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Biomedical subjects

M T Kelly

Publications and source records attributed to M T Kelly.

At least 109 records · Page 6Linked to original sources
PubMed1977

Plasma-dependent chemotaxis of macrophages toward BCG cell walls and the mycobacterial glycolipid P3.

BCG cell walls, associated with oil droplets in the form of emulsions in saline, generate macrophage chemotactic activity from fresh guinea pig plasma. Serum and heat-inactivated plasma were inactive, suggesting involvement of complement or fibrinogen-derived chemotactic factors. Suspensions of cell walls and oil droplets each generated chemotactic activity from plasma, and the activity of the cell wall vaccine was due to the additive effects of these two components. A mycobacterial glycolipid (P3), which is a constituent of BCG cell walls, also had plasma-dependent chemotactic activity. The results suggest that macrophage chemotaxis may be an important part of the immunopotentiating activity of these mycobacterial products.

Animals↗
PubMed1976

Immunotherapy with nonviable microbial components.

Structural components of microorganisms have been studied for immunopotentiating effect with the aid of transplantable (line 10) tumors in syngeneic guinea pigs. Microbial components were associated with oil droplets, suspended in Tween-saline, and injected intralesionally. BCG cell walls, given in this way, produced regression and cure of 50-60% of established tumors, as did viable BCG. Lipid extraction markedly reduced the tumor-regressing potency of cell walls, but P3, a trehalose mycolate present in the extract, restored full activity to the cell wall residue. P3 alone was nonsensitizing and had no antitumor activity, but it enhanced the latter property of various other microbial products. For example, the cure rates produced by cell walls of M. tuberculosis, M. bovis, M. phlei, or M. smegmatis were enhanced from 20-60% to as much as 90% by addition of P3. P3 also conferred antitumor activity on products from unrelated microbes, such as cell walls of E. coli, and in combination with endotoxins from rough Re mutant salmonellae, it produced cure rates of up to 93%. These results suggest that P3 is essential to the immunopotentiating activity of mycobacteria and that it may be broadly applicable in immunotherapy of cancer with microbial agents.

Animals↗
PubMed1976

In vitro activity, synergism, and testing parameters of amikacin, with comparisons to other aminoglycoside antibiotics.

The activity of the new aminoglycoside antibiotic, amikacin, was evaluated in vitro against 219 clinical bacterial isolates. One hundred eighty-nine of the 219 strains had agar dilution minimal inhibitory concentration values of 8.0 mug/ml or less for amikacin. Comparative agar dilution studies were performed for gentamicin, kanamycin, and tobramycin. Gentamicin was the most active overall, but tobramycin and amikacin also had significant activity against most bacterial groups. The effects of divalent cations on the susceptibility of Pseudomonas aeruginosa to amikacin were evaluated, and the minimal inhibitory concentration values varied sixfold over a range of divalent cation concentrations from 0.2 to 8.75 mg%. The effects of media and inoculum size on disk susceptibility testing with amikacin were also evaluated. In addition, a synergistic interaction between carbenicillin and amikacin against P. aeruginosa was demonstrated. Amikacin appears to be a promising new broad spectrum antimicrobial agent.

Amikacin↗
PubMed1974

An inhibitor of histamine release from human leukocytes.

Lysates of human leukocytes, prepared by ultrasonic disruption, contained heat-labile histamine-releasing factors. An inhibitor of histamine release was generated from such lysates during thermal inactivation of the histamine-releasing activity. Lysates inactivated at 38 degrees C for 60 min produced up to 90% inhibition of histamine release from human leukocytes. Heated lysates produced significant inhibition (P < 0.001) of leukocyte histamine release induced by goat antihuman IgE (51+/-3% inhibition), compound 48/80 (69+/-7% inhibition), and fresh leukocyte lysate (63+/-6% inhibition). Membrane ultrafiltration and gel-filtration chromatography suggested that the inhibitor was of less than 1,000 molecular weight. The partially purified inhibitor, eluted from Sephadex G-15 and lyophilized, contained no detectable protein or carbohydrate but produced 80-90% inhibition of histamine release at a concentration of only 10 ng/ml. The histamine-releasing factors from lysates of purified suspensions of lymphocytes and granulocytes were fractionated on Sephadex G-25. A single peak of histamine-releasing activity with an estimated molecular weight of 5,000 was detected from each cell type. Incubation of the partially purified histamine-releasing factors at 38 degrees C resulted in generation of an inhibitor of histamine release which was nearly identical to the inhibitor from crude lysates. This natural inhibitor of histamine release, derived from human leukocytes, may provide an endogenous mechanism for the control of histamine release in inflammation.

