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Biomedical subjects

X Xu

Publications and source records attributed to X Xu.

At least 361 records · Page 20Linked to original sources
PubMed2000

Effects of prolactin on osteoblast alkaline phosphatase and bone formation in the developing rat.

The purpose of the current study was to determine whether maternal prolactin (PRL) had any effects on bone formation in the developing rat pup. Because the most prevalent forms of PRL in rats are unmodified and phosphorylated PRL, both recombinant PRL and a molecular mimic of phosphorylated PRL (PP-PRL) were administered to pregnant animals. Blood samples from the dams showed normal estrogen and progesterone and no effect of extra PRL on parathyroid hormone (PTH), calcium, or alkaline phosphatase (AP). In newborn pups, however, there was a 30% decrease in blood AP in both PRL-treated groups, whereas PTH and calcium levels were not different from controls. When primary rat osteoblasts were exposed to both PRLs, AP activity was reduced, with PP-PRL being the more potent form of the hormone. Histological examination of pup bone formation showed reduced calvarial bone and reduced endochondral ossification in pups exposed to PP-PRL. These results are the first to show a direct inhibitory effect of PRL on osteoblast function.

Alkaline Phosphatase↗
PubMed2000

Reduced NO-dependent arteriolar dilation during the development of cardiomyopathy.

Our previous studies have suggested that there is reduced nitric oxide (NO) production in canine coronary blood vessels after the development of pacing-induced heart failure. The goal of these studies was to determine whether flow-induced NO-mediated dilation is altered in coronary arterioles during the development of heart failure. Subepicardial coronary arterioles (basal diameter 80 microm) were isolated from normal canine hearts, from hearts with dysfunction but no heart failure, and from hearts with severe cardiac decompensation. Arterioles were perfused at increasing flow or administered agonists with no flow in vitro. In arterioles from normal hearts, flow increased arteriolar diameter, with one-half of the response being NO dependent and one-half prostaglandin dependent. Shear stress-induced dilation was eliminated by removing the endothelium. Arterioles from normal hearts and hearts with dysfunction but no failure responded to increasing shear stress with dilation that reached a maximum at a shear stress of 20 dyn/cm(2). In contrast, arterioles from failing hearts showed a reduced dilation, reaching only 55% of the dilation seen in vessels of normal hearts at a shear stress of 100 dyn/cm(2). This remaining dilation was eliminated by indomethacin, suggesting that the NO-dependent component was absent in coronary microvessels after the development of heart failure. Similarly, agonist-induced NO-dependent coronary arteriolar dilation was markedly attenuated after the development of heart failure. After the development of severe dilated cardiomyopathy and heart failure, the NO-dependent component of both shear stress- and agonist-induced arteriolar dilation is reduced or entirely absent.

Animals↗
PubMed2000

Depressed modulation of oxygen consumption by endogenous nitric oxide in cardiac muscle from diabetic dogs.

Our previous study indicated that nitric oxide (NO)-dependent coronary vasodilation was impaired in conscious dogs with diabetes. Our goal was to determine whether modulation of O(2) consumption by NO is depressed in canine cardiac muscle after diabetes. Diabetes was induced by injection of alloxan (40-60 mg/kg iv), dogs were killed after diabetes was induced (4-5 wk), and the cardiac muscle from the left ventricle was cut into 15- to 30-mg slices. O(2) uptake by the muscle slices was measured polarographically with a Clark-type O(2) electrode. S-nitroso-N-acetylpenicillamine decreased O(2) consumption in normal and diabetic tissues (10(-4) M, 61 +/- 7 vs. 61 +/- 8%, P > 0.05). Bradykinin (10(-4) M)- or carbachol (CCh, 10(-4) M)-induced inhibition of O(2) consumption was impaired in diabetic tissues (51 +/- 6 vs. 17 +/- 4% or 48 +/- 4 vs. 19 +/- 3%, respectively, both P < 0.05 compared with normal). The inhibition of O(2) consumption by kininogen or kallikrein was depressed in diabetic tissues as well. In coronary microvessels from diabetic dogs, bradykinin or ACh (10(-5) M) caused smaller increases in NO production than those from normal dogs. Our results indicate that the modulation of O(2) consumption by endogenous, but not exogenous, NO is depressed in cardiac muscle from diabetic dogs, most likely because of decreased release of NO from the vascular endothelium.

