Superoxide anion production by neutrophils in myelodysplastic syndromes (preleukemia).

Superoxide anion (O2-) production by neutrophils from 14 untreated patients with acute nonlymphocytic leukemia (ANLL) was significantly less than that of healthy controls (4.93 +/- 1.99 vx 6.20 +/- 1.53 nmol/min/10(6) neutrophils, p less than 0.05). In 10 patients with myelodysplastic syndrome (MDS), however, it was not significantly different from the control level although 6 of the 10 patients had low levels, when individual patients were compared with the lower limit of the control range. An inverse correlation between the O2- production of neutrophils and the percentage of leukemic cells in the marrow existed in ANLL (r = -0.55, p less than 0.01), but not in MDS. Three of 4 MDS patients who died of pneumonia prior to leukemic conversion showed a low level of O2- production. The impaired O2- production by neutrophils from some MDS patients, probably due to the faulty differentiation from leukemic clones, may be one of the causes of enhanced susceptibility to infection.</p

Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome

AbstractOBJECTIVESThe study compared the influence of sympathetic stimulation on transmural and spatial dispersion of repolarization between LQT1 and LQT2 forms of congenital long QT syndrome (LQTS).BACKGROUNDCardiac events are more associated with sympathetic stimulation in LQT1 than in LQT2 or LQT3 syndrome. Experimental studies have suggested that the interval between Tpeak and Tend (Tp-e) in the electrocardiogram (ECG) reflects transmural dispersion of repolarization across the ventricular wall.METHODSWe recorded 87-lead body-surface ECGs before and after epinephrine infusion (0.1 μg/kg/min) in 13 LQT1, 6 LQT2, and 7 control patients. The Q-Tend (QT-e), Q-Tpeak (QT-p), and Tp-e were measured automatically from 87-lead ECGs, corrected by Bazett’s method (QTc-e, QTc-p, Tcp-e), and averaged among all 87-leads and among 24-leads, which reflect the potential from the left ventricular free wall. As an index of spatial dispersion of repolarization, the dispersion of QTc-e (QTc-eD) and QTc-p (QTc-pD) were obtained among 87-leads and among 24-leads, and were defined as the interval between the maximum and the minimum of the QTc-e and the QTc-p, respectively.RESULTSEpinephrine significantly increased the mean QTc-e but not the mean QTc-p, resulting in a significant increase in the mean Tcp-e in both LQT1 and LQT2, but not in control patients. The epinephrine-induced increases in the mean QTc-e and Tcp-e were larger in LQT1 than in LQT2, and were more pronounced when the averaged data were obtained from 24-leads than from 87-leads. Epinephrine increased the maximum QTc-e but not the minimum QTc-e, producing a significant increase in the QTc-eD in both LQT1 and LQT2 patients, but not in control patients. The increase in the QTc-eD was larger in LQT1 than in LQT2 patients.CONCLUSIONSOur data suggest that sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than in LQT2 syndrome, and this may explain why LQT1 patients are more sensitive to sympathetic stimulation

Differential effects of beta-blockade on dispersion of repolarization in the absence and presence of sympathetic stimulation between the lqt1 and lqt2 forms of congenital long qt syndrome

