TGF-beta and the endothelium during immune injury

During immune injury, activation of endothelial cells by inflammatory cytokines stimulates leukocyte adhesion to the endothelium, turns the endothelium from an anticoagulant surface to one that is frankly procoagulant, and results in the release of vasoactive mediators and growth factors. Cytokine activation of endothelial cells also results in increased endothelial cell TGF-beta 1 synthesis and enhanced activation of latent TGF-beta, the latter involving a shift of plasmin production from the apical to subendothelial surface. In cytokine-stimulated endothelial cells, TGF-beta hinders leukocyte adhesion and transmigration via inhibition of IL-8 and E-selectin expression. TGF-beta also profoundly diminishes cytokine-stimulated inducible nitric oxide synthase production and instead augments endothelial nitric oxide synthase expression. Thus, some of the TGF-beta actions on endothelium during immune activation can viewed as immunosuppressive. TGF-beta also influences mechanisms of vascular remodeling during the healing phase of immune injury. It stimulates PDGF-B synthesis by endothelial cells, causes bFGF release from subendothelial matrix, and promotes VEGF synthesis by non-endothelial cells. Together these mediators control angiogenesis, a critical component of the vascular repair phenomenon. Further, endothelial cell derived PDGF-B and bFGF influence the proliferation and migration of neighboring cells. Thus, endothelial cells and TGF-beta actions on the endothelium play important roles both during the initial phase of immune injury and during the later remodeling phase.     

The effect of keyboard keyswitch make force on applied force and finger flexor muscle activity

The design of the force-displacement characteristics or 'feel' of keyboard keyswitches has been guided by preference and performance data; there has been very little information on how switch 'feel' alters muscle activity or applied force. This is a laboratory-based repeated measures design experiment to evaluate the effect of computer keyboard keyswitch design on applied finger force and muscle activity during a typing task. Ten experienced typists typed on three keyboards which differed in keyswitch make force (0.34, 0.47 and 1.02 N) while applied fingertip force and finger flexor electromyograms were recorded. The keyboard testing order was randomized and subjects typed on each keyboard for three trials, while data was collected for a minimum of 80 keystrokes per trial. No differences in applied fingertip force or finger flexor EMG were observed during typing on keyboards with switch make force of 0.34 or 0.47 N. However, applied fingertip force increased by approximately 40% (p < 0.05) and EMG activity increased by approximately 20% (p < 0.05) when the keyswitch make force was increased from 0.47 to 1.02 N. These results suggest that, in order to minimize the biomechanical loads to forearm tendons and muscles of keyboard users, keyswitches with a make force of 0.47 N or less should be considered over switches with a make force of 1.02 N.     

Endogenous glutamate levels regulate nerve growth factor mRNA expression in the rat dentate gyrus

The levels of nerve growth factor (NGF) mRNA can be regulated in vitro and in vivo in the hippocampal formation by events associated with pharmacological activation of glutamate receptors. In the present study, the level of NGF mRNA in the hippocampal formation was examined following an intrahippocampal injection of 1 nmole fluorocitrate, which temporarily inhibits the astrocyte metabolic activity in vivo. Consistent with previous findings, fluorocitrate treatment significantly increased glutamate levels and decreased glutamine levels in the dentate gyrus as determined by in vivo microdialysis. The increased ratio of glutamate to glutamine was followed by a significant increase in NGF mRNA expression selectively in dentate gyrus granule cells. The effects of increasing glutamate levels were blocked by pretreatment with 50 nmole 2-amino-5-phosphonovalerate (AP5), a competitive antagonist that acts at the N-methyl-D-aspartate (NMDA) glutamate receptor subtype. These findings suggest that NGF mRNA expression is regulated, in part, by changes in endogenous glutamate levels, partially through enhanced excitatory neurotransmission through NMDA receptors.     

Biological effects of continuous exposure of embryos and young chickens to electromagnetic fields emitted by video display units

The effects of continuous exposure of embryos and young chickens to electromagnetic fields (EMFs) emitted by video display units (VDUs) were investigated. Embryos and brood were continuously exposed during embryonic and postembryonic phases to EMFs emitted by two types of VDU (TV or computer). Embryonic mortality was evaluated in three independent experiments. Young chickens were immunized three times by porcine thyroglobulin (Tg). Blood samples were assayed after each immunization for specific anti-Tg antibodies (IgG), plasma corticosterone (CORT), and plasma melatonin (MLT). In the sham-exposed samples, embryonic death (10-33%) was restricted to the perinatal period and the IgG, CORT, and MLT responses of young chickens crested after the second immunization. Constant EMF exposure was accompanied by significantly increased fetal loss (47-68%) and markedly depressed levels of circulating anti-Tg IgG, CORT, and MLT. Collectively, these findings indicate that continuous exposure to EMFs, issuing from VDUs, adversely affects embryos and young chickens.     

Comparison of Roth appliance and standard edgewise appliance treatment results

The effect of the betamethasone sodium phosphate (BSP) enema on the colonic mucosal lesions in the carrageenan induced colitis (rabbit) was examined laboratory and histologically. The effect of drugs were evaluated by the changes of body weight, fecal occult blood, blood analysis, and histological examinations. Fecal occult blood were highly positive in the physiological saline treated but less positive in the BSP groups. In the blood analysis, anemia was not detected in both groups. Histological findings such as the defect of superficial epithelium, crypt abscess, inflammatory cell infiltration, atrophic changes, defect of muscularis mucosae, goblet cell depletion, goblet cell depletion, ulcer formation, and edematous change were scored to evaluate the colonic mucosal lesions. These scores (Mean +/- S.D.) were 4.4 +/- 1.96, 7.7 +/- 3.67 for BSP, physiological saline groups respectively. From these results, BSP enema showed an antiulcerative effect on the entire colonic lesions in the carrageenan induced colitis in the rabbit.     

Induction of cyclooxygenase-2 expression by peroxisome proliferators and non-tetradecanoylphorbol 12,13-myristate-type tumor promoters in immortalized mouse liver cells

Increased expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin synthesis, has been associated with growth regulation and carcinogenesis in several systems. COX-2 is known to be induced by cytokines and the skin tumor promoter 12-tetradecanoylphorbol-13-myristate (TPA). In the present study, we investigated the effects of several non-TPA-type tumor promoters on COX-2 expression in immortalized mouse liver cells. Specifically, we tested peroxisome proliferators (PPs), which are rodent liver tumor promoters that cause gross alterations in cellular lipid metabolism, the rodent liver tumor promoter phenobarbital, and the skin tumor promoters okadaic acid and thapsigargin. The PPs Wy-14643, mono-ethylhexyl phthalate, clofibrate, ciprofibrate ethyl ester, and eicosatetraynoic acid each caused large increases in COX-2 mRNA and protein, with maximal expression seen approximately 10 h after treatment of quiescent cells. COX-2 expression was also induced by thapsigargin, okadaic acid, and calcium ionophore A23187, but not by phenobarbital or the steroid PP dehydroepiandrosterone sulfate. Induction of COX-2 expression generally resulted in increased synthesis of prostaglandin E2 (PGE2). However, the PPs caused little or no increase in PGE2 levels, and they inhibited serum-induced PGE2 synthesis. Unlike non-steroidal anti-inflammatory drugs, the PPs do not directly inhibit cyclooxygenase enzyme activity in vitro. Thus, PPs regulate prostaglandin metabolism via both positive (COX-2 induction) and inhibitory mechanisms. In summary, the strong induction of COX-2 expression by PPs, thapsigargin, and okadaic acid suggests a possible role for COX-2 in the growth regulatory activity of these non-TPA-type tumor promoters.