Acetylcholine↗
PubMed2000

Application of an algorithm for the diagnosis of asthma in Chinese families: limitations and alternatives for the phenotypic assessment of asthma in family-based genetic studies.

Phenotype assessment is a crucial issue in gene mapping studies of asthma. Recently, Panhuysen and coworkers proposed an algorithm to define the asthma phenotype in gene mapping family-based studies. We classified members of 2,756 Chinese families ascertained on the basis of the presence of two or more siblings and no more than one parent with asthma using a slightly modified version of the aforementioned algorithm. Among 4,097 Chinese parents, 404 (9.9%) were classified as having "definite asthma," 284 (6.9%) as "probable asthma," 1,193 (29.1%) as "unclassifiable obstructive airway disease, " 626 (15.3%) as "COPD," and 1,590 (38.8%) as "unaffected" (no obstructive airway disease). Among 6,424 Chinese offspring, 1,065 (16.6%) were classified as having "definite asthma," 820 (12.8%) as "probable asthma," 1,996 (31.1%) as "unclassifiable obstructive airway disease," 228 (3.5%) as "COPD," and 2,315 (36%) as "unaffected." The use of the algorithm proposed by Panhuysen and coworkers in a Chinese population with a high prevalence of smoking would result in the exclusion of subjects with asthma who smoke or who have severe airflow obstruction from linkage analysis, as well as in an inability to explore any potential interactions between genetic factors and cigarette smoking in the pathogenesis of asthma. In the absence of a "gold standard," definitions of asthma that incorporate a combination of respiratory symptoms, increased airway responsiveness or bronchodilator response, and a physician's diagnosis of asthma are reasonable. The choice of a particular diagnostic algorithm for family-based genetic studies of asthma should be made according to factors such as the prevalence of smoking in the study population. Genetic studies of intermediate phenotypes related to asthma, which are objectively defined and may be influenced by a smaller number of genes, continue to be of great importance.

Adolescent↗
PubMed2000

Familial aggregation of bronchodilator response: a community-based study.

We investigated familial aggregation of bronchodilator response (BDR) among 4,946 subjects selected from 1,161 index families with asthma in a rural community in China. Each family unit consisted of both parents and their first and subsequent offspring, aged 8-20. Raw BDR measurements, defined as the percentage change in FEV(1) after 180 microg of albuterol, were adjusted to account for sex, age, height, weight, education, smoking, asthma, wheeze, and allergy status. Using these adjusted BDR values, we found significant correlation for father-first offspring pairs, mother-first offspring pairs, mother-subsequent offspring pairs, and first offspring-subsequent offspring pairs. The overall magnitude of the correlation coefficient (0.088-0.165) suggests a modest degree of familial clustering. The largest odds ratio was seen for subsequent offspring who had mothers and first offspring with adjusted BDR values above the median: 3.10 (95% CI: 1.85-5.20) in these index families with asthma. Thus, our data support a significant familial aggregation of BDR in this Chinese population, which points to a role of genetic factors in BDR.

Administration, Inhalation↗
PubMed2000

Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women.

Soy isoflavones are hypothesized to exert hormonal effects in women and thus may play a role in bone metabolism throughout life. In 2 randomized, cross-over studies, 14 pre- and 17 postmenopausal women were given 3 soy protein isolates containing different amounts of isoflavones [control, 0.13; low isoflavone (low-iso), 1.00; and high-iso, 2.01 mg/kg body wt/day, averaging 8, 65, and 130 mg/day, respectively], for over 3 months each. Food records, blood samples, and 24-h urine collections were obtained throughout the studies. The endpoints evaluated included plasma or serum concentrations of bone-specific alkaline phosphatase, osteocalcin, insulin-like growth factor-I (IGFI), IGF binding protein-3 (IGFBP3), and urine concentrations of deoxypyridinoline cross-links and carboxy-terminal telopeptide of type I collagen. In premenopausal women, IGFI and IGFBP3 concentrations were increased by the low-iso diet, and deoxypyridinoline cross-links was increased by both the low- and high-iso diets during certain phases of the menstrual cycle. In postmenopausal women, bone-specific alkaline phosphatase was decreased by both the low- and high-iso diets, and there were trends toward decreased osteocalcin, IGFI, and IGFBP3 concentrations with increasing isoflavone consumption. Although soy isoflavones do affect markers of bone turnover, the changes observed were of small magnitude and not likely to be clinically relevant. These data do not support the hypothesis that dietary isoflavones per se exert beneficial effects on bone turnover in women.

