Phagocytic, antimicrobial, and metabolic functions were studied in leukocytes obtained from three patients with the Chediak-Higashi syndrome (CHS) and compared to normals, individuals, heterozygous for Chediak-Higashi syndrome, and two subjects with chronic granulomatous disease of childhood (CGD). Chediak-Higashi syndrome leukocytes showed normal ingestion of a variety of bacteria, Candida alb...

The phenylacetic acid (PA) degradative pathway is the central pathway by which various aromatic compounds (e.g., styrene) are degraded. Upper pathways for different aromatic compounds converge at common intermediate phenylacetyl-CoA (PA-CoA), which is then metabolized to succinyl-CoA and acetyl-CoA. We previously made a link in Burkholderia cenocepacia between PA degradation and virulence by sh...

Most isolates of Staphylococcus aureus produce a serotype 5 (CP5) or 8 (CP8) capsular polysaccharide. To investigate whether CP5 and CP8 differ in their biological properties, we created isogenic mutants of S. aureus Reynolds that expressed CP5, CP8, or no capsule. Biochemical analyses of CP5 and CP8 purified from the isogenic S. aureus strains were consistent with published structures. The deg...

OBJECTIVES To investigate the in vitro antifungal activity of the structurally different cathelicidin peptides SMAP-29, BMAP-27, BMAP-28, protegrin-1 (PG-1) and indolicidin. METHODS The in vitro antifungal and fungicidal activities of these antimicrobial peptides were respectively assessed via MIC determinations and killing kinetics assays. The effects of the peptides on membrane permeabiliza...

Enzyme-prodrug therapy for the treatment of cancer is an experimental procedure that is under intensive investigation. However, the relative merits of the various systems for use under specific conditions are still being determined. We have compared the efficacy of cell killing by the herpesvirus thymidine kinase (HSVTK)/ganciclovir and the purine nucleoside phosphorylase (PNP)/9-(beta-M-2-deox...

Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describ...

Rifampin is a cornerstone of modern antituberculosis therapy. However, rifampin's half-life of 3 h is believed to limit its utility for intermittent therapy, so new congeners with long half-lives are being developed. Using an in vitro pharmacokinetic-pharmacodynamic model of tuberculosis, we examined the relationships between rifampin exposure, microbial killing of log-phase-growth Mycobacteriu...

Granulocytes and monocytes/macrophages from patients suffering from chronic granulomatous disease (CGD) are ineffective in killing specific kinds of phagocytized bacteria, e.g., Staphylococcus aureus, due to decreased or lacking ability to produce reactive oxygen intermediates. Commonly used antibiotics like flucloxacillin are of limited therapeutic value, because the staphylococci are protecte...

Granulocytes and monocytes/macrophages from patients suffering from chronic granulomatous disease (CGD) are ineffective in killing specific kinds of phagocytized bacteria, e.g., Staphylococcus aureus, due to decreased or lacking ability to produce reactive oxygen intermediates. Commonly used antibiotics like flucloxacillin are of limited therapeutic value, because the staphylococci are protecte...

The destruction of infected cells by cytotxic T lymphocytes (CTL) is integral to the effective control of viral and bacterial diseases, and CTL function at large has long been regarded as a distinctive property of the CD8(+)T cell subset. In contrast, and despite their first description more than three decades ago, the precise contribution of cytotoxic CD4(+)T cells to the resolution of infecti...