Biomedical subjects

X Xu

Publications and source records attributed to X Xu.

At least 451 records · Page 25Linked to original sources

PubMed1999

Cortical mechanisms underlying point localization of pain spot as studied by event-related potentials following CO2 laser stimulation in man.

To elucidate cortical mechanisms underlying point localization of a pain spot, we investigated event-related potentials (ERPs) while using a CO2 laser beam to apply a pain stimulus to the hand dorsum in 16 healthy men. The stimulus spot (pain spot) was shifted for each stimulus, while the subject was requested to identify the stimulated spot as accurately as possible and to use a pointer in the non-stimulated hand to indicate the corresponding spot on a figure of a hand that was projected onto a screen (localization condition). For the control condition, the subject pointed to a single predetermined spot, regardless of the location of the stimulation (control motor task condition). Electroencephalograms were recorded from 21 electrodes, referenced to the linked earlobes, and were averaged time-locked to the stimulus onset for each task separately. Under the control rest condition (neither point localization nor motor task), only two early components (N2 and P2) were recorded. During the control motor task condition (no point localization), in addition to N2 and P2, a steep negative-going slope was recorded at the fronto-central region. Exclusively during the localization condition, a positive peak (647 ms, 5.6 microV for the left and 634 ms, 5.7 microV for the right hand stimulation) was identified; this was maximal at the midline centro-parietal area and distributed symmetrically over the scalp. It is suggested that the late positive component detected exclusively during the localization task is related to the somatotopic point localization of the pain spot. From the distribution of this ERP, the task most likely involves bilateral activation of the superior parietal cortices.

Adult↗

PubMed1999

The properties of the inward rectifier potassium currents in rabbit coronary arterial smooth muscle cells.

In freshly-isolated, single, smooth muscle cells of rabbit coronary arteries, an inward rectifier K+ current [IK(IR)] was identified using the whole-cell voltage-clamp technique. The current/voltage (I/V) relationship of IK(IR) showed strong inward rectification with a very small outward current when the smooth muscle cells were dialyzed with a pipette solution containing Mg2+. However, dialyzing the cells with a nominally Mg2+-free pipette solution revealed a significant outward current hump in the I/V relation of IK(IR), suggesting that the strong inward rectification of IK(IR) is partly due to the inhibitory effects of internal Mg2+. IK(IR) was unaffected by tetraethylammonium (1 mM), 4-aminopyridine (1 mM), or glibenclamide (1 microM), but was inhibited by extracellular Ba2+ with a concentration of 0.87 microM eliciting half-maximal inhibition at -120 mV. IK(IR) induced in rabbit coronary smooth muscle cells declined during very negative hyperpolarizing steps, due largely to a block by external Na+. IK(IR) was inhibited by alpha1-adrenergic stimuli. Methoxamine, an alpha1-adrenergic agonist, concentration dependently inhibited IK(IR) in the presence of the beta-adrenergic antagonist propranolol. The methoxamine concentration required for half-maximal inhibition was 205 microM. We conclude that inward rectifier K+ current is present in rabbit coronary smooth muscle cells and that it shares many properties with the inward rectifier K+ current described for other cell types.

Adrenergic alpha-Agonists↗

PubMed1999

Expression of transforming growth factor-alpha and epidermal growth factor receptor in gastrointestinal stromal tumours.

Activation of epidermal growth factor receptor (EGFR) is associated with cell growth and transformation. Both transforming growth factor-alpha (TGF-alpha) and epidermal growth factor bind to and activate EGFR. We studied the expression of TGF-alpha and two EGFRs (HER-1 and HER-2) in gastrointestinal stromal tumours (GISTs) of the stomach (n = 9) and small intestine (n = 6) using standard immunostaining techniques in paraffin-embedded sections. Most GISTs expressed TGF-alpha, and a few expressed HER-1. All HER-1-positive tumours expressed TGF-alpha. These results suggest that a TGF-alpha/EGFR autocrine loop is present in GIST and that TGF-alpha promotes proliferation of GIST tumour cells through its interaction with HER-1 in at least some GISTs. This is the first description of an autocrine loop in GIST. In contrast, HER-2 is not expressed in any GIST.

Adult↗

PubMed1999

A genome-wide scan for loci linked to forearm bone mineral density.

