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Biomedical subjects

D S Feingold

Publications and source records attributed to D S Feingold.

At least 91 records · Page 5Linked to original sources

Detection of agents that alter the bacterial cell surface.

Proteus mirabilis is not killed by polymyxin B, normal serum, or sodium deoxycholate. Exposure to polymyxin B renders the cells susceptible to killing by the latter two agents. The data suggest that this synergism is due to polymyxin B-induced surface changes. The results point out an inadequacy of existing methods of screening for antibiotics; they fail to detect agents which, while showing no in vitro effect on growth, may alter a resistant organism so that it becomes more susceptible to other antimicrobials or host defense mechanisms. A method is described which can be used to detect such cell surface-modifying agents.

Anti-Bacterial Agents↗

Phospholipids and fatty acids of Neisseria gonorrhoeae.

The phospholipids and fatty acids of two strains of Neisseria gonorrhoeae of different penicillin susceptibilities were examined. The phospholipids, which comprise about 8% of the dry weight of the cells, consisted of phosphatidylethanolamine (70%) and phosphatidylglycerol (20%); small amounts of phosphatidylcholine and traces of cardiolipin were also present. Growing and stationary-phase cells were similar in content and composition of phospholipids except for phosphatidylcholine, which increased two- to fivefold in the stationary-phase cells. The fatty acids of the phospholipids were characterized by two major acids, palmitic and a C16:1, with myristic and a C18:1 acid present in smaller amounts. The fatty acids present in purified phospholipid fractions varied considerably in relative proportions from fraction to fraction. No significant difference in the composition of phospholipids from the two strains was evident. Large amounts of beta-hydroxy lauric acid were detected only after saponification of the organisms. Differences in the lipid composition between the gonococcus and other gram-negative bacteria are discussed.

Cardiolipins↗

Infective and noninfective hemagglutinating particles of Newcastle disease virus: biological and chemical characterization.

Newcastle disease virus (Herts strain), grown in embryonated eggs or in a line of bovine kidney cells, was purified and then separated by sucrose density gradient centrifugation into infectious (IH) and noninfectious hemagglutinating (NIH) particles. These particles were morphologically similar, although the average size of IH was twice that of NIH particles. The activity of hemagglutinin per milligram of virus protein was two- to threefold higher in NIH particles than in IH particles, whereas the specific activity of neuraminidase did not differ in the two particle types. This was consistent with the observed particle size difference. The distribution of the major proteins in IH and NIH particles from egg-grown virus, determined by polyacrylamide gel electrophoresis (PAGE), was significantly different. In IH particles the molar ratio of protein 1 (74,000 daltons) to proteins 2 and 3 (56,000 daltons): protein 6 (41,000 daltons) was 1.0:2.5:2.5; in NIH particles the ratio was 1.0:0.6:1.0. When Newcastle disease virus was grown in bovine kidney cells, the molar ratio of proteins in IH particles resembled that of of egg-grown virus. However, in NIH particles from bovine kidney cells, only protein bands corresponding to protein 1 and proteins 2-3 were present and their molar ratio was 1.0:0.6. Protein 6 was marginally detectable in these particles. Analysis of the proteins in [3H]isoleucine- and [14C]glucosamine-labeled virus showed proteins 1 and 2 (glycoproteins) present in the ratio of 1.0:0.5; protein 3, the nucleoprotein, was not detected. These results are compatible with previous findings by others that NIH particles are deficient in RNA and nucleoprotein antigen, and suggest that formation of discrete particles of Newcastle disease virus by budding requires at most minimal amounts of proteins 3 or 6. The fatty acid composition of egg-grown IH and NIH particles was not significantly different and resembled that of normal allantoic fluid.

Cell Line↗

Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients.

All 744 patients admitted to a Respiratory-Surgical Intensive Care Unit (RSICU) were included in a prospective study of the effects of a polymyxin (2.5 mg/kg body wt/day in six divided doses) or a placebo aerosol sprayed into the posterior pharynx and tracheal tube (if present), during 11 alternating 2-mo treatment cycles. The incidence of upper airway colonization in the RSICU with Pseudomonas aeruginosa was 1.6% during the polymyxin treatment cycles (total 374 patients) and 9.7% during the placebo cycles (370 patients) (X2 equals 23.2, P less than 0.01). 3 patients in the RSICU acquired Pseudomonas pneumonia, as defined by independent "blinded" assessors, during the polymyxin cycles while 17 acquired a Pseudomonas pneumonia during the placebo cycles (X2 equals 10.2, P less than 0.01). The overall mortality was similar in both placebo and polymyxin-treated groups (12.2 vs. 12.0%). Systemic antibiotic usage was similar in the different cycles; 49% of patients in the placebo and 53% in the polymyxin-treated groups received systemic antibiotics while in the RSICU.

Aerosols↗

Interferon induction in mice by lipopolysaccharide from Brucella abortus.

Endotoxin or lipopolysaccharide isolated from Brucella abortus (strain 456) produced a typical endotoxin-type interferon response in mice with peak levels of the inhibitor occurring 2 h after intravenous injection of the stimuli. Brucella lipopolysaccharide was a much less effective interferon stimulus than the lipopolysaccharide isolated from Salmonella typhimurium (strain LT-2).

Animals↗

Antiviral activity of an ether-extracted nonviable preparation of Brucella abortus.

Extraction of living Brucella abortus (strain 456) with aqueous ether yielded a nonviable, insoluble residue (Bru-Pel). When injected into mice, Bru-Pel was an effective, nontoxic interferon stimulus. Mice pretreated with Bru-Pel were protected against challenge with otherwise lethal doses of Semliki Forest virus. Significant protection was afforded when Bru-Pel was given as many as 7 days before virus challenge. Evidence is presented dealing with the complex nature of Bru-Pel and with the possibility that the antiviral activity of Bru-Pel may be associated not only with the production of interferon, but with a general increase in the level of nonspecific resistance in animals.

Animals↗

Selective membrane toxicity of the polyene antibiotics: studies on lecithin membrane models (liposomes).

In the absence of sterol, amphotericin B at 5 x 10(-6) M caused maximum marker release from the saturated dipalmitoyl lecithin liposomes, minimum release from the unsaturated dioleoyl lecithin liposomes, and an in-between response from egg lecithin liposomes. Nystatin at 2.5 to 4.0 x 10(-5) M induced appreciable marker release from all three types of sterol-free liposomes. The amphotericin B- and nystatin-induced permeability changes in dipalmitoyl lecithin liposomes were drastically suppressed by the incorporation of cholesterol or stigmasterol (with identical Delta5 sterol nuclei), but were unaffected by the incorporation of ergosterol or 5,7-cholestadien-3beta-ol (with identical Delta5,7 sterol nuclei). The nystatin sensitivity of dioleoyl lecithin liposomes remained low after the incorporation of cholesterol or stigmasterol, but was greatly enhanced by the incorporation of ergosterol or 5,7-cholestadien-3beta-ol. Digitonin, a compound known to interact specifically with membrane sterol, induced marker release from liposomes in proportion to the amount of either cholesterol or ergosterol incorporated; epicholesterol did not sensitize to digitonin. These results lead to the following conclusions: (i) polyene-induced permeability alteration in model membrane systems is effected by the composition of membrane phospholipid fatty acyl chains; (ii) the distribution of double bonds in the sterol nucleus is related to the selective toxicity of the polyenes toward natural sterol-containing membranes; and (iii) polyenes differ in membrane selectivity.

Amphotericin B↗