We have shown that 1,2-diacylglycerol hydroperoxides activate protein kinase C (PKC) as efficiently as does phorbol ester Takekoshi S, Kambayashi Y, Nagata H, Takagi T, Yamamoto Y, Watanabe K. ...Activation of protein kinase C by oxidized diacylglycerol. Biochem Biophys Res Commun 1995; 217: 654-660. 1,2-Diacylglycerol hydroperoxides also stimulate human neutrophils to release superoxide whereas their hydroxides do not Yamamoto Y, Kambayashi Y, Ito T, Watanabe K, Nakano M. 1,2-Diacylglycerol hydroperoxides induce the generation and release of superoxide anion from human polymorphonuclear leukocytes. FEBS Lett 1997; 412: 461-464. One of the proposed mechanisms for the formation of 1,2-diacylglycerol hydroperoxides is the hydrolysis of phosphatidylcholine hydroperoxides by phospholipase C (PLC). To confirm this hypothesis, we incubated 1-palmitoyl-2-linoleoyl-phosphatidylcholine (PLPC) liposomes containing PLPC hydroperoxides (PLPC-OOH) with Bacillus cereus PLC and found 1-palmitoyl-2-linoleoylglycerol (PLG) and its hydroperoxide (PLG-OOH) were produced. PLC hydrolyzed the two substrates without preference, as the yields of PLG and PLG-OOH were the same even though cholesterol was incorporated into liposomes to increase bilayer integrity. Phospholipid hydroperoxide glutathione peroxidase (PHGPX) reduced PLG-OOH to its hydroxide in the presence of glutathione while the conventional cytosolic glutathione peroxidase did not. These data suggest that PLC hydrolyzes oxidized biomembranes to give 1,2-diacylglycerol hydroperoxides for PKC stimulation but PHGPX may prevent neutrophil stimulation by reducing 1,2-diacylglycerol hydroperoxides to their hydroxides.
Identification of biomarkers for Alzheimer's disease (AD) is important for its early diagnosis and prevention and a key in advancing our understanding of its pathophysiology. The aim of this study ...was to determine whether systemic inflammatory interleukin-1β (IL-1β) and interleukin-6 (IL-6) as well as hypertension (HT), diabetes mellitus (DM), and body mass index (BMI) are predictors of AD. We performed a 10-year follow-up study on 133 elderly who were institutionalized in a nursing home. The associations of IL-1β and IL-6 at both rest and agitation, as well as HT, DM, and BMI at baseline, were analyzed with the incidences of vascular dementia (VD) and AD during a 10-year follow-up period. The Kaplan-Meier method with log-rank test and Cox regression analyses for the total of 133 subjects showed significantly higher incidences of both VD and AD in subjects with DM or HT at baseline. Resting IL-1β or IL-6 value, or agitation score, was not significantly associated with the subsequent development of VD or AD. The analyses of 40 subjects who had shown agitation at least once in the previous 3 months demonstrated that IL-1β and IL-6 values at the agitation stage were significantly associated with AD, but not with VD. Our results indicate that systemic inflammatory IL-1β and IL-6 at the agitation stage are risk factors for the development of AD, but not VD. Inflammatory mechanisms for AD seem to be causal and specific to the development of AD.
Airway responses induced by intranasal administration of mite allergen without adjuvant were studied in NC/Nga mice. A crude extract of
Dermatophagoides farinae (Df) was administered for 5 ...consecutive days and a single intranasal challenge booster dose was given 1 week after the last sensitization. 24 h after the single challenge, the airway hyperresponsiveness (AHR) was measured and the bronchoalveolar lavage fluid (BALF) was analyzed for numbers of eosinophils and neutrophils, and both cytokine and chemokine levels. There were marked increases in number of eosinophils in the BALF, AHR, Th2 cytokines (IL-5 and IL-13), and chemokine (eotaxin-1 and eotaxin-2) levels in the BALF following Df exposure. C57BL/6N, A/J, BALB/c, and CBA/JN mouse strains were also exposed to Df crude extract, but all of the measured responses were strongest in NC/Nga mice. Furthermore, Df-exposed NC/Nga mice showed the goblet cell hyperplasia, pulmonary eosinophilic inflammation, and increases in both total serum IgE and Df-specific IgG1. After intranasal exposure of NC/Nga mice to crude extract of
Dermatophagoides pteronyssinus, the BALF eosinophilia and AHR were similar to responses induced by Df. None of the study parameters were increased in response to intranasal exposure to ovalbumin. These data demonstrated that NC/Nga mice developed allergic asthma-like responses after intranasal exposure to mite allergens.
Cold water-immersion induces vasoconstriction with an elevation of blood endothelin-1, which is a potent vasoconstrictor peptide, in patients with primary Raynaud's phenomenon (PRP). However, ...physiological involvement of endothelin-1 in cold-induced vasodilation (CIVD) remains to be elucidated.
We monitored changes of finger blood flow during cold water (10 degrees C) immersion and assayed blood endothelin-1 in 7 PRP patients and 7 workers with vibration-induced white finger (VWF) and in the respective control subjects.
While significant reductions in finger blood flow at 2 min after the immersion were observed in PRP patients and VWF workers, its elevation at 4 min, which was considered to reflect CIVD, was recognized only in PRP patients. In healthy controls, blood endothelin-1 increased at 4 min and returned to the basal level immediately after the immersion. The increase in blood endothelin-1 at 4 min in PRP patients was greater than that in controls, and continued even after the immersion. Conversely, the increase neither at 4 min nor after immersion was seen in VWF workers. Local vascular changes produced by repetitive vibration may be responsible for the attenuated CIVD and unchanged blood endothelin-1 during cold water-immersion in VWF workers.
Our results showing elevated blood endothelin-1 during and after immersion in PRP contrast with that in VWF suggesting that endothelin-1 is related to sympathetic hyperactivity which is more involved in PRP rather than VWF. It seems unlikely that endothelin-1 is functionally or directly associated with CIVD.
Based on the new concept of permissible functions, a heuristic procedure to design logic networks with as few gates as possible, without guaranteeing the minimality of designed networks, is ...developed. This procedure, which is drastically different from conventional logic-design procedures, is called the transduction method, because an initial network designed by any conventionally known logic-design method is first transformed into a different network configuration and then reduced to a simpler network by calculating permissible functions at the outputs of gates and connections throughout the network.< >
PDF
