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J G HIRSCH

Publications and source records attributed to J G HIRSCH.

At least 37 records · Page 2Linked to original sources
PubMed1960

Further studies on preparation and properties of phagocytin.

PHAGOCYTIN AND HISTONE DIFFER SIGNIFICANTLY IN THE FOLLOWING REGARDS: (a) the bactericidal action of histone is rapidly lost on peptic digestion, while that of phagocytin is but little affected; (b) the lethal effect of phagocytin on coliform bacteria is much more resistant than that of histone to antagonism by spermine or by increasing ionic strength of the medium; (c) phagocytin can be extracted from disrupted granulocytes with dilute citric acid whereas effective extraction of histone requires stronger mineral acid or strong salt solution; (d) phagocytin is limited in distribution to polymorphonuclear leucocytes while histone is demonstrable in many tissues. A new technique has been devised which permits extraction of phagocytin essentially free of lysozyme and histones. Phagocytin thus prepared kills certain Gram-positive bacteria as well as Gram-negative bacilli under appropriate in vitro test conditions. Among susceptible Gram-positive microbes are Group A streptococci and staphylococci. Phagocytin is demonstrable in citric acid extracts of granulocytes obtained from rabbit, man, horse, and guinea pig, the only species thus far investigated. Circulating blood leucocytes as well as exudate cells contain this bactericidal substance. The lethal effects of phagocytin on bacteria may be influenced, depending on the particular microorganism, by either pH or ionic strength of the medium. The bactericidal action of phagocytin is only slightly reduced following digestion with trypsin, chymotrypsin or papain. The active ingredient is, however, non-dialyzable and apparently precipitated by trichloracetic acid. Data available at present are insufficient to define the chemical nature of phagocytin.

Animals↗
PubMed1958

Bactericidal action of histone.

The arginine-rich fraction of calf thymus histone (histone B) exerts bactericidal activity on various coliform bacilli and micrococci under certain conditions in vitro. Final concentrations of less than 1 microg. histone per ml. kill susceptible microbes without detectable morphological alteration or lysis. Among the microorganisms highly susceptible to histone are Escherichia, Salmonella, Shigella, Pseudomonas, Klebsiella, and Micrococcus pyogenes var. albus. Less susceptible or completely resistant are Proteus, Serratia, Micrococcus pyogenes var. aureus, and various types of hemolytic streptococci. Coliforms grown on solid media are much more resistant to the lethal effect of histone than are those cultured in liquid media. This difference is apparently related to the physiological state of the bacteria; agar grown microorganisms washed with water remain resistant to histone, whereas incubation in broth rapidly renders them more susceptible. Histone is adsorbed onto heat-killed E. coli K-12 under conditions suitable for lethal action on this organism. The bactericidal activity of histone is but little affected by pH of the test system, but ionic strength of the medium exerts a marked influence, the lethal action being reduced or blocked as the salt concentration reaches levels higher than that of 0.15-0.2 M NaCl. Relatively high concentrations of rabbit serum or of bovine plasma albumin reduce the bactericidal activity of histone in a medium at pH 7; these serum preparations are, however, essentially without effect in the test system at pH 5.6. The bactericidal effect of histone is antagonized by addition to the medium of small amounts of certain basic substances (protamine, spermine), or of various acid polysaccharides (heparin, nucleic acid, bacterial lipopolysaccharides). The rate of killing of E. coli K-12 by histone increases as the temperature and the concentration of histone are raised. Within the limits studied, this rate also appears to be directly proportional to the concentration of bacteria in the system.

Animals↗
PubMed1958

The antibacterial activity of hemoglobin.

Low concentrations of hemoglobin (0.1 microg./ml. or less) exert a lethal action on some Gram-negative bacteria under certain conditions in vitro. Hemoglobins from various mammals and the distinct genetic types of human hemoglobin all manifest similar bactericidal activity. The bactericidal effect is a function of the globin moiety of the molecule; native and acid or acid-alcohol denatured globins have the same degree of activity. Hemoglobins kill enterobacteriaceae only under precisely controlled conditions. The test medium must be low in ionic concentration and acid in reaction. Various strains of Escherichia and Salmonella are susceptible to the lethal effect of hemoglobin, while the few strains of Shigella, Klebsiella, and Proteus examined were resistant. Certain acid polysaccharides and basic amines or proteins block the bactericidal effect when incorporated in the test in low concentration. Present evidence also suggests that exposure of the microorganisms to certain cations such as magnesium renders them resistant to the lethal action of globin. Hemoglobin loses its bactericidal power when complexed with haptoglobin, and serum fractions rich in free haptoglobin protect otherwise susceptible bacteria from killing by hemoglobin. The reaction appears to be a bactericidal rather than a bacteriostatic one. At 38 degrees C. maximal killing requires approximately 30 minutes; at temperatures of 28 degrees C. or 0 degrees C. the bactericidal action does not take place. The minimal concentration of hemoglobin required to kill 50 per cent of the microorganisms in the test is unrelated to the size of the bacterial inoculum. Under conditions suitable for bactericidal action, hemoglobin is adsorbed onto heat-killed susceptible strains of coliform bacteria; material possessing bactericidal activity can be eluted with dilute mineral acid.

Animals↗
PubMed1956

Phagocytin: a bactericidal substance from polymorphonuclear leucocytes.

