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R D Klein

Publications and source records attributed to R D Klein.

77 records · Page 5Linked to original sources
PubMed1972

An analysis-of-variance model for the intrasubject replication design.

One- and two-way analysis-of-variance procedures are shown logically to be appropriate for testing hypotheses in successive treatment reversal designs for one-subject and N-subject experiments, respectively. The applicability of these designs is demonstrated through analyses of typical data.

Journal Article↗
PubMedDate not supplied

Interleukin-1beta-induced promatrilysin expression is mediated by NFkappaB-regulated synthesis of interleukin-6 in the prostate carcinoma cell line, LNCaP.

Previously, our laboratory showed that interleukin-1beta (IL-1beta) secreted by lipopolysaccharide-activated monocytes induces promatrilysin expression in the prostate carcinoma cell line, LNCaP. We now demonstrate that IL-1beta-induced promatrilysin expression is mediated by an indirect mechanism that requires nuclear factor Kappa B (NFkappaB)-dependent synthesis of IL-6. Inhibition of protein synthesis with cycloheximide blocked IL-1beta-mediated induction of matrilysin mRNA suggesting that synthesis of one or more additional factors is required for IL-1beta-induced promatrilysin protein expression. Blockage of NFkappaB transactivation activity abrogated IL-1beta-induced promatrilysin expression to baseline levels suggesting that NFkappaB transactivation activity is necessary. Inhibition of IL-6 activity attenuated IL-1beta-induced promatrilysin, but not NFkappaB transactivation activity indicating that IL-6 acts downstream of NFkappaB in potentiation of IL-1beta-mediated promatrilysin expression. Inhibition of protein synthesis with cycloheximide did not alter IL-6-induced induction of matrilysin mRNA indicating that, contrary to the mechanism by which IL-1beta regulates promatrilysin expression, IL-6-mediated matrilysin mRNA expression does not require new protein synthesis. Transient transfection with dominant negative STAT3 inhibited IL-1beta- and IL-6-induced promatrilysin. These data provide evidence that NFkappaB-mediated IL-6 synthesis is required for IL-1beta-induced promatrilysin expression, and IL-6 signaling through STAT3 plays a role in IL-1beta-induced promatrilysin expression.

Adenocarcinoma↗
PubMedDate not supplied

Skin lipopolysaccharide-binding protein and IL-1beta production after thermal injury.

In response to a burn injury, skin can have an inflammatory response characterized by the production of inflammatory cytokines, recruitment of immune cells, containment of invading organisms, and clearance of noxious substances from the wound. Lipopolysaccharide-binding protein (LBP) is a molecule that is capable of coordinating all 4 functions; we previously found evidence that suggested that LBP is produced within surgical wounds. Because of the central role of LBP in the response to bacterial infection, as well as in the high rate of infection after burn injuries, we sought to determine whether a thermal injury could affect wound LBP production and thereby affect host responses against bacterial infection. Rats were given either a burn or a sham burn and were killed 24, 48, and 72 hours after the injuries. Wound specimens were assayed for bacterial counts and for the presence of LBP, messenger (m)RNA, and interleukin (IL)-1beta mRNA. Wound LBP mRNA was significantly upregulated at 24 hours in the group with burn injuries (P < .05; burn vs sham burn); this was followed by decreases at 48 and 72 hours. Immunohistochemistry showed LBP protein in the epidermis of animals with burns. Bacterial counts increased in the group with burn injuries (P < .05; burn vs sham burn) and continued to rise for 72 hours. IL-1beta mRNA levels were elevated at all time points in the group with burn injuries (P < .05). These results suggest an inverse correlation between burn wound LBP expression and bacterial wound counts. This failure to maintain local LBP production after severe thermal injury despite localized inflammation shown by high IL-1beta levels may predispose local wounds to bacterial invasion.

Acute-Phase Proteins↗