Biomedical subjects

X Xu

Publications and source records attributed to X Xu.

At least 829 records · Page 46Linked to original sources

PubMed1995

Selective impairment of vagally mediated, nitric oxide-dependent coronary vasodilation in conscious dogs after pacing-induced heart failure.

BACKGROUND: Activation in conscious dogs of the carotid chemoreflex or cardiac receptors results in coronary vasodilation that is mediated by a vagal cholinergic mechanism. Our previous study showed that the coronary vasodilation following activation of carotid chemoreflex is also mediated by nitric oxide (NO). In addition, NO production is depressed after the development of heart failure. Therefore, we hypothesized that the coronary vasodilation after activation of reflexes that elicit efferent vagal coronary vasodilation would be blunted in conscious dogs after pacing-induced heart failure due to the disappearance of NO. METHODS AND RESULTS: Mongrel dogs were chronically instrumented using sterile techniques for measurements of systemic hemodynamics and left circumflex coronary blood flow (CBF). Without the heart rate controlled, intra-atrial injection of veratrine (4 micrograms/kg) caused bradycardia (-36 +/- 3 beats per minute). With the heart rate controlled, veratrine increased CBF in a dose-dependent manner: for example, 4 micrograms/kg of veratrine increased CBF by 54 +/- 5% from 38 +/- 4.9 mL/min (P < .05). The increases in CBF induced by veratrine were markedly blunted by nitro-L-arginine (NLA). Activation of carotid chemoreflex by nicotine increased CBF by 121 +/- 9% from 32 +/- 4 mL++/min (P < .05) with the heart rate controlled and caused bradycardia (-32 +/- 5 beats per minute) without the heart rate controlled. After the development of heart failure, in response to activation of carotid chemoreflex or cardiac receptors the coronary vasodilation was almost abolished (CBF increased by only 23 +/- 8% or 11 +/- 3%, P < .05 compared with control). There still was a marked bradycardia after injections of nicotine or veratrine (-50 +/- 11 or -48 +/- 7 beats per minute). CONCLUSIONS: Our results indicate that vagally mediated coronary vasodilation is selectively attenuated in conscious dogs after pacing-induced heart failure, whereas the vagally mediated bradycardia is preserved. Since muscarinic receptor-induced coronary vasodilation is mediated by NO, the disappearance of NO from blood vessels leads to a defect in the integrated neural regulation of coronary blood flow and myocardial function during heart failure.

Acetylcholine↗

PubMed1995

Immortalization of human cells by mutant and chimeric primate polyomavirus T-antigen genes.

Human fibroblasts were morphologically transformed with wild type and mutant SV40 T-antigens (T-Ags) and with SV40/JCV and SV40/BKV chimeric T-Ags. The transformants were then assayed for the attainment of immortal cell growth. Several observations relating T-Ag and T-Ag domains to immortalization were made. Approximately 10% of SV40-transformants became immortal. Transformants generated by transfection or infection of cells with C-terminal T-Ag deletion mutants of SV40 did not immortalize. SV40/JCV and SV40/BKV chimeric T-Ags, containing C-terminal sequences from JCV or BKV, immortalized cells more efficiently than did the intact SV40 T-Ag, suggesting that the C-termini of the JCV and BKV T-Ags contain an enhanced immortalization function. However, chimeras in which the N-terminal or proximal-central portions of T-Ag were composed of JCV sequences failed to immortalize but did induce transformation. Constructs in which the JCV T-Ag Rb binding domain was replaced with SV40 sequences transformed human cells, but again the cells failed to immortalize. Transformants and immortalized cell lines produced by some SV40/JCV chimeras, contained p53 which was unbound by T-Ag. This occurred under conditions where p53 from SV40 and SV40/BKV transformants was bound to T-Ag. This may reflect the reduced stability of the SV40/JCV T-Ags.

Antigens, Polyomavirus Transforming↗

PubMed1995

Age, period, and cohort effects on pulmonary function in a 24-year longitudinal study.

