two possibilities: (a) that there might be two antigens, one proteolipide and the other non-proteolipide; or (b) that a small specific proteolipide is responsible for all the observed activity. The high concentration of acetal phosphatide in the ether-soluble lower phase suggested pounds of this type might be the hypothetical non-proteolipide antigen, but this hypothesis was disproved by analytic study of active and inactive materials. The possibility that proteolipide might account for all the antigenic activity was strongly supported by the experimental finding that total lipide and proteolipide progressively lost activity as proteolipide was degraded by adequate processing. The use of an entirely different method for preparing total lipides free of proteolipide (the colloidal iron technique) indicated that this loss of activity did not result from incidental removal of some non-proteolipide antigen. These tentative conclusions are in agreement with those of Tal and Olitsky and provide a satisfactory interpretation of the findings of Goldstein et al. The very fact, however, that the suggested proteolipide antigen would amount to no more than 1 per cent of the total chloroform-methanol extractives leaves open the possibility that some unrecognized trace substance may be the antigen. Skin tests with the various fractions indicated some cross-reactivity between proteolipides A and B and the ether-soluble lower phase fraction and a fair correlation of positive skin reactions with disease. This finding patible with the suggestion that the same antigen is present in both of these types of material. When the disease produced by whole tissue or fractions was evaluated by the use of the proportion of animals developing disease, the day of onset, and the severity of the histologic lesions, it was found that fractions produced milder disease of later onset than intact tissue at all dose levels. The disease-producing activity was not enhanced by increasing the dose; i.e., it appeared to reach an asymptotic maximum below that obtainable with whole fresh tissue. This finding suggests both a quantitative loss of activity and a qualitative change during the initial chloroform-methanol extraction, a procedure which denatures all proteins in the tissue residue. parable change appeared to occur in whole white matter stored at -15 degrees C. for 15 months and thawed and refrozen several times during this period. The later fractionation steps resulted in no apparent loss of antigenic activity. A scoring method employing the same type of data to estimate the actual relative antigen contents of different preparations is presented in the Appendix. |
13211908 | Some observations on the intracellular localization of the virus of herpes simplex in the chick embryo liver. | The growth cycle of the virus of herpes simplex in chick embryo liver has been shown to follow the same pattern as in the chorioallantoic membrane and the rabbit's corneal cells. However, there is considerable variability in the time taken for the yolk sac-inoculated virus to get from the yolk sac into the liver. A brief description has been given of various fractionation procedures employed for obtaining isolated nuclei. It has been shown that free virus is not selectively adsorbed to isolated nuclei. Evidence has been presented to show that in the herpes-infected chick embryo liver, large proportions of the total virus can at times be found associated with the nuclear fraction. The percentage of the total virus in the nuclear fraction varies inversely with the titer of virus in the whole liver, and the number of hours after inoculation of the virus; only a negligible amount pared with that in the total) being associated with the nuclear fraction when a period of over 12 hours has elapsed after reappearance of virus. Furthermore, demonstration of virus in the isolated nuclei following extraction with hypertonic NaCl provides additional evidence that this virus is intimately associated with the nuclei. |
13211909 | Immunochemical studies of antitoxin produced in normal and allergic individuals hyperimmunized with diphtheria toxoid. V. Peculiar electrophoretic configuration of serum proteins and protein-bound polysaccharides in certain antitoxic sera; demonstration of serum changes in certain severe manifestations of allergy. | The method of filter paper electrophoresis was used to study proteins and protein-bound polysaccharides in sera obtained from subjects before and after a single booster dose of diphtheria toxoid, and in sera from allergic subjects. The electrophoretic patterns of precipitating antitoxic sera resembled those found in normal non-immune sera. However, skin-sensitizing antitoxic sera were distinguished by a relatively large beta ponent and a small or indistinct alpha(2) globulin. Fusion of ponents was present in some sera containing this variety of antitoxin. Considerable amounts of serum-bound polysaccharides in these sera migrated relatively slowly in contrast to the behavior of polysaccharides of precipitating antitoxic sera which migrated faster when tested under similar conditions. Alterations in proteins and carbohydrates were most readily observed in specimens containing high titers of antitoxin. There were no demonstrable differences between the electrophoretic behavior of sera obtained from subjects before or after immunization with toxoid. Electrophoretic patterns of serum from allergic subjects who developed marked eosinophilia showed attenuation of the alphas globulin associated with a relative preponderance of slow migrating protein-bound polysaccharides. These alterations were not present in sera obtained from the same persons before and after the development of eosinophilia. Changes in the proteins and polysaccharides could not be demonstrated with consistency in subjects with mild to moderate hay-fever symptoms. One person who developed severe acute hay-fever symptoms showed alterations in the beta and alpha(2) globulins. Rheumatic fever subjects showed no unusual changes in the distribution of ponents. However, transition from the acute process to convalescence is graphically demonstrated by the marked decreases in gamma and alpha globulins and in protein-bound carbohydrates. |
13211910 | I. Antigenicity of oxypolygelatin and gelatin in man. | It has been demonstrated that there are normally occurring antibodies to gelatin in human sera. Immunization with gelatin can in many cases increase the antibody level. The presence of these antibodies does not result in cutaneous reactions of the wheal and erythema type after injection of antigen. Many of the properties of the gelatin-antigelatin reaction and the precipitates formed are those of a truly specific antigen-antibody aggregate. Explanations have been advanced both as to the possible sources of the gelatin antibody and its significance. |
13211911 | II. Antigenicity of gelatin in rabbits and other species. | Normally occurring antibodies to gelatin have been demonstrated in sera from many species. Immunization of rabbits with gelatin has been successful when adjuvant techniques were employed. |
13211912 | The nature of prophage in lysogenic Bacillus megatherium. | 1. plement-fixation tests it has been shown that the lysogenic and sensitive strains of B. megatherium share one or more ponents which are serologically related but not identical. 2. Bacilli of the lysogenic strain of B. megatherium, when grown under conditions such that little extracellular phage is produced, fail to evoke antibodies in rabbits which react either plement-fixation or neutralization tests with purified megatherium T phage. From this it must be concluded either that prophage is not antigenic or that any antibody which it might elicit does not react with the antigens of the mature virus. The observations reported in munication accord with the hypothesis that prophage is a genetic structure. |
13211913 | Influenza virus multiplication in the chorioallantoic membrane in vitro: kinetic aspects of inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. | A procedure is described for kinetic studies on the multiplication of Lee virus in the chorioallantoic membrane in vitro employing the hemagglutination technique for measurement of virus concentration. A linear relationship was found between the logarithm of virus adsorbed and the amount of membrane used. Of the virus adsorbed less than 10 per cent could be recovered from the membrane. Of the recoverable virus 90 per cent was eliminated by specific immune serum. Lee virus was adsorbed by the allantoic and chorionic layers of the membrane to a similar degree. Multiplication occurred in both layers and to a similar extent. When 10(7.66) EID(50) of Lee virus was inoculated per 2.9 cm.(2) of chorioallantoic membrane, the ratio of infectivity to hemagglutination titer in the yield was low, although the rate of appearance of virus particles was not diminished despite the large inocula. Virus produced in membranes was liberated rapidly and continually into the medium. 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), 0.000055 M, prolonged the latent period by more than 100 per cent. The rate of increase during the period of rapid rise was similar in the presence or absence of DRB, but the yield was markedly reduced at the end of this period in the presence of DRB. The amount of the virus in the membranes continued to rise in the presence of DRB and eventually approached the maximal levels reached much earlier in the controls. Measurement of the amount of virus in the media indicated a greater degree of inhibition than did measurement in the membranes. Comparative studies with two benzimidazole derivatives on the dependence of the inhibitory effect on the time of addition of pound showed that processes which could be inhibited by DRB were of shorter duration than those inhibited by 2,5-dimethylbenzimidazole (MB). With MB the relationship between the time of addition and the inhibitory effect was similar both for virus and for plement-fixing antigen; with DRB the inhibitable processes were of shorter duration for plement-fixing antigen than for virus particles. DRB was not only 35 times more active on a molar basis but also was more selective in its action than MB. DRB interfered with processes which preceded the emergence of either plement-fixing antigen or virus particles. Some of the implications of these findings are discussed in relation to the mechanism of inhibition of influenza virus multiplication by benzimidazole derivatives. |
13211914 | Relation of certain endocrine disturbances to susceptibility of golden Syrian hamster to experimental poliomyelitis. | Alterations in susceptibility of the Syrian hamster to poliomyelitis virus (MEF1) inoculated intracerebrally appeared closely related to seasonal changes and experimental disturbances in the adreno-testes equilibrium. Enhanced susceptibility coincided with seasonal enlargement of adrenals, followed cortisone and DOCA treatment and appeared during the initial postorchiectomy period. Increased resistance occurred incidentally to adrenalectomy, seasonal diminution in adrenal weight, testosterone overdosage, and testicular hypertrophy induced by treatment with GTH or chorionic gonadotrophin. The effect of certain hormonal interactions, the interference of conditioning factors and the role pensatory reactions are discussed. |
13211915 | Intracellular forms of meningopneumonitis virus. | Electron micrographs of intracellular memngopneumonitis virus have shown several types of particles which are presumably representative of different stages of a life cycle. They are: (a) Elementary bodies-dense particles 250 to 300 mmicro in diameter with very dense central granules. (b) Intermediate forms-less dense than elementary bodies and larger. They are 300 to 400 mmicro in diameter, contain a very dense central granule, and often have two or three limiting zones, (c) Circles 400 to 500 mmicro in diameter-homogeneous structures with single membranes and no internal granules. They are often elongated and constricted at the center in the manner of budding yeast cells, (d) Circles 500 to 600 mmicro in diameter with single membranes.mdash;One, two, and three dense granules may be present in some of these structures, (e) "Larger" structures, circular to elliptical, often with discontinuities or ruptures in their membranes. They sometimes seem to have internal septa. It has been inferred from these observations that the virus can multiply by binary fission or by multiple endosporulation and that elementary bodies are a spore-like stage. |
13211916 | Formation of non-infectious influenza virus in mouse lungs: its dependence upon extensive pulmonary consolidation initiated by the viral inoculum. | Formation of non-infectious virus-particles which hemagglutinate red blood cells and react with antibody to plement but do not infect the chick embryo or mouse-occurred when large quantities of certain strains of influenza viruses were inoculated intranasally into mice. Dependent upon the agent employed, 10(6.5) to 10(8.5) E.I.D. was essential to elicit this phenomenon. To plish this unusual multiplication it was essential to use a strain of virus which effected extensive pulmonary consolidation; strains of virus which did not produce marked lung lesions, even when as much as 10(8.5) E.I.D. was inoculated, did not form non-infectious virus. The development of this viral form was directly dependent upon the extent of cell damage obtained: consolidation of more than 50 per cent of the lung volume was required. The majority of non-infectious particles developed during the initial cycle of viral multiplication, and concurrently with the formation of non-infectious virus there was a corresponding decrease in the number of infectious viral particles. Non-infectious virus could not be propagated on serial passage in mouse lungs: on second lung passage only fully infectious virus was detectable. The formation of the non-infectious viral form was not the result of interference with synthesis of infectious virus by inactivated virus in the inoculum; for inoculation of heated infected allantoic fluid which contained more than 99 per cent of non-infectious virus did not result in the development of new non-infectious virus. Although inoculation of a large quantity of virus resulted in infection which yielded a relatively low titer of infectious and high titer of non-infectious virus, inoculation of a small quantity of the agent resulted in a high yield of infectious virus and no non-infectious that was detectable. In both instances the total quantity of antigenic viral material synthesized in the mouse lungs was the same. These data do not support the hypothesis that the non-infectious virus formed consisted of immature or plete viral particles, but suggest instead that non-infectious virus is inactivated virus or some aberrant form of the agent. |
13211917 | The effect of alcohol on the choline requirement. I. Changes in the rat's liver following prolonged ingestion of alcohol. | Rats maintained for a period of 7 months on a fluid intake of 15 per cent alcohol and a diet marginal in lipotropic activity developed fatty infiltration and mild fibrosis of the liver. Similar changes were observed in pair-fed controls given an isocaloric equivalent of sucrose instead of alcohol, but not in pair-fed controls receiving neither alcohol nor sucrose supplements. To exclude the possibility that the alcohol effect was related to an augmentation of the caloric intake, a third group of controls was given the same amount of alcohol, but a limited number of calories. This was plished by subtracting from the basal diet an amount of sucrose equivalent in calories to the alcohol consumed. Under these conditions the hepatic changes following alcohol ingestion appeared to be enhanced. Choline or methionine, on the other hand, abolished the effects of both alcohol and sucrose supplements. There was no increase in fecal nitrogen excretion following alcohol ingestion, and no histological changes were observed in the pancreas. These results are consistent with the hypothesis that alcohol increases the choline requirement of the rat, but do not support the contention that this effect is the consequence of an augmented caloric intake. Further studies are needed to establish conclusively the relationship between alcohol ingestion and the choline requirement, and to elucidate the mechanisms involved. |
