Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maturation of human myeloid cells is associated with quantitative and qualitative changes in protein kinase C (PKC) and increases in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) receptors, actin, and actin regulatory proteins. We have studied the actin responses and cell shape changes caused by FMLP and its second messenger pathways in HL60 cells undergoing neutrophilic maturation. In uninduced cells, the PKC activators 12-O-tetradecanoyl phorbol-13-acetate (TPA), bryostatin, and 1-oleyl-2-acetylglycerol (OAG) resulted in 15% to 30% decreases in F-actin, whereas FMLP had no effect. Ionomycin had no effect on actin but did cause a 10-fold increase in intracellular calcium. Cells grown for 24 hours in 1% dimethyl sulfoxide (DMSO) acquired the ability to polymerize actin in response to FMLP and ionomycin. TPA continued to cause a decrease in F-actin at 24 hours, but caused an increase in F-actin at 48 to 72 hours of maturation. The PKC inhibitor 1-5-isoquinolinesulfonyl 2-methylpiperazine (H7) partially blocked the F-actin increase caused by TPA in induced cells, but had no effect on the decrease in F-actin caused by TPA in uninduced cells or the increase in F-actin seen in FMLP-treated neutrophils. F-actin rich pseudopods developed following TPA or FMLP stimulation of induced HL60 cells; in uninduced cells neither agent caused pseudopod formation but TPA caused a dramatic loss of surface ruffles. The ability of FMLP and ionomycin to elicit a neutrophil-like actin response in HL60 cells within 24 hours after DMSO treatment shows that the actin regulatory mechanism is mature by that time. The inability of ionomycin to increase F-actin in uninduced cells supports the view that calcium increases alone are insufficient for actin polymerization. The longer maturation time required for HL60 cells to develop an actin polymerization response to TPA compared with FMLP, coupled with the inability of H7 to block the FMLP-mediated F-actin increase in neutrophils, suggests that the F-actin increase caused by FMLP is not mediated solely by PKC. Lastly, the TPA-induced F-actin decrease and shape changes in uninduced HL60 cells, and the longer time required for a "mature" response to TPA, may reflect immaturity in the PKC isoenzyme pattern rather than immaturity of the actin regulatory mechanism.
 ...
PMID:Signal transduction and the regulation of actin conformation during myeloid maturation: studies in HL60 cells. 198 1

The purpose of this study was to establish the effects of intravenous dimethyl sulfoxide (DMSO), a solvent used in a wide variety of products (medicines), on kidney function in the newborn rabbit. Three groups of anesthetized, ventilated, normoxemic 4- to 8-day-old New Zealand White rabbits received a 90-min intravenous infusion of DMSO at a dose of 1.11 (group 1), 16.5 (group 2) or 111 microgram/ kg/h (group 3). The only change observed in the animals of group 1 was a significant increase in filtration fraction (FF; p < 0. 001), whereas no change at all was observed in the renal functional parameters of the animals of group 2. The highest dose of DMSO (group 3), however, caused a very significant (p < 0.001) decrease in renal blood flow (RBF) and a rise in renal vascular resistance (RVR), FF and urine volume (UV). Glomerular filtration rate (GFR) and systemic parameters such as pH, mean arterial blood pressure and heart rate did not change. The rise in GFR, RVR, UV (group 3 vs. 2) and FF (groups 3 vs. 2 and 2 vs. 1) was dose-dependent. No significant dose-dependent decrease in RBF was found. To the best of our knowledge, there are no previous reports on the effect of DMSO on renal function in the solvent doses used in this study. We ascribe the reported effects to the 'immaturity' of the newborn rabbit kidney. Consequently, this agent should be used with great caution in developmental studies.
 ...
PMID:The effects of dimethyl sulfoxide on renal function of the newborn rabbit. 1056 64