This paper proposes the use of two-factor models (age-period and age-cohort models) to estimate age, period, and cohort effects on pulmonary function by using the data collected in a 24-year longitudinal study in the Netherlands from 1965 to 1990. The analysis included 18,363 pulmonary function measurements on 6,148 subjects aged 20-54 years at the initial visit. The subjects were grouped into four birth cohorts (before 1923, 1923-1934, 1935-1946, and after 1946) and four survey periods (1965-1972, 1973-1978, 1979-1984, and 1985-1990). In the age-cohort model, the decrement in forced expiratory volume in 1 second (FEV1) associated with a yearly increase in age was 28.3 +/- 3.7 ml/year for a man 176 cm tall and 16.0 +/- 1.9 ml/year for a woman 163 cm tall. The estimated acceleration of decline with aging was significant for both men (beta = -0.212; standard error = 0.079 ml) and women (beta = -0.346; standard error = 0.058 ml). Compared with that of the cohort born before 1923, the average level of FEV1 was estimated to increase by 156, 277, and 379 ml, respectively, for the three younger cohorts in men (p = 0.01) and by 133, 213, and 328 ml for the three younger cohorts in women (p < 0.01). In the age-period model, the estimated linear age effect on FEV1 was 36.2 +/- 4.2 ml/year for a man and 30.5 +/- 2.3 ml/year for a woman. The age quadratic term was significant for women, but not for men. Average FEV1 was estimated to be increased by 141, 169, and 250 ml, respectively, for the periods 1973-1978, 1979-1984, and 1985-1990 in men and by 131, 138, and 219 ml in women. These period effects were significant for both men and women. In summary, this study applied the two-factor models to estimate cross-sectional and longitudinal effects of aging on FEV1 and demonstrated significant period and cohort effects, which could be attributed in part to changes in air pollutants, respiratory infections, vaccinations, types of cigarettes, diet, and lifestyles over time.

Age Factors↗

PubMed1995

The v-Rel oncoprotein complexes with new Rel- and RelA-related proteins in transformed cells.

The v-Rel oncoprotein of the Rev-T retrovirus interacts with a number of cellular proteins in transformed chicken spleen cells including p40/I kappa B alpha, p68c-Rel, hsc70, and the p124 and p115 precursors for the p50 and p52 subunits of NF kappa B. Here we report that v-Rel associates with at least three other cellular proteins of 75-85 kDa in these cells, as well as with a protein related to human RelA. Western blot analysis of v-Rel immune complexes showed cross-reactivity between all of these factors and antibodies raised against Rel sequences, but none appeared to represent isoforms of c-Rel. Synchronization experiments revealed that the expression and/or association of these proteins with v-Rel varied throughout the cell cycle. Combined with the previously described interaction of v-Rel with known members of the Rel family, these studies strengthen the hypothesis that the interaction of v-Rel with multiple Rel-related proteins may be important for the transformation of lymphoid cells.

Animals↗

PubMed1995

Creation of a high cytotoxic active human tumor necrosis factor having the truncated and more basic amino terminus.

In order to define the structure-functional relationship of tumor necrosis factor(TNF), a mutant TNF gene was created by site-specific mutagenesis based on the PCR technique. This gene was highly expressed in E.coli cells. The amount of the recombinant protein was up to about 80% of the total cellular proteins. Through one-step ion exchange chromatography, the mutant TNF could be purified to homogeneity. This mutein showed the molecular weight of a dimer but not a trimer. It bears the features of truncated amino terminus and increase of the basicity of amino terminal residues. Compared with the wild type TNF, the specific activity of mutant TNF was increased by fourfold.

Amino Acid Sequence↗

PubMed1995

Synthesis, conformation and opioid activity of deltorphins.

A series of deltorphin analogues was prepared by solid-phase peptide synthesis. Their opioid activity was evaluated in rat opiatic assay and their conformation was determined by two-dimension Nuclear Magnetic Resonance Spectroscopy. The analogues containing D-alanine acid at position 2 were much more potent in the assay than their corresponding isomers containing L-alanine acid at this position. The conformational analysis on NMR study in DMSO showed that C-terminal tetrapeptides of both deltorphin II and its L-alanine analog might form a 3(10) helix, which confirms that the substitution of D-amino acid at position 2 decreased the opioid activity.

Analgesics↗

PubMed1995

Helix formation in model peptides based on nucleolin TPAKK motifs.