13211918 | The effect of alcohol on the choline requirement. II. Incidence of renal necrosis in weanling rats following short term ingestion of alcohol. | The effect of alcohol on the choline requirement was assayed in weanling rats maintained on a basal diet of relatively low lipotropic activity containing the equivalent of 0.089 per cent choline. Alcohol was administered as a 15 per cent solution in lieu of drinking water. The incidence of renal cortical necrosis, the increase in kidney weight, and the mortality rate at the end of 14 days served as indices of choline deficiency. Under these conditions alcohol-fed animals developed more severe signs of choline deficiency than either pair-fed controls or pair-fed isocaloric controls receiving a sucrose supplement instead of alcohol. The addition of as little as 0.08 per cent of choline to the basal diet abolished these differences. It was concluded that (a) alcohol increases the choline requirement, and may, thus, induce a state of relative deficiency when the diet is marginal in lipotropic activity, and (b) this effect is independent of the caloric intake. The possible significance of these observations in relation to chronic alcoholism in the pathogenesis of Laennec's cirrhosis has been discussed. |
13211919 | Studies on a lipoproteinase of group A streptococci. | The opalescence produced in serum by group A streptococci has been investigated. The development of opalescence is shown to be initiated by an enzyme attached to the bacterial cell which acts upon the alpha(1)-lipoprotein fraction of serum liberating the lipids from the protein. This enzyme has been termed a lipoproteinase. Evidence is presented which suggests that the degree of opalescence which develops following lipoproteinase activity is influenced not only by factors attached to the bacterial cell but also by substances present in serum. The lipoproteinase is antigenic and many human sera contain specific antibodies which inhibit the action of the enzyme. |
13211920 | Studies on the endoplasmic reticulum. I. Its identification in cells in situ. | A series of representative cell types including avian fibroblasts, and macrophages; rabbit mesothelia, endothelia, and nephron epithelia; and rat glandular epithelia (parotid) were paratively in vitro and in situ with the electron microscope. Cells in vitro were examined in whole mounts and in sections whereas cells in situ were observed exclusively in sections. It was found that an endoplasmic reticulum similar to that previously described in cultured material is present in situ in all cell types examined. Modifications in its appearance introduced by the sectioning technique were discussed and explained. The observations showed in addition that the endoplasmic reticulum is a network of cavities which may enlarge into relatively vast, flattened vesicles here described as cisternae. |
13211921 | Some mutant phages produced directly by Bacillus megatherium 899a with their rate of occurrence. | The rate at which cultures of B. megatherium 899a produce certain mutants of its phage T (wild type) has been investigated in two media; one (peptone) in which reinfection of sensitive cells, if present, is virtually certain, and one (asparagine) in which reinfection is extremely unlikely. Little difference either in the number or types of mutants produced has been detected. It is concluded that phage mutants are produced directly by B. megatherium 899a and that no intermediate passage through a sensitive cell is necessary for the mutation. 396 individual mutant plaques have been isolated and classified into at least 18 types of plaque-forming mutants of B. megatherium 899a. The over-all mutant ratio found was in the order of 1:2000 while individual mutants appeared with rates between 1:7000 and less than 1:100,000. |
13211922 | Viral hepatitis associated with transplantable mouse leukemia. I. Acute hepatic manifestations following treatment with urethane or methylformamide. | An hepatic disease caused by a filterable agent carried in leukemic mice is described. Ordinarily the virus remains latent and asymptomatic. If, however, the mice are treated with urethane or methylformamide before and after virus inoculation, the disease es manifest and is characterized by extremely marked liver necrosis. Infant mice, a large percentage of weanlings, and adult Bagg albino mice are killed when injected with a filtrate from organs of diseased animals. Adult F1 and Swiss mice show signs of the disease but generally recover. They succumb, however, when simultaneously treated with urethane or methylformamide. By continuing the treatment of consecutive transfer generations an acute disease can be induced which finally kills all adult F1 mice without the treatment. At this stage the original leukemia may be lost. Mice which have recovered from the subacute disease are resistant to the acute disease, and mice injected with the latent form of the agent are immune to the subacute disease. However, even immunized animals lose their resistance if they are treated with urethane. The acute or subacute disease can be reduced to the latent stage by passing the agent through several generations of immunized animals. The relationship of this hepatitis virus of mice to viruses causing similar diseases is discussed, as is the possibility that these agents are closely related, if not identical. |
13211923 | Tissue reactions to anaphylactic and anaphylactoid stimuli; proteolysis and release of histamine and heparin. | Addition of the specific antigen to slices of liver or lung taken from sensitized guinea pigs, or the addition of anaphylactoid agents (tween 20, octadecylamine, morphine, and 48/80) to tissue slices from normal animals, or the perfusion of lung with these agents, has been shown to cause protein breakdown and liberation of histamine and heparin. The dose correlation between these phenomena raises the question of which is the causal event. Suppression of histamine and heparin release by inhibition of proteolysis suggests that the latter is the more fundamental reaction, but the problem probably can not be decided on the basis of present knowledge. Tissue proteolysis induced by the agents investigated in this work results from the action of a protease present in normal tissues as an inactive precursor. Conversion of the proenzyme requires the intervention of a kinase. The tissue kinase seems to be different from the serum kinase which has been shown to be related plement. Serum kinase, however, also acts on tissue proenzyme and probably plays an important role in tissue reactions as elicited in the intact animal. |
13211924 | The effects of drugs upon a graded cough response obtained in sensitized guinea pigs exposed to aerosol of specific antigen. | A technique is described for measuring objectively and quantitatively the reaction of sensitized guinea pigs when exposed to an aerosol of specific antigen. The principle involves registration by semi-automatic means of the number of coughs produced in animals passively sensitized with known amounts of antibody. The number of coughs is shown to be linearly related to log dose of antibody within a limited range and a dose-response curve is presented. The cough produced by this procedure is not inhibited by the antitussive drugs, codeine and propadrine, but can be inhibited by anti-allergic agents, such as cortisone and an antihistaminic drug. It is also inhibited by narcotine. The last is the pound so far tested which suppresses both the cough produced by this procedure and that produced by a simple irritant. The action of cortisone and the antihistaminic drug, pyrilamine, is shown to be synergistic. A small dose of pyrilamine in animals pretreated with cortisone gives a degree of inhibition which cannot be obtained by increasing the dose of pyrilamine in animals not treated with cortisone. |
13211925 | A non-transmissible cytopathogenic effect of influenza virus in tissue culture accompanied by formation of non-infectious hemagglutinins. | Various strains of influenza virus produce a cytopathogenic effect in cultures of HeLa cells. The virus could not be passed in series. Virus partially or pletely inactivated with respect to infectivity by exposure to 37 degrees C. or ultraviolet light retained some of its cytopathogenic effect. No evidence has been obtained of an increase in infectious virus in HeLa cultures, but an increase in hemagglutinins and in both viral and plement-fixing antigens became detectable during incubation. These virus materials apparently were not released from these cells prior to their destruction. These results suggested that HeLa cells are capable of supporting an plete reproductive cycle of influenza virus. The fact that radioactive phosphorus was readily incorporated into the hemagglutinin supplies strong evidence for this interpretation. |
13211926 | Resistance to fibroma virus infection; the role of immune leukocytes and immune macrophages. | Leukocytes and macrophages, obtained from fibroma-immune rabbits and added to immune serum-fibroma virus mixtures, significantly increased the neutralization of fibroma virus pared with immune serum alone. Immune cell suspensions from peritoneal exudates, regional lymph nodes, buffy coats, spleen, and liver were all effective in inhibiting fibroma virus. Approximately 2000 to 4000 immune cells/mm.(3) were necessary to cause an effect but no particular cell type could be implicated as responsible for the inhibition of fibroma virus. Normal cells did not consistently and significantly inhibit fibroma virus and cells from rabbits immunized with other viruses did not inhibit fibroma virus. Studies of the mechanism of action of the immune cells revealed: (a) that living cells were essential; (b) that normal cells, sensitized with immune serum, did not simulate the effects of immune cells; (c) that immune cells contained less preformed neutralizing antibody than an equivalent volume of immune serum, and (d) that inhibition of fibroma lesions was not the result of viral interference. It is suggested that the fibroma-neutralizing effect of immune cells is related to intracellularly placed antibody or to cellular transfer of an ability to form specific antibody in recipient animals. |
13211927 | Effect of metabolic factors on the susceptibility of albino mice to experimental tuberculosis. | Mice maintained on various types of diets were found to e more susceptible to tuberculosis when deprived of food for periods of 30 hours shortly after infection. In contrast, the susceptibility of the animals to the disease was unaffected by undernutrition resulting from limitation of food intake to a low but constant daily level. The resistance of mice to tuberculosis appeared to be independent-within wide limits-of the protein content of the diet. It is true that mice fed a diet very low in protein and high in carbohydrate proved highly susceptible, but resistance was normal if part of the carbohydrate was replaced by fat (peanut oil)-without any change in the protein content of the food. Resistance to tuberculosis could be consistently and markedly decreased by adding sodium citrate (or glutarate) to a variety of diets. The survival time following infection was greatly shortened if dinitrophenol or thyroxine were administered per os in amounts sufficient to limit the weight gains of non-infected controls. There was usually a lag period of several days before the infection-enhancing effect of these metabolic stimulants became manifest. The procedures which increased the susceptibility of mice to infection with virulent tubercle bacilli also made it possible to establish in these animals a fatal infection with BCG. There was no constant relation between weight gains of uninfected mice on the various regimens, and the effect of the latter on susceptibility to tuberculosis. These findings patible with, but do not prove, the hypothesis that a decrease in resistance to infection can be brought about by metabolic disturbances which cause either a depletion of the glycogen reserves of the body, or a reduction in the glycolytic activity of inflammatory cells, or an increase in the concentration of certain polycarboxylic acids and ketones in the tissues. |
13211928 | Immunological relationships among the myeloma proteins. | An immunological study of 21 myeloma sera was carried out to determine their relationship ponents of normal gamma-globulin and to each other. Ten proteins were separated for detailed characterization. Every one of the myeloma proteins studied was immunologically different, indicating individual specificity. The gamma-type myeloma proteins were all related to normal gamma-globulin or a fraction thereof, and although each was distinct from the others, all were related. The beta-type myeloma proteins likewise were related to one another, though individually specific. Evidence was found favoring the view that some of the gamma-type myeloma proteins are related to the beta-type myeloma proteins although most of them pletely unrelated. Likewise the results indicated a definite but distant relationship between the beta-myeloma proteins and normal gamma-globulin. Certain of the beta-myeloma proteins were more closely related to a fraction of normal serum of similar electrophoretic mobility. It is suggested that most multiple myeloma proteins fall into two groups or families of cross-reacting abnormal proteins, one closely related to normal gamma-globulin, the other distantly related to gamma-globulin with marked individual specificities. |
13211929 | Immunochemical studies of antitoxin produced in normal and allergic individuals hyperimmunized with diphtheria toxoid. VI. Further investigations on the identity and specificity of non-precipitating skin-sensitizing antitoxin. | Studies were carried out on sera from eight subjects hyperimmunized with toxoid who developed marked immediate skin reactivity to toxoid associated with circulating non-precipitating antitoxin. With the use of the rabbit skin test, the agar diffusion technique, and three different methods for passive transfer of skin sensitivity, it was possible to obtain detailed qualitative and quantitative data relating to the antitoxin in these sera. It was found that specimens from six individuals contained only skin-sensitizing antitoxin. Two sera showed a lack of parallelism between antitoxin titers as obtained by rabbit skin test and titers as demonstrated by tests in human skin. It was presumed that these sera contained two different varieties of non-precipitating antitoxins, and that only one of them was skin-sensitizing antitoxin. A new technique is described for measurement of skin-sensitizing antitoxin. Its specificity is based upon the ability of this antitoxin to remain at skin sites and later neutralize the delayed specific toxic effects of intradermal Schick test reagent. |
13211989 | A theory of taste stimulation. | The treatment in this paper of available quantitative data on the response of taste receptors to sodium salt stimulation clearly indicates that the ions of the chemical stimulus are loosely bound to some substance of the taste receptor. This can be thought of as an initial reaction which ultimately leads to stimulation of the receptor and an eventual depolarization of the associated sensory neuron. The speed of the total reaction suggests that the receptor substance is located on or near the surface of the receptor. The recently proposed (7) enzymatic reactions for chemoreceptors do not appear plausible for sodium salt stimulation of the taste receptors of the rat. |
13211990 | Distribution of esterase in gastric mucosa. | Sections of frozen-dried stomach mucosa of the rabbit cut at various levels from the surface were analyzed for esterase activity in relation to the proportions of cell types present. Aside from the fraction attributable to extracellular esterase all the esterase activity appears to be in proportion to the numbers of foveolar and neck mucous cells present in the sample. |