Adult↗
PubMed2000

Prospective study of exposure to environmental tobacco smoke and dysmenorrhea.

Dysmenorrhea is a common gynecologic disorder in women of reproductive age. Previous studies have found an association between current cigarette smoking and prevalence of dysmenorrhea. This study investigated the association between exposure to environmental tobacco smoke (ETS) and the occurrence of dysmenorrhea among women without a history of this disorder. The study population consisted of 165 newly wed, nonsmoking Chinese women (in Shenyang, China), who intended to get pregnant and who had no past history of dysmenorrhea at the time of enrollment. These women completed a baseline questionnaire interview upon enrollment and were prospectively followed by daily diary. Dysmenorrhea was defined as a diary recording of abdominal pain or low back pain for at least 2 days during a menstrual period. A subject's ETS exposure was defined as the mean number of cigarettes smoked per day at home by household members over an entire menstrual cycle before the menstrual period. A logistic regression model was used to assess the effect of ETS on the risk of dysmenorrhea, with adjustment for age, body mass index, education, season, area of residence, occupation, shift work, perceived stress, passive smoking at work, and occupational exposure to chemical hazards, dust, and noise. Generalized estimating equations were used to account for autocorrelations as a result of multiple cycles per subject. This report is based on 625 prospectively followed menstrual cycles with complete baseline and diary data. ETS exposure was reported in 77% of cycles, within which average daily exposures throughout the cycle ranged from 0.02 to 10. 3 cigarettes. The incidence of dysmenorrhea was 9.7% and 13.3% among nonexposed and exposed cycles, respectively. Among ETS-exposed cycles, there was a positive dose-response relationship between the numbers of cigarettes smoked and the relative risk of dysmenorrhea. The adjusted odds ratios of dysmenorrhea associated with "low," "middle," and "high" tertiles of ETS exposure versus no exposure were 1.1 [95% confidence interval (CI), 0.5-2.6], 2.5 (CI, 0.9-6.7), and 3.1 (CI, 1.2-8.3), respectively. The findings were consistent with those of analyses limited to the first follow-up menstrual cycle from each woman. These data suggest a significant dose-response relationship between exposure to ETS and an increased incidence of dysmenorrhea in this cohort of young women.

Adult↗
PubMed2000

Undesirable cytokeratin immunoreactivity of native nonepithelial cells in sentinel lymph nodes from patients with breast carcinoma.

CONTEXT: Use of cytokeratin immunohistochemistry on histologically negative sentinel lymph nodes (SLNs) in patients with breast carcinoma has been shown to be efficient in detecting false-negative nodes. Several recent studies have shown that micrometastases detected by immunohistochemistry constitute an independent predictor of disease-free period and overall survival for breast cancer patients. It has been demonstrated that the fibroblastic type of reticulum cells in lymph nodes also express cytokeratin, and unawareness of such cytokeratin reactivity in SLNs could result in difficulty in the interpretation of the results of immunohistochemistry. OBJECTIVES: To study the incidence of undesirable cytokeratin reactivity in reticulum cells and other native nonepithelial cells of SLNs and to compare the immunoreactivity of 3 commonly used cytokeratin antibodies (AE1/AE3, pancytokeratin [pan-CK], and CAM5.2). DESIGN: Immunohistochemistry with pan-CK, AE1/AE3, and CAM5.2 antibodies was performed on paraffin sections of SLNs from patients with breast cancer. Correlation of undesirable cytokeratin reactivity with size and metastatic status of the SLNs was also analyzed. PATIENT MATERIAL: Paraffin sections of 84 SLNs from 38 consecutive patients with breast cancer in our tertiary-care, teaching hospital. RESULTS: Cytokeratin reactivity was found in reticulum cells and plasma cells in 29 (35%) and 9 (10%) of the 84 SLNs, respectively, with pan-CK and CAM5.2 but not with AE1/AE3 (P <.001). The presence of cytokeratin-positive reticulum cells did not correlate with the size and metastatic involvement of the SLNs. CONCLUSIONS: The incidence of undesirable keratin reactivity in SLNs from breast cancer patients could be limited by using an AE1/AE3 antibody cocktail. The AE1/AE3 antibody cocktail is a sensitive epithelial marker and appears to be more specific in recognizing epithelial cells in SLNs.