Osteoporosis is a chronic disorder characterized by low bone mass and fragility fractures. It affects more than 25 million men and women in the United States alone. Although several candidate genes, such as the vitamin-D-receptor gene or the estrogen-receptor gene, have been suggested in the pathogenesis of osteoporosis, the genetic dissection of this disorder remains a daunting task. To search systematically for chromosomal regions containing genes that regulate bone mineral density (BMD), we scanned the entire autosomal genome by using 367 polymorphic markers among 218 individuals (153 sibpairs) from 96 nuclear families collected from three townships of Anqing, China. In these 96 families, DNA samples from both parents were available for 82 (85.4%) families. By using age- and gender-adjusted forearm BMD measurements, a peak on chromosome 2 near D2S2141, D2S1400, and D2S405, a region previously linked to spinal BMD, showed evidence of linkage to both proximal and distal forearm BMD (multipoint LOD=2.15 and 2.14 for proximal and distal forearm BMD, respectively). One region on chromosome 13 (multipoint LOD=1.67) in the proximity of D13S788 and D13S800 showed evidence of linkage to distal forearm BMD only. Possible candidate genes included CALM2 (calmodulin 2) at 2p21.3-p21.1, a putative STK (serine/threonine kinase) at 2p23-24, POMC (pro-opiomelanocortin) at 2p23.3, and COL4A1 and COL4A2 (collagen IV alpha-1 and alpha-2 subunits) at 13q34. Because of the limited sample size, the suggestive evidence of linkage of this study should be considered as tentative and needs to be replicated in other larger populations.

Adolescent↗

PubMed1999

Fibroblast growth factor receptors (FGFRs) and their roles in limb development.

Fibroblast growth factor (FGF) receptors constitute a family of four membrane-spanning tyrosine kinases (FGFR1-4) which serve as high-affinity receptors for 17 growth factors (FGF1-17). To study functions of FGF/ FGFR signals in development, mice that carry mutations in each receptor have been created by gene targeting. Analysis of these mutant mice revealed essential functions of FGF receptors in multiple biological processes, including mesoderm induction and patterning, cell growth and migration, organ formation and bone growth. In this review we discuss recent work with FGF receptors to illustrate mechanisms, through which the FGF/FGFR signals specify vertebrate limb initiation, outgrowth and patterning.

Animals↗

PubMed1999

Solubilization and stabilization of carotenoids using micelles: delivery of lycopene to cells in culture.

The use of the organic cosolvents tetrahydrofuran and dimethylsulfoxide was found to be unsuitable for prostate tumor cell cultures because of solvent cytotoxicity and the poor solubility and instability of lycopene. For example, the half-life of lycopene in organic/aqueous solution was found to be less than 2 h. Therefore, a micellar preparation of lycopene was developed for the solubilization and stabilization of lycopene in cell culture media. Neither the micelles themselves nor lycopene solubilized in micelles at concentrations up to 10 microg/mL in the cell culture media produced cytotoxicity or inhibition of cell proliferation in either LNCaP human prostate cells or Hs888Lu human lung cells. Lycopene solubilized in micelles was stable for at least 96 h under standard cell culture conditions so that a constant lycopene supply could be provided to the cells. During the culture process, lycopene was taken up by LNCaP cells and reached a plateau at approximately 12 h. Micelles provide a convenient, inexpensive, and nontoxic vehicle for dissolving and stabilizing carotenes such as lycopene in tissue culture media and then delivering them to cells growing in culture.

Anticarcinogenic Agents↗

PubMed1999

Heat shock protein suppresses the senescent lung cytokine response to acute endotoxemia.

BACKGROUND: Previous reports demonstrate that heat shock protein (HSP) can alter the pulmonary inflammatory cascade. We wished to determine if this mechanism is active in the senescent mouse. METHODS: A dose-response and time-response curve for sodium arsenite (SA) induction of HSP was constructed. Eight 25-month-old B6C3F1 mice were given either 1, 2, 4, or 6 mg/kg SA. At 4 hours, the lungs were harvested and assayed for HSP by Western blot. Next, 8 mice were given 4 mg/kg SA and the lungs harvested at either 1, 2, 4, or 6 hours after injection and assayed for HSP. Next, 12 mice were prepared: Half received 4 mg/kg SA and 4 hours later, all received 0.5 mg/kg lipopolysaccharide (LPS). After 4 hours, lungs were harvested and Interleukin-1beta mRNA was assayed by Northern blot and semi-quantified by densitometry. RESULTS: The optimum SA dose was determined to be 4 mg/kg. The maximum HSP production was at 4 hours. Mice receiving LPS only showed a marked increase (3-fold) in IL-1 message compared with the mice pretreated with SA. CONCLUSIONS: These data suggest that in the senescent as in the mature mouse lung, HSP downregulates the inflammatory cascade in response to LPS.