13211991 | Conservation of nucleic acids during bacterial growth. | In experiments of 6 hours duration, no replacement of phosphorus or purine and pyrimidine carbon in DNA, nor flow of these atoms from RNA to DNA, could be detected in rapidly growing cultures of E. coli. The slow replacement that has been demonstrated for many substances in non-proliferating tissues of other organisms, though it may occur also in bacteria, is not greatly accelerated under conditions of rapid cellular growth, and therefore cannot be a characteristic feature of synthetic processes. |
13211992 | Relaxation in extracted muscle fibers. | 1. Ethylenediamine tetraacetic acid (EDTA) in low concentrations imitates all the known effects of the relaxation factor ("Marsh factor"). In extracted muscle fibers which have contracted in a solution containing adenosinetriphosphate (ATP), the addition of EBTA causes relaxation, the subsequent addition of CaCl(2), contraction. 2. In fibers which have been briefly immersed in 5 MM EDTA, ATP causes rapid relaxation if Mg is also present. These fibers have essentially the same properties as briefly extracted fibers. Brief immersion into a solution containing CaCl(2) restores at once the original condition. It is concluded that EDTA produces its action by bining with bound Ca, thereby inactivating it. 3. In relaxed muscle fibers not only Ca, but also lowering the concentration of Mg below a critical level, causes contraction. In such fibers Mg in the lowest effective concentrations increases contraction, but the effect reverses above a certain concentration. 4. At 0 degrees Mg in the presence of ATP has a relaxing effect without the relaxation factor. 5. The results indicate that Mg has two distinct effects in the presence of ATP. It causes contraction at low concentrations, but above a critical concentration its relaxing action prevails. The last of these effects is blocked by bound Ca. If the latter is inactivated by EDTA, Mg in sufficiently high concentrations causes relaxation. The action of the relaxation factor can similarly be explained by assuming that it acts as plexing agent which inactivates bound Ca. 6. Previous evidence that the relaxed state depends on the formation of an enzymatically inactive plex was confirmed. It was found that PP in low concentrations strongly increases the relaxing effect of ATP in briefly extracted fibers. |
13211993 | Characteristics of a new vibrio-bacteriophage system. | A vibrio-bacteriophage system isolated from San Francisco Bay mud is described. The vibrio lyses readily in distilled water and appears to be a new species. In contact with the phage it es lysogenic and forms large clumps. The phage presents no unique features. |
13211994 | Reversible inactivation of typhus Rickettsiae. I. Inactivation by freezing. | Rickettsiae that have been frozen and thawed in isotonic salt solutions show greatly decreased toxicity for mice, hemolytic activity, respiration, and infectivity for eggs. All these properties can be partially restored by incubation of the rickettsiae in the presence of DPN and coenzyme A for 2 hours at 34 degrees C. The extent of both inactivation and of subsequent reactivation is markedly affected by the presence of low concentrations of sucrose during the process of freezing and thawing. It has been shown that DPN is present in rickettsial suspensions and that in preparations that have not been frozen, the DPN sediments with the rickettsiae. After freezing in isotonic salt solution the DPN es non-sedimentable. |
13211995 | Enzymatic breakdown of threonine by threonine aldolase. | 1. The enzyme which splits threonine to acetaldehyde and glycine has been partially purified from rat liver (five- to sixfold purification) and the name threonine aldolase proposed for it. 2. The general properties of threonine aldolase have been studied. The enzyme is unstable to a pH below 5. The pH optimum of the enzyme reaction is at 7.5-7.7. The initial rate of production of acetaldehyde is proportional to the enzyme concentration, and when the enzyme concentration is constant, the production of acetaldehyde is proportional to the time, provided that the substrate is in excess. The enzyme is inhibited by the carbonyl group reagent, hydroxylamine. Attempts to demonstrate that pyridoxal phosphate is a cofactor were unsuccessful. 3. The enzyme splits only L-allothreonine and L-threonine and is inactive against the D-forms of these amino acids. 4. The enzyme reaction on DL-allothreonine follows first order kinetics. From the first order velocity constants and the initial rates of the rates of the reaction at various substrate concentrations the Michaelis constant, Ks, for this substrate has been evaluated. Michaelis constants have also been determined for threonine. 5. The optimum temperature for the enzymatic breakdown of DL-allothreonine at pH 7.65 was found to be 50 degrees C. in phosphate buffer and 48 degrees C. in tris-maleate buffer. The rate of thermal inactivation of the enzyme threonine aldolase obeys a first order reaction. The heat of thermal inactivation was calculated by the aid of the van't Hoff-Arrhenius equation to be 43,000 cal. per mole for the temperature range 41.2-46.6 degrees C. 6. Equivalent amounts of acetaldehyde and glycine were formed from DL-allothreonine and the enzymatic breakdown of DL-allothreonine was found to be irreversible. |
13211996 | The alteration of intracellular enzymes. II. The relation between the surface and the biological activities of altering agents. | 1. The ability of homologous series of alcohols, ketones, and aldehydes to cause alteration of intracellular catalase increases approximately threefold for each methylene group added, thus following Traube's rule. Equiactive concentrations of alcohols (methanol to octanol) varied over a 4,000-fold range, yet the average corresponding surface tension was 42 +/- 2 dynes/cm., that for ketones 43 +/- 2, and for aldehydes (above C(1)) 41 +/- 3. 2. Above C(8) the altering activity of alcohols ceased to follow Traube's rule, and at C(18) was nil. Yet the surface activities of alcohols from nonanol to dodecanol did follow Traube's rule. These two facts show that the interface which is being affected by these agents is not the cell surface, for if it were, altering activity should not fall off between C(9) and C(12) where surface activity is undiminished; they show also that micelle formation by short range association of hydrocarbon "tails," usually invoked to explain decrease in biological activity pounds above C(8), is not responsible for this effect in these experiments, in which permeability of the cell membrane probably is involved. 3. The most soluble alcohols and aldehydes (alcohols C(1) to C(8); aldehydes C(1), C(2)), but not ketones, cause, above optimal concentration, an irreversible inhibition of yeast catalase. 4. The critical concentration of altering agent (i.e., that concentration just sufficient to cause doubling of the catalase activity of the yeast suspension) was independent of the concentration of the yeast cells. 5. Viability studies show that the number of yeast cells killed by the altering agents was not related to the degree of activation of the catalase produced. While all the cells were invariably killed by concentrations of altering agent which plete activation, all the cells had been killed by concentrations which were insufficient to cause more than 50 per cent maximal activation. Further, the evidence suggested that the catalase may be partially activated by concentrations of altering agent which cause no decrease in viability at all. Hence alteration, unlike death, may not be all-or-none per cell. 6. The fact that the biological criterion being examined was the activation of a water-soluble enzyme rules out the possibility that the reason for the logarithmic increase in altering activity with chain length was increase in concentration of the altering agent in some intracellular fat phase. It is concluded that these surface-active agents cause enzyme alteration by ing adsorbed at some intracellular interface and thus causing, directly or indirectly, the modification of catalase properties. 7. It is considered that these data support, but do not provide critical proof for, the interfacial hypothesis, which states that catalase is present at the intracellular interface in question, but is desorbed into solution as a consequence of the alteration process. |
13211997 | Reversal of the streptomycin injury of Escherichia coli. | The number of viable Escherichia coli in a young, actively growing culture is decreased approximately 99.9 per cent by a 30 second exposure to 25 phig. streptomycin/ml. The injury induced by the antibiotic is only potentially lethal, however, and may be reversed by subculture within 5 minutes into fresh culture medium, NH(4)NO(3), NH(4)Cl, (NH(4))(2)HPO(4), NH(4) citrate, and NH(4) tartrate. Subculturing into water, glucose, or MgSO(4) results in a more marked decrease in the number of viable organisms. In KNO(3), NaNO(3), K(2)HPO(4), and Na(2)SO(4) solutions reversal occurs first, followed by a rapid decrease in viability. True reversal of the streptomycin injury takes place, as demonstrated by the rapid rate of recovery to the viable count of the original culture. Development of resistance has been eliminated as the cause of regrowth since the streptomycin sensitivity of recovered cultures remained the same as that of the original culture. The use of water as diluent for viability determinations potentiates the lethal effect of streptomycin activity. pounds, at various dilutions, substituted for water as the diluent gave rise to four types of responses, group I, NH(4)NO(3), NH(4)Cl, KNO(3), NaNO(3), Ca(NO(3))(2), plete reversal of the streptomycin injury at all levels of the salts tested, from 0.01 to 0.5 M concentrations. Group II, NaCl and K(2)HPO(4) plete reversal at 0.03 and 0.1 M. Group III, glucose and urea plete reversal at 0.5 M. Group IV, glycerol and glycerine showed no reversal at 0.5 M concentration. The reversal of the streptomycin injury to young actively growing bacteria is suggested as a tool for studying the pathology of the injury to the cells. |
13211998 | Filtration, diffusion, and molecular sieving through porous cellulose membranes. | 1. A study has been made of the diffusion and filtration of a graded series of molecules (including tritium-labelled water, urea, glucose, antipyrine, sucrose, raffinose, and hemoglobin) in aqueous solution through porous cellulose membranes of three degrees of porosity. 2. Experimental results were in close agreement with predictions based on the membrane pore theory of Pappenheimer et al. (1,2). Restriction to molecular diffusion is a function of pore radius and molecular radius described by equation (11) in the text. Molecular sieving during ultrafiltration is a function of total pore area per unit path length, pore radius, molecular radius, and filtration rate given by equations (16) and (19). 3. Estimates of average pore radius made by means of this theory were considerably larger than estimates made by the method of Elford and Ferry (3) (Table II). Sources of error in the latter method are discussed and a new method of membrane calibration is proposed in which the total cross-sectional area of the pores is measured by direct diffusion of isotope-labelled water. 4. Steady-state osmotic pressures of solutions of sucrose and raffinose measured during molecular sieving through cellulose membranes were found to be close to the "ideal" osmotic pressures calculated by van't Hoff's law. Thus the present experimental data support the methods used by Pappenheimer et al. in their studies on living capillary walls as well as their theory of membrane pore permeability. |
13211999 | Bioelectric effects of ions microinjected into the giant axon of Loligo. | 1. A technique is described for recording the bioelectric activity of the squid giant axon during and following alteration of the internal position with respect to ions or other substances. 2. Experimental evidence indicates that the technique as described is capable of measuring changes in local bioelectric activity with an accuracy of 10 to 15 per cent or higher. 3. Alterations of the internal K(+) or Cl(-) concentrations do not cause the change in resting potential expected on the basis of a Donnan mechanism. 4. The general effect of microinjection of K(+) Rb(+), Na(+), Li(+), Ba(++), Ca(++), Mg(++), or Sr(++) is to cause decrease in spike amplitude, followed by propagation block. 5. The resting potential decreases when the amplitude of the spike es low and block is incipient. 6. The decrease in resting potential and spike amplitude may be confined to the immediate vicinity of the injection. 7. At block, the resting potential decreases up to 50 per cent, but injection of small quantities of divalent cations may cause much larger localized depolarization. 8. The blocking effectiveness of K(+), Na(+), and Ca(++) expressed as reciprocals of the relative amounts needed to cause block is approximately 1:5:100. Rb(+) has the same low effectiveness as does K(+). Li(+) resembles Na(+). Ba(++) and Mg(++) are approximately as effective as Ca(++). 9. Microinjection of Na(+) may cause marked prolongation of the spike at the injection site as well as decrease in its amplitude. 10. The anions used (Cl(-), HCO(3) (-), NO(3) (-), SO(4) (-), aspartate, and glutamate) do not seem to exert specific effects. 11. A tentative explanation is offered for the insensitivity of the resting potential to changes in the axonal position. 12. New data are presented on the range of variation, in a large sample, of the magnitude of the resting potential and spike amplitude. |
13216232 | Enzymatic conversion of delta-amino levulinic acid to porphobilinogen. | An enzyme has been found in extracts of chicken erythrocytes which converts delta-amino levulinic acid to the monopyrrole porphobilinogen. Some of its properties have been described (6). |
13221773 | Kinetics of amino acid incorporation into serum proteins. | 1. The effect of varying body temperature on the rate of amino acid incorporation into serum protein does not give support to the idea that the rate of this process is adjusted in vivo to restore those protein molecules destroyed by thermal denaturation. The experimentally observed Q(10) was about 3.9. 2. When amino acids are injected into the blood of animals in a steady state of serum protein turnover, a period of time elapses before these amino acids can be found in the serum proteins. This has been called transit time. At a given temperature (31 degrees ) it is the same in rabbits, turtles, and Limulus (1 hour). In rabbits and turtles it has a Q(10) of 3.2. It appears to be specifically related to the process of synthesis (or release) of serum proteins. 3. It was not possible to affect the transit time or the incorporation rate by the administration of amino acid analogues. |
13221774 | The effect of nutritional state on photoreversal of ultraviolet injuries in Didinium nasutum. | 1. The effect of the nutritional state of Didinium nasutum on its resistance to short ultraviolet (UV) radiation (2654 A) and its recovery from the injury following illumination with visible light (4350 A, blue) was studied. 2. The resistance of a didinium to UV is considerably increased by feeding it a paramecium 15 to 60 minutes before exposure to UV. If fed just before exposure to UV, the resistance is less than that of an unfed control. 3. Photoreversal is only slightly greater in didinia fed after irradiation with UV but before exposure to visible light pared to those fed after exposure to visible light. 4. Irradiated paramecia are eaten by didinia, provided they have not started to cytolyze. Didinia fed on irradiated paramecia divide at about the same rate as controls or slightly faster. 5. The available stock of Didinium declines in vigor with lapse of time after excystment, as measured by the time required for division. The sensitivity of Didinium to UV did not change essentially during the 5 month period over which tests were made. 6. The theoretical implications of the results are considered. |