Antibody Specificity↗
PubMed2000

Effects of captopril treatment of renovascular hypertension on beta-adrenergic modulation of L-type Ca(2+) current.

beta-Adrenergic stimulation of cardiac L-type Ca(2+) channels is severely impaired in hypertrophied and failing hearts of both experimental animals and humans. The aim of this study was to test the hypothesis that chronic treatment of renovascular hypertension with captopril restores normal beta-adrenergic responsiveness of L-type Ca(2+) channels in cardiac myocytes. Left ventricular hypertrophy was induced in rabbits by unilateral renal artery banding and contralateral nephrectomy. Beginning at 3 months after banding, hypertensive rabbits were treated with captopril for 3 months. The responsiveness of L-type Ca(2+) current (I(Ca,L)) to (+/-)-isoproterenol was investigated with the whole-cell patch-clamp technique. (+/-)-Isoproterenol (1 microM) induced an increase of I(Ca,L) at 0 mV of 126 +/- 20% (n = 13) in control myocytes versus 69 +/- 11% (n = 18) in hypertrophied myocytes from rabbits 3 months after banding. The half-maximal activation concentration of (+/-)-isoproterenol was similar between control and hypertrophied myocytes. Forskolin (10 microM) induced a similar percentage of increase of I(Ca,L) in control and hypertrophied myocytes, 109 +/- 13% (n = 12) versus 120 +/- 14% (n = 11) at 0 mV. The responsiveness of I(Ca,L) to (+/-)-isoproterenol remained depressed in untreated hypertensive rabbits. (+/-)-Isoproterenol (1 microM) increased I(Ca, L) at 0 mV by 64 +/- 8% (n = 14) in myocytes isolated from rabbits 6 months after banding versus 111 +/- 15% (n = 16) in age-matched controls. In captopril-treated rabbits, 1 microM (+/-)-isoproterenol increased I(Ca,L) by 110 +/- 11% (n = 17). We conclude that the maximal response of I(Ca,L) to (+/-)-isoproterenol was severely depressed in hypertrophied myocytes. Chronic treatment of renovascular hypertension with captopril can restore normal responsiveness of I(Ca,L) to (+/-)-isoproterenol in cardiac myocytes.

Animals↗
PubMed2000

Premenopausal equol excretors show plasma hormone profiles associated with lowered risk of breast cancer.

Increased urinary excretion of equol, a metabolite of the isoflavone daidzein, has been associated with a reduced risk of breast cancer. This risk reduction has generally been presumed to be a consequence of increased isoflavone consumption. However, only 30-40% of the population excretes more than trace amounts of equol, regardless of isoflavone intake. Accordingly, we hypothesized that the observed apparent protective effect of equol is at least in part attributable to hormonal differences between equol excretors and non-excretors, and that these differences are largely independent of isoflavone intake. We measured plasma hormone and sex hormone binding globulin (SHBG) concentrations in 14 normally cycling premenopausal women during each of three diet periods in which they consumed differing isoflavone doses (0.15, 1.0, and 2.0 mg/kg of body weight/day) as a component of soy protein isolate. The plasma hormone and SHBG concentrations of equol excretors (n = 5) were then compared with those of the non-excretors (n = 9). Results showed that even at the lowest dose, urinary equol excretion values for excretors far exceeded those for non-excretors consuming the highest dose. At all doses, equol excretors generally had lower concentrations of estrone, estrone-sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA-sulfate, and cortisol and higher concentrations of SHBG and midluteal progesterone, a hormonal pattern overall consistent with lowered breast cancer risk. In conclusion, the association of equol excretion and lowered breast cancer risk may largely reflect the tendency of equol excretors to have more favorable hormonal profiles, as opposed to merely reflecting increased isoflavone intake. Equol may be a marker for the presence of colonic bacterial enzymatic activity that increases fecal steroid excretion. Alternatively, equol itself, even with very modest isoflavone intake, may exert beneficial effects on the regulation of endogenous hormones.