Animals↗
PubMed1973

Histamine release induced by human leukocyte lysates: effect of metabolic inhibitors and carbohydrates.

The effects of metabolic inhibitors and carbohydrates on histamine release induced by human leukocyte lysates have been studied to gain an understanding of the mechanism of histamine release in this system. Dinitrophenol produced 80% inhibition of histamine release at a concentration of 10(-3) M. Iodoacetic acid inhibited release to a lesser extent, and deoxyglucose had relatively little effect. Colchicine was a potent inhibitor of release and produced 88% inhibition at a 10(-3) M concentration. Puromycin and cycloheximide had essentially no effect on histamine release. Various sugars inhibited release with mannitol and glucose, producing greater than 50% inhibition at 10(-3) M concentrations. Other sugars inhibited histamine release to a lesser degree with the following order of potency: mannitol > glucose > sucrose > galactose > fructose. These studies suggest that intact, metabolically active cells are required for histamine release induced by human leukocyte lysates and that a secretory process is involved. The results also provide information on the possible nature of the histamine-releasing factor(s) in human leukocyte lysates.

Antimetabolites↗
PubMed1973

Histamine release induced by himan leukocyte lysates: implication of a specific, complement-independent, noncytotoxic reaction.

The characteristics of histamine release induced by human leukocyte lysates were determined. Intact human leukocytes released histamine during incubation with leukocyte lysates. Maximal release occurred under physiological conditions of temperature and pH, and both Ca(2+) and Mg(2+) were required. The addition of ethylenediaminetetraacetic acid abruptly inhibited release. Complement was not required, and serum actually inhibited release. Histamine release was maximal at lysate concentrations of 0.25 to 1.0 mug of protein per ml, and it was reduced at either higher or lower concentrations. Leukocytes continued to exclude trypan blue and maintained chemotactic activity after histamine release. Leukocytes released histamine independently of cellular protein or enzymes. Histamine release induced by leukocyte lysates was interrupted by subsequent removal of the lysate. The data suggest that this histamine release occurs by a specific, complement-independent, noncytotoxic process which resembles, but is not identical with, antigen-induced histamine release. The system has several unique characteristics which suggest that it is a novel form of inflammatory histamine release. This system should provide a useful in vitro model for studies of cellular processes in human inflammation.

Calcium↗
PubMed1973

Histamine release induced by human leukocyte lysates. Reabsorption of previously released histamine after exposure to cyclic amp-active agents.

The role of cyclic AMP in histamine release induced by human leukocyte lysates was investigated. Leukocytes were incubated with leukocyte lysates prepared by ultrasonic disruption, and histamine was determined fluorimetrically. Several cyclic AMP-active agents had a marked inhibitory effect on histamine release. Theophylline and isoproterenol produced 50% inhibition at concentrations of less than 10(-5) M. Prostaglandin E(1) and dibutyryl cyclic AMP inhibited release by 50% at 7 x 10(-8) M and 6 x 10(-5) M concentrations, respectively. Histamine, which has recently been shown to increase leukocyte cyclic AMP, had a pronounced inhibitory effect on lysate-induced histamine release, producing 50% inhibition at a concentration of only 2.5 x 10(-12) M.Leukocytes, incubated with leukocyte lysates, were sampled at various times and assayed for free histamine released into the incubation mixture supernates, and for bound histamine associated with the leukocyte buttons after centrifugation. Theophylline, prostaglandin E(1) and dibutyryl cyclic AMP not only blocked histamine release, but also caused a progressive decrease in free histamine when added at any time up to 30 min after initiation of the release reaction. As the free histamine decreased after addition of the inhibitors, there was a corresponding increase in the bound histamine, suggesting that previously released histamine was reabsorbed by the leukocytes after exposure to cyclic AMP-active agents. Continued incubation of leukocytes in their own histamine after completion of the release reaction also resulted in reabsorption of the previously released histamine. Previous studies have indicated that cyclic AMP inhibits leukocyte histamine release. The results of the present studies suggest that cyclic AMP modulates histamine release induced by human leukocyte lysates by stimulating reabsorption of histamine from the extracellular environment. These studies also suggest that previously released extracellular histamine may stimulate its own reabsorption by increasing the intracellular level of cyclic AMP.