13221775 | Transmission in fractionated monosynaptic spinal reflex systems. | A study has been made of conditions that support monosynaptic reflex transmission from afferent fibers of one part of a synergic muscle mass to motoneurons of another part. Heteronymous response so called can be brought on by prior tetanization of the afferent pathway and by asphyxiation to a critical stage. The response is facilitated by cooling and may appear in the cold preparation without need for prior tetanization. By appropriate asymmetrical subdivision of a monosynaptic reflex system an afferent inflow can be obtained that is sufficiently powerful to secure heteronymous transmission without the need for prior tetanization or cooling. Each junction between a monosynaptic afferent fiber and a motoneuron possesses some degree of potentiality for transmitting. Transmitter potentiality of an afferent fiber at its several junctions with motoneurons varies widely. Reasons are advanced for supposing the variation to be graded rather than stepwise, and quantitative rather than qualitative. |
13221777 | Active sodium uptake by the toad and its response to the antidiuretic hormone. | A method has been described in which sodium uptake may be studied in the intact, anesthetized toad. Sodium uptake is determined by "counting" the whole animal in a special chamber after suspending it in a frog Ringer bath containing radioactive Na(24). The effects of subcutaneous injection of the neurohypophyseal antidiuretic factor were studied with these results: 1. There was a pronounced increase in sodium influx following treatment with the hormone. 2. Sodium outflux was small in both experimental and control animals. 3. There was an increase in water uptake in both experimental and control animals after 1 hour in the bathing solution. This increase was greater in the experimental toads in which it is believed to be related, at least in part, to sodium transport. 4. Potentiometric measurements were made on the skin membrane potential of the whole animal while suspended in bathing solutions. These results were in essential agreement with those found for isolated frog skin. However, there was no apparent influence of the antidiuretic factor on the skin potential. |
13221776 | Mechanisms of direct and neural excitability in electroplaques of electric eel. | 1. Current flow outward through the caudal, reactive membrane of the cell causes direct stimulation of the electroplaque. The electrical response in denervated as well as in normal preparations recorded with internal microelectrodes is first local and graded with the intensity of the stimulus. When membrane depolarization reaches about 40 mv. a propagated, all-or-nothing spike develops. 2. Measured with internal microelectrodes the resting potential is 73 mv. and the spike 126 mv. The latter lasts about 2 msec. and is propagated at approximately 1 M.P.S. 3. The latency of the response decreases nearly to zero with strong direct stimulation and the entire cell may be activated nearly synchronously. 4. Current flow inward through the caudal membrane of the cell does not excite the latter directly, but activation of the innervated cell takes place through stimulation of the nerve terminals. This causes a response which has a latency of not less than 1.0 msec. and up to 2.4 msec. 5. The activity evoked by indirect stimulation or by a neural volley includes a prefatory potential which has properties different from the local response. This is a postsynaptic potential since it also develops in the excitable membrane which produces the local response and spike. 6. On stimulation of a nerve trunk the postsynaptic potential is produced everywhere in the caudal membrane, but is largest at the outer (skin) end of the cell. The spike is initiated in this region and is propagated at a slightly higher rate than is the directly elicited response. Strong neural stimulation can excite the entire cell to simultaneous discharge. 7. The postsynaptic potential caused by neural or indirect stimulation may be elicited while the cell is absolutely refractory to direct excitation. 8. The postsynaptic potential is not depressed by anodal, or enhanced by cathodal polarization. 9. It is therefore concluded that the postsynaptic potential represents a membrane response which is not electrically excitable. Neural activation of this therefore probably involves a chemical transmitter. 10. The nature of the transmitter is discussed and it is concluded that this is not closely related to acetylcholine. 11. Paired homosynaptic excitation discloses facilitation which is not present when the conditioning stimulus is direct or through a different nerve trunk. These results may be interpreted in the light of the existence of a neurally caused chemical transmitter or alternatively as due to presynaptic potentiation. 12. The electrically excitable system of the electroplaque has ponents. In the normal cell a graded reaction of the membrane develops with increasing strength of stimulation until a critical level of depolarization, which is about 40 mv. 13. At this stage a regenerative explosive reaction of the membrane takes place which produces the all-or-nothing spike and propagation. 14. During early relative refractoriness or after poisoning with some drugs (eserine, etc.) the regenerative process is lost. The membrane response then may continue as a graded process, increasing proportionally to the stimulus strength. Although this pathway is capable of producing the full membrane potential the response is not propagated. 15. Propagation returns when the cell recovers its regenerative reaction and the all-or-nothing response is elicited. 16. Excitable tissues may be classified into three categories. The axon is everywhere electrically excitable. The skeletal muscle fiber is electrically excitable everywhere except at a restricted region (the end plate) which is only neurally or chemically excitable. The electroplaque of the eel, and probably also cells of the nervous system have neurally and electrically excitable ponents intermingled. The electroplaques of Raia and probably also of Torpedo as well as frog muscle fibers of the "slow" system have membranes which are primarily neurally and chemically excitable. Existence of a category of invertebrate muscle fibers with graded electrical excitability is also considered. 17. In the eel electroplaque and also probably in the cells of neurons, tests of the mode of neural activation carried out by direct or antidromic stimulation cannot reveal the neurally and chemically ponent. The data of such tests though they appear to prove electrical transmission are therefore inadequate for the detection and study of the chemically initiated process. |
13221778 | Potassium transport in human erythrocytes: evidence for a three compartment system. | Whole human blood is incubated for periods of (1/2) to 3 hours with K(42) at 37 degrees C. At the close of this period, called pre-incubation, the plasma is removed from the cells and the cells, now e radioactive, are again incubated in a mixture of plasma and buffer for periods of up to 10 additional hours. The time course of the K(42) activity of the incubating medium is followed. Characteristically, after 2 hours of pre-incubation, the activity in the medium rises to a peak about 1 and (1/2) hours after resuspension, and then falls slowly until at 10 hours it is very close to its initial value at the beginning of the resuspension interval. This transient rise in K(42) activity in the medium is taken to indicate that the red cell does not consist of a single uniform partment, but contains at least partments. Thus one partment contains a reservoir of high specific activity K which provides the specific activity gradient necessary to drive the K(42) content of the medium to its transient peak. Experiments with Na indicate that its behavior in this respect is unlike that of K. The experimental data are matched to a simple model system which is capable of theoretical analysis with the aid of an puter. The model system, whose characteristics agree fairly well with those observed experimentally on red cell prises two partments, one containing 2.35 m.eq. K/liter blood, and the other 44.1 m.eq. K/liter blood. The plasma K content is 2.64 m.eq./liter blood. The flux between plasma and the smaller partment is 0.65 m.eq. K/liter blood hour; that between the smaller and the larger partment, 1.77 m.eq. K/liter blood hour; and that between the larger partment and the plasma is 0.34 m.eq. K/liter blood hour. |
13221779 | The transport of sodium into human erythrocytes in vivo. | The relative Na(24) specific activity of red cells and plasma was measured at periods up to 30 hours following a single intravenous injection of Na(24) in normal healthy young adults. The average specific activity of the red cells relative to that of the plasma at 24 hours and beyond was found to average 0.83 +/- 0.05 in a series of five normal individuals, significantly different from 1.0. This indicates that all the intracellular Na is not exchangeable in 24 hours, and confirms earlier in vitro results. The red cell Na concentration in man was shown to be 12.1 +/- 1.1 m.eq. Na/liter red cell, as measured in a series of nineteen normal healthy young adults. A theoretical analysis of the data on exchangeable cell Na suggests that the red cell Na (5.3 m.eq. Na/liter blood) is divided into a prising 4.25 m.eq. Na/liter blood, and a prising 1.07 m.eq. Na/liter blood. If partments are arranged in parallel, the flux between plasma and partment is 1.32 m.eq. Na/liter blood hour, and that between plasma and partment is 0.016 m.eq. Na/liter blood hour. Results of experiments on two patients with congenital hemolytic jaundice suggest that the fraction of slowly exchanging Na may increase with the age of the red cell. |
13221780 | Histones with high lysine content. | 1. The preparation and properties of lysine-rich histones, which differ in a number of respects from the classical arginine-rich histones, have been described. 2. Lysine-rich histones, like those previously known, are located in cell nuclei. 3. Lysine-rich histones dissociate more readily bination with nucleic acid than do other histones. |
13221781 | Some observations on protein metabolism in chromosomes of non-dividing cells. | 1. The metabolism of chromosomal proteins has been studied in the pancreas, liver, and kidney of adult mice (a) by measuring the rates of glycine-N(15) incorporation into histones and residual chromosome fractions, and (b) by measuring the extent to which N(15), once incorporated into chromosomal proteins, is retained. 2. The uptake of isotopic nitrogen by these nuclear constituents pared with that of protein fractions prepared from the cytoplasm by differential centrifugation in sucrose solutions. One such fraction, prises the bulk of the ribosenucleoprotein of the cell sediments as a pellet on high speed centrifugation. The supernatant remaining after this centrifugation is a fraction which, in the pancreas, is rich in the secretory enzymes synthesized by the cell. 3. parison of the rates of glycine-N(15) uptake shows that cytoplasmic ribonucleoprotein is the most active of the protein fractions analyzed. In the pancreas it meets the conditions required of a precursor for the secretory enzymes of the supernate. 4. In all tissues considered the rates of glycine-N(15) uptake into histone and residual chromosome fractions are lower, that for histone being the lowest of any of the ponents considered and that for residual protein approximating the over-all rate for cytoplasmic protein. 5. The effects of feeding and fasting upon glycine-N(15) incorporation have been studied. In the pancreas, feeding causes a sharp increase in N(15) uptake by the mixed tissue proteins and by the nucleoprotein and supernatant protein of the cytoplasm. There is a parallel increase in N(15) uptake by the chromosomal constituents-histone and residual protein. 6. A parallelism between N(15) uptake in cytoplasmic and chromosomal proteins is also observed in the liver and kidney when over-all protein metabolism is altered by feeding and fasting. 7. The responsiveness of the histones and residual proteins to changes in the environment has also been demonstrated in N(15) retention experiments. The loss of isotope once incorporated into chromosomal proteins is much more rapid in fed than in fasted animals. |
13163317 | Studies on susceptibility to infection following ionizing radiation. I. The time of onset and duration of the endogenous bacteremias in mice. | Daily cultures of blood obtained from the tail were made on mice from the 7th day to the 17th or 22nd days after exposure to 550 r total body x-irradiation. Seven mice with negative blood cultures survived to the 27th day when they were sacrificed and found to have negative heart's blood cultures. Every mouse with bacteremia died. Heart's blood cultures post mortem always confirmed the bacteriological findings in the serial cultures. Most of the bacteremias occurred between the 7th and 15th days. The duration of the bacteremia varied with the microorganism which caused it. Pseudomonas bacteremia was always rapidly fatal. Those caused by Proteus and E. coli continued for a maximum of 72 and 48 hours. Of longest duration was bacteremia caused by Paracolobactrum which was tolerated for as long as 5 days. |
13163318 | Studies on susceptibility to infection following ionizing radiation. II. Its estimation by oral inoculation at different times post irradiation. | Mice were inoculated by mouth at different times (2 hours, 5 days, and 11 days) after a single exposure to 550 r total body x-irradiation. The inocula contained approximately 10(7)Pseudomonas aeruginosa which was found to be quite harmless for unirradiated mice. Comparison of the cumulative mortality curves and of the incidence of Pseudomonas bacteremia showed their susceptibility to infection by this route to be greatest on the 11th day, somewhat less on the 5th day post irradiation, and least of all directly after irradiation. Since damage to the intestinal mucosa has been found to be maximal within the first few hours after exposure to doses of x-irradiation in this range, it seems reasonable to conclude that the increased susceptibility is not due to increased permeability of the mucosa of the gut, but to impairment of the animal's natural defenses against infection. |
13163319 | Studies of influenza virus infection in the chick embryo using fluorescent antibody. | As evidenced by specific staining with fluorescent antibody, the major sites of multiplication of the PR8 and Lee B strains of influenza virus in chick embryos injected by the amniotic route were in the cells lining the amnion and in the epidermal and pharyngeal epithelium. Varying amounts of virus were also present in the epithelium of the allantois and less frequently in the peritoneum. No virus was detectable in any of the other tissues of 25 embryos injected between the 7th and 11th days of incubation and examined 48 hours later. Three out of five of the embryos inoculated with the PR8 strain of influenza virus on the 12th day of incubation, on the other hand, showed in addition extensive involvement of the cells lining the respiratory tract. Specific staining of the tissues was first detectable when the ID(50) of the amniotic fluids attained a level of greater than 4.5, which corresponded to the time of the appearance of hemagglutinins. With the inocula used this was generally achieved sometime between the 18th and 24th hour of the infection with the PR8 strain of virus and between the 24th and 48th hour of the infection with the Lee B strain of virus. Cytologically, the multiplication of the influenza viruses was characterized by a diffuse type of immunospecific staining which was first detectable in the nuclei and later in the cytoplasm of the cells. The infection progressed rapidly and despite the restricted distribution of the viruses resulted in the death of the embryo in from 3 to 6 days. The results obtained in the present experiments pared with the findings previously reported in similar studies of mumps virus (6). |