Adult↗
PubMed2000

[QRS detection based on neural-network].

In this paper, we have developed an adaptive matched filtering algorithm based upon an artificial network (ANN) for QRS detection. We used an ANN adaptive whitening filter to model the lower frequencies of the ECG signals which are inherently nonlinear and non-stationary. The residual signal which contained mostly higher frequency QRS complex energy was then passed through a linear matched filter to detect the location of the QRS complex. The results demonstrate that this ANN whitenting filter is very effective for removing the time-varying, nonlinear noise characteristic of ECG signals. With this novel approach, the detection rate for a very noisy patient record in the MIT/BIH arrhythmia database in 99.2%, which compares favorably to the 97.8% achieved with a band-pass filtering method.

Electrocardiography↗
PubMed2000

Soy consumption alters endogenous estrogen metabolism in postmenopausal women.

Isoflavones are soy phytoestrogens that have been suggested to be anticarcinogenic. Our previous study in premenopausal women suggested that the mechanisms by which isoflavones exert cancer-preventive effects may involve modulation of estrogen metabolism away from production of potentially carcinogenic metabolites [16alpha-(OH) estrone, 4-(OH) estrone, and 4-(OH) estradiol] (X. Xu et al., Cancer Epidemiol. Biomark. Prev., 7: 1101-1108, 1998). To further evaluate this hypothesis, a randomized, cross-over soy isoflavone feeding study was performed in 18 healthy postmenopausal women. The study consisted of three diet periods, each separated by a washout of approximately 3 weeks. Each diet period lasted for 93 days, during which subjects consumed their habitual diets supplemented with soy protein isolate providing 0.1 (control), 1, or 2 mg isoflavones/kg body weight/day (7.1 +/- 1.1, 65 +/- 11, or 132 +/- 22 mg/day). A 72-h urine sample was collected 3 days before the study (baseline) and days 91-93 of each diet period. Urine samples were analyzed for 10 phytoestrogens and 15 endogenous estrogens and their metabolites by a capillary gas chromatography-mass spectrometry method. Compared with the soy-free baseline and very low isoflavone control diet, consumption of 65 mg isoflavones increased the urinary 2/16alpha-(OH) estrone ratio, and consumption of 65 or 132 mg isoflavones decreased excretion of 4-(OH) estrone. When compared with baseline values, consumption of all three soy diets increased the ratio of 2/4-(OH) estrogens and decreased the ratio of genotoxic: total estrogens. These data suggest that both isoflavones and other soy constituents may exert cancer-preventive effects in postmenopausal women by altering estrogen metabolism away from genotoxic metabolites toward inactive metabolites.

Analysis of Variance↗
PubMed2000

N-(4-hydroxyphenyl)retinamide in the chemoprevention of squamous metaplasia and dysplasia of the bronchial epithelium.

Lung cancer remains the number one cause of cancer-related deaths in the United States. To reduce the mortality associated with this disease, individuals at risk must be identified prior to the development of lung cancer, and effective prevention strategies must be developed. One such strategy is to use retinoids like N-(4-hydroxyphenyl)retinamide (4-HPR), which has been found to possess chemopreventive activities in preclinical studies. In this study, 139 smokers were registered and 82 were randomized onto a double-blinded, placebo-controlled chemoprevention trial of 4-HPR administered p.o. (200 mg once daily). Of these, 70 participants were eligible for response evaluation. Biopsies were obtained at six predetermined sites in the bronchial tree from participants before and at the completion of 6 months of treatment. 4-HPR treatment had no measurable effect on histopathology (squamous metaplasia and dysplasia) in the bronchial epithelium of current smokers. 4-HPR was detected (104.5+/-64.0 ng/ml, mean +/- SD) in the serum of participants, supporting its potential bioavailability. Serum retinol levels decreased markedly (44% of placebo-treated patients) as a consequence of 4-HPR treatment. Notably, the mRNA level of retinoic acid receptor beta, which is typically increased by retinoid treatment, did not change in the bronchial epithelium of 4-HPR-treated participants. Clonal populations of bronchial epithelial cells were detected by analysis of loss of heterozygosity at putative tumor suppressor loci on chromosomes 3p, 9p, and 17p, and these changes were not altered by 4-HPR treatment. In conclusion, at this dose and schedule, 4-HPR was not effective in reversing squamous metaplasia, dysplasia, or genetic and phenotypic abnormalities in the bronchial epithelium of smokers.

