U73122 and U73343 inhibit receptor-mediated phospholipase D activation downstream of phospholipase C in CHO cells

We investigated the effects of nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside on basal and K+-evoked release of [3H]noradrenaline from superfused synaptosomes from the rat cerebral cortex. Both substances produced concentration-dependent increases in the release of the labeled transmitter under basal and depolarized conditions. The effects of the donors on basal release were Ca2+-independent but were not inhibited by the carrier-uptake blocker, desipramine; the effects were abolished by hemoglobin (an NO scavenger). Thirty-five minutes after stimulation with sodium nitroprusside, the synaptosomes were still responsive to KCl stimulation, indicating that the donor's effects were not caused by damage to the synaptosome membrane. The cGMP analogue, 8-bromo-cGMP, had no effect on basal release, and the enhanced release produced by sodium nitroprusside was not inhibited by the specific inhibitor of soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, indicating that NO's effects on basal release of the neurotransmitter are guanylate cyclase-independent. Both of the NO donors had more marked effects on release of [3H]noradrenaline during K+-stimulated depolarization. The NO-mediated increase in this case was partially antagonized by 10 microM LH-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, and 8-Br-cGMP was also capable of producing concentration-dependent increases in the K+-stimulated release of the transmitter. These findings indicate that the effects of the NO donors on [3H]noradrenaline release during depolarization are partially mediated by the activation of guanylate cyclase.     

The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion

The classical action of the hormone 1,25-dihydroxyvitamin D3 (VD) is the regulation of calcium metabolism. In contrast, the peptide hormone atrial natriuretic factor (ANF) is one of the few known nonclassical VD responding genes. We screened the promoter of the rat ANF gene and identified a typical VD receptor (VDR) binding site formed by a direct repeat of two hexameric core binding motifs spaced by three nucleotides, between positions -907 and -891. Like most of the DR3-type VD response elements this sequence is bound with high affinity (Kd = 0.53 nM) by a heterodimer formed by VDR and retinoid X receptor. In a heterologous promoter context one copy of this sequence mediated an about fourfold gene activation by VD and a half-maximal activation (EC50) value of 0.48 nM VD. This characterizes the identified sequence as one of the most potent VD response elements.     

Color-luminance interaction: data produced by oblique cross masking

Threshold-elevation (TE-) versus-mask-spatial-frequency (SF) curves and TE-versus-mask-contrast curves, produced by the oblique-masking technique, were reported for uncrossed stimuli (color-test-on-color-mask and luminance-test-on-luminance-mask) [Invest. Ophthalmol. Visual Sci. Suppl. 34, 751 (1993) and Vision. Res. 23, 873 (1983)]. The technique minimizes the artifacts that are due to spatial phase effects, spatial beats, spatial probability summation, and local cues. My goal was to measure these curves for crossed stimuli (color-test-on-luminance-mask and luminance-test-on-color-mask) by this oblique-masking technique and to compare the curves with those reported in previous studies. For this purpose threshold contrasts were measured by a yes-no procedure with randomized double staircases. Test targets were vertical spatially localized (D6) patterns, and masks were oblique sinusoidal patterns; both the test and the mask were presented simultaneously, for 2 s (Gaussian window), on a color monitor interfaced with an ATVista system and a Powell achromatizing lens. The test SF's were 0.125, 0.5, 2, 4, and 8 cycles per degree (cpd); mask SF's were 0.031-16 cpd; and mask contrasts were 6.25%-50%. Furthermore, the Red-Green channel was defined by the minimum flicker and the hue cancellation techniques. Results show mostly masking effect (TE > 1) at contrasts above threshold; sometimes, separability (TE = 1) and above-threshold facilitation (TE < 1) effects were also observed, depending on the test SF, the mask SF, the mask contrast, and the subject. In general, the magnitudes of TE's are smaller and the TE-versus-mask-SF curves are slightly narrower for the oblique-cross-masking conditions than those for the respective oblique uncross masking. In addition, the TE-versus-mask-contrast curves for the crossed conditions are mostly shallower than those for the respective uncrossed conditions. Furthermore, mostly the color-luminance asymmetry (color masks luminance more than luminance masks color) is found, in mild form, for SF's > or = 0.5 cpd. For the lower SF of 0.125 cpd, there is either a lack of asymmetry or a very mild asymmetry of the opposite kind (luminance masks color slightly more than color masks luminance) seems to prevail. In general, the oblique-masking data shows mild asymmetry and reduced facilitation; both are consistent with reduced local cues, similar to those shown by randomized phase data, thus making the data suitable for SF analysis; moreover, at high contrast, the masking data are consistent with those reported in previous studies.     

