DNA damage induced by m-phenylenediamine and its derivative in the presence of copper ion

We have previously reported that long-term priming of human polymorphonuclear neutrophilic granulocytes (PMN) with interferon-gamma (IFN-gamma) increased the fMLP-stimulated calcium influx. We now show that also after short-term incubation with IFN-gamma, PMN calcium metabolism is modulated. Single adherent cells in three different calcium-containing buffers (high, normal, and low [Ca2+]) were stimulated with the bacterial peptide fMLP or the Ca-ATPase inhibitor thapsigargin (Tg) after about 5 min preincubation with IFN-gamma. The results of this protocol indicated that IFN-gamma increases both calcium influx and calcium sequestration. Store dependent Ca2+ influx, directly measured on readdition of calcium to Tg-treated cells incubated in EGTA buffer, was significantly enhanced in IFN-gamma-treated cells. This effect of IFN-gamma was enhanced by the tyrosine kinase inhibitor herbimycin A. Strikingly, in low extracellular calcium concentrations, IFN-gamma induced calcium transients in 20%-60% of the cells. The proportion of PMN responding with Ca2+ transients increased with decreasing extracellular calcium concentration. Average lagtime from addition of IFN-gamma to a response that could be measured was 7.3 sec, and average increase in [Ca2+] above the basal level was 790 nM. These IFN-gamma-induced transients could not be depressed by herbimycin A. Thus, IFN-gamma can increase capacitative calcium influx, induce calcium transients, and possibly affect calcium sequestration in human PMN.     

Structure-activity relationships of alkylxanthines: alkyl chain elongation at the N1- or N7-position decreases cardiotonic activity in the isolated guinea pig heart

Relationships between the alkyl substitutions (C1-C6) and cardiac inotropic activities of xanthine derivatives were studied in isolated guinea pig heart muscles. Most of the alkylxanthines exhibited positive inotropic activity on the left atrium, which was increased with an elongation of alkyl chain at the N3-position but decreased by substitution of a long alkyl group at the N1- or N7-position of the xanthine skeleton. Although positive inotropic activity in the right ventricular papillary muscle was also increased by longer alkyl groups at the N3-position, the inotropic activity became negative with an increment in alkyl chain length at the N1- or N7-position. The positive inotropic activity of alkylxanthines was correlated with their inhibitory activity on the phosphodiesterase (PDE) III isoenzyme. Adenosine A1 antagonism and PDE IV inhibitory activity were also partly associated with the inotropic activity because H-89, an inhibitor of cyclic AMP-dependent protein kinase, diminished the positive inotropic action and potentiated the negative inotropic action. These results indicate that the positive inotropic activity of alkylxanthines becomes weak with elongation of alkyl chains at the N1- and N7-positions; In particular, xanthines having two long alkyl chains show a negative inotropic activity on the right ventricular papillary muscle, an effect that could not be elucidated from their cyclic AMP-dependent action.     

Diarrhea in young children associated with Escherichia coli non-O157 organisms that produce Shiga-like toxin

The aim of this study was to evaluate the way in which short-term protection declines and is eventually lost in preconditioning and to determine the efficacy of a second preconditioning at various reperfusion intervals. Male rabbits were divided into six groups. Forty-five minutes (sustained) ischemia followed by 120 minutes reperfusion was applied 60, 65, 70, 75, and 80 minutes after a 5 minute preconditioning (groups A, B, C, D, and E) and in a control group (F) after no preconditioning. The infarct to risk ratio (I/R) was 38.3 +/- 3.5% in group A, 46.0 +/- 7.8% in B, 61.6 +/- 9.7% in C, 68.1 +/- 4.2% in D, 64.5 +/- 7.8% in E, and 61.0 +/- 7.7% in F. Group A had a smaller I/R compared with groups C, D, E, and F (p < 0.05). In another series, groups G, H, and I were exposed to two 5-minute preconditioning stimuli, separated, respectively, by 45, 60, and 75 minutes of reperfusion; 10 minutes after the last preconditioning, the animals were exposed to 45-minutes ischemia and 120 minutes reperfusion. Groups A and D (with the smaller and higher I/R ratio) were also incorporated into this protocol in order to compare the effect of the additional preconditioning with the single one. The I/R ratio was 25.4 +/- 8.5% in group G, 22.8 +/- 7.0% in group H, and 14.7 +/- 4.0% in group I (p = NS). Group D showed a higher I/R compared with groups G, A, and H (p < 0.01), and group I had a smaller I/R compared with groups A (p < 0.01) and D (p < 0.001). Cardioprotection after a first preconditioning declines gradually and is eventually lost. An additional preconditioning is always effective, and the longer the interval from the first preconditioning, the more potent is the effect.     

