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Biomedical subjects

D A Steinberg

Publications and source records attributed to D A Steinberg.

15 recordsLinked to original sources
PubMed1999

Effect of local application of the antimicrobial peptide IB-367 on the incidence and severity of oral mucositis in hamsters.

OBJECTIVE: The purpose of this animal study was to determine whether IB-367, an antimicrobial peptide, is able to ameliorate oral mucositis by reducing microflora densities on the mucosal surfaces of the mouth. STUDY DESIGN: Oral mucositis was induced in hamsters by intraperitoneal injection of 5-fluorouracil followed by superficial abrasion of the buccal mucosa. A test formulation was applied topically to the buccal mucosa 5 or 6 times per day starting 6 to 8 hours before abrasion. RESULTS: Mucositis scores were significantly lower (P < .05) in hamsters given formulations containing 0.5 or 2.0 mg/mL of IB-367 than in placebo-treated controls. Treatment with IB-367 produced a more than 100-fold reduction in oral microflora densities. In a second experiment, treatment of hamsters with a formulation containing IB-367 at 0.12, 0.5 or 2.0 mg/mL resulted in a dose-dependent reduction in mucositis severity. CONCLUSION: The results indicate that reduction of local microflora densities through use of IB-367 may improve clinical outcomes in patients at risk for the development of oral mucositis.

Animals↗
PubMed1997

Protegrin-1: a broad-spectrum, rapidly microbicidal peptide with in vivo activity.

Protegrin-1 (PG-1) is a cysteine-rich, 18-residue beta-sheet peptide isolated from porcine leukocytes with antimicrobial activity against a broad range of microorganisms. The MICs of PG-1 against representative gram-positive and gram-negative bacteria ranged from 0.12 to 2 microg/ml. At these levels, PG-1 was rapidly bactericidal in vitro, reducing the number of viable CFU of either methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa by more than three log units in less than 15 min. Resistance to PG-1 did not develop after 11 subculturings of P. aeruginosa or 18 subcultures of MRSA in Mueller-Hinton broth containing PG-1 at one-half the MIC. Under similar conditions of serial passage, the MICs of norfloxacin and gentamicin against P. aeruginosa increased 10 and 190 times, respectively. Similarly, the MIC of norfloxacin against MRSA increased 85 times. Immunocompetent mice inoculated intraperitoneally (i.p.) with P. aeruginosa or S. aureus exhibited 93 to 100% mortality in the vehicle control group compared with 0 to 27% mortality in animals that received a single i.p. injection of PG-1 (0.5 mg/kg of body weight). Mice inoculated with S. aureus by intravenous (i.v.) injection and dosed 0 to 60 min later with a single i.v. injection of PG-1 (5 mg/kg) had a mortality of 7 to 33%, compared to a mortality of 73 to 93% in the vehicle controls. In leukopenic mice inoculated i.v. with vancomycin-resistant Enterococcus faecium, mortality was 87% in the vehicle control group and 33% in animals that received a single i.v. injection of PG-1 (2.5 mg/kg). Taken together, these data indicate that PG-1 has potential for use as an antimicrobial agent in the treatment of local or systemic infections caused by clinically relevant pathogens.

Animals↗
PubMed1995

Hughlings Jackson's theory of recovery.

John Hughlings Jackson proposed a mechanism of neurologic compensation based on his theory of cerebral localization. According to Hughlings Jackson, there are three levels of evolution of the nervous system. Each element of each level contains a complete representation of the next lower level. Each element of the middle and highest levels contain a representation of the entire body, weighted for a particular part of the body. If the nervous system is damaged so that an area heavily weighted for a particular part of the body is destroyed, less heavily weighted areas are immediately activated according to their weighting. This activation partially compensates for the function of the destroyed tissue. As time passes, the weighting of representation in the unaffected areas changes, amplifying the degree of recovery. Recent clinical studies and PET cerebral blood flow studies show that various ipsilateral and contralateral areas are activated in recovery. The activated areas reside in what Hughlings Jackson would call the middle and highest evolutionary levels. Modern clinical and neurophysiologic observations are therefore consistent with Hughlings Jackson's theory of compensation.

