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Biomedical subjects

D Wald

Publications and source records attributed to D Wald.

9 recordsLinked to original sources
PubMed2001

IRAK and TAK1 are required for IL-18-mediated signaling.

Interleukin-18 (IL-18), a pleiotropic cytokine produced by activated macrophages, plays significant roles in the immune response, inducing the secretion of IFN-gamma, TNF-alpha and IL-2, enhancing NK cell activity and potentiating the differentiation of Th1 cells. The intercellular signal transduction pathways through which IL-18 functions have not been thoroughly defined. We have generated a mutant cell line, I1A, that lacks the IRAK protein. In this line which has low or no expression of the other known IRAK family members, we find that the IL-1 receptor-associated kinase (IRAK) is essential for the activation of NFkappaB and JNK in response to IL-18. Furthermore, the death domain, but not the kinase activity of IRAK, is necessary for NFkappaB activation in response to IL-18. Interestingly, the N-proximal undetermined region of IRAK is necessary for NFkappaB activation, but not for JNK activation in response to IL-18, indicating IRAK may be a branchpoint in IL-18 signaling. In addition to IRAK, we implicate two other components in IL-18 signaling, TAK1 (TGF-beta-activated kinase 1) and its activator and substrate TAB1. A dominant negative mutant of TAK1 inhibits the IL-18-mediated NFkappaB activation, while IL-18 stimulation leads to the phosphorylation of TAB1. Finally, analysis of IL-18 signaling in IL-1-unresponsive mutant cell lines suggests that the IL-1- and IL-18-mediated pathways are similar, but may not be identical.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Act1, an NF-kappa B-activating protein.

Use of an NF-kappaB-dependent selectable marker facilitated the isolation of a cell line containing a cDNA encoding Act1, an NF-kappaB activator. Act1 associates with and activates IkappaB kinase (IKK), leading to the liberation of NF-kappaB from its complex with IkappaB. Many signaling pathways that liberate NF-kappaB also activate activating transcription factor (ATF) and activator protein 1 (AP-1) through Jun kinase (JNK). Act1 also activates JNK, suggesting that it might be part of a multifunctional complex involved in the activation of both NF-kappaB and JNK. Act1 fails to activate NF-kappaB in an IL-1-unresponsive mutant cell line in which all known signaling components are present, suggesting that it interacts with an unknown component in IL-1 signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Fire hazards and CO2 laser resurfacing.

The purpose of this study was to investigate the fire risk of laser resurfacing in the presence of supplemental oxygen. This study aims at defining safety parameters of variables such as laser energy level, oxygen flow rate, and "oxygen to laser target distance" when oxygen is delivered through a nasal cannula or nasopharyngeal tube. The typical operating room environment was simulated in the laboratory using the Yucatan minipig animal model. The energy source was a Coherent Ultrapulse CO2 laser. It was found that combustion did not occur at laser settings of 500 mJ, 50 W, 100 kHz, and a density of 5, used in conjunction with an oxygen flow rate of 6 liter/minute with the target area as close as 0.5 cm to the oxygen delivery. A total of 400 computer pattern generator treatments were delivered using this energy setting without observation of any combustion (p < 0.001). This provides evidence that while using even somewhat high laser settings and oxygen flow rate, laser induced fires can be avoided. We conclude that use of the laser in the presence of oxygen is safe, provided the target area is free of combustible fuels. Despite this assurance, laser mishaps are serious because they lead to both morbidity and mortality. It is our recommendation that close attention be constantly paid to all details, thus reducing the hazard potential of laser energy on local factors in an oxygen-rich environment.

Animals↗
PubMed1978

Haloperidol and lithium blocking of the mood response to intravenous methylphenidate.

The euthymic manic-d-pressive patients with therapeutic plasma lithium levels were each given two i.f. infusions of 30 mg of methylphenidate. The infusions were separated by at least 3 days. Before one infusion each patient was given 5 mg of haloperidol i.v. and before the other infusion each was given an identical volume of saline. A psychiatric observer was blind to the nature of the pretreatment and the order of pretreatment was randomized. Saline pretreated patients showed marked activation and euphoriant responses despite therapeutic lithium levels. Haloperidol pretreatment reduced this response in three patients and eliminated the euphoriant and activating response in the remaining seven patients. These results agree with the existence of a dopaminergic step in the induction of methylphenidate-induced activation and euphoria.

Adult↗