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N Harvey

Publications and source records attributed to N Harvey.

36 records · Page 2Linked to original sources

Normal molecular size of the Na(+)-phosphate cotransporter and normal Na(+)-dependent binding of phosphonoformic acid in renal brush border membranes of X-linked Hyp mice.

X-linked Hyp mice have a specific defect in Na(+)-dependent phosphate (Pi) transport at the renal brush border membrane (BBM). In the present study we examined the effect of the Hyp mutation on the molecular size of the Pi transporting unit and on Na(+)-dependent 14C-phosphonoformic (PFA) binding in renal BBM vesicles. By radiation inactivation analysis, we demonstrated that the molecular size of the Na(+)-Pi cotransporter is similar in normal (242 +/- 16 kDa) and Hyp mice (227 +/- 39 kDa). Moreover, while BBM Na(+)-dependent Pi transport is significantly reduced in Hyp mice (249 +/- 54 vs 465 +/- 82 pmol/mg protein/6s), genotype differences in (1) Na(+)-dependent PFA binding (1020 +/- 115 vs 1009 +/- 97 pmol/mg protein/30 min), (2) Pi-displaceable Na(+)-dependent PFA binding (605 +/- 82 vs 624 +/- 65 pmol/mg protein/6s), and (3) phosphate uptake at Na(+)-equilibrium (67 +/- 10 vs 54 +/- 7 pmol/mg protein/6s) are not apparent. The present data demonstrate that the molecular size of the renal BBM Na(+)-Pi cotransporter is normal in Hyp mice and suggest that the number of Na(+)-Pi cotransporters may not be reduced in the mutant strain.

Animals↗

The 'worried well'.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Stereoselective recognition in phospholipid monolayers.

During the past ten years we have investigated the stereochemistry of intermolecular interactions in monolayers at the air-water interface, a field which has never been developed explicitly before to our knowledge. Although we demonstrated clear enantiomeric and diastereomeric interactions for a number of chiral surfactants, we found no evidence whatsoever for stereoselective interaction in dipalmitoylphosphatidylcholine (DPPC) monolayers or vesicles by standard monolayer techniques, differential scanning calorimetry or ultra-highfield NMR. The present article extends these observations to dimyristoyl- and dilauroylphosphatidylcholine. Results from dynamic surface tension studies are also reported. In no case could chiral recognition be demonstrated using the 95% confidence limit as the criterion. In our previous study of DPPC mixtures with another chiral surfactant the question arose as to whether chiral interactions could be transmitted through intervening phospholipid molecules. This question is addressed by examining the force-area curves for a variety of mixed monolayers composed of chiral surfactants and phospholipids. We conclude that the chiral discrimination observed in some of these mixed monolayers is due to the direct interaction of chiral centers, and not due to the transmission of chirality from one stereocenter to the next through intermediate achiral molecules. Finally, we will consider the question of why phospholipids, the most ubiquitous of natural chiral surfactants, should show so little chiral discrimination in view of the wide occurrence of high stereoselectivity in many natural processes.

Dimyristoylphosphatidylcholine↗

No phospholipid monolayer-sugar interactions.

Studies by a number of workers using the Langmuir film balance have shown that when carbohydrates, such as sucrose or glycerol, are dissolved in a subphase on which a phospholipid is spread, film expansion occurs (Cadenhead & Demchak, 1969; Cadenhead & Bean, 1972; Maggio et al., 1976; Maggio & Lucy, 1978). Recently such effects have been observed again, particularly with the carbohydrates galactose and trehalose (Johnston et al., 1984). The origin of these film expansions was uncertain, and various suggestions have been made to explain them. One idea was that they might be due to interactions which these carbohydrates have with the water molecules close to the polar head groups of the lipids. Recent studies in our two laboratories, described here, show that the magnitude of the expansion effects is variable and that in general they arise from surfactant impurities in the sugars. These impurities are observed in carbohydrates which are reputedly of high grade; the amount of impurity present can vary from batch to batch, and sometimes they can be difficult to remove. Film balance techniques or subphase preparation can mask the detection of minor impurities. The presence of surfactant impurities in reputedly pure carbohydrates needs to be considered in other biochemical and biophysical studies of lipids and cell membranes.

