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Biomedical subjects

F Xu

Publications and source records attributed to F Xu.

At least 109 records · Page 6Linked to original sources

Tyrosine phosphorylation of myelin P(0) and its implication in signal transduction.

P(0), a major structural protein of peripheral myelin, belongs to the immunoglobulin superfamily. Sequence comparison of P(0) with PZR, a tyrosine phosphatase SHP-2 binding protein we recently cloned, revealed the presence of an immunoreceptor tyrosine-based inhibitory motif (ITIM) in the intracellular portion of the P(0) molecule. To study the role of this putative ITIM in signal transduction, we have expressed P(0) in HT-1080 and 293 cells. Stimulation of the transfected cells with pervanadate, a powerful inhibitor of tyrosine phosphatases, resulted in tyrosine phosphorylation of P(0) and its association with several tyrosine-phosphorylated proteins. Mutation of Y(220) embedded in the ITIM to phenylalanine abolished the tyrosine phosphorylation and the association. Tyrosine phosphorylation of P(0) and its association with other signaling proteins were also observed in pervanadate-treated RN22 Schwannoma cells, which express endogenous P(0). Furthermore, injection of pervanadate induced tyrosine phosphorylation of P(0) in peripheral nerves of newborn but not adult mice. The physiological importance of the ITIM in P(0) is implied by the fact that a naturally occurred P(0) mutant with a disrupted ITIM has a dominant role in causing Dejerine-Scotts syndrome. Taken together, P(0) is phosphorylated on Try(220). The presence of an ITIM in P(0) and its ability to mediate protein-protein interaction through tyrosine phosphorylation indicate that P(0) is not merely a structural protein but may also be a crucial player in cell signaling.

Amino Acid Sequence↗

Large number discrimination in 6-month-old infants.

Six-month-old infants discriminate between large sets of objects on the basis of numerosity when other extraneous variables are controlled, provided that the sets to be discriminated differ by a large ratio (8 vs. 16 but not 8 vs. 12). The capacities to represent approximate numerosity found in adult animals and humans evidently develop in human infants prior to language and symbolic counting.

Child Development↗

Myxoid chondrosarcoma of the sphenoid sinus and chondromyxoid fibroma of the iliac bone: cytomorphologic findings of two distinct and uncommon myxoid lesions.

Myxoid chondrosarcoma (MCS) and chondromyxoid fibroma (CMF) are two uncommon myxoid cartilaginous neoplasms with distinct cytologic features, histologic patterns, and immunoprofiles. Because these neoplasms have characteristic biological behaviors and management, their correct diagnosis is crucial to avoid debilitating and unnecessary surgical procedures. We report the imprint cytology (IC) preparation findings along with the differential diagnosis in one case each of myxoid chondrosarcoma and chondromyxoid fibroma of the splenoid sinus and iliac bone, respectively. The two great mimickers for these neoplasms, chordoma and chondrosarcoma, represent difficult diagnostic challenges, especially when MCS and CMF occur in unusual locations. IC in conjunction with the clinical and radiologic findings can provide a rapid preliminary intraoperative diagnostic interpretation which can aid in planning the immediate surgical management, as well as guide specific tissue triage for key ancillary studies such as electron microscopy and cytogenetic analyses. To the best of our knowledge, there have been no cytologic reports of MCS of the sphenoid sinus and CMF of the iliac bone.

Adult↗

Uptake of cadmium adsorbed on particulates by gills of goldfish (Carassius auratus).

Goldfish (Carassius auratus) were exposed to mixtures of constant dissolved cadmium (0.01 mg/L) and cadmium adsorbed on gibbsite particles at concentrations of 0, 0.025, 0.050, 0.075, and 0.100 mg/L. The gills of the fish were excised after a 5-day exposure experiment and both cadmium and aluminum in the gills were measured. The gills were also examined with a light microscope for surface adherence of the particles after the exposure. The evidence collected demonstrated that the concentration of cadmium in the gills increased with increased concentration of particulate cadmium during the exposure while the dissolved cadmium remained constant. The ratio of cadmium to aluminum in the gills was apparently higher than that in the solution, indicating the stripping and translocation of cadmium from the particles. A multistep uptake process is proposed and the bioavailability of particulate cadmium to fish gills is discussed.

