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P B Fernandes

Publications and source records attributed to P B Fernandes.

68 records · Page 4Linked to original sources
PubMed1986

In vitro and in vivo evaluation of A-56268 (TE-031), a new macrolide.

The in vitro and in vivo antibacterial activity of A-56268 (TE-031), the 6-O-methyl derivative of erythromycin, was compared with those of erythromycin and other reference drugs. A-56268 had the same spectrum of antibacterial activity as erythromycin. A-56268 was generally 1 log2 dilution more potent or equal to erythromycin against all organisms except haemophilus influenzae and Propionibacterium acnes, for which A-56268 was 1 log2 dilution and 3 log2 dilutions, respectively, less potent. The MBC of A-56268 and erythromycin was not significantly different from the MIC against Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus epidermidis, and H. influenzae but was more than 2 log2 dilutions higher than the MICs for some Staphylococcus aureus strains. Human serum at a concentration of 50% did not change the in vitro potency of A-56268 or erythromycin. A-56268 was similar to erythromycin in being more active at pH 8.0 than at the physiologic pH of 7.3. The activity of A-56268 was synergistic with sulfamethoxazole against 4 of 12 strains of H. influenzae. In mouse protection tests, when administered orally A-56268 was more potent than erythromycin against H. influenzae, S. pyogenes, S. pneumoniae, and S. aureus. After subcutaneous administration the potencies of A-56268 and erythromycin were not statistically different from each other. A-56268 was more potent than erythromycin against Legionella infection in guinea pigs. The concentration of A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In mice, the peak levels in serum of A-56268 and erythromycin were similar after subcutaneous administration and seven times higher for A-56268 after oral administration. The serum half-life of A-56268 was approximately twice that of erythromycin after administration by both routes.

Administration, Oral↗
PubMed1985

Synthesis and structure-activity relationships of novel arylfluoroquinolone antibacterial agents.

A series of novel arylfluoroquinolones has been prepared. These derivatives are characterized by having a fluorine atom at the 6-position, substituted amino groups at the 7-position, and substituted phenyl groups at the 1-position. Structure-activity relationship (SAR) studies indicate that the in vitro antibacterial potency is greatest when the 1-substituent is either p-fluorophenyl or p-hydroxyphenyl and the 7-substituent is either 1-piperazinyl, 4-methyl-1-piperazinyl, or 3-amino-1-pyrrolidinyl. The electronic and spatial properties of the 1-substituent, as well as the steric bulk, play important roles in the antimicrobial potency in this class of antibacterials. As a result of this study, compounds 45 and 41 were found to possess excellent in vitro potency and in vivo efficacy.

Acinetobacter↗
PubMed1984

Spenolimycin, a new spectinomycin-type antibiotic. III. Biological properties.

Spenolimycin is a new spectinomycin-type antibiotic isolated from Streptomyces gilvospiralis sp. nov. In vitro, it was active against a wide variety of aerobic Gram-positive and Gram-negative bacteria and Neisseria gonorrhoeae. It was two to four-fold more active against N. gonorrhoeae than spectinomycin. Spenolimycin was effective in the standard mouse protection test against Escherichia coli, Klebsiella pneumoniae and Streptococcus pneumoniae.

Animals↗
PubMed1983

Purification and characterization of a bacteriocin from Bacteroides fragilis.

A bacteriocin produced by Bacteroides fragilis 1356 was purified from culture medium and characterized. The spectrum of the inhibitory activity of this bacteriocin was species specific. The bacteriocin was recovered from the initial stages of purification as a complex, greater than 2 X 10(7) daltons in mass, containing protein, lipid, and carbohydrate. The dissociation of this complex by 6.0 M guanidine hydrochloride permitted further purification of the bacteriocin by removal of lipid and carbohydrate. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the purified bacteriocin was homogeneous, with a relative molecular weight of 5,000. The activity of the purified bacteriocin was not affected by RNase, DNase, phospholipase A, pancreatic lipase, or dextranase, but was destroyed by trypsin, proteinase K, heat (80 degrees C, 30 min), or a pH below 5 or above 8. Amino acid analysis indicated a predominance of acidic and polar amino acids.