Separation of septal influences on lordosis, ultrasound production, and body weight

It is well known that macromolecules like albumin are markedly restricted in their passage across the glomerular capillary wall. However, the relative importance of solute size, charge and shape is currently debated since much of the previous work is based on dextran in neutral or charge-modified forms. These polymers have certain drawbacks that make them less suitable for analysis of capillary permeability and the notion of a glomerular charge barrier has therefore been questioned. Moreover, macromolecules larger than albumin (mol. wt. 69,000) have been suggested to pass through nonselective 'shunt' pathways. In order to study glomerular permeability, isolated rat kidneys were perfused with albumin solutions containing trace amounts of two differently radiolabelled isoenzymes of lactate dehydrogenase (LDH) at low temperature to inhibit tubular function. The isoenzymes have similar size (mol. wt. 140,000) and shape but differ in charge, one carrying a negative net surface charge (LDH1, -19) and the other being slightly cationic (LDH5, +2). The urine and perfusate samples were subjected to high pressure liquid chromatography (HPLC) gel-filtration to allow for measurements of intact LDH. The fractional clearance was 0.11% +/- 0.04% for the anionic LDH1 and 0.56% +/- 0.07% for LDH5, whereas that for albumin was 0.21% +/- 0.03% at a glomerular filtration rate of 0.11 +/- 0.01 mL min-1 g-1 kidney wet weight. The results were analysed using a homogenously charged membrane model and are compatible with a charge density of 35 mEq L-1, with 95% confidence interval of 26-41 mEq L-1. These findings suggest a significant glomerular charge selectivity for proteins substantially larger than albumin. The charge density is, however, far less than estimated from dextran studies.     

A prolonged QRS duration on surface electrocardiogram is a specific indicator of left ventricular dysfunction [see comment

OBJECTIVE: We sought to determine whether a prolonged QRS-interval duration is associated with decreased left ventricular (LV) systolic function. BACKGROUND: The 12-lead electrocardiogram (ECG) is a routine test for suspected cardiac disease. Although several scoring systems have been devised to estimate LV systolic function, no studies have examined the direct relationship between QRS duration alone and LV systolic function. METHODS: We analyzed the standard 12-lead surface ECG of 270 consecutive patients, referred for radionuclide ventriculography. Patients (n = 44) with bundle branch blocks, atrial flutter or fibrillation, pacemaker rhythm, recent myocardial infarction or bypass surgery, and patients on antiarrhythmic drugs were excluded. In the remaining patients (n = 226), we correlated the QRS duration on standard resting ECG, and the resting LV ejection fraction (EF), end-systolic and end-diastolic counts (ESC and EDC, respectively; LV volume indices), as obtained by radionuclide angiography. We used a multivariate analysis to identify independent predictors of reduced ventricular function entering QRS duration, the previously described R-wave score and clinical variables in our model. RESULTS: The QRS duration in the abnormal EF group was significantly longer than in the normal EF group (0.102 vs. 0.091 s, p < 0.0001). A QRS duration >0.10 s was highly specific (83.6%), but modestly sensitive (43.8%), for the prediction of abnormal EF. Furthermore, an abnormal EF was predicted with incrementally increased specificity (83.6% to 99.3%) and a corresponding decrease in sensitivity (43.8% to 13.8%) for each 0.01-s increase in the definition of prolonged QRS (from >0.10 to >0.12 s). Accordingly, the positive likelihood ratio for the prediction of decreased LV function was increased from 2.67 to 19.7 as the definition of prolonged QRS duration was increased from >0.10 to >0.12 s. In the multivariate analysis, a prolonged QRS duration and a low R-wave score were the only independent predictors of decreased LV systolic function. CONCLUSIONS: Prolonged QRS duration (>0.10 s) obtained from a standard resting 12-lead ECG is a specific, but relatively insensitive indicator of decreased LV systolic function. Further prolongation of the QRS had a higher specificity for decreased LV EF and a higher positive likelihood ratio for predicting abnormal LV EF.     

Four-level cervical corpectomy

STUDY DESIGN: Retrospective analysis of 31 cases of cervical spondylotic myelopathy treated by four-level subaxial cervical corpectomy. OBJECTIVE: To determine whether extremes of anterior decompression and fusion have inordinate or unique levels of morbidity. SUMMARY OF BACKGROUND DATA: There is a paucity of data on experience with four-level corpectomy. However, counsel against such surgery can be found. MATERIALS AND METHODS: The records and studies of 31 consecutive cases of cervical spondylotic myelopathy, treated by four-level corpectomy, were retrospectively analyzed. Patients in 26 cases were observed longer than 2 years. No hardware was used in the procedures. External orthosis, worn for 6 months, was a Philadelphia-type collar in 25 patients and a halo vest in 6. RESULTS: Three patients died within 3 weeks of surgery (9.7%). Delayed radiculopathy occurred in four patients after surgery, three had acute graft complications, and one had pseudomeningocele, for a morbidity rate of 25.8%. There was no infection or worsened myelopathy. CONCLUSIONS: No unique morbidity is associated with extremes of subaxial decompression when compared with surgery of lesser extent.