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Biomedical subjects

N Xu

Publications and source records attributed to N Xu.

At least 145 records · Page 8Linked to original sources
PubMed1992

Mutated alpha subunit of the Gq protein induces malignant transformation in NIH 3T3 cells.

The discovery of mutated, GTPase-deficient alpha subunits of Gs or Gi2 in certain human endocrine tumors has suggested that heterotrimeric G proteins play a role in the oncogenic process. Expression of these altered forms of G alpha s or G alpha i2 proteins in rodent fibroblasts activates or inhibits endogenous adenylyl cyclase, respectively, and causes certain alterations in cell growth. However, it is not clear whether growth abnormalities result from altered cyclic AMP synthesis. In the present study, we asked whether a recently discovered family of G proteins, Gq, which does not affect adenylyl cyclase activity, but instead mediates the activation of phosphatidylinositol-specific phospholipase C harbors transforming potential. We mutated the cDNA for the alpha subunit of murine Gq in codons corresponding to a region involved in binding and hydrolysis of GTP. Similar mutations unmask the transforming potential of p21ras or activate the alpha subunits of Gs or Gi2. Our results show that when expressed in NIH 3T3 cells, activating mutations convert G alpha q into a dominant acting oncogene.

3T3 Cells↗
PubMed1992

Evidence for endothelium-dependent and endothelium-independent vasodilation in human skin flaps.

Acetylcholine (ACh) and nitroglycerin (NTG) were used as probes to study endothelium-dependent and endothelium-independent vascular relaxation in isolated perfused transverse paraumbilical human skin flaps. It was observed that ACh (10(-6) M) significantly (p < 0.05) decreased the vascular resistance and increased dermal capillary perfusion (assessed by surface fluorometry) in norepinephrine (NE, 10(-6) M) preconstricted skin flaps, despite the presence of a cyclooxygenase inhibitor (indomethacin, 3 x 10(-5) M) and a beta-adrenergic receptor antagonist (propranolol, 10(-6) M). The ability of ACh to induce vascular relaxation in NE-preconstricted skin flaps was lost after damaging the vascular endothelial lining with saponin perfusion (100 mg.L-1, 5 min). In contrast, NTG (10(-6) M) induced vascular relaxation to a similar extent before and after saponin treatment. In a separate study, ACh was seen to induce vascular relaxation in a concentration-dependent manner in skin flaps preconstricted with NE (10(-6) M). This vascular relaxation effect of ACh over the dose range of 10(-9)-10(-5) M was significantly (p < 0.01) inhibited in the presence of N omega-nitro-L-arginine (10(-5) M), a nitric oxide (NO) synthesis inhibitor. These observations were taken to indicate the presence of endothelium-dependent and endothelium-independent vascular relaxation in human skin flaps and that the ACh-induced endothelium-dependent relaxation is probably mediated by NO. The importance of impairment of endothelium-dependent relaxation in the pathogenesis of skin flap ischemia, and the potential use of topical nitrovasodilators or NO donors for prevention and (or) treatment of skin flap ischemia were also discussed.

Acetylcholine↗
PubMed1992

Brain aluminum in Alzheimer's disease using an improved GFAAS method.

Aluminum (Al) has been determined in autopsy brain samples (20 mg, dry weight) from 10 histologically verified Alzheimer's disease (AD) patients and 10 neurologically normal controls using an improved graphite furnace atomic absorption method. The method makes use of a potassium dichromate matrix modifier to circumvent interferences to the Al determination by the high levels of phosphorus and alkali metals in brain tissue. Brain regions studied included middle frontal gyrus, hippocampus, inferior parietal lobule, and the superior and middle temporal gyri. Small, but significant (p < 0.05) elevations of Al were observed in AD hippocampus, inferior parietal lobule and superior and middle temporal gyri, compared to corresponding control tissues. In contrast to other reports in the literature, no extremely high Al levels (> 20 micrograms/g, dry weight) were observed in our samples. Our highest value for Al in AD brain was 8.0 micrograms/g. These results suggest that there is a small focal increase of Al in specific regions of AD brain compared to age-matched controls. The fact that the increase is small, coupled with the analytical difficulties of accurate bulk sample Al determinations by any technique in the brain matrix, may account for the discordant literature reports for Al in AD brain.

Aged↗
PubMed1991

D2O as a substitute for 3H2O, as a reference indicator in liver multiple-indicator dilution studies.

The hepatic space of distribution and the processes underlying uptake of tracer substrate may be appraised by the multiple-indicator dilution technique after simultaneous injection of noneliminated vascular (51Cr-labeled red blood cells), extracellular 125I-labeled albumin and [14C]sucrose (or [58Co]EDTA) as high- and low-molecular-weight interstitial references, respectively], and cellular (3H2O or [14C]urea) indicators, together with the tracer-labeled substrate. The use of 3H2O or [14C]urea, with [14C]- or [3H]sucrose, however, precludes the simultaneous introduction and analysis of the behavior of 3H- and 14C-labeled substrate and metabolite. An assay for the quantitation of D2O in plasma by Fourier transform infrared spectrometry was therefore developed such that D2O could be used in lieu of 3H2O in multiple-indicator dilution studies in the blood-perfused rat liver. In experiments performed with an injection dose containing 51Cr-labeled red blood cells, 125I-labeled albumin, [14C]sucrose, 3H2O, and D2O, D2O was found to behave virtually identical to 3H2O in blood and liver; the accessible cellular water spaces were 0.625 and 0.621 ml/g liver for 3H2O and D2O, respectively, and the corresponding ratios of the sum of the cellular water plus the interstitial water space to the sinusoidal water space were 3.87 and 3.89. D2O was found to be an ideal substitute and is much superior to [14C]urea, which exhibits a small red blood cell carriage effect and which is slightly less dispersed than 3H2O.

Animals↗