AbstractObjectivesThis study compared the effects of beta-blockade on transmural and spatial dispersion of repolarization (TDR and SDR, respectively) between the LQT1 and LQT2 forms of congenital long QT syndrome (LQTS).BackgroundThe LQT1 form is more sensitive to sympathetic stimulation and more responsive to beta-blockers than either the LQT2 or LQT3 forms.MethodsEighty-seven-lead, body-surface electrocardiograms (ECGs) were recorded before and after epinephrine infusion (0.1 μg/kg body weight per min) in the absence and presence of oral propranolol (0.5–2.0 mg/kg per day) in 11 LQT1 patients and 11 LQT2 patients. The Q-Tendinterval, the Q-Tpeakinterval and the interval between Tpeakand Tend(Tp-e), representing TDR, were measured and averaged from 87-lead ECGs and corrected by Bazett’s method (corrected Q-Tendinterval [cQTe], corrected Q-Tpeakinterval [cQTp] and corrected interval between Tpeakand Tend[cTp-e]). The dispersion of cQTe(cQTe-D) was obtained among 87 leads and was defined as the interval between the maximum and minimum values of cQTe.ResultsPropranolol in the absence of epinephrine significantly prolonged the mean cQTpvalue but not the mean cQTevalue, thus decreasing the mean cTp-evalue in both LQT1 and LQT2 patients; the differences with propranolol were significantly larger in LQT1 than in LQT2 (p < 0.05). The maximum cQTe, minimum cQTeand cQTe-D were not changed with propranolol. Propranolol completely suppressed the influence of epinephrine in prolonging the mean cQTe, maximum cQTeand minimum cQTevalues, as well as increasing the mean cTp-eand cQTe-D values in both groups.ConclusionsBeta-blockade under normal sympathetic tone produces a greater decrease in TDR in the LQT1 form than in the LQT2 form, explaining the superior effectiveness of beta-blockers in LQT1 versus LQT2. Beta-blockers also suppress the influence of sympathetic stimulation in increasing TDR and SDR equally in LQT1 and LQT2 syndrome

Superoxide anion (O2-) production by neutrophils in refractory anemia with excess of blasts.

The O2- production by neutrophils was examined in 4 cases of refractory anemia with excess of blasts (RAEB) in order to evaluate the possible causes of enhanced susceptibility to infection and to gain some informations on the differentiation of neutrophils in this hematological disorder. In three of the four RAEB cases there was little O2- production by neutrophils, in addition to there being morphological anomalies of the neutrophils such as a Pelger-Huet-like anomaly, granular deficiency and binucleated cells. These results suggest that the impairment of O2- production by neutrophils in RAEB is one of the possible causes of susceptibility to infection and also suggest that the differentiation of neutrophils in this hematological disorder is faulty. The estimation of O2- production by neutrophils may be a useful diagnostic method for preleukemia.</p

Processing of D1 Protein: A Mysterious Process Carried Out in Thylakoid Lumen

In oxygenic photosynthetic organisms, D1 protein, a core subunit of photosystem II (PSII), displays a rapid turnover in the light, in which D1 proteins are distinctively damaged and immediately removed from the PSII. In parallel, as a repair process, D1 proteins are synthesized and simultaneously assembled into the PSII. On this flow, the D1 protein is synthesized as a precursor with a carboxyl-terminal extension, and the D1 processing is defined as a step for proteolytic removal of the extension by a specific protease, CtpA. The D1 processing plays a crucial role in appearance of water-oxidizing capacity of PSII, because the main chain carboxyl group at carboxyl-terminus of the D1 protein, exposed by the D1 processing, ligates a manganese and a calcium atom in the Mn4CaO5-cluster, a special equipment for water-oxidizing chemistry of PSII. This review focuses on the D1 processing and discusses it from four angles: (i) Discovery of the D1 processing and recognition of its importance: (ii) Enzyme involved in the D1 processing: (iii) Efforts for understanding significance of the D1 processing: (iv) Remaining mysteries in the D1 processing. Through the review, I summarize the current status of our knowledge on and around the D1 processing

Superoxide anion (O(2)(－)) production by neutrophils in myelodysplastic syndrome (MDS)