Carbohydrates↗

Isotonic vocalis contraction as a means of producing rapid decreases in Fo.

In a first experiment, subjects were presented with frequency modulated tones and instructed to vary their own vocal pitch to match what they were hearing. It was found that the faster a subject modulated his voice, the higher the carrier frequency he produced became relative to that specified as his target. In a second experiment, subjects were presented with one or two target tones. After one was presented, they were required to reproduce its pitch with their own voice. They did so accurately. After two were presented, they were asked to oscillate the pitch of their voice as rapidly as possible between them. In this case, it was found that the tones which were produced were higher than those specified by the targets. It is argued that the results from both experiments indicate that fast decreases in voice pitch are produced by isotonic contraction of the vocalis muscles.

Adult↗

Effect of phosphate supplementation on the expression of the mutant phenotype in murine X-linked hypophosphatemic rickets.

The X-linked Hyp mouse, a murine homologue of X-linked hypophosphatemia in humans, is characterized by rachitic bone disease, hypophosphatemia, impaired renal brush-border membrane Na(+)-phosphate cotransport and abnormal regulation of renal vitamin D metabolism. We demonstrated that short-term phosphate supplementation decreases renal 1,25-dihydroxyvitamin D3 (1,25-(OH)2D) catabolism and increases serum 1,25-(OH)2D levels in Hyp mice (Tenenhouse & Jones 1990). In the present study, we compared several other parameters in normal and Hyp mice fed control (1%) and high (1.6%) phosphate diets for 4 days. Phosphate supplementation significantly raised serum phosphate levels and decreased renal brush-border membrane Na(+)-phosphate but not Na(+)-glucose, cotransport in both genotypes (67% of control diet, p < 0.05). However, under both dietary conditions, the phosphate/glucose transport ratio was significantly reduced in Hyp mice (58% of normal littermates, p < 0.05). Renal PTH-stimulated cAMP accumulation, which was significantly blunted in Hyp mice compared to normal mice under control dietary conditions (p < 0.05), was not altered by phosphate supplementation in either genotype. Serum alkaline phosphatase activity was significantly higher than normal in Hyp mice on the control diet and was further increased in mutants but not in normals fed the high phosphate diet (p < 0.05). Measurements of serum bilirubin and electrophoresis of serum alkaline phosphatase suggested that the elevation in serum alkaline phosphatase activity in phosphate-supplemented Hyp mice represents the bone-derived isozyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Nimodipine inhibits the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb) in the rat.

Impaired nitric oxide (NO) activity is associated with an increase in blood pressure in rats. Voltage-regulated calcium channels are believed to participate in this hemodynamic event. To further test this hypothesis, we examined the effect of nimodipine and verapamil (calcium antagonists) on the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb), a well-known NO scavenger, in anesthetized rats. Nimodipine, the most potent of the two calcium antagonists used, was also tested against phenylephrine (alpha1-adrenoceptor agonist). The pressor effect of DCLHb was reduced markedly by nimodipine and verapamil, whereas that elicited by phenylephrine, particularly the tonic phase of its pressor response, was resistant to blockade by nimodipine. The bradycardia and tachycardia associated with the pressor effects of DCLHb and phenylephrine, respectively, were not affected by nimodipine. The pressor effect elicited by DCLHb and its alteration by nimodipine were also examined in rats pretreated with 100% O2. This treatment was found to potentiate the pressor effect of DCLHb. However, this synergism did not impair the inhibitory action of nimodipine towards the pressor activity of DCLHb. Altogether these results suggest that the pressor activity of DCLHb in our animal model might involve the participation of voltage-regulated calcium channels.

Animals↗