13163320 | Hemagglutination with arthropod-borne viruses. | Through the use of acetone and ether extraction of brain tissue from newborn mice infected with certain arthropod-borne viruses, it has been possible to demonstrate hemagglutinins for chick erythrocytes associated with the following viruses: dengue Type 1, dengue Type 2, Eastern equine encephalitis, Ilhéus, Japanese B, Ntaya, St. Louis, Sindbis, Uganda S, Venezuelan equine encephalitis, West Nile (Egypt 101 strain), Western equine encephalitis, and yellow fever (viscerotropic and neurotropic strains). On the basis of the temperature and pH required for reaction, the viruses can be assembled in two groups: A-those that require 37 degrees C. and a pH of about prising Eastern, Venezuelan, and Western equine encephalitis and Sindbis viruses; and B-those that require either 4 degrees or 22 degrees C. and a pH of about prising dengue Types 1 and 2, Ilhéus, Japanese B, Ntaya, St. Louis, Uganda S, West Nile, and yellow fever viruses. A method of eliminating non-specific inhibitory substances present in sera was developed. The method consists essentially of filtration through Seitz pads. Extensive serological crossings were found among viruses of each group, while antisera of one group failed consistently to cross-react with antigens of the other. Antisera deriving from animals immunized with certain viruses for which no hemagglutinins could be developed by the present method, reacted with members of either one or the other group. Thus Semliki Forest virus would appear to belong to Group A, and Russian Far Eastern and louping ill viruses to Group B. |
13163321 | Factors related to the growth of psittacosis virus (strain 6BC). IV. Certain amino acids, vitamins, and other substances. | The analogues of amino acids, beta-2-thienylalanine, ethionine, and 6-methyltryptophane, inhibited the growth of psittacosis virus (6BC) in tissue culture without evidence of serious toxicity for the host cells. Of a number of vitamin analogues tested, only salicyl-beta-alanide inhibited viral multiplication in the absence of toxic effects on the host cells. 6,7-Diethylriboflavin, desoxypyridoxine, and oxythiamine reduced viral growth in concentrations that possessed some toxicity for host tissue. In tolerated amounts, 3-acetylpyridine, pyridine-3-sulfonic acid, pantoyl sulfanilamide, and desthiobiotin did not effect viral multiplication. Sodium malonate inhibited psittacosis virus growth in non-toxic amounts, whereas sodium monofluoroacetate was ineffective. Colchicine suppressed multiplication of virus only after a prolonged period of exposure and subsequent delay before producing inhibition, suggesting that the effect was secondary to its antimitotic action which suppressed multiplication of the host cells. |
13163322 | Studies on the factors essential to the initiation and maintenance of multiplication of psittacosis virus (6BC strain) in deficient cells in tissue culture. | The growth of psittacosis virus (6BC) was studied in cultures of minced whole chick embryo tissue maintained in either Hanks-Simms solution or Hanks's balanced salt solution (BSS), and in neither medium could sustained, long-term virus growth take place. Addition of beef embryo extract (BEE) to cultures at a time when virus multiplication was declining reversed this general trend and resulted in greater virus growth. This virus-stimulating action of BEE was only partially diminished by colchicine, a mitotic inhibitor, indicating that the action of BEE was not due entirely to the development of a larger population of cells as a result of its enhancement of cell proliferation. Chick embryo tissue cultivated for 13 days in BSS prior to infection lost its ability to support the growth of psittacosis virus, but this capacity could be restored by the addition of BEE, alone or with colchicine, at the time of infection. A significant amount of virus was adsorbed to tissue in BSS alone, indicating that the failure of virus to grow in depleted tissue maintained only in BSS after infection was not due entirely to failure of virus to attach to and invade the cells. It was found that an ultrafiltrate and a dialysate of BEE contained the major part of the stimulating capacity of the whole extract, indicating that the active materials were substances of low molecular weights. Autoclaved lactalbumin hydrolysate was an active stimulator, suggesting that the materials responsible for its activity were relatively heat-stable. Since a chemically defined medium (Parker 199) was equally effective in stimulating viral growth, it should be possible eventually to define the chemical nature of the virus stimulators. The implications of the findings are discussed with special reference to their application in the study of tissue tropisms and of latency in viral infections of cells. |
13163323 | Mechanism of cell wall penetration by viruses. I. An increase in host cell permeability induced by bacteriophage infection. | Treatment of radioactively labelled host cells with T1 or T2 bacteriophages induces a leakage of cellular P and S into the medium. Evidence is presented showing that this increased cell permeability is not the result plete lysis of a small fraction of the cells, but rather is made up of contributions from all or most of the infected population. This leakage of cellular constituents exhibits the following characteristics: (a) Infection of a cell with a single virus suffices to evoke the reaction; (b) Increasing the multiplicity up to 7 to 8 virus particles per cell does not affect the extent of leakage produced; (c) Some leakage does occur at 0 degrees C., but much less than at 37 degrees C.; (d) Infection by T1 virus results in a smaller amount of leakage than in the case of T2, but the pattern of response to varying virus multiplicity is the same; (e) The P resulting from such leakage contains no DNA and chemically resembles that which elutes in smaller amounts from uninfected cells; (f) At 37 degrees C. the virus-induced leakage reaction appears within a matter of seconds, and usually decreases after 2 to 3 minutes; (g) The reaction is inhibited by 0.025 M Mg(++). Theoretical considerations are presented suggesting the place of this reaction in the sequence of events constituting the virus penetration reaction; its relationship to the phenomenon of lysis-from-without; and its resemblance to the leakage reaction produced by electrostatic binding of pounds to cell surfaces. The existence of similar effects in avian-mammalian virus systems is noted. |
13163324 | Myocardial necrosis produced in animals by means of crystalline streptococcal proteinase. | Focal myocardial necrosis that was often extensive was found in a high percentage of rabbits, guinea pigs, and mice given a single intravenous injection of crystalline streptococcal proteinase. The findings are discussed in relation to their possible implications for the pathogenesis of the cardiac lesions of rheumatic fever. |
13163325 | Studies on the nature of hemophilus influenzae cells susceptible to heritable changes by desoxyribonucleic acids. | In E. influenzae the highly specific desoxyribonucleic acids (DNA's) which play the role of heredity determinants of type specificity and SM resistance, have induced these traits in only a small proportion of the population exposed to their action. The evidence suggests that this small proportion, "the susceptible cells" possess a property or substance needed by the DNA in order to induce an heritable change. The size of the small proportion of susceptible cells can be influenced significantly by a number of factors; when all the factors now to be listed are operating the frequency has not exceeded 1:1000. The Type of Origin of Recipient Cells.-Type a exhibits the lowest frequency, about 1:10,000,000, and type d the highest, approximately 1 per 1000 cells exposed. This type-specific property which controls the frequency of susceptible cells is an inherited trait; repeated change to a heterologous type shows no influence on the incidence of these cells. Concentration of DNA.-Within certain limits increase in the concentration of DNA controlling streptomycin resistance can increase the size of the proportion of cells in which streptomycin resistance can be induced. However, increases in concentrations greater than 10(-1) microg. per ml. have not induced streptomycin resistance in a higher proportion of cells. Phase of Growth Cycle.-Predictable fluctuations in frequency of induced heritable changes have been demonstrated in both Rb and Rd populations during growth. There is no evidence that susceptible cells reproduce their kind; they emerge in all experiments when the population reaches the end of the logarithmic period and a density of 2 to 4 x 10(8) cells per ml. In the early logarithmic phase it is difficult to demonstrate the presence of susceptible cells. The peak frequency of susceptible cells occurs in the early stationary phase of the growth cycle. Thereafter, the decline in frequency is a gradual one. The data suggest that in a given population the same cells are susceptible to a number of different type-specific DNA's and the DNA controlling SM resistance. Comparison of Frequency of Cells Susceptible to Different DNA's.-In a given population the frequency of cells susceptible to different type-specific DNA's and the DNA controlling streptomycin resistance is not significantly different. Competition between Type-Specific DNA's-The data suggest that DNA's of types a, b, and pete for the same cells in Rd populations. When Rd populations are exposed simultaneously to 2 of these 3 DNA's in different concentrations the proportion which each type contributes to the total type-specific cells induced is closely correlated with the concentration of the corresponding DNA. Exclusion of DNA's.-Induction of one type specificity or streptomycin resistance can pletely prevented in a population containing susceptible cells by previous exposure for 15 minutes to a 1000-fold higher concentration of another type-specific DNA. |
13163326 | The antigenicity of rat collagen. | A method is described for preparing purified collagen from the tail tendons of rats with minimal alteration from its native state. This purified collagen is soluble in dilute acetic acid and when injected intraperitoneally into rabbits plement-fixing antibodies in low titer. It has been demonstrated by the use of certain immunological tests, enzymatic analyses, and electron microscopy that these antibodies are probably directed specifically toward collagen rather than toward panying impurities such as tissue proteins or polysaccharides. Evidence is presented suggesting that collagen exhibits species specificity. |
13163327 | Studies on variants of poliomyelitis virus. I. Experimental segregation and properties of avirulent variants of three immunologic types. | Attempts were made to "convert" highly virulent strains of the 3 immunologic types of poliomyelitis virus (Mahoney, Y-SK, and Leon) into avirulent variants. Tests involving intracerebral, intramuscular, or oral administration of virus to cynomolgus monkeys indicated that mere propagation in cultures of kidney tissue of cynomolgus monkeys had no effect on virulence when single or small numbers of virus particles were used as seed, and harvests were delayed for 24 hours or more after the appearance of cytopathogenic change. On the other hand, passages at 24 hour intervals with large inocula (10(5) to 10(6) TCD(60)) produced culture fluids with diminished virulence and unusual patterns of response in cynomolgus monkeys. Purification of such culture fluids by the terminal dilution technique yielded modified strains which proved to be avirulent after administration by the intracerebral, intramuscular, or oral routes in cynomolgus monkeys. Neither paralysis nor CNS lesions were found in any of more than 80 monkeys inoculated intracerebrally with various amounts of virus. However, focal neuronal lesions were found in the spinal cord of 3 of 48 monkeys inoculated intramuscularly with various amounts of the Mahoney variant, in 2 of 20 receiving the Y-SK variant, though in none of 40 inoculated with various amounts of the Leon variant. Virus recovered from the spinal cord of one of the monkeys in the Mahoney group produced no paralysis on intracerebral passage in monkeys. It is assumed that all 3 modified viruses possess a limited capacity to affect lower motor neurones of cynomolgus monkeys when these are directly exposed to them by accidental intraneural or traumatic intracerebral injection. On propagation in cynomolgus kidney cultures the modified viruses reached titers of approximately 10(7) TCD(50) per ml., as measured by cytopathogenic activity on renal epithelial cells in vitro, yet produced no perceptible pathologic changes in the muscles, kidneys, testes, ovaries, heart, pancreas, adrenals, liver, or spleen of cynomolgus monkeys inoculated intramuscularly. The modified viruses were immunogenic after intramuscular injection, but a large proportion of cynomolgus monkeys failed to develop antibody after small doses, indicating that in this host the experimentally produced variants multiplied less readily in non-nervous tissue than the virulent parent strains. Tests with the Type 1 virus showed that the orally administered avirulent variant can induce the formation of antibody and bring about resistance to the occurrence of paralysis such as results from ingestion of the virulent, parent strain. The Types 1 and 2 modified viruses are paralytogenic in mice after direct spinal inoculation whereas the Type 3 virus is not. The Type 1 virus became paralytogenic for mice when it lost its virulence for cynomolgus monkeys by the indicated routes. The Type 2 virus lost its virulence for mice by the intracerebral but not intraspinal routes when it was still fully virulent for cynomolgus monkeys, and retained its paralytogenic activity in intraspinally inoculated mice after it had lost its virulence for cynomolgus monkeys by the indicated routes. The parent Type 3 virus was paralytogenic in intraspinally inoculated mice when it was still fully virulent for cynomolgus monkeys, but this property disappeared in the modified virus when it became avirulent for monkeys. |
13163328 | Immunochemical studies of antitoxin produced in normal and allergic individuals hyperimmunized with diphtheria toxoid. IV. Differences between human precipitating and non-precipitating skin-sensitizing diphtheria antitoxin as shown by electrophoresis. | Electrophoresis on a starch-supporting medium was used to fractionate sera containing human diphtheria antitoxin of the following varieties (a) precipitating antitoxin, (b) non-precipitating skin-sensitizing antitoxin, and (c) mixtures containing precipitating and skin-sensitizing antitoxins. Aliquots of the protein fractions thus separated were tested for activity using the rabbit toxin neutralization test, precipitin techniques, and passive transfer tests in human skin. Non-precipitating, skin-sensitizing diphtheria antitoxin migrated largely as a fast moving gamma (gamma(1)) globulin. Passive transfer studies of isolated antitoxic fractions showed that they were as potent as whole serum in the ability to cause immediate wheal reactions. These fractions were not precipitable using appropriate quantities of purified toxoid. Precipitating diphtheria antitoxin migrated largely as a slow moving gamma (gamma(2)) globulin. Isolated antitoxic fractions of appropriate strength obtained from representative sera were precipitable by toxin and were unable to cause immediate wheal reactions upon toxoid challenge in human recipients. Mixtures of skin-sensitizing and precipitating antitoxins were separable by the technique of starch electrophoresis. The ponents removed from mixtures by this method retained the properties by which they could be characterized in whole serum. |
13163329 | Cellular mechanisms of protein metabolism in the nephron. I. The structural aspects of proteinuria; tubular absorption, droplet formation, and the disposal of proteins. | When proteins pass the glomerular filter they are in part directly absorbed by the epithelial cells of the proximal convolution of the nephron with no apparent alteration of the cytological pattern. If the capacity of the tubule cells to thus absorb protein from the tubule fluid is exceeded either by the amount or the nature of the protein the accessory mechanism of droplet formation occurs. This accessory mechanism is an intracellular process in which cytoplasmic elements, the mitochondria with their enzymes, and the absorbed bine to form droplets. As the droplets form and then disappear from the renal cells their evolution presents a constantly changing picture depending on the varying nature of their protein and cytoplasmic content. The droplet is therefore not a cytological structure of fixed characteristics (hyaline droplet) but a locus of metabolic activity and varied structural aspect. |