Acute Disease↗

PubMed1999

Co-expression of lens fiber connexins modifies hemi-gap-junctional channel behavior.

Lens fiber cells contain two gap junction proteins (Cx56 and Cx45.6 in the chicken). Biochemical studies have suggested that these two proteins can form heteromeric connexons. To investigate the biophysical properties of heteromeric lens connexons, Cx56 was co-expressed with Cx45.6 (or its mouse counterpart, Cx50) in Xenopus oocytes. Whole-cell and single-channel currents were measured in single oocytes by conventional two-microelectrode voltage-clamp and patch clamp techniques, respectively. Injection of Cx56 cRNA induced a slowly activating, nonselective cation current that activated on depolarization to potentials higher than -10 mV. In contrast, little or no hemichannel current was induced by injection of Cx50 or Cx45.6 cRNA. Co-expression of Cx56 with Cx45.6 or Cx50 led to a shift in the threshold for activation to -40 or -70 mV, respectively. It also slowed the rate of deactivation of the hemichannel currents. Moreover, an increase in the unitary conductance, steady state probability of hemichannel opening and mean open times at negative potentials, was observed in (Cx56 + Cx45.6) cRNA-injected oocytes compared with Cx56 cRNA-injected oocytes. These results indicate that co-expression of lens fiber connexins gives rise to novel channels that may be explained by the formation of heteromeric hemichannels that contain both connexins.

Animals↗

PubMed1999

Nitric oxide controls cardiac substrate utilization in the conscious dog.

OBJECTIVES: The aim of this study was to determine whether the acute inhibition of nitric oxide (NO) synthase causes changes in cardiac substrate utilization which can be reversed by a NO donor. METHODS: NO synthase was blocked by giving 30 mg/kg of nitro-L-arginine (NLA) i.v. to 15 chronically instrumented dogs. Hemodynamics and blood samples from aorta and coronary sinus were taken at control and at 1 and 2 h after NLA. In five dogs, 0.4 mg/kg of the NO donor 3754 was given i.v. 1 h after NLA. In six dogs, angiotensin II was infused over 2 h (20-40 ng/kg/min) to mimic the hemodynamic effects of NLA. RESULTS: Two h after NLA: mean arterial pressure was 153 +/- 4 mmHg; MVO2 increased by 38%; cardiac uptake of lactate and glucose increased, respectively, from 20.0 +/- 5.0 to 41.0 +/- 9.3 mumol/min and from 1.1 +/- 0.7 to 6.8 +/- 1.5 mg/min (all P < 0.05 vs. control). Cardiac uptake of free fatty acids decreased by 43% after 1 h (P < 0.05) and returned to control values at 2 h. Cardiac respiratory quotient increased from 0.76 +/- 0.03 to 1.05 +/- 0.07, indicating a shift to carbohydrate oxidation. All these changes were reversed by the NO donor. In the dogs receiving angiotensin II infusion, MVO2 increased by 28% and lactate uptake doubled (both P < 0.05), but no other metabolic changes where observed. CONCLUSIONS: The acute inhibition of NO synthase by NLA causes a switch from fatty acids to lactate and glucose utilization by the heart which can be reversed by a NO donor, suggesting an important regulatory action of NO on cardiac metabolism.

Analysis of Variance↗

PubMed1999

A further study on asymmetric cross-sensitization between MK-801 and phencyclidine-induced ambulatory activity.

Our previous study found that MK-801-sensitized rats showed cross-sensitization to the locomotor stimulant effects of phencyclidine, but phencyclidine sensitized rats did not show cross-sensitizaton to MK-801. This study was designed to determine whether the asymmetric cross-sensitization was due to injection-environment conditioning or possibly reduced phencyclidine-like effects following further repeated injections of phencyclidine. Adult female Sprague-Dawley rats were used in this study, and their activity was assessed with an automated photoelectric system. Results confirmed the early finding that four daily injections of phencyclidine (3.2 mg/kg) or MK-801 (0.32 mg/kg) produced locomotor sensitization, and that the two drugs showed asymmetric cross-sensitization. Moreover, injection-environment conditioning was ruled out as a possible cause for cross-sensitization from MK-801 to phencyclidine, and possibly reduced phencyclidine-like effects following further repeated injections was also ruled out as a cause for the failure of cross-sensitization from phencyclidine to MK-801. These additional results further confirm our previous finding, and indicate that there are significant differences in the neural mechanisms underlying phencyclidine- and MK-801-induced sensitization.

Animals↗

PubMed1999

Determination of ephedrine, theophylline and phenobarbital in a tablet dosage form by capillary electrophoresis.