The structures formed by peptide models of the N-terminal domain of the nucleolar protein nucleolin were studied by CD and nmr. The sequences of the peptides are based on the putative nucleic acid binding sequence motif TPAKK. The peptides TP1 and TP2 have the sequence acetyl-G(ATPAKKAA)nG-amide, with n = 1 and 2, respectively. CD measurements indicate structural changes in both peptides when the lysine side chains are uncharged by increasing the pH or acetylation of the side-chain amines. When trifluoroethanol (TFE) is added, more extensive structural changes are observed, resembling helical structure based on nmr nuclear Overhauser effect (NOE) and C alpha proton chemical shift changes, and CD spectra. The structure formed in 0.5M NaClO4 as observed by nmr is similar to that when the lysine side chains are acetylated, due presumably to interactions of perchlorate ion with side-chain charges on lysines. The helical structure observed in TPAKK motifs may be stabilized via N-capping interactions involving threonine. The structures observed in TFE suggest that the Thr-Pro sequence initiates short helical segments in TPAKK motifs, and these helical structures might interact with nucleic acids, presumably via interactions between lysines and threonines of nucleolin.

Amino Acid Sequence↗

PubMed1995

A new protein folding recognition potential function.

On the study of protein inverse folding problem, one goal is to find simple and efficient potential to evaluate the compatibility between structure and a given sequence. We present here a novo empirical mean force potential to address the importance of electrostatic interactions in protein inverse folding study. It is based on protein main chain polar fraction and constructed in a way similar with Sippl's from a database of 64 known independent three-dimensional protein structures. This potential was applied to recognize the protein native conformations among a conformation pool. Calculated results show that this potential is powerful in picking out native conformations, in addition it can also find structure similarity between proteins with low sequence similarity. The success of this new potential clearly shows the importance of electrostatic factors in protein inverse folding studies.

Electrochemistry↗

PubMed1995

Expression of selected osteogenic markers in the fibroblast-like cells of rat marrow stroma.

The fibroblast-like cells in the marrow stromal system were separated from endothelial cells and macrophages by negative selection of magnetic beads. Immunocytochemistry confirmed that these fibroblast-like cells expressed fibronectin and collagen Type III, but not Factor VIII and epithelial membrane antigen (endothelial cell markers) or Mac I (macrophage marker). The fibroblast-like stromal cells (FSC) synthesized the insulin-like growth factors (IGF)-I and -II in amounts equivalent to that produced by unfractionated marrow stromal cells (UMSC); in both, the concentration of IGF-II was 10 times higher than that of IGF-I. Northern analysis revealed that FSC and UMSC expressed identical patterns of mRNAs for IGF-I and transforming growth factor (TGF) -beta 2, for osteopontin, and for procollagen Types I and III (Type I > Type III). Type II procollagen mRNA was not expressed in both cell populations. The TGF-beta 2 gene mRNA was expressed at a lower level by the FSC than UMSC. The pattern of gene expression in these cells is consistent with an osteoprogenitor phenotype. Both FSCs and UMSCs express parathyroid hormone (PTH) and estrogen receptor genes (rtPCR technique). The study provides additional evidence that fibroblast-like marrow stromal cells have an osteoblast signature, and that they are largely responsible for the osteogenic performance of cells in unfractionated marrow.

Animals↗

PubMed1995

Comparative anterograde amnestic and anticonvulsant effects of two types of NMDA receptor antagonists: MK-801 and HA-966.

The anterograde amnestic effects of non-competitive NMDA antagonists MK-801 and HA-966 on classic fear conditioning in goldfish (Carassius auratus) were examined in a series of experiments. Experiments 1 and 2 contrasted the anterograde amnestic effects of MK-801, (+)HA-966, and (-)HA-966. Experiment 3 examined the effects of MK-801 and (+)HA-966 on the expression of conditioned responses. Experiments 4 and 5 investigated whether the potency of MK-801, (+)HA-966 or (-)HA-966 in blocking NMDA-induced convulsions paralleled their potency in producing amnesia. The results showed that MK-801 was more potent than (+)HA-966 in producing anterograde amnesia and impairing expression, while (-)HA-966 did not produce anterograde amnesia. The anticonvulsant potency of MK-801, (+)HA-966, and (-)HA-966 paralleled their amnestic potency. These findings suggested that MK-801 and (+)HA-966 produced anterograde amnesia by their specific antagonism of the NMDA receptor complex.

Amnesia↗

PubMed1995

Pain-related somatosensory evoked potentials following CO2 laser stimulation of foot in man.

