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Biomedical subjects

F Xu

Publications and source records attributed to F Xu.

At least 271 records · Page 15Linked to original sources
PubMed1994

Cerebellar modulation of ventilatory response to progressive hypercapnia.

The cerebellar contribution to the ventilatory response to progressive hypercapnia was examined in 18 anesthetized tracheotomized spontaneously breathing cats. The absolute values for minute ventilation (VE), tidal volume (VT), respiratory frequency (f), inspiratory duty cycle (TI/TT), and mean inspiratory flow (VT/TI) were measured. Progressive hypercapnia [35-65 Torr end-tidal PCO2 (PETCO2)] was induced using the rebreathing method. The respiratory variables at each level of PETCO2 and the slopes of ventilatory (VT and f) responses to hypercapnia were compared across the intact, decerebellate, and decerebellate-vagotomized preparations. In 12 cats, decerebellation preceded vagotomy, and in 6 cats the order of the surgical procedures was reversed. The results show that, compared with intact control, decerebellation had little effect on respiratory variables when PETCO2 was 30-35 Torr. However, during a hypercapneic challenge (40-65 Torr PETCO2), VE and the slope of the VE response were significantly reduced. Bilateral vagotomy increased VT and decreased f but failed to alter the ventilatory response in the PETCO2 range of 35-55 Torr. However, combination of decerebellation and vagotomy, regardless of the surgical order, severely blunted VE (35-65 Torr PETCO2) and the slopes of VE, VT and f responses. When decerebellation followed vagotomy, significant decreases in VT (absolute values and slopes) were noted with little further alteration in f response. We conclude that the cerebellum and its interaction with the vagus nerves play a facilitatory or disinhibitory role in the ventilatory responses to hypercapnia.

Animals↗
PubMed1994

Cerebellar role in the load-compensating response of expiratory muscle.

The hypothesis that the cerebellum is involved in the load-compensating response of expiratory muscles to expiratory tracheal occlusion was tested in anesthetized cats. A continuous expiratory threshold load (ETL; 5 cmH2O) was applied to elicit consistent phasic baseline electromyographic activity in the transversus abdominis muscle (EMGab). Tracheal occlusion for single expirations (TOE) were applied, and the evoked responses were compared in the intact and decerebellate preparation. Cold blockade of the dorsal spinal column (C5-7) and bilateral vagal inactivation (cold blockade or transection) were employed to determine the role of afferents from the lung, airways, chest wall, and diaphragm in shaping the cerebellar involvement in the motor response. The results showed that 1) decerebellation increased the baseline amplitude of the integrated EMGab (fEMGab) activity (P < 0.05) with little change in expiratory duration, 2) TOE applied after decerebellation markedly increased the expiratory duration compared with the intact values (P < 0.05), with little effect on the peak fEMGab, 3) cooling the dorsal spinal columns (C5-7) did not significantly affect EMGab responses in the intact or decerebellate preparations, and 4) vagal inactivation in the intact or decerebellate preparation significantly eliminated the fEMGab responses to ETL and TOE. We conclude that the cerebellum is involved in the modulation of transversus abdominis activity during ETL and TOE. Vagal afferents provide the major sensory input for the cerebellar modulation of the expiratory loading response.

Abdominal Muscles↗
PubMed1994

Effects of recombinant human Steel factor (c-kit ligand) on early cord blood hematopoietic precursors.

The purpose of this study was to define the effects of recombinant human Steel factor (rhSF) (c-kit ligand) on early and late cord blood hematopoietic progenitors. In the presence of recombinant human erythropoietin (rhEpo), rhSF supported the development of granulocyte/macrophage, erythroid, and mixed colonies from CD34-positive cord blood cells. With increasing concentrations of rhSF, an increase in the number of mixed colonies was observed. This increase was paralleled by a decrease in the number of erythroid colonies, such that the total number of the two colony types was always constant. Similar results were observed when CD34+ cells were cultured in the presence of a combination of rhEpo, rhSF, and rhIL-3. These results indicate that the presence of rhSF enhanced the detectability of the nonerythroid components of mixed colonies. The effect of rhSF on early progenitors (pre-colony-forming units [pre-CFU]) was studied in a two-step assay. In this assay, cells positive for CD34 and resistant to treatment with 4-hydroperoxycyclophosphamide (CD34+/4-HCres) were cultured in suspension for 7 days with rhSF, rhIL-3, or rhSF plus rhIL-3 and then plated in clonogenic assays. Before suspension culture, CD34+/4-HCres cells had a low clonogenic potential (0.37%). After being cultured in suspension, however, these cells gave rise to a large number of colonies of all types when replated. Cells cultured in suspension with the combination of rhSF and rhIL-3 increased significantly in number and gave rise to more colonies, when compared to cells cultured with either factor alone (synergistic effect). In identical experiments, such as effect had not been observed with combinations of rhIL-3 and either rhIL-1 or rhIL-6. Thus, rhSF supports the expansion and differentiation of early progenitors in human cord blood.