Amino Acids↗
PubMed1981

Antibodies to cell envelope proteins of Pseudomonas aeruginosa in cystic fibrosis patients.

Many vaccines containing somatic and secreted antigens of Pseudomonas aeruginosa have been reported. The vaccines containing lipopolysaccharide have been found to provide type-specific protection, but the endotoxin content of these vaccines does not make it feasible to use them in patients who are already debilitated. Outer membrane proteins could be effective as vaccines, as they can be purified free of lipopolysaccharide, and also because they are common to all serotypes of P. aeruginosa. To be effective as a vaccine, such proteins must be immunogenic and accessible from the outside of the intact bacterial cell. In this study, we showed that systemic antibodies were produced frequently to two cell envelope proteins with masses of 58,500 and 37,500 daltons and occasionally to 34,000-dalton protein of P. aeruginosa in cystic fibrosis patients with chronic lung infections. In rabbits immunized with whole, fixed cells of P. aeruginosa, antibodies were also produced against the 58,500-dalton proteins. Thus, the 58,500-dalton cell envelope protein of P. aeruginosa was the only immunogenic protein that was accessible to the immune system when whole, fixed cells were used for immunization. These serum antibodies did not protect the cystic fibrosis patients against further lung infection with P. aeruginosa.

Adolescent↗
PubMed1980

Demonstration of cell envelope-bound exotoxin A in Pseudomonas aeruginosa.

The quantity of membrane-bound and extracellular exotoxin A in four strains of Pseudomonas aeruginosa was investigated. In strain PA-103, which is the prototype strain used for toxin production, all of the toxin was released into the growth medium and little toxin remained with the cell envelope. In a virulent strain from a clinical source, strain 119, exotoxin A was found in equal amounts in the growth medium and in the cell envelopes. An avirulent mutant of this strain, strain 119 (AP-), which was resistant to 800 microgram of polymyxin B per ml, had all the exotoxin A in a membrane-bound state and was unable to release exotoxin A into the growth medium. Thus, exotoxin A can be found in the membrane-bound form, in the extracellular form, or in both. The quantities of membrane-bound toxin and extracellular toxin vary with the strain P. aeruginosa. The polymyxin B-resistant mutant which is blocked in toxin release will be useful in studies of exotoxin A secretion.

Cell Membrane↗
PubMed1978

The resolution of membrane proteins based upon size, charge, and hydrophobicity.

Currently available systems for resolving membrane proteins are based only on size and charge differences. Recently, it has been shown that Triton-urea-acetic acid gels which separate proteins on the basis of charge, size and hydrophobicity are capable of resolving proteins differing only by the substitution of a single neutral amino acid. We have applied this new method to the resolution of bacterial envelope proteins. Conditions for optimal resolution of different bacterial envelope proteins were determined by electrophoresis through transverse urea and Triton X-100 gradient gels. We have also correlated the components resolved in this system with those resolved by classical sodium dodecyl sulfate-gel electrophoresis by using two-dimensional slab gels combining the two systems. Furthermore, envelope protein fractions from different species and strains of bacteria were compared to identify specific proteins. This system appears to be a promising method for investigating envelope proteins which are due to missense mutations.

Acetic Acid↗
PubMed1977

Membrane-bound enterotoxin of Vibrio cholerae.

The mode of transport of the complex toxin molecule of Vibrio cholerae (which has a mol. wt of 84000 and consists of several subunits) across the inner and outer membranes of V. cholerae is not known. In this study we found two peptides in the outer and inner membranes of V. cholerae which may be the form in which the toxin subunits are transported across the membrane. We examined two growth conditions: aerobic growth at 37 degrees C, when most of the synthesized toxin is membrane-bound; and anaerobic growth at 37 degrees C, when little toxin remains membrane-bound, the toxin being released into the growth medium. When V. cholerae was grown aerobically at 37 degrees C, the outer and the inner membranes contained two peptides with mol. wts of approximately 22000 and 6000 which were not found in the outer or the inner membrane of anaerobically grown cells. Sodium deoxycholate, which releases membrane-bound toxin, released several peptides including the 22000 and the 6000 mol. wt peptides. Trypsin also released the 22000 and 6000 mol. wt peptides. Purified cholera toxin had three kinds of peptides, of mol. wt 21000 (A1 peptide), 11000 (B subunit) and 5000 (A2 peptide). We postulate that the membrane peptides may be precursors of the A subunit of the toxin molecule.