Since our previous study of pain somatosensory evoked potentials (SEPs) following CO2 laser stimulation of the hand dorsum could not clarify whether the early cortical component N1 was generated from the primary somatosensory cortex (SI) or the secondary somatosensory cortex (SII) or both, the scalp topography of SEPs following CO2 laser stimulation of the foot dorsum was studied in 10 normal subjects and was compared with that of the hand pain SEPs and the conventional SEPs following electrical stimulation of the posterior tibial nerve recorded in 8 and 6 of the 10 subjects, respectively. Three components (N1, N2 and P2) were recorded for both foot and hand pain SEPs. N1 of the foot pain SEPs was maximal at the midline electrodes (Cz or CPz) in all data where that potential was recognized, but the potential field distribution was variable among subjects and even between two sides within the same subject. N1 of the hand pain SEPs was maximal at the contralateral central or midtemporal electrode. The scalp distribution of N2 and P2, however, was not different between the foot and hand pain SEPs. The mean peak latency of N1 following stimulation of foot and hand was found to be 191 msec and 150 msec, respectively, but there was no significant difference in the interpeak latency of N1-N2 between foot and hand stimulation. It is therefore concluded that N1 of the foot pain SEPs is generated mainly from the foot area of SI. The variable scalp distribution of the N1 component of the foot pain SEPs is likely due to an anatomical variability among subjects and even between sides.

Adult↗

PubMed1995

Mutant frequency at the hprt locus in human lymphocytes in a case-control study of lung cancer.

A clonal assay to determine the mutant frequency (MF) at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in human lymphocytes has been used by a number of investigators to study exposure to mutagens and carcinogens in a variety of populations. We have studied hprt MF in 106 subjects (40 controls and 66 cases) enrolled in a case-control investigation of lung cancer. Epidemiological data collected included smoking history, intake of dietary micronutrients, and occupational and environmental exposures as well as medical history, all obtained from an interviewer-administered questionnaire. All subjects were also genotyped for the known polymorphism in glutathione S-transferase class mu (GST-mu). In analysis of cases and controls, hprt MF was not associated with age, smoking, the polymorphism in GST mu, dietary intake, occupational exposures, family history of cancer or usage of medications. Since MF and cloning efficiency (CE) are not independent when CE is low, further analysis in cases and controls with a CE greater than or equal to 30% (27 cases and 22 controls) was also conducted. In analysis of controls, hprt MF increased with age and was inversely associated with intake of folate and vitamins A and C. The presence of lung cancer was not associated with hprt MF. Thus, our study supports the previous observation that dietary components may affect the MF at the hprt locus.

Age Factors↗

PubMed1995

The determination of strong mutagen MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone] in drinking water in China.

The strong mutagen, [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone] (MX) was found to occur in chlorinated drinking water in China. Some tap water samples from Jiangsu province, which contained MX of 3-60ng/L, were analyzed. Quantitation is based on gas chromatography-mass spectrometry, using peak area of selective ion monitoring of the methyl derivative of MX.

China↗

PubMed1995

Autoimmune enteropathy with anti-goblet cell antibodies.

A 9-year-old boy with a 5-year history of severe protracted diarrhea requiring home parenteral nutrition and a 1 year history of abnormal liver function tests was admitted for duodenal, rectal, and liver biopsy. Duodenal biopsy results showed mild villus blunting, a mild lymphocytic infiltrate, and absent goblet cells. Paneth cells and endocrine cells could not be identified. Review of several previous biopsies showed an almost total absence of goblet cells by light microscopy. Anti-goblet cell antibodies of the immunoglobulin (Ig)G class were shown by immunofluorescence with a titer of 1:512. Histological examination of rectal mucosa also showed a total lack of goblet cells, orderly surface epithelial cells, and infiltration of the colonic crypts by lymphocytes. Immunoperoxidase staining of rectal mucosa showed increased numbers of lymphocytes with an excess of CD3+, CD45RO+ T cells, and increased numbers of B cells labeling with B1 and L26. Increased numbers of CD25+ (activated) lymphocytes were also observed. HLA/DR expression was striking and observed in both the crypt and surface enterocytes, as well as in the lamina propria. Immunological assessment of the patient showed an inverted CD4/CD8 ratio and IgA/IgG4 deficiency. The liver biopsy and radiological investigation were in keeping with chronic sclerosing cholangitis. Although a slight and transient improvement in histological appearances was observed with prednisolone there was no significant improvement of diarrhea. Trials of azothiaprine and oral cyclosporin did not result in clinical or histological improvement.

Autoantibodies↗

PubMed1995

Comparison of sister chromatid exchange frequency in peripheral lymphocytes in lung cancer cases and controls.