13163330 | Cellular mechanisms of protein metabolism in the nephron. II. The histochemical characteristics of protein absorption droplets. | Histochemical methods show not only the presence of absorbed protein in the cellular droplet, but also the general identity of its constituent substances with those of the mitochondrial rodlets. Both contain considerable amounts of phospholipid and probably some PNA. The reactivity of the cytoplasmic constituents in droplet and in rodlet are different, however, since in the droplet these substances stain more intensely. As judged by variations observed in this intensity during the evolution of the droplet, these constituents and the absorbed protein vary in their proportions and amount. The droplet would appear to be a highly active center of protein metabolism. |
13163331 | Cellular mechanisms of protein metabolism in the nephron. III. The histochemical characteristics of amino acid droplets. | 1. The cells of the proximal convolutions of the rat can be filled with fine droplets by the administration of certain amino acids in non-toxic dosage. 2. These minute droplets resemble in their Gram positivity and in their phospholipid and PNA content on biochemical analysis (3) the larger droplets that form in the cells of the proximal convolution during the absorption of certain proteins. 3. The positive or negative reaction to 3 specific histochemical procedures of the fine droplets forming after administration of 7 amino acids gave such a high positive correlation with theoretical assumption as to warrant the following inferences: (a) that the methods are specific under the conditions of the experiment; (b) that the droplets contain a higher concentration of the administered amino acid than the general cytoplasm of the cells which contain them. 4. The mitochondrial rodlets of epithelium of the proximal convolution contain sulfhydryl in high concentration, a finding which correlates well with their enzymatic activity. |
13163332 | Cellular mechanisms of protein metabolism in the nephron. IV. The partition of succinoxidase and cytochrome oxidase activities in the cells of the proximal convolution of the rat after intraperitoneal injection of egg white. | 1. Shifts of enzymatic activity have been followed during the formation and evolution of the droplets that form in the cells of the proximal convolution of the nephron of the rat after the injection of a 50 per cent solution of egg white in isotonic saline. 2. Twelve hours after injection there is a 35 to 40 per cent decrease in succinoxidase and cytochrome oxidase activities in the fraction containing the larger particles; i.e. mitochondria and droplets in equal concentration. Although after 30 hours the quantitative proportion of droplets and mitochondria is the same as previously, the activities of the fraction have returned to the normal observed originally in the uninjected rat in a corresponding fraction consisting of mitochondria only. 3. The microsome fraction shows an average increase of 35 per cent in oxidative enzyme activities during the early period following injection, and decreases to the original figure in the later period of droplet formation. 4. It is concluded from the shifting pattern of localization of oxidative enzyme activity within the cell particulates that the absorption droplets arise by the incorporation of the mitochondrial elements, which originally contain the highest enzyme activity, with absorbed protein through the intermediate stage of smaller (microsomal) particles. |
13163333 | Cellular mechanisms of protein metabolism in the nephron. V. The intracellular partition and the incorporation into protein of intravenously injected L-lysine. | Parenteral injection of amino acids resulted in the formation of Gram-positive droplets in the cytoplasm of the proximal convoluted tubule cells of the kidney of the rat within 15 minutes after intravenous administration. At this time the free alpha amino nitrogen in the cortex of the kidney had increased 2-fold. At the end of 1 hour this level was still somewhat higher than that of the control animals. The administration of increasing amounts of the amino acid disclosed the existence of a maximal concentration level in the renal cortex. When it was reached droplets appeared. Fractionation of the cells 15 minutes after the injection of lysine resulted in the recovery of free amino acid in the supernatant fluid but 1 hour after the injection lysine was contained within the particulate protein of the fractions which contain droplets. The increase in lysine was of the order of 2- 3-fold. It is concluded that the plex is a locus of amino acid concentration and metabolism within the cytoplasm of the renal cell. A method is described for the determination of lysine in micro quantities. |
13163334 | Filtration and reabsorption of protein by the kidney. | Plasma proteins of the rat have been labelled by the in vivo injection of the dye T-1824. From a study of the rate of disappearance of T-1824 from the circulating blood, and the total T-1824 content of the perfused kidney the rate of protein reabsorption from the glomerular fluid by the cells of the renal tubule has been calculated. It is concluded that protein reabsorption by the cells lining the proximal convoluted tubule of the rat kidney proceeds at a rate of at least 5 mg. per hour, equivalent to a daily filtration and reabsorption of 33 per cent of the circulating plasma protein. |
13163335 | Vitamin A and endochondral ossification in the rat as indicated by the use of sulfur-35 and phosphorus-32. | The administration of vitamin A to vitamin A-deficient rats resulted in a decreased concentration of inorganic sulfate-sulfur in the serum from a value of 2.5 mg. per cent to 1.8 mg. per cent, the latter being close to the value of 2.0 mg. per cent found in normal rats of the same age. The uptake of sulfate and phosphate by femurs and tibiae of vitamin A-deficient rats was less than that in normal rats of the same age. An increased uptake followed the administration of vitamin A: radioautography indicated that in the case of sulfate, its uptake was particularly increased in the epiphyseal cartilage; an increased uptake of phosphate was particularly evident in the diaphysis immediately adjacent to the epiphyseal cartilage plate. The specific activity of the sulfate-sulfur in the chondroitin sulfate samples isolated from the skeletons of vitamin A-deficient rats fell progressively as the deficiency continued. Following administration of vitamin A, the specific activity approached and exceeded the value given by the sample from the skeletons of normal rats of the same age. A substantial increase was found in the value of the specific activity of the sulfate-sulfur of sulfomucopolysaccharides isolated from skins of vitamin A-deficient rats that had been given vitamin A. Following administration of vitamin A to rats deficient in this vitamin, an increased accumulation of some sulfur-containing material was found in regions of active calcification. |
13163336 | Vitamin D and endochondral ossification in the rat as indicated by the use of sulfur-35 and phosphorus-32. | The concentration of inorganic sulfate-sulfur in the serum of vitamin D-deficient rats, 2.6 to 3.5 mg. per cent, was found to be higher than that in the serum of normal rats of the same age, 2.0 mg. per cent. No change was observed following the administration of 25 gamma of vitamin D(2). In accord with the results of others, it was found that a definitely increased deposition of phosphorus in femurs and tibiae had occurred 36 to 48 hours after the administration of vitamin D(2) to vitamin D-deficient rats. An immediate increase in the uptake of sulfate by the skeleton was found using sodium sulfate-S(35). As measured by the specific activity of sulfate-sulfur in samples of chondroitin sulfate isolated from the skeletons of the vitamin D-deficient animals and from normal controls receiving equal doses of sulfur-35, the rate of synthesis of chondroitin sulfate in rachitic rats is similar to the rate in normal rats of the same age. Likewise, the incorporation of labelled sulfate into the sulfomuco-polysaccharides of the pelts was found to be equal at 12 hours to that in normal rats. Following the administration of vitamin D(2) to deficient animals an increase in the rate of synthesis of the chondroitin sulfate of the skeletons was noted. The radiochemical and radioautographic evidence suggest that there is in vitamin D-deficient rats an impaired utilization of chondroitin sulfate and that vitamin D(2) is able to accelerate this process. |
13163337 | Studies on host-virus interactions in the chick embryo-influenza virus system. | The usefulness of the deembryonation technic has been analyzed as a tool in the study of various problems in the growth cycle of influenza virus in the entodermal cells of the allantoic of chick embryos. Various improvements in the deembryonation technic have been described. The method readily permits repeated sampling of the medium at various stages after infection (cumulative growth curves) or frequent exchanges of the medium (differential growth curve). However, the yield of infectious virus or of hemagglutinins is less than that observed in the intact chick embryo. The difference observed is greater than can be accounted for by the reduction in the available host cells and is assumed, therefore, to be due in part to interruption of blood and nutrient supply to the cells. This handicap can be e by bined in ovo-deembryonation technic, in which deembryonation is performed at any desired time after infection of the intact chick embryo, and the medium is collected and analyzed after 1 to 3 hours of further incubation. The value of the technic is demonstrated by the fact that liberation of virus from infected cells can be detected earlier than in the intact egg. Furthermore, it continues at a nearly constant rate for many hours, thus proving to be erroneous previous inference which had been based upon in ovo experiments. The technic also permits readily the addition and subsequent removal of substances that might interfere with viral propagation. As an example a study was made of the effect of the receptor-destroying enzyme of V. cholerae (RDE) when added to the medium of eggs infected prior to deembryonation. By carefully grading the dose of virus and using an appropriate amount of RDE, one-step growth curves were obtained indicating that those cells not directly invaded by the seed virus were subsequently protected against infection by action of the enzyme. The smaller the amount of virus the less RDE was required in order to note a protective effect. With a decrease in the period of exposure to RDE regeneration of cell receptors became increasingly more apparent in that correspondingly greater amounts of virus were produced and liberated late in the incubation periods. These results confirmed and extended those reported by Stone. More extensive applications of these technics will be reported in subsequent papers of this series. |
13163338 | Studies on host-virus interactions in the chick embryo-influenza virus system. IX. The period of liberation of virus from infected cells. | The period and rate of liberation of influenza virus from entodermal cells of the allantois have been studied by deembryonating eggs within a few minutes after infection, exchanging the medium thereafter at hourly intervals and assaying the virus concentration in the harvests thus obtained (differential growth curves). If the inoculum was sufficiently large, presumably all available cells immediately became infected and only 1 infectious cycle was expected to occur. If the inoculum was small, so that only a fraction of the cells adsorbed virus, the infectious process was held to 1 cycle by continuous exposure of the remaining susceptible cells to RDE. In either case, the results obtained indicate that once cells have been infected they produce and liberate virus at nearly constant rates for periods of 30 hours or longer before the yields decrease rapidly. Evidence has been presented which strongly suggests that such prolonged periods of liberation are observed not only in deembryonated eggs but also in the intact chick embryo. Attempts have been made in the discussion to reconcile these findings with previous estimates of the liberation period and to integrate them with histologic observations and electron micrographs of thin sections of infected allantoic membranes having a bearing on the mode of liberation. |
13163339 | The occurrence during acute infections of a protein not normally present in the blood. V. Physical-chemical properties of the C-reactive protein crystallized by a modified technique. | A method is described for obtaining crystalline C-reactive protein from serous fluids in which the protein is associated with lipid. Most pathological fluids currently available as a source of this protein appear to fall in this category. Crystalline C-reactive protein has its isoelectric point at pH 4.82 as determined by free electrophoresis in McIlvaine's buffer. Its mobility in the electrophoresis cell, both alone and after addition to normal serum, coincides with that of the beta-globulin fraction of the serum. In contrast to this finding, by the method of zone electrophoresis on a starch supporting medium the protein migrates with the gamma(1)-globulin. The significance of this discrepancy is discussed. Studies in the ultracentrifuge indicate an s(20,w) of 7.5. |
13163340 | The effects on biological materials of freezing and drying by vacuum sublimation. I. Development and testing of apparatus. | A vacuum sublimation apparatus is described which will permit, (a) the removal of water from virus suspensions at temperatures ranging down to -80 degrees C., (b) continuous operation with a minimum of attention from the investigator, (c) sealing off of samples at operating pressures (10(-5) mm. Hg), (d) simultaneous lyophilization of aliquot samples at different temperatures, (e) isolation of a portion of the apparatus without disturbing the remainder of the system, and (f) determination of the end-point of sublimation without disturbing the samples. The time required for drying 0.1 ml. of influenza virus suspension was shown to increase markedly with decrease of temperature, 8 days being required for dehydration at -80 degrees C. in contrast to 2 days at -30 degrees C. and 1 day at 0 degrees C. |
13163341 | The effects on biological materials of freezing and drying by vacuum sublimation. II. Effect on influenza virus. | The infectivity titre of influenza virus-infected allantoic fluid was determined after a variety of procedures involving cyclic slow freezing and thawing, freezing at various rates with subsequent storage at different temperatures freezing at various rates with subsequent dehydration at various temperatures, and different degrees of dehydration. All these factors were found to influence the survival rate of the virus particles. Five freeze-thaw cycles resulted in a fall in titre from 10(-8.6) to 10(-0.8) cycles 2, 3, and 4 causing much greater losses than cycles 1 and 5. Rapid cooling to -40 degrees C. or slow cooling to -80 or 190 degrees C. did not cause significant titre loss, but rapid cooling to temperatures above -40 degrees or slow cooling to temperatures above -80 degrees C. caused definite titre loss. Loss of titre on storage occurred only at temperatures above -40deg;C. The effect of lyophilization depends both on the preliminary treatment and on the dehydration temperature. Better conservation of titre was obtained after preliminary cooling to -190 or -80 degrees C. than after preliminary cooling to higher temperatures. The most effective sublimation temperatures were 0 and -80 degrees .; the least effective was +20 degrees C. Titre losses in suspensions sublimated at -10, -30, and -60 degrees C. were in general intermediate. No loss in titre occurred after preliminary cooling to -80 or -190 degrees C. and subsequent dehydration at -80 or 0 degrees C. The degree of dehydration definitely affects the survival of virus on storage at 0 degrees C., but sublimation for 4 hours at 0 degrees C. plete protection against titre loss on storage at this temperature. Possible explanations of the observations made are suggested, based on known physiochemical phenomena such as supercooling, vitrification, variations in size and shape of ice crystals with different freezing speeds, differential enzyme inactivation, changes in salt concentration, and changes in energy levels. |