Aerobiosis↗
PubMed1977

The effect of anaerobiosis and bile salts on the growth and toxin production by Vibrio cholerae.

Environemntal conditions which might be present in the human intestinal lumen, such as anaerobiosis, a temperature of 37 degrees C and the presence of bile salts, were examined for their effects on the growth and toxin production by Vibrio cholerae strains 569B and B1307 in Syncase and in peptone water media. Using aerobic conditions at 30 degrees C, which are commonly used for enterotoxin production, toxin (5 mug ml(-1)) and pleomorphic cells were detected during the exponential phase of the growth cycle. When the incubation temperature was raised to 37 degrees C, no toxin ( less than 0-1 mug ml(-1)) and no pleomorphic forms were found. In cultures incubated anaerobically at 30 or 37 degrees C, the organisms grew poorly, forming pleomorphic cells which lysed after the cultures reached a maximum turbidity at 640 nm of 1-45 at 12 h. Toxin (2-5 mug ml(-1)) was present at 12, 24 and 48 h. When 0-1% sodium deoxycholate was incorporated into the culture medium, growth was inhibited under aerobic conditions at 30 and 37 degrees C. At 30 degrees C under aerobic conditions and at 37 degrees C under anaerobic conditions, the toxin yield was not significantly affected by the presence of sodium deoxycholate; but at 37 degrees C under aerobic conditions, sodium deoxycholate caused an increase in the toxin yield (5 mug ml(-1)) due to the release of cell-bound toxin.

Aerobiosis↗
PubMed1977

Wall-less microbial isolate from a human renal biopsy.

An orgainsm was isolated from a kidney biopsy of a patient with renal failure. Electron microscopy revealed an ultrastructure very similar to that of a bacterial L-form or mycoplasma. But macroscopically, its colonial morphology was unusual and distinct from that ascribed to these wall-less organisms. This isolate lacked a rigid cell wall and required a hypertonic medium with serum for growth. Also, a long incubation period was essential for its growth, and use of hand lens was necessary for detection on solid medium.

Biopsy, Needle↗
PubMed1976

Persistence, pathogenesis, and morphology of an L-form of Streptococcus pyogenes adapted to physiological isotonic conditions when in immunosuppressed mice.

Evidence obtained using nonimmunosuppressed and newborn mice suggests that the immune response of the host plays a role in the rapid removal of a physiologically isotonic L-form of Streptococcus pyogenes, since its inability to persist in vivo was not due to osmotic lysis. With mice immunosuppressed with methylprednisolone sodium succinate, viability and detection of this L-form by fluorescent antibody was prolonged for at least 2 weeks, the approximate duration of immunosuppression in these mice. However, heat-killed L-form cells only persisted for 3 days in such mice. Therefore, persistence of a viable L-form in these treated mice was not simply due to the lack of removal of L-forms by a compromised host. At no time was there any indication of illness in nonimmunosuppressed or immunosuppressed mice after L-form injection, and all internal organs, when examined macroscopically, remained normal. Thus, overt pathogenesis was not a characteristic of this L-form in a suitable host even when its immune response had been compromised. The microscopic morphology of the L-form after isolation from immunosuppressed mice changed drastically. It was typically micrococcal in appearance and exemplified the cellular variability achievable by this organism in vivo. Also, streptolysin S production was increased markedly by passage of the L-form in immunosuppressed mice. However, M protein, as a cellular component, was not detected serologically, nor was any reformation of a rigid cell wall apparent by electron microscopy after isolation of this streptococcal L-form from such mice.

Animals↗