Myelodysplastic syndrome (MDS) are hematological disorders with the potential of progressing to acute leukemia. MDS patients occasionally die of infection despite the absence of severe pancytopenia prior to overt leukemia. Superoxide anion (O(2)(－)) production leads to intracellular bactericidal activity by neutrophils, particularly in an oxygen-dependent system. In this paper, O(2)(－) production by neutrophils in 15 MDS patients [11 patients with refractory anemia with excess of blasts (RAEB) and 4 patients with RAEB in transformation (RAEB-t)] was examined to evaluate possible causes of enhanced susceptibility to infection and to gain information concerning the pathophysiology and prognosis. The following results were obtained : (1) The O(2)(－) production by neutrophils (O(2)(－) production) in 15 MDS patients was lower than that in healthy controls (3.75±2.93 vs 6.20±1.53 nmol/min/10(6) neutrophils, p<0.05). Three of the 15 MDS patients showed little O(2)(－) production. (2) There was inverse correlation between O(2)(－) production and the percentage of leukemic cells in the marrow in acute leukemia (r=0.55, p<0.01), but not in MDS. (3) The O(2)(－) production in 5 MDS patients showing morphological anomalies in a high percentage of neutrophils significantly lower than that in 10 MDS patients showing morphological anomalies in a low percentage of neutrophils (1.04±1.37 vs 5.15±2.50 nmol/min/10(6) neutrophils, p<0.05). (4) The O(2)(－) production in 5 patients with frequent fever (≧38℃) -episodes was significantly lower than that in 10 MDS patients with infrequent fever-episodes (2.22±2.15 vs 4.49±2.83 nmol/min 10(6) neutrophils, p<0.05). (5) Comparison of the O(2)(－) production between MDS patients with and without progression to overt leukemia showed no significant difference (4.25±3.26 vs 3.28±2.76 nmol/min/10(6) neutrophils). These findings suggest that impaired O(2)(－) production by neutrophils, probably due to the faulty differentiation from abnormal hematopoietic clones, is one possible cause of enhanced susceptibility to infection in MDS, and may provide clues for clinical management of infection, but is not useful for early detection of progression to overt leukemia

Superoxide anion (O(2)(－)) production by neutrophils in myelodysplastic syndrome (MDS)

Myelodysplastic syndrome (MDS) are hematological disorders with the potential of progressing to acute leukemia. MDS patients occasionally die of infection despite the absence of severe pancytopenia prior to overt leukemia. Superoxide anion (O(2)(－)) production leads to intracellular bactericidal activity by neutrophils, particularly in an oxygen-dependent system. In this paper, O(2)(－) production by neutrophils in 15 MDS patients [11 patients with refractory anemia with excess of blasts (RAEB) and 4 patients with RAEB in transformation (RAEB-t)] was examined to evaluate possible causes of enhanced susceptibility to infection and to gain information concerning the pathophysiology and prognosis. The following results were obtained : (1) The O(2)(－) production by neutrophils (O(2)(－) production) in 15 MDS patients was lower than that in healthy controls (3.75±2.93 vs 6.20±1.53 nmol/min/10(6) neutrophils, p<0.05). Three of the 15 MDS patients showed little O(2)(－) production. (2) There was inverse correlation between O(2)(－) production and the percentage of leukemic cells in the marrow in acute leukemia (r=0.55, p<0.01), but not in MDS. (3) The O(2)(－) production in 5 MDS patients showing morphological anomalies in a high percentage of neutrophils significantly lower than that in 10 MDS patients showing morphological anomalies in a low percentage of neutrophils (1.04±1.37 vs 5.15±2.50 nmol/min/10(6) neutrophils, p<0.05). (4) The O(2)(－) production in 5 patients with frequent fever (≧38℃) -episodes was significantly lower than that in 10 MDS patients with infrequent fever-episodes (2.22±2.15 vs 4.49±2.83 nmol/min 10(6) neutrophils, p<0.05). (5) Comparison of the O(2)(－) production between MDS patients with and without progression to overt leukemia showed no significant difference (4.25±3.26 vs 3.28±2.76 nmol/min/10(6) neutrophils). These findings suggest that impaired O(2)(－) production by neutrophils, probably due to the faulty differentiation from abnormal hematopoietic clones, is one possible cause of enhanced susceptibility to infection in MDS, and may provide clues for clinical management of infection, but is not useful for early detection of progression to overt leukemia