Brain Diseases↗
PubMed1994

Mechanistic studies and biological activity of bioxalomycin alpha 2, a novel antibiotic produced by Streptomyces viridodiastaticus subsp. "litoralis" LL-31F508.

The bioxalomycins, a novel complex of broad-spectrum antibiotics, were isolated from fermentations of Streptomyces viridodiastaticus subsp. "litoralis" LL-31F508. Bioxalomycin alpha 2, the major component of this complex, exhibited antibacterial activity. The MICs ranged from < or = 0.002 to 0.008 micrograms/ml for gram-positive organisms and from 0.50 to 4 micrograms/ml for gram-negative organisms. Bioxalomycin alpha 2 was found to be bactericidal and to inhibit bacterial DNA synthesis preferentially. Bioxalomycin alpha 2 protected mice from a lethal challenge with Staphylococcus aureus Smith. The 50% effective dose of bioxalomycin alpha 2 administered orally was 10 times greater than that when the drug was given subcutaneously or intravenously. These data suggest a stability or bioavailability problem when the compound is administered orally.

Animals↗
PubMed1994

Pyrroindomycins, novel antibiotics produced by Streptomyces rugosporus LL-42D005. II. Biological activities.

The pyrroindomycins, a complex of novel antibiotics identified in fermentation broths of "Streptomyces rugosporus" LL-42D005, demonstrated excellent in vitro activity against Gram-positive bacteria. The semisynthetic diacetyl derivative of pyrroindomycin B (pyrroindomycin B-Ac2) was bactericidal for exponential-phase cells, but not for stationary-phase cells. This compound also exhibited marginal protection against a lethal Staphylococcus aureus challenge in mice. The poor in vivo activity of this antibiotic complex may be related to binding to blood components, as suggested by elevated MICs observed in blood-containing media. Incorporation of radiolabeled precursors into DNA, RNA, and protein was inhibited in an exponential-phase culture of Bacillus subtilis within ten minutes of exposure to pyrroindomycin B-Ac2. Microscopic examinations of drug-treated cells revealed lysis within the same ten minute period. These data are consistent with an effect of pyrroindomycin B-Ac2 on the integrity of the bacterial membrane.

Animals↗
PubMed1994

Bioxalomycins, new antibiotics produced by the marine Streptomyces sp. LL-31F508: taxonomy and fermentation.

An actinomycete strain designated LL-31F508 was isolated from an intertidal sediment sample collected in Key West, Florida. Culture LL-31F508 was assigned to the Streptomyces genus based on the presence of LL-diaminopimelic acid (DAP) in the cell wall and observations of spiny spores using scanning electron microscopy (SEM). Excellent antimicrobial activity against Staphylococcus and Enterococcus spp. were detected in both the supernatant and cell extract samples from fermentations of culture LL-31F508. Production of antibiotic activity peaked at 48-50 hours and closely paralleled cell growth, during which time glucose was more rapidly assimilated than dextrin. A series of new antibiotics called the bioxalomycins was identified as the antibacterial products from fermentations of this culture. Fermentation conditions for production of bioxalomycin alpha differed substantially from those required for production of a related compound, naphthyridinomycin, by the reference culture Streptomyces lusitanus NRRL 8034.

Anti-Bacterial Agents↗
PubMed1994

Glycothiohexides, novel antibiotics produced by "Sebekia" sp. LL-14E605. I. Taxonomy, fermentation and biological evaluation.