A capillary electrophoresis method was developed to separate and quantitate ephedrine (ED), theophylline (TP) and phenobarbital (PB) in a tablet dosage form. Tablets were ground and extracted with methanol using ultrasonication. Aliquots of standard stock solution were hydrodynamically injected for 5 s at the anodic end. Separation was performed on a fused silica capillary (72 cm x 50 microm i.d.; 50 cm to detector) at an applied voltage of 20 kV with a phosphate run buffer (pH 8.0, 50 mM). Analysis was performed at ambient temperature (23+/-1 degrees C) and the total run time was 9 min with detection at 220 nm. Calibration curves were prepared for ED, TP and PB with methyl p-hydroxy benzoate as internal standard. For each analyte, the correlation coefficients were >0.999 (n = 4). The RSD% of ten replicate injections for each analyte were <1%. The method was applied to the quantitation of ED, TP and PB in a commercial tablet dosage form.

Calibration↗

PubMed1999

Blood pressure and the T174M and M235T polymorphisms of the angiotensinogen gene.

PURPOSE: The angiotensinogen gene (AGT), which encodes the precursor of the vasoactive hormone angiotensin II, has been reported to be associated with hypertension in Caucasian and Japanese populations. We examined the relationship between two common molecular variants of AGT, T174M and M235T and blood pressure in two cohorts from the Anqing region of China. Cohort I (N = 794) consisted of families ascertained by either hypertensive or hypotensive siblings; and Cohort II (N = 761) represented a collection of randomly selected families. METHODS: Blood pressure was measured according to standard protocols, and information on age, sex, body mass index, alcohol consumption, and cigarette smoking was collected by trained interviewers using standardized questionnaires. The association of AGT genotypes and blood pressure was examined in multivariate linear regression models, with adjustment for potential intrafamilial correlations. The respective T and M allele frequencies for T174M were 0.93 and 0.07, and 0.80 and 0.20 for M235T among the parents for randomly selected families. All the analyses were conducted after exclusion of individuals currently under antihypertensive medication. RESULTS: In the pooled analysis of the two cohorts, neither the T174M nor the M235T polymorphism was significantly associated with variations of blood pressure assuming a recessive (T174M: p = 0.73 and 0.61; M235T: p = 0.99 and 0.24; for SBP and DBP), dominant (T174M: p = 0.54 and 0.72; M235T: p = 0.79 and 0.12; for SBP and DBP), or additive (T174M: p = 0.52 and 0.67, M235T: p = 0.91 and 0.11; for SBP and DBP) model. Likewise, no statistically significant association was detected when the two cohorts were analyzed separately. The logistic regression analysis of hypertension also failed to reveal any association with these markers. CONCLUSIONS: In summary, our analyses suggest that the molecular variants of AGT may not be associated with variations of blood pressure in this rural Chinese population.

Adolescent↗

PubMed1999

Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells.

Germline mutations of the Brca1 tumor suppressor gene predispose women to breast and ovarian cancers. To study mechanisms underlying BRCA1-related tumorigenesis, we derived mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of the Brca1 gene. We show that the mutant cells maintain an intact G1-S cell cycle checkpoint and proliferate poorly. However, a defective G2-M checkpoint in these cells is accompanied by extensive chromosomal abnormalities. Mutant fibroblasts contain multiple, functional centrosomes, which lead to unequal chromosome segregation, abnormal nuclear division, and aneuploidy. These data uncover an essential role of BRCA1 in maintaining genetic stability through the regulation of centrosome duplication and the G2-M checkpoint and provide a molecular basis for the role of BRCA1 in tumorigenesis.

Alternative Splicing↗

PubMed1999

Secular trend in age at menarche in China: a case study of two rural counties in Anhui Province.

There is increasing evidence that age at menarche has decreased in Europe and the United States during the last century and in Japan over the last several decades. Data from a community-based survey conducted in two rural counties of Anhui Province in China indicate a similar, downward secular trend in age at menarche for Chinese women. The present study shows the mean age at menarche decreased by 2.8 years, from 16.5 to 13.7, over an approximate 40-year time interval. This rapid decrease in age at menarche may partly be due to better nutrition and living standards reflected by the improved socioeconomic standards experienced in China over the past few decades. To test this hypothesis, a number of determinants of age at menarche were assessed; year of birth, literacy status, county of residence, amount of physical labour, general health status, pesticide exposure before age at menarche, and drinking water source were all found to be associated with age at menarche.