Adult↗
PubMed2000

Myxoma virus expresses a TNF receptor homolog with two distinct functions.

Myxoma virus, a member of the poxvirus family of DNA viruses, encodes many virulence factors to combat and evade the host immune responses. Among the virus-encoded immuno-modulators is M-T2, a tumor necrosis factor receptor (TNF-R) homologue. M-T2 is secreted as monomeric and dimeric species that bind and inhibit rabbit TNF in a species-specific manner. Deletion analysis indicates that the anti-TNF function is mediated by the first three of four cysteine rich domains (CRDs) of M-T2. In addition, the intracellular form of M-T2 has the ability to block virus-induced apoptosis in lymphocytes, and the first two CRDs appear to be sufficient for this function. Although the mechanisms for the anti-TNF and anti-apoptotic functions of M-T2 are not yet fully defined, we postulate that these dual activities of M-T2 are mediated through different functional motifs and abrogate distinct cellular responses to virus infection.

Amino Acid Sequence↗
PubMed2000

Studies of MAL gene in human esophageal cancer by RNA in situ hybridization.

OBJECTIVE: To observe the expression of MAL gene mRNA in esophageal cancer tissue and adjacent epithelial mucosa. METHODS: Non-radioactive RNA in situ hybridization. RESULTS: MAL gene was expressed in all epithelia of 33 matched samples but only in 8 of esophageal cancer tissues. Differential expression between esophageal cancer tissues and adjacent epithelia was not related to clinical parameters. CONCLUSION: Down-regulation of MAL may be an important event in the development of esophageal cancer.

Down-Regulation↗
PubMed2000

Metabolites of caspofungin acetate, a potent antifungal agent, in human plasma and urine.

Caspofungin acetate (MK-0991) is a semisynthetic pneumocandin derivative being developed as a parenteral antifungal agent with broad-spectrum activity against systemic infections such as those caused by Candida and Aspergillus species. Following a 1-h i.v. infusion of 70 mg of [(3)H]MK-0991 to healthy subjects, excretion of drug-related material was very slow, such that 41 and 35% of the dosed radioactivity was recovered in urine and feces, respectively, over 27 days. Plasma and urine samples collected around 24 h postdose contained predominantly unchanged MK-0991, together with trace amounts of a peptide hydrolysis product, M0, a linear peptide. However, at later sampling times, M0 proved to be the major circulating component, whereas corresponding urine specimens contained mainly the hydrolytic metabolites M1 and M2, together with M0 and unchanged MK-0991, whose cumulative urinary excretion over the first 16 days postdose represented 13, 71, 1, and 9%, respectively, of the urinary radioactivity. The major metabolite, M2, was highly polar and extremely unstable under acidic conditions when it was converted to a less polar product identified as N-acetyl-4(S)-hydroxy-4-(4-hydroxyphenyl)-L-threonine gamma-lactone. Derivatization of M2 in aqueous media led to its identification as the corresponding gamma-hydroxy acid, N-acetyl-4(S)-hydroxy-4-(4-hydroxyphenyl)-L-threonine. Metabolite M1, which was extremely polar, eluting from HPLC column just after the void volume, was identified by chemical derivatization as des-acetyl-M2. Thus, the major urinary and plasma metabolites of MK-0991 resulted from peptide hydrolysis and/or N-acetylation.

Anti-Bacterial Agents↗