Phagocytic Activation of Macrophages with Serum MAF Depends on Engulfment Efficiency and Not Migratory Activity.

BACKGROUND/AIM: Serum-derived macrophage activating factor (serum MAF) is known to increase the phagocytic activity of macrophages and potentially plays a role in activating cancer immunity. In order to reveal the contributing factors for phagocytic activation, the migratory activity and the efficiency of engulfment was analyzed. MATERIALS AND METHODS: THP-1 macrophages were induced by 12-O-tetradecanoyl-13-acetate (TPA). The migratory activity and efficiency of engulfment were analyzed by time-lapse imaging and suspension assay, respectively. RESULTS: While the distance of migration did not change before and after activation with serum MAF, the efficiency of beads internalisation was significantly increased. CONCLUSION: Phagocytic activation of serum-MAF-treated macrophages was caused by increasing the efficiency of engulfment. This study contributes to the knowledge about the activation of the immune system through phagocytic activation of macrophages.

Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors.

BACKGROUND/AIM: Macrophages are important components of human defense systems and consequently key to antitumor immunity. Human-serum macrophage activation factor (serum MAF) can activate macrophages, making it a promising reagent for anticancer therapy. MATERIALS AND METHODS: We established four different macrophage subtypes through introduction of different culture conditions to THP-1- and U937-derived macrophages. We assessed phagocytic activity to understand subtype responses to typical macrophage activation factors (MAFs) and the activation mechanisms of serum MAF. RESULTS: All four macrophage subtypes differed in their response to all MAFs. Moreover, serum MAF had two different activation mechanisms: N-acetylgalactosamine (GalNAc)-dependent and GalNAc-independent. CONCLUSION: Macrophage activation states and mechanisms are heterogeneous.

Association of the mitochondrial DNA 5178 A/C polymorphism with serum lipid levels in the Japanese population.

As one approach to exploring whether the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is associated with atherosclerosis, we genotyped 461 healthy Japanese individuals and studied the relationship of mt5178 A/C genotypes to serum lipid levels. Blood specimens were obtained after at least a 12-h fasting period from the subjects. The mt5178 A/C was genotyped by the polymerase chain reaction/restriction fragment length polymorphism method. The relative frequency of mt5178 A was 41.6% (192/461) and of mt5178 C was 58.4% (269/461). After adjustments for age and body mass index, the high-density lipoprotein cholesterol concentration in males carrying mt5178 A was significantly higher than that in males carrying mt5178 C ( P=0.026). The tryglyceride (TG) concentration in females carrying mt5178 A was significantly lower than that in females carrying mt5178 C ( P=0.012). This difference in the TG level between the two genotypes was more evident in postmenopausal females than in premenopausal females. Mt5178 A seems to have an antiatherogenic effect. This is the first genetic epidemiological report on the association of mt5178 A/C polymorphism with serum lipid levels in the Japanese population.

Magnitude of the regression to the mean within one-year intra-individual changes in serum lipid levels among Japanese male workers.

To investigate the magnitude of the 'regression to the mean' effect for the changes in serum total cholesterol (TC), triglycerides (TG), and high density lipoprotein cholesterol (HDLC) levels during one-year interval between annual health check-ups in occupational settings, the relationships between the baseline level and subsequent one-year change in TC, TG or HDLC were analyzed using paired health check-up data in 1998 and 1999 of 547 Japanese male clerical workers. After adjustment for age, body mass index (BMI), yearly change in BMI, drinking score and smoking score by the multivariate analyses, the yearly changes in each serum lipid (deltaTC, deltaLn(TG) or deltaHDLC) were clearly inversely associated with the lipid levels in 1998. For example, in the multiple linear regression analyses setting delta value in each serum lipid as a dependent variable, the partial regression coefficients for the baseline lipid levels (beta1) were - 0.21 (p<0.001) for the TC, -0.39 (p<0.001) for the Ln(TG) and -0.15 (p<0.001) for the HDLC, respectively. These results suggest that the observed yearly change in each serum lipid level may largely reflect the 'regression to the mean' effect in addition to the real yearly biological change.

Excessive release of [3H] noradrenaline by veratridine and ischemia in spinal cord.

