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.     

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.     

Breast disease: dynamic spiral MR imaging

The cochleo- and tonotopic organization of the second auditory area (AII) was investigated in cats anaesthetized with pentobarbital using a combination of macro- and microelectrode recording technique. The results obtained following electrical stimulation of the neural fibres innervating different regions of the organ of Corti indicate the existence of two complete representations of the cochlea in area AII: one in the dorsocaudal portion, the other in its ventrorostral portion. These two cortical representations of the cochlea differ in size and spatial orientation. The dorsocaudal projection area extends over a distance of 2.6-3.2 mm from the basal to the apical focus and is arc-shaped. The spatial orientation of cochlea representation within the dorsocaudal region of AII is similar to that described in AI, in that stimulation of the cochlea base results in maximal responses in the more rostral portion of AII and stimulation of the apex evokes cortical responses more caudally. The ventrorostral region within AII is smaller (1.4-2.5 mm length), and has the opposite cochleotopic orientation (base and apex stimulation represented caudally and rostrally, respectively). In both AII zones, there was a proportionally greater cortical representation of basilar membrane than of middle and apical portions. Although two distinct zones with the overall cochleotopic pattern described above were noted in all cats, their precise size and location considerably varied in different animals. Using microelectrode recordings, a cortical tonotopic organization can be observed that was consistent with and expanded on the earlier cochleotopic data. Within the dorsocaudal region of AII, neurons with higher best frequency responses were located in more rostral regions, while those with lower best frequencies were located caudally. An orderly progression of best frequency responses was noted as serial recordings carried out along the full extent of the representation. Neurons within the ventrorostral region of AII also displayed an orderly progression of best frequencies, but in the opposite direction, with higher best frequencies noted more caudally and lower best frequencies more rostrally.