Antigens, CD↗
PubMed1994

[Report on the first nationwide survey of the distribution of human parasites in China. 1. Regional distribution of parasite species].

A nationwide (Taiwan Province not included) survey of the distribution of human parasites in China during 1988-1992 was conducted under the auspices of the Ministry of Public Health, with stratified masses randomly sampling. A total of 2,848 pilot sites in 726 counties with a population of 1,477,742 were surveyed, according to unified standard, unified diagnostic method and control quality. The overall infection rate of parasites was 62. 632%. Among them, the infection rate was over 50% in 17 provinces/autonomous regions/municipalities (P/A/M), over 80% in Hainan, Guangxi, Sichuan, Fujian, Zhejiang and Guizhou, being highest in Hainan (94. 735%). Altogether 56 species were detected. Centrocestus formosanus is reported for the first time at home, Echinochasmus liliputanus and Echinostoma angustitestis are reported for the first time at home and abroad. Echinochasmus fujianensis is a new species. E. histolytica, G. lamblia, A. lumbricoides, whipworm and pinworm were distributed nationwide, while Cysticercus (27 P/A/M), Taenia (27), hookworm (26), Balantidium coli (22), Clonorchis sinensis (22), Paragonimus westermani (21), H. diminuta (21), Echinococcus (18), H. nana (17), Fasciolopsis buski (16), T. spiralis (12) were distributed non-nationwide. A preliminary suggestion on intervention of the common and/or most detrimental parasitic diseases was submitted, including hydatidosis, taeniasis, cysticercosis, clonorchiasis, paragonimiasis, trichinellosis, hookworm disease, ascariasis, trichuriasis and enterobiasis.

Animals↗
PubMed1994

[Effect of anti-fibronectin-serum on fertilization capacity of human spermatozoa].

Using the in vitro penetration test, we initially studied effects of anti-fibronectin (FN)-serum on fertilization capacity of human spermatozoa. Owing to the coincubation of anti-FN-serum in a heterologous system (human spermatozoa and zona-free gold hamster oocyte), a certain increase was found in the penetration rate at a low concentration of anti-FN-serum. The penetration rate in the treated group was 20% higher than that in the control group at an anti-FN-serum concentration of 10 microliters/ml (P < 0.05), but at a higher concentration of anti-FN-serum, the penetration rate was not affected. The results suggest that anti-FN-serum can improve the fertilization capacity of human spermatozoa, help to treat the unexplained infertility, and increase the repregnancy rate of vasovasotomy.

Animals↗
PubMed1993

The Escherichia coli pcnB gene promotes adenylylation of antisense RNAI of ColE1-type plasmids in vivo and degradation of RNAI decay intermediates.

Previous work has shown that RNase E-mediated cleavage of RNAI, an antisense repressor of the replication of ColE1-type plasmids, relieves repression in vivo by endonucleolytically converting RNAI to a rapidly decaying product. We report that mutations in the Escherichia coli pcnB gene result in a 10-fold prolongation of the half-life of RNAI decay intermediates and also of truncated RNAI primary transcripts lacking sites attacked by RNase E. Using Northern blotting, primer extension analysis, [32P]GTP capping of 5'-triphosphate termini, and PCR amplification methods, we show that pcnB-mediated acceleration of RNAI degradation is associated with posttranscriptional 3' addition of adenosine residues in vivo to native and processed forms of RNAI. Accumulation of antisense RNAI decay products in pcnB mutants potentially explains the reduced copy number of ColE1-type plasmids seen in the mutated bacteria.

Adenosine Monophosphate↗
PubMed1993

Sodium/proton transport by apical membranes of type-II pneumocytes.

Recent studies fail to confirm the coexistence of Na+ channels and Na+/H+ exchange at the apical membranes of lower airway epithelia. Availability of plasma membrane vesicles simplifies the investigation of membrane transport processes. Apical and basolateral plasma membrane vesicles of disrupted type-II pneumocytes were fractionated upon nonlinear, continuous sucrose gradients. To investigate sodium transport, 22Na+ uptake by apical membrane vesicles was assayed in the presence and absence of transmembrane sodium diffusion potentials. Interior-negative sodium diffusion potentials promoted 22Na+ uptake 1.5-fold. Internally-directed H+ gradients or NH+4 gradients inhibited 22Na+ uptake 40-50%. Amiloride (1-1000 microM) inhibited uptake 10-79%. To investigate H+ transport, decay of transmembrane pH gradients was monitored with pH probe acridine orange. In the presence or absence of externally-directed H+ gradients, external sodium promoted internal alkalinization, except in the presence of external amiloride. These observations of amiloride-sensitive, electrogenic Na+ uptake and amiloride-sensitive, electroneutral, Na+/H+ coupling indicate coexistence of Na+ channels and Na+/H+ exchange at the apical membrane of type-II pneumocytes.