In this study, the properties of ischemic condition-induced and veratridine-evoked [3H]noradrenaline ([3H]NA) release from rat spinal cord slices were compared. It was expected that ischemia mimicked by oxygen and glucose deprivation results in the impairment of Na+/K+ -ATPase with a consequent elevation of the intracellular Na+ -level which reverses the NA carrier and promotes excessive NA release, and veratridine, by the activation of Na+ channels, releases NA both carrier-mediated and Ca2+ -dependent, i.e. vesicular manner. In our experiments, veratridine (1-100 microM) dose-dependently increased the resting [3H]NA release, and its effect was only partially blocked by low temperature or the lack of external calcium, whereas the sodium channel inhibitor tetrodotoxin (TTX, 1 microM) completely prevented it, indicating that veratridine induces NA release via axonal depolarization and reversing the transporters by eliciting Na+ -influx. In contrast to TTX, the local anesthetic lidocaine (100 microM) only partially blocked the veratridine-induced [3H]NA release due to its inhibitory action on K+ channels. The ischemia-induced [3H]NA release was abolished at 12 degrees C, a temperature known to block only the transporter-mediated release of transmitters. However, lidocaine was also partially effective to reverse the action of ischemia on the NA release, indicating that lidocaine is not a useful compound in the treatment of spinal cord-injured patients against the excessive excytotoxic NA release.

[A new sedation technique with propofol during spinal anesthesia].

We compared our new sedation technique with propofol during spinal anesthesia (Group B, n = 50) with a previously described method by Mackenzie et al. (Group A, n = 20). In Group A, propofol was started at a rate of 6 mg.kg-1.h-1 for 10 minutes, followed by continuous infusion at a rate of 4 mg.kg-1.h-1 till the end of surgery. In Group B, propofol 0.4 mg.kg-1 was administered by a bolus injection at the beginning. One-hundred and fifty minutes after the first injection, propofol 0.2 mg.kg-1 was added. The third dose of 0.1 mg.kg-1 of propofol was given 150 seconds after the second dose, followed by continuous infusion at a rate of 4 mg.kg-1.h-1 till the end of surgery. When adequate sedation was not obtained in Group B, propofol 0.1 mg.kg-1 was added by bolus fashion occasionally. In Group A, it took 9 min. 29 sec. to complete adequate sedation assessed by Mackenzie and Grant's sedation score. On the other hand, in Group B, it was 7 min. 27 sec. (P < 0.05 compared with Group A). There was neither excitation nor movement during sedation in Group B, while 5 patients experienced such events in Group A. The blood concentrations of propofol in Group B was 0.946 +/- 0.076 microgram.ml-1 and 0.693 +/- 0.136 microgram.ml-1 at 5 minutes and 10 minutes after the beginning of propofol, respectively. These values were significantly lower than those reported by Kugimiya. Our newly developed method for sedation with propofol during spinal anesthesia would be safer and more effective than that previously described by Mackenzie et al.

Abdominal macronodular tuberculomas: MR findings.

PURPOSE: Our goal was to determine the appearance of abdominal macronodular tuberculomas on MRI. METHOD: MR findings of two patients with abdominal macronodular tuberculoma, one of the liver and the other in the kidney, were reviewed. RESULTS: The two tuberculomas, histologically confirmed to have no calcification, hemorrhaging, or fibrosis, commonly showed low signal intensity on both T1- and T2-weighted images. CONCLUSION: We report two cases of a macronodular tuberculoma in the liver and kidney, which is visualized as a region of hypointensity on T2-weighted MR images. This finding appears to be important in reaching a definitive diagnosis of an abdominal tuberculoma.

Searching for risk factors using multilayer neural network as a classifier.

A method to determine risk factors for particular outcomes using trained multilayer neural networks is proposed. The basic idea is to measure the partial differentials of the output with respect to input variables of the network. Differentiable activation functions and continuity of input variables is assumed.

[Comparative study of postoperative complications in primary and secondary implantation of posterior chamber intraocular lens in cataract surgery for diabetic patients].

Postoperative complications of diabetic cataract cases with active stage diabetic retinopathy, which underwent simultaneous extracapsular lens extraction (ECCE) and posterior chamber intraocular lens (PC-IOL) implantation in 84 eyes, ECCE only in 38 eyes and secondary implantation of PC-IOL after ECCE in 23 eyes, were studied. In the eyes of the primary PC-IOL implantation group, fibrous response in 35 eyes (42%), posterior iris synechia in 10 eyes (12%), progression of diabetic retinopathy in 13 eyes (16%), after cataract in 11 eyes (13%), pupil capture in 4 eyes (5%) and decentration of lens optics in 3 eyes (4%) were appeared, while in the ECCE only group, fibrous response in 11 eyes (29%), posterior iris synechia in 4 eyes (11%), after cataract in 11 eyes (29%), progression of diabetic retinopathy in 6 eyes (16%) were observed. On the other hand, in the secondary PC-IOL implantation group, only fibrous response was appeared in 1 eye (4%), Although PC-IOL implantation has been so far considered contraindication in cases with cataract combined with active stage retinopathy, the present studies strongly suggest that secondary PC-IOL implantation would be good indication in these cases whose blood sugar was properly controlled and the retinopathy was burned out by panretinal photocoagulation soon after ECCE.