13163342 | The binding of penicillin in relation to its cytotoxic action. II. The reactivity with penicillin of resistant variants of streptococci, pneumococci, and staphylococci. | 1. In a previous study, the differing sensitivity of bacterial strains as they occur in nature appeared to be correlated with their correspondingly differing reactivity with penicillin. Presumably, the over-all reactivity of the cell with penicillin paralleled that of the vulnerable ponent(s). However, when penicillin-resistant variants of these strains (Streptococcus pyogenes, Micrococcus pyogenes, Diplococcus pneumoniae, and Streptococcus faecalis) were produced by serial passage through increasing concentrations of antibiotic, this correlation between resistance and the ability of the cell to bind penicillin was no longer apparent. Some resistant variants bound more penicillin than the parent, sensitive cell (Streptococcus faecalis, Micrococcus pyogenes), some were unchanged in their reactivity (Diplococcus pneumoniae, Micrococcus pyogenes), and some bound less (Streptococcus pyogenes, Micrococcus pyogenes). One resistant variant of Micrococcus pyogenes at first showed enhanced reactivity with penicillin; on continued passage through antibiotic, there was a further increase in resistance, but now associated with a significantly decreased reactivity. In the case of Diplococcus pneumoniae, a resistant variant at first reacted normally with penicillin; on continued passage in antibiotic, its binding affinity for penicillin gradually decreased, but with no associated further increase in resistance. 2. The reactivity with penicillin of cell-free sonic extracts of the resistant variants paralleled that of the intact organisms. Permeability considerations therefore did not seem involved in the increased resistance produced by serial passage in antibiotic. 3. The penicillin-resistant variants did not have an enhanced capacity to degrade the free intracellular antibiotic. 4. Possible alternative explanations are discussed in the text. |
13163343 | The binding of penicillin in relation to its cytotoxic action. III. The binding of penicillin by mammalian cells in tissue culture (HeLa and L strains). | 1. (a) Mammalian cells in tissue culture (mouse fibroblasts and malignant human uterine epithelium) did not concentrate penicillin from the culture medium. Even at low concentrations, the cellular accumulation was usually less than that in the surrounding fluid, and most of it was removed by washing. The radioactive material in such eluates was actively bactericidal, and was presumably in large part unchanged penicillin. (b) Penicilloic acid, produced by the action of penicillinase, was bound to the same (limited) extent as the active antibiotic. In both these respects mammalian cells behaved like naturally penicillin-resistant bacteria, and unlike such penicillin-sensitive bacteria as Streptococcus pyogenes or Diplococcus pneumoniae. 2. Cell-free sonic extracts of the L strain had the same limited reactivity with penicillin as the intact cells. The relatively minute amounts bound by the cells are therefore not due to their impermeability, but instead reflect the inherently low reactivity of the cellular constituents with penicillin. 3. It is suggested that the relative non-toxicity of penicillin for the mammalian host, and for mammalian cells in tissue culture, may be related to this low order of reactivity with the antibiotic. |
13163358 | Photosynthesis by protoplasm extruded from Chara and Nitella. | (a) Photosynthesis with protoplasm isolated from Chara or Nitella as measured by C(14) fixation has been obtained at a rate 12 to 15 per cent of that of the whole cells. (b) Photosynthesis by cut cells of Chara or Nitella with the vacuolar sap removed was at a parable to that of the whole cells. (c) Both the protoplasm and the cut cells reduced CO(2) in the light to sucrose and hexose phosphates. Other products formed were also detected by paper chromatography. In contrast, dark controls fixed the C(14) into products associated with plant respiration. (d) An important difference in the products from the extruded protoplasm was the absence of C(14)-labelled pentoses or sedoheptulose which were formed, however, by the whole or cut cells. This suggests that the most sensitive site affected by disruption of the cells may be the steps involved in the regeneration of the "C-2 acceptor" for CO(2) fixation in photosynthesis. |
13163359 | Silicon metabolism in diatoms. I. Evidence for the role of reduced sulfur compounds in silicon utilization. | 1. Cells of the fresh water diatom Navicula pelliculosa may be grown in a mineral medium containing a low concentration of silicon. When transferred to a fresh silicate solution and incubated under non-growing conditions such deficient cells rapidly take up silicon from the medium. 2. The utilization of silicon is an aerobic process. 3. When deficient cells are washed with distilled water or saline, their ability to utilize silicon is impaired whereas respiration is unaffected. 4. The ability of washed cells to take up silicon can be partially restored with sulfate or ascorbic acid, and pletely restored by Na(2)S, Na(2)S(2)O(3), glutathione, l-cysteine, dl-methionine, or ascorbic acid plus sulfate. 5. The sulfhydryl reagent, CdCl(2), inhibits silicon utilization of unwashed cells at concentrations which do not affect respiration. This inhibition similarly is reversed by glutathione or cysteine. 6. However, sodium iodoacetate or sodium arsenite inhibits respiration and silicon utilization at the same concentrations. 7. The silicon taken up by deficient cells is deposited at the cell surface as a thickening of the existing silica frustules. 8. Sulfhydryl groups in the cell membrane may be involved in silicon uptake by diatoms. |
13163360 | Evidence for the presence of separate mechanisms regulating potassium and sodium distribution in Ulva lactuca. | 1. The methods employed in these and preceding (25-27) studies were shown to allow analysis of true cellular sodium and potassium concentrations. 2. The rate of reaccumulation of potassium by potassium-deficient cells is independent of the presence or absence of sodium in the external medium. 3. Phenylurethane (10(-3)M), a photosynthetic and metabolic inhibitor, causes a marked progressive loss of potassium and gain of sodium, both of which changes pletely reversible on transferring the samples to running sea water. 4. Iodoacetate, while not effective in causing potassium and sodium shifts in the light, effects a loss of potassium and a gain of sodium in the light in the presence of phenylurethane. 5. Arsenate (5 x pletely protects Ulva against the potassium loss usually observed with iodoacetate in the dark while it affords no protection against the sodium influx under the same conditions. Arsenate given after 18 to 20 hours in iodoacetate gives significant protection against potassium loss in the dark, and allows a slight net reaccumulation of potassium in the light. Arsenate in the dark after iodoacetate affords no protection against the sodium uptake caused by iodoacetate in the dark, while in the light under the same conditions sodium is rapidly secreted to the control level within a few hours. This resecretion of sodium is thought to be primarily an effect of light, the presence of arsenate being incidental. 6. The "decoupling agent" 4,6-dinitro-o-cresol causes a marked progressive increase in cellular sodium and a drop in cellular potassium, though the kinetics of these two movements are distinctly different from each other. 7. Pyruvate (50 mg. per cent) given with iodoacetate (2 x 10(-3)M) for 5 hours in the pletely prevents the sodium increase caused by iodoacetate, while affording less protection against the potassium loss. Phosphoglycerate, on the other hand, offers more protection against potassium loss, and essentially none against the sodium gain. 8. ATP added in small amounts at short intervals to samples maintained in 10(-3)M iodoacetate in the dark affords significant protection against the potassium loss observed in iodoacetate. Cellular sodium is somewhat higher in the ATP-iodoacetate samples than in the iodoacetate samples. 9. In the discussion of the data presented two major points are emphasized: (1) the close correlation between cellular metabolism and normal cation control; (2) two mechanisms must be operative in cation regulation in this organism: one for moving potassium inwards and the other for transporting sodium outwards. These mechanisms are independent of each other. |
13163361 | Experimental variations in sonic fragility of red cells. | A magnetostriction oscillator has been used for determining the relative fragility of human red cells to 9000 cycle vibrations under some different environmental conditions. The destruction of the cells is a logarithmic function of time according to the equation See PDF for Equation. Hypertonic saline solution, saponin, preheating, alcohol, and ether in subhemolytic concentrations decrease the fragility of human red cells subjected to sonic oscillation. Hypotonic saline, preheating to 50 degrees C. for 3 minutes, and hemolytic concentrations of ether increase the fragility of red cells to 9 kc. vibrations. Following preheating of the cells, and in the presence of saponin the destruction deviates slightly from a true logarithmic rate of hemolysis. |
13163362 | Potassium uptake by the dog erythrocyte. | The inward transport of potassium by separated dog erythrocytes has been studied at concentrations of potassium in the medium from 2.9 to 25.0 m.eq./liter and at 38.0 and 33.0 degrees C. At the physiological concentration of external potassium (4.06 m.eq./liter medium), the inward potassium flux is 0.11 m.eq./liter cells hour and the glucose consumption is 2.0 mM/liter cells hour. The dependence of potassium influx on extracellular potassium concentration is given by the following equation, K influx (m.eq./liter cells hour) = 0.028 [K](amb.) - 0.003 in which [K](amb.) refers to the potassium concentration in the medium. In a single 93 hour experiment, 94 per cent of the intracellular potassium was exchanged at an apparently uniform rate. The average apparent activation energy for the process is 7,750 calories +/- 2,000 calories/mol and there is some indication that the apparent activation energy of inward K transport decreases with increasing external K concentration. |
13163363 | The effect of ACTH and adrenal steroids on K transport in human erythrocytes. | The effect of ACTH and adrenal steroids on K transport in human erythrocytes has been studied. A new method of calculation has revealed that in normal human erythrocytes the K transport is not independent of external K concentration as had previously been thought. The equation describing the relationship is, K influx (m.eq./liter cells hour) = [K](pi)/(0.697 + 0.329 [K](pi)) in which [K](pi) refers to the plasma K concentration at the beginning of the experiment. At the physiological plasma K concentration of 4.65 m.eq./liter, K influx is 2.09 m.eq./liter cells hour; K efflux is 1.95 m.eq./liter cells hour and is independent of plasma K concentration. The effect of the infusion of ACTH and adrenal steroids on the K content of the erythrocytes was also studied. Infusions of ACTH or cortisone do not cause the expected loss in erythrocyte K content and may well cause a gain. Infusions of ACTH and cortisone decrease the rate of K influx and efflux slightly at all stages of the infusion, as measured in vitro in blood samples drawn at various times during and following the infusion. However, the erythrocytes incubated in vitro do not exhibit the same changes in K content as are found in vivo. Hydrocortisone added to normal cells in vitro also decreases both influx and efflux of K, without affecting the K content of the cells. |
13163364 | The role of high ionic concentrations in protection against X-irradiation. | Various levels of protection against x-irradiation damage in bacteriophage T1 may be obtained by the addition of inorganic salts to the aqueous virus suspensions during irradiation. The highest survival values are obtained with the nitrite salts, and their protective power is attributed primarily to their function as reducing agents. The nitrate ion shows greater protection than the corresponding sulfate or chloride ions. This may be due in part to the lower energy level of the nitrate ion, by reason of resonance. Since greater expenditure of incident energy is required to raise the ion from the ground state, the energy thus dissipated may be ineffective in the inactivation of virus particles. The ammonium salts exhibit protection of a different order of magnitude from that of the metallic salts. It is postulated that NH(4) (+) protects in a threefold way: (a) dehydration, (b) reduction, in which the ammonia is oxidized to nitrite and the nitrite to nitrate, and (c) stabilization of the virus protein. Metallic salts likewise protect, but a point of maximum protection is reached in lower concentrations than in the case of the ammonium salts. After this maximum protection is reached, there is a rapid decline in survival with increased concentration. This prevents protection of the order of magnitude that can be obtained with the ammonium salts. It is postulated that a specific cationic interaction with the phage may be responsible for the decreased protection. Bacteriophage is protected during x-irradiation by an alkaline pH, in the case of NH(4)OH. This protection could not be produced with NaOH, presumably because of the greater hydrolysis of the ponents of the virus particle in solutions of NaOH, whereas NH(4)OH stabilizes the protein. |
13163365 | The identity of the fluorescent and delayed light emission spectra in Chlorella. | 1. The delayed light emission of Chlorella pyrenoidosa over the wave length range 400 to 950 mmicro has been investigated. 2. Emission of delayed light is confined to the range 600 to 800 mmicro. 3. To the precision with which the low light intensities involved can be measured with the apparatus in these experiments, the emission spectrum of the delayed light is the same as the spectrum of the fluorescent light. 4. Thus the delayed light e from excited chlorophyll. |
13163366 | The isolation of a staphylococcal phage variant susceptible to an unusual host control. | A series of phage P(1) variants was isolated from plaques developing on S. aureus WF 145. One in particular, phage 14, was studied in detail because its host range appeared to be dependent on the previous host of production; i.e., it was subject to a host control. When this phage was produced on host K(1) its lysate assayed equally well on both 145 and K(1) cells. When produced on host 145, however, it assayed manyfold higher on 145 than on host K(1). All its particles adsorbed on K(1) cells, but only a small percentage were able to produce plaques. No differences could be found in adsorption rates, latent periods, or burst sizes of the phage on the two hosts. No extracellular inactivating substances could be detected which could account for such changes, nor could the results be explained readily on a mutational basis, since distinct phage strains could not be isolated. The change in virus properties was found to occur in the first burst of singly infected host 145 cells, regardless of the previous host or its prior lytic abilities. Heat inactivation destroyed activity for K(1) cells more rapidly than for 145 cells. This was found to be a property of both the stock phage P(1) and phage 14. Phage 14 could be heated until there remained particles which could multiply only on strain 145. When the plaques of such survivors were examined they were found to contain phage which could multiply on both hosts in a ratio characteristic of the original unheated preparation. The data suggest that the observed changes were caused by a host control over the formation of a phage material(s) necessary for successful infection of host K(1). Such a substance theoretically could be related to the labile material destroyed by heat and required for plaque formation on host K(1). |