Amiloride↗
PubMed1993

Pyrroloquinoline quinone acts with flavin reductase to reduce ferryl myoglobin in vitro and protects isolated heart from re-oxygenation injury.

Pyrroloquinoline quinone has been isolated from bacteria and recently has been detected in mammalian tissues and fluids. We report in vitro studies which show that pyrroloquinoline quinone serves as a high-affinity substrate for an erythrocyte "flavin reductase" and that the pyrroloquinoline quinol generated by this catalysis reacts rapidly with ferryl myoglobin radical. Western blot analysis of rat and rabbit heart homogenates detects a cross-reactive protein which has a molecular weight identical to the erythrocyte reductase from the same species. Low concentrations of pyrroloquinoline quinone protect isolated rabbit heart from re-oxygenation injury, serving as an effective tissue-protective agent in this model for cellular oxidative damage. We propose that this tissue protection is due to a pyrroloquinoline quinol-mediated reduction of reactive oxygen species.

Animals↗
PubMed1993

Androgen-induced inhibition of cell proliferation in an androgen-insensitive prostate cancer cell line (PC-3) transfected with a human androgen receptor complementary DNA.

A full length human androgen receptor complementary DNA was introduced into androgen receptor-negative PC-3 cells to determine if androgen sensitivity could be established in this cell line and to assess what influence, if any, androgen exposure would have on the growth of these cells. The androgen receptor complementary DNA was inserted into pSG5 in the region controlled by the SV40 promoter. This construct was cotransfected with pSR1neo into PC-3 cells and stably transfected cells were selected and screened for the expression of the androgen receptor. Active expression of the receptor was demonstrated by Western blotting using a rabbit anti-androgen receptor antiserum and by [3H]methyltrienolone binding to cytosol extracts. Saturation ligand-binding analysis revealed the presence of a single class, high affinity (Kd = 0.122 nM) androgen-binding site in cytosol extracts of transfected cells but not in extracts from mock-transfected cells. In cells expressing the transfected androgen receptor, androgen decreased the proliferation rate and cloning efficiency and induced a more differentiated phenotype. These results demonstrate that PC-3 cells have retained the mechanisms required to respond to the activated androgen receptor and that the loss of androgen sensitivity in these cells is due to the lack of functional androgen receptor. This also provides a technique for determining whether androgen-resistant tumor cells contain functional androgen receptors or whether androgen sensitivity is due to abnormalities in downstream signaling pathways. The apparent androgen-induced decreased malignant state of these transfected cells suggests new directions for the treatment of prostate cancer.

Animals↗
PubMed1993

Hydrogen peroxide-dependent formation and bleaching of the higher oxidation states of bovine erythrocyte green hemeprotein.

The ferric and ferrous forms of bovine erythrocyte green hemeprotein react with hydroperoxides to form higher oxidation state intermediates with absorbance maxima in the Soret region at 426 and 422 nm, respectively. In the absence of an appropriate reductant, these intermediates undergo rapid bleaching reactions. 2,2'-Azinobis(3-ethylbenzthiazoline-6-sulfonic acid) rapidly reduces the intermediate formed by reaction of ferric green hemeprotein with hydrogen peroxide, thereby preventing bleaching and allowing the rate of the intermediate formation to be calculated from the coupled dye oxidation. This rate constant of 70 M-1 s-1 at 23 degrees C is similar to those determined by bleaching and by direct photometric detection of the intermediate. Dihydroriboflavin rapidly reduces the intermediate formed by reaction of ferrous green hemeprotein with hydrogen peroxide, thereby preventing bleaching and allowing the rate of the intermediate formation to be calculated from the coupled dihydroriboflavin oxidation; the rate constant of 2 x 10(4) M-1 s-1 at 23 degrees C is similar to the value calculated by direct detection of the intermediate. The results demonstrate that, in contrast to the reductase activity of its heme-free form, the green heme form of the protein reacts with hydroperoxides to generate highly unstable peroxide complexes.

Animals↗
PubMed1993

Antibody-induced growth inhibition is mediated through immunochemically and functionally distinct epitopes on the extracellular domain of the c-erbB-2 (HER-2/neu) gene product p185.