Adsorption↗

Pulmonary surfactant proteins insert cation-permeable channels in planar bilayers.

Pulmonary surfactant, a mixture of lipids and proteins, promotes lung ventilation by reduction of surface tension at air-fluid interfaces. Exogenous surfactants containing hydrophobic proteins induce biological effects in lungs that are not fully explained by reduction of surface tension and are not induced by surfactants lacking proteins. We hypothesized that hydrophobic proteins from surfactant insert in membranes to induce channel activities that contribute to the observed biological effects of surfactant. To test for channel insertion by surfactant, planar lipid bilayers were monitored electrophysiologically in the presence of either intact pulmonary surfactant or extracted surfactant proteins reconstituted with phospholipids or directly added to bilayer lipids prior to membrane casting. In this in vitro model, both intact surfactant and extracted surfactant proteins initiated gated channel activities with slope conductances averaging 40 pS. Observed reversal potentials confirmed monovalent cation conductance, and conductance of smaller monovalent cations was selective. Voltage dependence of channel openings and rectification of channel current were not observed. These results confirm that hydrophobic surfactant proteins induce channel-mediated transport in artificial membranes. We speculate that pulmonary surfactants, in addition to reducing surface tension at air-fluid interfaces, initiate physiological and therapeutic effects in lung by cation channel insertion at exposed epithelial membranes.

Cations↗

Fragment constant method for prediction of fish bioconcentration factors of non-polar chemicals.

A fragment constant method for prediction of fish bioconcentration factor (BCF) was established based on experimental BCF values for 80 non-polar chemicals from nine classes. The model was evaluated using coefficients of determination and mean residuals, which are 0.995 and 0.1836, respectively. Jackknife tests were applied to examine the robustness of the prediction model on a class-by-class basis.

Animals↗

Mice lacking the norepinephrine transporter are supersensitive to psychostimulants.

The action of norepinephrine (NE) is terminated, in part, by its uptake into presynaptic noradrenergic neurons by the plasma-membrane NE transporter (NET), which is a target for antidepressants and psychostimulants. Disruption of the NET gene in mice prolonged the clearance of NE and elevated extracellular levels of this catecholamine. In a classical test for antidepressant drugs, the NET-deficient (NET-/-) animals behaved like antidepressant-treated wild-type mice. Mutants were hyper-responsive to locomotor stimulation by cocaine or amphetamine. These responses were accompanied by dopamine D2/D3 receptor supersensitivity. Thus altering NET expression significantly modulates midbrain dopaminergic function, an effect that may be an important component of the actions of antidepressants and psychostimulants.

Amphetamine↗

Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony-stimulating factor associated with the acute chest syndrome in patients with sickle cell disease.

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL-8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL-8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso-occlusive crises. The differences in mean IL-8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0.0001 and 0.04 respectively). The mean IL-8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 +/- 1400 pg/ml vs. 1900 +/- 470 pg/ml, P = 0.03). Granulocyte colony-stimulating factor (G-CSF) (2000 +/- 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL-8 and other chemokines. These findings suggest that IL-8 and G-CSF may play a role in the development of the ACS and the complications associated with it.

Acute Disease↗

Halothane and isoflurane augment depolarization-induced cytosolic CA2+ transients and attenuate carbachol-stimulated CA2+ transients.