The new glycothiohexide antibiotics, which are related to nosiheptide, were identified in fermentations of an actinomycete belonging to the genus "Sebekia". Strain LL-14E605 was classified as a "Sebekia" based on the presence of both mesodiaminopimelic acid and madurose in the cell wall and the presence of pseudosporangia encasing the spores. Culture LL-14E605 was successfully fermented in 10 to 3,000 liters of a complex medium. Antibiotic activity closely followed cell mass accumulation and usually peaked after 4 to 5 days of incubation. Glycothiohexide alpha demonstrated excellent in vitro activity against Gram-positive bacteria with MICs of 0.03 to 0.06 microgram/ml against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. However, glycothiohexide alpha failed to protect mice against a lethal challenge with Staphylococcus aureus Smith unless it was administered prior to challenge.

Actinomycetales↗
PubMed1993

A study on the mechanism of action of sceptrin, an antimicrobial agent isolated from the South Pacific sponge Agelas mauritiana.

The mechanism of action of sceptrin, an antimicrobial agent isolated from the sponge Agelas mauritiana, was investigated. Sceptrin has been reported to exhibit antibacterial and antifungal activities. In our studies, sceptrin demonstrated a bacteriostatic rather than bactericidal effect on exponentially growing Escherichia coli cells at the MIC. Under these conditions, the culture produced chains of cells, and incorporation of radio-labelled precursors into DNA, protein, and cell wall was unaffected, whereas incorporation of 3H-uridine into RNA was slightly inhibited. At concentrations higher than the MIC, sceptrin was bactericidal, inhibited the incorporation of all radiolabelled precursors, and induced the formation of unusual spheroplasts. Peptidoglycan turnover in E. coli appeared to be stimulated by sceptrin as demonstrated by a release of diaminopimelic acid-containing high molecular weight material. Subsequent studies of the release of potassium ions from E. coli and the lysis of red blood cells suggested that sceptrin disrupts the cell membranes of both prokaryotic and eukaryotic cells. It is proposed that spheroplasts formation may reflect a cell wall effect that occurs subsequent to membrane damage.

Animals↗
PubMed1986

Synthesis of fused glycoprotein D of herpes simplex virus type 1 but not type 2 inhibits Escherichia coli hosts.

Glycoprotein D from either Herpes simplex virus type 1 (gD-1) or type 2 (gD-2) has been expressed in Escherichia coli as a series of chimeric proteins. The expression vector used in this study, pJS413, was derived from pBR322 and contains several cloning sites between the lacZ promoter-operator and the phage lambda cro gene. Plasmids containing fusions between the cro gene, gD-related sequences and lacZ was constructed and shown to direct the synthesis of 160-kDa proteins. The accumulation of fusion protein could be visualized as inclusion bodies when the cells were examined by dark phase-contrast or transmission electron microscopy. None of the plasmids that encoded cro::gD gene fusions yielded significant amounts of material upon induction with isopropyl-beta-D-thiogalactopyranoside. In addition, certain plasmids produced a form of Cro-gD-1 fusion protein which resulted in severe growth inhibition of E. coli. These inhibitory effects were attributed to the presence of specific gD-1 sequences, i.e., the transmembrane and cytoplasmic anchor region of the protein.

Amino Acid Sequence↗
PubMed1985

The stimulation of bioluminescence in Photobacterium leiognathi as a potential prescreen for antitumor agents.

The stimulation of bioluminescence in Photobacterium leiognathi has previously been described as a test for genotoxic compounds. An adaptation of this procedure has been developed which uses a dim variant of P. leiognathi and permits the prescreening of microbial fermentation broths for potential antitumor agents. Bioluminescence in this organism was stimulated by compounds which bind to DNA or affect DNA synthesis. Antibiotics with target sites such as protein, cell wall or RNA synthesis, did not alter bioluminescence. Fermentation broths from over 5,000 soil isolates were prescreened in this assay and 95 (1.6%) were defined as active. Further analysis of selected cultures suggested that about half produced compound(s) with DNA-binding activity. These results suggest that the photobacterium induction assay (PIA) may be useful as a prescreen for potential antitumor agents. The assay is rapid, simple and requires only microgram quantities of material for testing.

Antibiotics, Antineoplastic↗