Over-expression of the c-erbB-2 (HER-2/neu) gene product p185 occurs in 30% of breast and ovarian cancers. The p185 protein might serve as a target for serotherapy in that antibodies against different epitopes on the extracellular domain of p185 can inhibit growth of tumor cells in the absence of cellular or humoral effector mechanisms. To define epitopes of functional relevance, 11 monoclonal antibodies (MAbs) were evaluated for their ability to bind to the extracellular domain of p185. Results of competition studies with 125I-labeled and non-labeled antibodies indicated that 10 of 11 epitopes were grouped in a linear array. Antibodies against 7 epitopes inhibited anchorage-independent growth and antibodies against 2 of these epitopes also inhibited anchorage-dependent growth of SKBr3 breast-cancer cells that over-expressed p185. Treatment with antibodies exerted cytotoxic rather than cytostatic effects. When antibodies were used in combination, additive or supra-additive inhibition of anchorage-independent and anchorage-dependent growth was observed between pairs of antibodies. Growth inhibition did not relate to the affinity of the antibody or its isotype. Two antibodies that inhibited both anchorage-dependent and anchorage-independent growth also blocked binding of the HER-2/neu ligand, whereas 5 antibodies that inhibited only anchorage-independent growth had no effect on ligand binding. Inhibition of cell growth did not correlate with internalization of p185 or down-regulation of p185 on the cell surface. Fab fragments of active antibodies could also inhibit anchorage-independent growth of SKBr3. Thus, murine MAbs and their fragments recognized both immunochemically distinct and functionally distinct epitopes on the p185 molecule. Whereas inhibition of anchorage-dependent growth correlated with the ability of antibodies to block ligand binding, inhibition of anchorage-independent growth did not correlate with effects on ligand binding, internalization, cell-surface expression or cross-linking of p185.

Antibodies, Monoclonal↗
PubMed1993

Evidence that NADPH-dependent methemoglobin reductase and administered riboflavin protect tissues from oxidative injury.

NADPH-dependent methemoglobin reductase, first detected in erythrocytes sixty years ago, has subsequently been purified and characterized as a methylene blue reductase and a flavin reductase. The reductase plays no role in methemoglobin reduction under normal conditions, but its activity serves as the basis for the treatment of methemoglobinemia with methylene blue or flavin. On-going studies demonstrate that this cytosolic protein is also present in liver and that its primary structure distinguishes it from other known proteins. The bovine erythrocyte reductase tightly binds hemes, porphyrins, and fatty acids with resulting loss of activity. Pyrroloquinoline quinone serves as a high-affinity substrate of the reductase, suggesting that this naturally-occurring compound may be a physiological substrate. The ability of the reductase to catalyze the intracellular reduction of administered riboflavin to dihydroriboflavin suggested that this system might be exploited to protect tissues from oxidative damage. This hypothesis was supported by our finding that dihydroriboflavin reacts rapidly with Fe(IV)O and Fe(V)O oxidation states of hemeproteins, states that have been implicated in tissue damage associated with ischemia and reperfusion. Preliminary studies demonstrate that, as predicted, administration of low concentrations of riboflavin protects isolated rabbit heart from reoxygenation injury, rat lung from injury resulting from systemic activation of complement, and rat brain from damage caused by four hours of ischemia. Data from these animal studies suggest that flavin therapy holds promise in protecting tissue from the oxidative injuries of myocardial infarction, acute lung injury, stroke, and a number of other clinical conditions.

Animals↗
PubMed1993

The effect of antibodies and immunotoxins reactive with HER-2/neu on growth of ovarian and breast cancer cell lines.

OBJECTIVE: Because HER-2/neu is overexpressed in one third of breast and ovarian cancers, we examined the effect of unconjugated monoclonal antibodies (ID-5, PB-3, TA-1) and an immunotoxin (TA-1-ricin) reactive with this protooncogene on the growth of breast and ovarian cancer cell lines. STUDY DESIGN: The tritiated thymidine incorporation assay was used to examine the effect of unconjugated antibodies on proliferation. A limiting dilution clonogenic assay was used to assess the effect of immunotoxin on cellular cytotoxicity. RESULTS: Scatchard analysis revealed that OVCA 420, OVCA 429, OVCA 432, and OVCA 433 cells had approximately 10(4) HER-2/neu receptors per cell, whereas the SKOv3 and SKBr3 cell lines expressed 10(5) and 10(6) receptors per cell, respectively. Monoclonal antibody ID-5 caused significant inhibition of tritiated thymidine incorporation in SKBr3, SKOv3, and OVCA 420 cells (p < 0.002). The TA-1-rich immunotoxin significantly inhibited the clonogenic growth of only SKBr3 and SKOv3 cells. CONCLUSION: HER-2/neu may be a useful target for immunotherapy with unconjugated antibodies and immunotoxins in ovarian and breast cancers that overexpress this protooncogene.

Antibodies, Monoclonal↗