Biomedical subjects

B Goodson

Publications and source records attributed to B Goodson.

5 recordsLinked to original sources

PubMed2001

T7 displayed peptides as targets for selecting peptide specific scFvs from M13 scFv display libraries.

M13 scFv display libraries are frontline research tools due to the rapidity in which target binding scFv can be obtained. Simple modifications of the standard affinity selection and amplification protocol allow for multiple targets to be panned simultaneously. Target peptide or protein production can become the rate-limiting step in a high throughput approach to antibody selection. To overcome this obstacle and to save both time and money, we have displayed the target peptides on T7 phage particles. In this paper we demonstrate that these particles can be used directly to select peptide specific scFv. We have discovered that the selection is most efficient when a linker separates the display from the T7 coat protein and when a continuous subtraction is employed. We have used antibodies selected in this fashion to characterize target proteins in cell lysates, immuno-precipitations and immuno-histochemistry.

Antibody Specificity↗

PubMed1999

Combinatorial discovery process yields antimicrobial peptoids.

N-alkylated glycine trimers are generically referred to as peptoids. The identification of antimicrobial peptoids from a statistically unbiased diverse combinatorial chemistry library led to the design of the optimization peptoid library that we describe in this manuscript. This optimization library was designed using structural information from the most active peptoids in the unbiased library. Screening of the optimization library for antimicrobial activity identified a single pool of peptoids with activity against both Staphylococcus aureus and Escherichia coli. The active peptoids from this pool were active against drug sensitive and drug resistant organisms and represent novel antibacterial compounds.

Anti-Bacterial Agents↗

PubMed1999

Characterization of novel antimicrobial peptoids.

Peptoids differ from peptides in that peptoids are composed of N-substituted rather than alpha-carbon-substituted glycine units. In this paper we report the in vitro and in vivo antibacterial activities of several antibacterial peptoids discovered by screening combinatorial chemistry libraries for bacterial growth inhibition. In vitro, the peptoid CHIR29498 and some of its analogues were active in the range of 3 to 12 microg/ml against a panel of gram-positive and gram-negative bacteria which included isolates which were resistant to known antibiotics. Peptoid antimicrobial activity against Staphylococcus aureus was rapid, bactericidal, and independent of protein synthesis. beta-Galactosidase and propidium iodide leakage assays indicated that the membrane is the most likely target of activity. Positional isomers of an active peptoid were also active, consistent with a mode of action, such as membrane disruption, that does not require a specific fit between the molecule and its target. In vivo, CHIR29498 protected S. aureus-infected mice in a simple infection model.

Animals↗

PubMedDate not supplied

Serious renal impairment is associated with long-term parenteral nutrition.

Thirty-three current long-term total parenteral nutrition (TPN) patients (13 men, 20 women) aged 21 to 79 years were prospectively studied to evaluate their change in glomerular filtration rate since beginning TPN. Creatinine clearance (CrCl) from the subject's initial home TPN clinic visit and at present were estimated from standard formulas and compared. The CrCl in 12 patients who had received home TPN for > 10 years was estimated retrospectively on a yearly basis. The estimated CrCl as an accurate measure of glomerular filtration rate was confirmed by measuring plasma indium-111 diethylenetriamine pentaacetic acid clearance. The mean daily intravenous protein intake and days during which nephrotoxic medications were used and number of bacteremic/fungemic episodes were determined for each subject. CrCl declined by 3.5 +/- 6.3% per year (p = .004). Twenty-nine of 33 patients had decreases of 0.6% to 15.4% per year. Tubular function, as determined by the tubular reabsorption of phosphate, was impaired in 52% of the subjects. The intravenous protein load averaged 1.28 +/- 0.32 g/kg per day, nephrotoxic drug use averaged 3.4 +/- 4.0% of all days on home TPN, and each patient averaged 2.3 episodes of bacteremia or fungemia since home TPN was started (0.5 +/- 0.5 episodes per year). When all factors were assessed simultaneously, nephrotoxic drug use, episodes of bacteremia/fungemia, and age accounted for approximately 46% of the variability in CrCl. When bacteremia/fungemia was expressed as a yearly rate, nephrotoxic drug use assumed no role in the glomerular filtration rate determination; infection rate and age alone accounted for 53% of the CrCl variability. We describe a profound decrease in renal function associated with long-term TPN, most of which is largely unexplained.

Adult↗

PubMedDate not supplied

Catheter-related infections associated with home parenteral nutrition and predictive factors for the need for catheter removal in their treatment.

The inpatient and outpatient records were reviewed for 527 patients, including 138 children, who were discharged on home total parenteral nutrition and followed by the University of California, Los Angeles, home total parenteral nutrition service for a minimum of 1 week between April 1973 and October 1991. The total follow-up time was 1154 patient years; the median follow-up time was 206 days (range 7 to 6344 days). Thirty-six patients were followed for more than 10 years (median 12.7 years). Three hundred fifteen adults (but only four children) were never infected. A total of 427 catheter-related infections occurred, giving an overall infection rate of 0.37 per patient year (0.51 per patient year in children and 0.28 per patient year in patients followed for more than 10 years). Seventy percent of the infections overall were sepsis (0.26 per patient year); of those, 17% were exit site (0.06 per patient year), and 2% were tunnel (0.01 per patient year) infections. In children, 67% of the infections were sepsis (0.37 per patient year) and 24% were exit site (0.13 per patient year). Fifty-four different organisms were responsible, and 12% of the infections were polymicrobial in origin. Sixty percent of sepsis in all patients was caused by Gram-negative organisms (44% of the catheters were removed). Forty-three percent of sepsis in children was caused by Gram-negative organisms. Twenty-six percent of sepsis in all patients was caused by Gram-positive organisms (40% of the catheters were removed). Thirty-six percent of sepsis in children was caused by Gram-positive organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Candidiasis↗