Multiple coronary artery aneurysm

Co-Cinobufotalin Oral Liquor (CCOL) was studied for its ability to inhibit hepatitis B virus DNA replication, HBsAg and HBeAg expression in a HBV-transfected cell line (2.2.15 cell). The result showed that ID50 (the drug concentration that inhibits HBsAg or HBeAg secretion by 50%) was 0.08 mg/ml and 0.07 mg/ml on HBsAg and HBeAg respectively. CD50 (the drug concentration that reduces cell growth by 50%) was 2.5 mg/ml. TI (therapeutic index) was 31.3 and 35.7 respectively. The present data suggest that CCOL could exert a potent antiviral activity against HBV in vitro. Southern blot showed that CCOL inhibited HBV-DNA repication in a dose-dependent manner.     

Application of HUMF13A01 (AAAG)n STR polymorphism to the genetic diagnosis of coagulation factor XIII deficiency

Deficiency of the A subunit of coagulation factor XIII causes a severe bleeding disorder requiring life long replacement therapy. The mutations causing A subunit deficiency appear to be very heterogeneous, and it is impractical to identify each mutation before genetic counselling or prenatal diagnosis can be attempted. In this study we have shown that a highly polymorphic short tandem repeat element, HUMF13A01 (AAAG)n that occurs in the 5' flanking sequence of the factor XIII A subunit gene, can be used to follow the segregation of deficiency causing mutations. We studied 6 families with factor XIII A subunit deficiency from 5 different ethnic groups. All parents were heterozygous for the repetitive element and therefore all the families were informative. The linked polymorphism was used to carry out the first prenatal diagnosis of factor XIII A subunit deficiency. The analysis of this polymorphism by the polymerase chain reaction is rapid, reliable, requires little DNA and is ideal for the genetic analysis of factor XIII A subunit deficiency.     

Binding of mutated Ras- and p53-derived peptides to HLA-DR molecules

We investigated retrospectively 132 cases of open wedge high tibial osteotomy using an external fixation device, concentrating on the rate of neurological complications. One group of patients underwent surgery according to the conventional technique (n = 89). The rate of transient neurological complications was 15.7%; 7 months after surgery the rate of persistent deficits was 12.4%. For the second group (n = 43) a modified surgical technique was used that lowered the complication rate significantly (transient deficits 14%, persistent deficits 4.7%). In the modified technique the osteotomy is not performed in the conventional way using an oscillating saw but through consecutive drill holes of increasing diameter followed by osteoclasis. The lower complication rate in the second group is mainly due to the less extensive approach that leads to a smaller number of postoperative tibialis anterior syndromes (type B lesion). No differences were found with type C lesions (extension deficit of D1). No complete peroneal nerve palsy (type A) occurred in either group. We conclude that the reduction of neurological complications in group 2 is related to the less extensive approach of the proposed technique.     

Spherical-multipole analysis of electromagnetic and acousticalscattering by a semi-infinite elliptic cone

The spherical-multipole analysis of scalar scattering by an acoustically soft or hard elliptic cone, and of electromagnetic scattering by a perfectly conducting elliptic cone, are presented. The series expansions of the exact solutions are of poor convergence, if both source and field points are far from the cone's tip. A mathematical transformation for the acceleration of convergence-due to Euler-is applied to these expansions, to numerically determine the scattering cross sections of these objects. This powerful method can also be used for the numerical evaluation of diffraction coefficients. The paper contains a review of scientific work concerning scattering by objects with edges, corners, tips, etc     

Neurocontrol for lateral vehicle guidance

A solution to autonomous lateral vehicle guidance using a neurocontroller that can learn from measured human-driving data without knowledge of the physical car parameters is discussed. Simulations and practical tests confirm that a small-size feedforward autonomous neural network (21 neurons) can learn to steer a vehicle at high speeds only from looking at human-driving examples. In this way, the network learns the total closed-loop behavior, including the nonlinear dynamics of the vehicle and the driver's individual driving style. The main result of practical investigations is that the neutral controller trained on human-driving examples exhibits an aperiodic behavior that does not vanish at higher speeds (tests performed up to 130 km/h) and produces fewer lateral deviations than the linear state controller