A technique has been developed for collecting large numbers of polymorphonuclear leucocytes from peritoneal exudates in rabbits. These cells are obtained essentially free from other cell types and from debris. When microphages so procured are disrupted by physical methods and extracted with aqueous salt solutions, the soluble fraction manifests striking bactericidal activity, especially on Gram-negative enteric bacilli. The susceptible microorganisms are not lysed. This bactericidal substance, which has been called phagocytin, appears to be limited in distribution mainly to the polymorphonuclear leucocyte. No phagocytin is present in extracts of rabbit heart, kidney, or skeletal muscle, and rabbit liver and spleen contain much less than do packed leucocytes. Extracts of human and of guinea pig microphages show less bactericidal activity than rabbit cell preparations. Similar extracts of rat and mouse polymorphonuclear leucocytes contain no demonstrable phagocytin. As indicated by its behavior on dialysis, on exposure to proteolytic enzymes, and on salt fractionation, phagocytin appears to be a protein with general properties characteristic of a globulin. It is clearly different from lysozyme and from properdin. Although phagocytin is reasonably stable at temperatures of 65 degrees C. and lower for several hours, solutions of it gradually lose bactericidal activity on standing for prolonged periods at 4 degrees C. This instability, and also the ease with which phagocytin is inactivated, presumably by adsorption, on exposure to a variety of materials, have thus far rendered fruitless efforts to isolate it.

Animals↗
PubMed1956

Studies of the bactericidal action of phagocytin.

The bactericidal activity of phagocytin on Gram-negative enteric bacilli is influenced by the reaction of the medium; the more acid the environment, the more marked is the activity. Phagocytin exerts approximately the same action whether citrate, acetate, or phosphate salts are used as buffer, and the addition of glucose, casein hydrolysate, or cation binding agents does not produce notable change. Although proteins in general have but little effect, the inclusion in the medium of a high concentration of bovine plasma albumin neutralizes the lethal action of phagocytin on enteric bacilli. Very high concentrations of magnesium or calcium ions antagonize but do not completely block the bactericidal effect. The bactericidal activity of phagocytin is essentially independent of the numbers of bacteria exposed; a 100-fold increase m the numbers of enteric bacilli results in approximately a 2-fold increase in the concentration of phagocytin required to kill 90 per cent of them. When susceptible microorganisms are exposed to phagocytin at 0 degrees C., practically no killing takes place. At higher temperatures the bactericidal action is rapid, being well advanced in 5 minutes and complete within 30 minutes.

Animals↗
PubMed1954

The antimycobacterial activity of a peptide preparation derived from calf thymus.

A stable, water-soluble substance which possesses potent antimycobacterial activity under certain conditions in vitro has been prepared from calf thymus. This substance has been tentatively named thymus peptide. In final concentrations of 1 to 10 microg. per ml. of an albumin medium it inhibits the growth of various strains of mammalian mycobacteria, but manifests only little or no inhibitory activity against a variety of other microbial species. The ability of thymus peptide to inhibit the multiplication of tubercle bacilli diminishes when the inoculum is large, or when the medium is acidic. It is also markedly antagonized by addition of enzymatic hydrolysate of casein or beef heart infusion broth to the culture medium. Thymus peptide does not exert a rapid bactericidal action on tubercle bacilli, but organisms exposed to this compound for longer than 2 weeks could not be made to multiply in ordinary culture media. Substances similar or identical to the thymus peptide preparation could be extracted from calf spleen, sheep thymus, beef lymph nodes, and calf pancreas, but not from calf lung or calf liver.

Animals↗
PubMed1954

Chemical studies on a basic peptide preparation derived from calf thymus.

A substance possessing antimycobacterial activity under certain conditions in vitro has been prepared from aqueous extracts of calf thymus. Chemical studies have demonstrated that the activity of this substance is due to a basic peptide or a mixture of basic peptides. Although this thymus fraction has been shown to be essentially free of compounds other than peptides, it has not been obtained in a homogeneous state. The thymus peptide preparation is soluble in water and in the lower alcohols. Its solubility is minimal between pH 10 and 11, suggesting that its isoelectric point may be in this vicinity. The microbiological activity of thymus peptide is destroyed by acid or alkaline hydrolysis and also by trypsin digestion, but is unaffected by pepsin digestion. Cellulose membranes are permeable to thymus peptide. The most noteworthy finding concerning the amino acid composition of thymus peptide is the preponderance of the basic amino acids lysine and arginine, which together account for about 40 per cent of the weight of this substance. No cystine, and only trace amounts of other amino acids containing sulfur, are present in the thymus peptide preparation.

Amino Acids↗
PubMed1954

Mechanisms involved in the antimycobacterial activity of certain basic peptides.

The antimycobacterial activity of thymus peptide under certain conditions in vitro can be partially neutralized by increasing the concentration of sulfate ions in the medium, and to a lesser extent by the addition of certain organic compounds which contain sulfur. It is suggested that thymus peptide suppresses the growth of tubercle bacilli by interfering with the normal sulfur metabolism of these microorganisms. Polylysine peptide and pituitary adrenocorticotropic hormone, other basic peptides derived from animal tissues, also inhibit the multiplication of tubercle bacilli in vitro, and their antimycobacterial activity is also antagonized by sulfate ions. Basic peptide hormones prepared from the posterior pituitary gland do not affect the growth of acid-fast bacteria under the conditions of the test.

Animals↗