Absorption↗
PubMed1971

Histamine release in the dog after leukocyte lysate injection.

Mixed leukocyte suspensions, containing 10(6) leukocytes per ml, were prepared from dog peripheral blood by dextran sedimentation. Lysates of these suspensions, prepared by sonification, were administered intravenously to the autologous dogs. The plasma histamine levels were increased to an average value 320% above the control values (P < 0.001). The individual elements in the mixed leukocyte suspensions were separated by sucrose gradient and glass bead column fractionation procedures, and purified suspensions of platelets (no other formed elements present), lymphocytes (95 to 100%), and granulocytes (90 to 98%) were obtained. Lysates of these suspensions all had significant histamine-releasing activity when administered intravenously to dogs. Although leukocytes and platelets from other species are known to harbor mediators of histamine release, this study provides the first demonstration of the histamine-releasing activity of dog leukocytes and platelets. Many of the studies of leukocyte and platelet histamine-releasing factors have employed in vitro systems leaving the in vivo role of these factors in doubt. The present studies provide evidence that leukocyte and platelet histamine-releasing factors have in vivo activity.

Animals↗
PubMed1971

Mediators of histamine release from human platelets, lymphocytes, and granulocytes.

Lysates of mixed human leukocyte suspensions released histamine from intact human leukocytes in vitro. Microgram quantities of leukocyte lysate protein released up to 90% of the total available histamine. The mixed leukocyte lysates were separated by differential centrifugation into nuclear (800 g pellet), lysosomal (25,000 g pellet), and postlysosomal supernatant (25,000 g supernatant) fractions. The degree of separation of the lysosomal from the other two fractions was assessed by measuring the relative activities of four lysosomal enzymes. The average distribution of enzyme activity was 11 +/-2% (mean +/-1 SD), 72 +/-10%, and 17 +/-8% for the nuclear, lysosomal, and supernatant fractions respectively. The histamine-releasing activity was equally distributed between the lysosomal and supernatant fractions, each of which had 5-fold greater activity than the nuclear fraction. Purified suspensions of platelets, lymphocytes, and granulocytes were prepared, and the lysates of these suspensions all had histamine-releasing activity. Centrifugation at 100,000 g for 18 hr sedimented the histamine-releasing activity from all three types of lysate. After 20% ethanol fractionation for the preparation of cationic protein, only the activity from the platelet lysates was found in the 20% ethanol insoluble fraction. These mediators of histamine release from human platelets, lymphocytes, and granulocytes may play a role in the development of the vasodilation and increased vascular permeability which characterize the acute inflammatory response.

Acid Phosphatase↗
PubMed1969

Molecular heterogeneity of isolates of the marine bacterium Leucothrix mucor.

Two collections of strains of Leucothrix mucor were isolated, one of world-wide origin and the other originating from a restricted area around San Juan Island, Friday Harbor, Washington. These two collections were compared on the basis of morphological, nutritional, and physiological properties, deoxyribonucleic acid base composition, and mobility by starch-gel electrophoresis of isocitric dehydrogenase and malic dehydrogenase. Despite the fact that all the strains were similar in most characteristics, significant molecular heterogeneity was found in the enzyme electrophoresis studies. This heterogeneity was just as great in the local collection as it was in the world collection. Even strains originating from the same microenvironment exhibited molecular heterogeneity.

Bacteria↗
PubMed1969

Warm-water strain of Leucothrix mucor.

The physiological properties and temperature responses of the first strain of Leucothrix mucor ever to be isolated from a warm, tropical seacoast area are described.

Bacteria↗