Adolescent↗

PubMed1999

Isolation and chemical analysis of a lipopolysaccharide from the outer membrane of the oral anaerobic spirochete Treponema pectinovorum.

Isolation of a putative lipopolysaccharide from the surface of the oral treponeme, Treponema pectinovorum, revealed it to contain larger amounts of 3-deoxy-D-manno-octulosonic acid compared with other oral Treponema species. This molecule was isolated from the outer membrane of T. pectinovorum and had chemical characteristics of a putative lipopolysaccharide. The yield of lipopolysaccharide was between 0.6% and to 1.1% of the bacterial dry weight. The purified molecule was resistant to the action of proteinases and consisted of both sugars and lipids. 3-Deoxy-D-manno-octulosonic acid and hexoses accounted for 6.1-8.7% and 17.6-20.2%, respectively of the dry weight. Carbohydrate compositional analysis revealed the presence of glucose, galactose, 2-acetamido-2-deoxy-glucose, rhamnose and 6-deoxy-talose in the molar ratio of 1.00:0.96:0.19:0.88:0.98, respectively. No heptose was detected. The fatty acid analysis determined the presence of straight chain, C13:00, C14:00, C15:00 and C17:00 acids, as well as branched chain, C13:00, C14:00 and two species of C15:00, acids. Electrophoretic analysis indicated that the lipopolysaccharide was present as two major species.

Cell Membrane↗

PubMed1999

Globozoospermia in mice lacking the casein kinase II alpha' catalytic subunit.

Protein kinase casein kinase II (Ck2) is a cyclic-AMP and calcium-independent serine-threonine kinase that is composed of two catalytic subunits (alpha and alpha') and two regulatory beta-subunits. Ck2 is not a casein kinase in vivo, but over 100 substrates are known. The highly conserved amino acid sequences of its subunits and their broad expression suggest that Ck2 may have a fundamental role in cell function. Ck2 has been implicated in DNA replication, regulation of basal and inducible transcription, translation and control of metabolism. The Ck2alpha and Ck2alpha' isoforms (products of the genes Csnk2a1 and Csnk2a2, respectively) are highly homologous, but the reason for their redundancy and evolutionary conservation is unknown. We find here that Csnk2a2 is preferentially expressed in late stages of spermatogenesis, and male mice in which Csnk2a2 has been disrupted are infertile, with oligospermia and globozoospermia ('round-headed' spermatozoa). This is the first demonstration of a unique role for a Ck2 isoform in development. The primary spermatogenic defect in Csnk2a2-/- testis is a specific abnormality of anterior head shaping of elongating spermatids; this is the first defined gene that regulates sperm head morphogenesis. As the germ cells differentiate, they are capable of undergoing chromatin condensation, although many abnormal cells are deleted through apoptosis or Sertoli cell phagocytosis. The few that survive to populate the epididymis exhibit head abnormalities similar to those described in human globozoospermia, thus Csnk2a2 may be a candidate gene for these inherited syndromes.

Animals↗

PubMed1999

Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor.

Although insulin-like growth factor 1 (IGF-1) has been associated with retinopathy, proof of a direct relationship has been lacking. Here we show that an IGF-1 receptor antagonist suppresses retinal neovascularization in vivo, and infer that interactions between IGF-1 and the IGF-1 receptor are necessary for induction of maximal neovascularization by vascular endothelial growth factor (VEGF). IGF-1 receptor regulation of VEGF action is mediated at least in part through control of VEGF activation of p44/42 mitogen-activated protein kinase, establishing a hierarchical relationship between IGF-1 and VEGF receptors. These findings establish an essential role for IGF-1 in angiogenesis and demonstrate a new target for control of retinopathy. They also explain why diabetic retinopathy initially increases with the onset of insulin treatment. IGF-1 levels, low in untreated diabetes, rise with insulin therapy, permitting VEGF-induced retinopathy.

Animals↗

PubMed1999

Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation.

Cre-mediated excision of exon 11 of the breast-tumour suppressor gene Brca1 in mouse mammary epithelial cells causes increased apoptosis and abnormal ductal development. Mammary tumour formation occurs after long latency and is associated with genetic instability characterized by aneuploidy, chromosomal rearrangements or alteration of Trp53 (encoding p53) transcription. To directly test the role of p53 in Brca1-associated tumorigenesis, we introduced a Trp53-null allele into mice with mammary epithelium-specific inactivation of Brca1. The loss of p53 accelerated the formation of mammary tumours in these females. Our results demonstrate that disruption of Brca1 causes genetic instability and triggers further alterations, including the inactivation of p53, that lead to tumour formation.

Alleles↗