Cytogenetic alterations have been associated with the occurrence of many cancers. However, limited data exist to address whether increased chromosomal changes in surrogate normal tissue are similarly associated with malignancy. As part of an ongoing case-control study of lung cancer, we have studied the factors that affect sister chromatid exchange (SCE) frequency in lymphocytes from lung cancer patients. Further, we sought to investigate whether the factors that affect SCE frequencies were comparable in lung cancer cases and controls. Cases had newly diagnosed, operable primary lung cancer. Controls were friends and spouses of cases. Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was obtained in an interviewer-administered questionnaire. Intake of antioxidants was also determined through the administration of a validated semiquantitative food frequency questionnaire. Metabolic traits studied included the polymorphic glutathione-S-transferase class mu (GST-mu) and variants of P450 isoenzymes CYP1A1 and CYP 2D6. Overall, 78 cases and 78 controls were included in the analysis. Although there was a small number of lung cancer patients who had never smoked in the study (9% of cases), these patients had higher SCE frequencies than current or former smokers. This suggests that factors associated with genomic instability may also play a role in the pathogenesis of lung cancer. The best fit model for SCE frequency, which had been previously generated from control data alone, included age, gender, smoking, GST-mu, and vitamin A intake. However, when this model was applied to lung cancer patients, smoking was not associated with an elevated SCE frequency. Thus, it is not clear that SCE frequency data in prevalent lung cancer cases and controls are comparable.

Age Factors↗

PubMed1995

Peri-rolandic and fronto-parietal components of scalp-recorded giant SEPs in cortical myoclonus.

Scalp topography of giant SEPs to median nerve stimulation was studied in 4 patients with cortical myoclonus of various etiology. The positive peak (P30) at the contralateral parietal area was simultaneously accompanied by a negative peak at the frontal area (N30), and at least one of these two peaks was enhanced in 2 patients. Another positive peak (P25) and a negative peak (N35) were also identified at the peri-rolandic area with different latency from P30 and N30, respectively, in all patients. N35 was enhanced in 3 patients, and P25 in 2 patients. It is concluded that, as seen in normal subjects, tangential (P30-N30) and radial (P25 and N35) components of SEPs are most likely distinguishable in giant SEPs, and that either one or both of those components is enhanced in different ways depending on the patients.

Adolescent↗

PubMed1995

Insulin-like growth factor-1 stimulation of protein synthesis is attenuated in cerebral cortex of aging rats.

It has been postulated that brain aging and the accompanying neurodegenerative processes associated with aging result from a deterioration of mechanisms that regulate the maintenance of basic cellular processes. In the present study, it was hypothesized that decreased availability and/or diminished responsiveness of tissues to growth factors such as insulin-like growth factor-1 may be partly responsible for decreases in total protein synthesis previously observed in aging animals. Male Brown Norway rats (5-7 and 27-28 months old) were used to determine (1) whether in vivo protein synthesis in cortex, hippocampus, hypothalamus and cerebellum decreases with age and (2) whether these deficiencies are associated with age-related alterations in response to insulin-like growth factor-1, des (1-3) IGF-1 or insulin. Analysis of in vivo protein synthesis rates revealed a decline of 20% in cortex of old rats (P < 0.05) but no changes were observed in hippocampus, hypothalamus, or cerebellum. Stimulation of cortical slices in vitro with insulin-like growth factor-1, des (1-3) insulin-like growth factor-1, or insulin increased protein synthesis rates in young animals, but the response to these growth factors was blunted in old animals. Analysis of type 1 insulin-like growth factor receptor densities by quantitative autoradiography demonstrated age-related decreases in receptor levels in cerebellar cortex and dentate gyrus of the hippocampus but no changes in cortex. Regional distribution of type 1 insulin-like growth factor receptors within each of these tissues did not appear to change with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1995

Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins.

The activation of cytokine genes in response to antigenic stimulation of T cells is mediated by NF-AT proteins. Previous studies have identified two NF-AT proteins, NF-ATp and NF-ATc, that are homologous within a 290 aa domain distantly related to the Rel domain. We have isolated two additional members of this gene family, NF-AT3 and NF-AT4, which encode proteins 65% identical to the other NF-AT proteins within the Rel domain. The four NF-AT genes are transcribed in different sets of tissues that included many sites of expression outside the immune system. The Rel homology domain is sufficient for DNA recognition and cooperative binding interactions with AP-1. Although other members of the Rel family bind DNA as dimers, NF-AT proteins are monomers in solution or bound to DNA. Transfection assays indicate that each of the four NF-AT proteins can activate the IL-2 promoter in T cells.

Amino Acid Sequence↗