13174778 | Membrane potentials in the Donnan equilibrium. II. | Measurements were made of electromotive force in the Donnan equilibrium of systems containing dilute solutions of protein and acid. Removal of the membrane produced a decrease of no more than 2 to 4 mv. in electromotive force, while the membrane potentials, as estimated by the usual arbitrary assumption, were of the order of 12 to 34 mv. Ion ratios, as calculated from analyses for total chloride, were definitely greater than those calculated from the electromotive force of cells with salt bridges, as if there had bination of some of the chloride ion with protein. |
13174779 | Nutritional control of sexuality in Chlamydomonas reinhardi. | 1. Cells of Chlamydomonas reinhardi grown in the light or dark on standard medium require an additional exposure to light in the absence of a nitrogen source, in order to e sexually active. As the culture ages, the light requirement decreases. 2. This light requirement is a function of nitrogen depletion, as shown by the observation that cells from cultures grown to maturity on a low nitrogen medium in the light or in the dark, have no additional light requirement for zygote formation. The withholding of no ponent of the medium has this effect. 3. In cells requiring light for zygote formation, the light can be supplied before the mating types are mixed, indicating that light is required, not for mating per se, but for the conversion of vegetative cells to gametes. 4. Gametes can be dedifferentiated to the vegetative state by any pound which the cells can use for growth; and by further exposure to light in the absence of a nitrogen source, these vegetative cells can again e gametic. 5. Cells grown at different nitrogen levels e gametic at widely different cell concentrations of nitrogen and carbon and C/N ratios. 6. It is postulated that the role of light in gametic differentiation is indirect, providing by photosynthesis, energy for the mating process and carbohydrates to tie up excess nitrogenous reserves; and that the concentration of some particular nitrogen fraction pound determines whether or not gametic differentiation is initiated. |
13174780 | Olfactory responses of blowflies to aliphatic aldehydes. | The response of the blowfly Phormia regina to stimulation by aldehydes in the vapor phase has been studied by means of a specially designed olfactometer. The median rejection threshold and the maximum acceptance threshold were selected as criteria of response. For both acceptance and rejection the distribution of thresholds in the population is normal with respect to the logarithm of concentration. When thresholds are expressed as molar concentrations, the values decrease progressively as chain length is increased. There is no attraction beyond decanal and no rejection beyond dodecanal. When thresholds are expressed as activities, most members of the aldehyde series are approximately equally stimulating at rejection and equally stimulating at acceptance. The relationship is most exact over the middle range of chain lengths. There is a tendency for the terminal members to stimulate at higher activities. These relationships are in close agreement with those which were found earlier to apply to the normal aliphatic alcohols. The similarity between the relative actions of the members of the two series suggests that the relation of equal olfactory stimulation at equal thermodynamic activities by homologous pounds at least for homologues of intermediate chain length may be of rather general application in olfaction. |
13174781 | Use of a glass electrode for measuring rapid changes in photosynthetic rates. | 1. A continuously recording glass electrode apparatus has been described for measuring carbon dioxide concentration changes in solution. The limits of applicability of the apparatus have been analyzed. 2. The glass electrode apparatus has been used for the measurement of transient rates of photosynthesis by algal suspensions. 3. The decline of the photosynthetic rate in high light at carbon dioxide partial pressures less than 0.5 per cent atmosphere, observed in the glass electrode apparatus, has been confirmed by steady state experiments in which flowing gas streams were analyzed. |
13174782 | The effect of formaldehyde on the oxygen equilibrium of hemoglobin. | 1. When formaldehyde (0.10 M) is added to solutions of human hemoglobin, the oxygen affinity of the hemoglobin increases considerably (more than tenfold near pH 7). The interaction between hemes of the same hemoglobin molecule decreases, as shown by a drop in the value of n in Hill's equation from 2.9 to 1.5 or less. 2. In the presence of formaldehyde, both n and the oxygen pressure for half-saturation fall gradually as the pH rises in the range from pH 6.2 to 7.2. 3. Some of the effect of formaldehyde on the oxygen equilibrium may be due bination with sulfhydryl groups of the protein, but nitrogenous groups are probably also involved. |
13174783 | The compound of potential in a stimulated dorsal root. | The electrotonic potential appearing in a stimulated dorsal root is found to be the resultant of two independent systems of current of different origin. ponent, labelled DRalpha, is non-occluding. The ponent, labelled DRbeta, occludes strongly and has the characteristics of the potential which appears in a neighboring unstimulated rootlet (DRIV-V). Because DRalpha does not occlude, its origin is assigned to the primary afferent neuron. The result of a general examination of its origin leads to the additional conclusion that it must arise from a physiological spatial gradient in the post-spike recovery cycle of membrane potential along the afferent neuron. The specific locus of this gradient within the primary neuron is the subject of the succeeding paper (16). |
13174784 | On the role of the spinal afferent neuron as a generator of extracellular current. | The prediction that a system of currents flows between the dorsal column and the dorsal root due to differences in their after-potentials was found to be consistent with the experimental findings. The form, magnitude, duration, and sign of the ponent DRalpha fulfill the requirements of the postulated system. A contribution of tract after-potentials to the evoked potential of intramedullary structures is indicated. It is a conclusion of this and previous studies that profound changes occur in certain membrane properties of myelinated primary afferent axons as they penetrate the central nervous system. The working concept of abrupt intraaxonal junctional regions is therefore justifiable. |
13174785 | Apparent violations of the all-or-none law in relation to potassium in the protoplasm. | The protoplasm of Nitella forms a thin layer surrounding a large central vacuole filled with sap. At the inner surface of the protoplasm is a non-aqueous layer called Y and at the outer surface is a similar layer called X. At each of these layers there is a potential due to the diffusion of KCl in contact with the layer. We thus have P = P(X) + P(Y) in which P is the total potential, P(X) is the potential at X, and P(Y) the potential at Y. We assume that when stimulation occurs P(Y) disappears and P(X) remains unaltered. The loss of part of the potential therefore involves no violation of the all-or-none law since the Y layer loses all of its potential and the X layer loses nothing. If the concentration of KCl in the external solution and in the sap is known the concentration in the protoplasm can be calculated at each stimulation by measuring the height of the spike. |
13174786 | Electrical studies on the compound eye of Ligia occidentalis Dana (Crustacea: Isopoda). | The ERG of pound eye in freshly collected Ligia occidentalis, in response to high intensity light flashes of (1/8) second or longer duration, begins with a negative on-effect quickly followed by an early positive deflection, rapidly returns to the baseline during illumination, and ends with a positive off-effect. As the stimulus intensity is decreased the early positivity progressively decreases and the rapid return to the baseline is replaced by a slowing decline of the negative on-effect. Responses were recorded with one active electrode subcorneally situated in the illuminated eye, the reference electrode in the dark eye. The dark-adapted eye shows a facilitation of the amplitude and rates of rise and fall of the on-effect to a brief, high intensity light stimulus. This facilitation may persist for more than 2 minutes. Following light adaptation under conditions in which the human eye loses sensitivity by a factor of almost 40,000 the Ligia eye loses sensitivity by a factor of only 3. The flicker fusion frequency of the ERG may be as high as 120/second with a corneal illumination of 15,000 foot-candles. Bleeding an otherwise intact animal very rapidly results in a decline of amplitude, change of wave form, and loss of facilitation in the ERG. When the eye is deganglionated without bleeding the animal the isolated retina responds in the same manner as the intact eye. Histological examination of the Ligia receptor layer showed that each ommatidium contains three different retinula cell types, each of which may be responsible for a different aspect of the ERG. |
13182587 | Long-term studies of results of penicillin therapy in early syphilis. | In 1945, the US Public Health Service and co-operating treatment centres began a study of the results of penicillin therapy in a group of syphilis patients selected for intensive post-treatment observation. One objective was to test the hypothesis that patients lapsing from follow-up have the same experience as those remaining under observation, and evidence is presented which indicates that this is the case. The major objective was to evaluate the long-term results of penicillin in early syphilis. At the sixth year following penicillin treatment, satisfactory results were recorded for 98%-99% of the patients with primary and secondary syphilis (including those re-treated). There is no evidence that the cure of syphilis is enhanced by the addition of arsenic and bismuth. Seronegativity rates at the sixth post-treatment year were 81.0% for patients bined penicillin-arsenic-bismuth therapy, and 80.7% for those treated with penicillin alone, while re-treatment rates were 17.4% and 16.3%, respectively. When cases treated with "adequate" dosage of arsenic and bismuth are analysed by the same statistical method as that employed in evaluating penicillin, the superiority of penicillin is clearly evident. A minimum of 4,800,000 units of penicillin is mended for the treatment of early infectious syphilis. |
13182586 | A decade of reorientation in the treatment of venereal syphilis. | As experience with penicillin in the treatment of venereal syphilis has grown over the last decade, this drug, used without adjuvants, has e increasingly widely accepted as being effective, convenient, non-toxic, and relatively inexpensive. Metal chemotherapy required the use of repeated subcurative doses over a long period of time and was essentially suppressive in character; penicillin can be given in the form of repository preparations which ensure a treponemacidal blood-level of long duration. These can be given in large single doses or in repeated smaller doses; the therapeutic results will not vary whichever of these procedures is used.In the first part of this paper, the authors discuss the effect of penicillin and the time factor, the choice of penicillin preparation, the mode of administration, and the reaction to infection with Treponema pallidum. In the second part, they consider the present status of penicillin therapy in venereal syphilis, dealing with the principles of follow-up and control; with the treatment of early, latent, late, and congenital syphilis; and with the treatment of incubating syphilis and contacts. |
13182588 | A WHO study of treatment schedules for early syphilis in use throughout the world. | Ten years have elapsed since penicillin was introduced in the treatment of syphilis. In order to appraise recent trends in syphilotherapy in the world, WHO carried out a detailed study of treatment practices in early syphilis. A questionnaire was circulated to leading venereologists and clinics in the world, and 277 replies were received from 55 countries giving particulars of 294 schedules.A total of 65.3% of the participants used penicillin alone and 28.9% used it bination with other drugs. In North America all clinics relied solely on penicillin as against 52.2% in Europe; and procaine penicillin G in oil with aluminium monostearate (PAM) was used in 91% of clinics in the Americas and Asia and in 60.6% of European clinics. The mon dosage of penicillin in all stages of early syphilis was 4.8-6.0 million units; but appreciably larger doses were used in Europe than elsewhere, some 39.4% of schedules using 10.8 million units or more. There were single instances of 36 million units being given. Consolidation treatment was given in none of the North American clinics; seldom in Asia; by about one-third of the participants in Central and South America; and, for secondary syphilis, in 59% of European schedules.This study shows that with intensive treatment with PAM the saving in drug cost to clinics over the classical courses of arsenic and bismuth may be as much as pound4 per case, but the overhead expenses are, of course, not reduced. |
13182589 | Treatment of early infectious syphilis with N,N'-dibenzylethylenediamine dipenicillin G; a second report. | A new penicillin salt-N,N'-dibenzylethylenediamine dipenicillin G (Bicillin)(a)-was given, in single injections of 2,500,000 units, to 196 patients with early infectious syphilis. The seronegativity rates after three months were 65% for primary syphilis cases and 25% for secondary syphilis patients; after six months, the rates were 80% and 60%, respectively. At the end of the 21-month observation period, satisfactory results were recorded in 96.6%-100.0% of the primary syphilis patients, and in 92%-95% of those treated for secondary syphilis. The respective cumulative re-treatment rates were 3.4% and 4.1%.The results of the secondary syphilis treatment were pared with those obtained with single-injection schedules of 2,400,000 and 4,800,000 units of procaine penicillin G in oil with 2% aluminium monostearate (PAM). The cumulative re-treatment rates 21 months after treatment were: Bicillin, 4.1%; PAM (2.4 million units), 14.2%; and PAM (4.8 million units), 5.1%. It would thus appear that a single injection of 2,500,000 units of Bicillin is as effective as one of 4,800,000 units of PAM. |
13182590 | A report on syphilis control in Turkey. | This report presents the results of a six-month survey of the nature and extent of venereal diseases in Turkey which was undertaken by the author, on behalf of WHO, at the request of the Turkish Government. The first part of the report outlines the present venereal-disease-control system and includes descriptions of the work undertaken by public authorities, hospitals and dispensaries, mobile venereal-disease-control teams, and laboratories; in the second part, the author enumerates certain mendations for the intensification of the current control programme. These mendations are particularly concerned with the control of syphilis (since the incidence of other venereal diseases in Turkey is of very secondary importance), and with the expansion, standardization, and co-ordination of serodiagnostic facilities and services. It is suggested that there might be a gradual intensification and reorientation of the present programme. A proposed plan of operations for an eight-year period is described. |