BACKGROUND: Neuronal excitability is in part determined by Ca2+ availability that is controlled by regulatory mechanisms of cytosolic Ca2+ ([Ca2+]cyt). Alteration of any of those mechanisms by volatile anesthetics (VAs) may lead to a change in presynaptic transmission and postsynaptic excitability. Using a human neuroblastoma cell line, the effects of halothane and isoflurane on cytosolic Ca2+ concentration ([Ca2+]cyt) in response to K+ and carbachol stimulation were investigated. METHODS: Volatile anesthetic (0.05-1 mm) action on stimulated [Ca2+]cyt transients were monitored in suspensions of SH-SY5Y cells loaded with fura-2. Potassium chloride (KCl; 100 mm) was used to depolarize and activate Ca2+ entry through voltage-dependent calcium channels; 1 mm carbachol was used to activate muscarinic receptor-mediated inositol triphosphate (IP3)-dependent intracellular Ca2+ release. Sequential stimulations, KCl followed by carbachol and vice versa, were used to investigate interactions between intracellular Ca2+ stores. RESULTS: Halothane and isoflurane in clinically relevant concentrations enhanced the K+-evoked [Ca2+]cyt transient whether intracellular Ca2+ stores were full or partially depleted. In contrast, halothane and isoflurane reduced the carbachol-evoked [Ca2+]cyt transient when the intracellular Ca2+ stores were full but had no effect when the Ca2+ stores were partially depleted by KCl stimulation. CONCLUSIONS: Volatile anesthetics acted on sites that differently affect the K+- and carbachol-evoked [Ca2+]cyt transients. These data suggest the involvement of an intracellular Ca2+ translocation from the caffeine-sensitive Ca2+ store to the inositol triphosphate-sensitive Ca2+ store that was altered by halothane and isoflurane.

Anesthetics, Inhalation↗

Isoflurane pretreatment ameliorates postischemic neurologic dysfunction and preserves hippocampal Ca2+/calmodulin-dependent protein kinase in a canine cardiac arrest model.

BACKGROUND: Inhalational anesthetics are neuroprotective in rat models of global ischemia. To determine whether isoflurane at a clinically relevant concentration is neuroprotective in a canine model of cardiac arrest, we measured neurologic function and hippocampal Ca2+/calmodulin-dependent protein kinase II (CaMKII) content 20 h after cardiac arrest. METHODS: We tested the neuroprotective effect of 30 min of 1.5% isoflurane exposure before 8 min of global ischemia induced with ventricular fibrillation. Animals were randomized to four groups: control, isoflurane-control, ischemia, and isoflurane-ischemia. After resuscitation and 20 h of intensive care, each animal's neurologic deficit score was determined by two blinded evaluators. The hippocampal content of CaMKII, determined by immunoblotting, was measured by an individual blinded to the treatment groups. CaMKII activity was measured in samples from the cortex, hippocampus, and striatum of animals in each group. RESULTS: Isoflurane-ischemic animals had a median neurologic deficit score of 22.6% compared with 43.8% for the ischemic animals (P < 0.05). Hippocampal levels of the beta-subunit of CaMKII (CaMKIIbeta) were relatively preserved in isoflurane-ischemic animals (68 +/- 4% of control) compared with ischemic animals (48 +/- 2% of control; P < 0.001), although both groups were statistically significantly lower than control (P < 0. 001 ischemia vs. control and P < 0.05 isoflurane-ischemia vs. control). CONCLUSIONS: Isoflurane is an effective neuroprotective drug in a canine cardiac arrest model in terms of both functional and biochemical criteria.

Anesthetics, Inhalation↗

Redox chemistry in laccase-catalyzed oxidation of N-hydroxy compounds.

1-Hydroxybenzotriazole, violuric acid, and N-hydroxyacetanilide are three N-OH compounds capable of mediating a range of laccase-catalyzed biotransformations, such as paper pulp delignification and degradation of polycyclic hydrocarbons. The mechanism of their enzymatic oxidation was studied with seven fungal laccases. The oxidation had a bell-shaped pH-activity profile with an optimal pH ranging from 4 to 7. The oxidation rate was found to be dependent on the redox potential difference between the N-OH substrate and laccase. A laccase with a higher redox potential or an N-OH compound with a lower redox potential tended to have a higher oxidation rate. Similar to the enzymatic oxidation of phenols, phenoxazines, phenothiazines, and other redox-active compounds, an "outer-sphere" type of single-electron transfer from the substrate to laccase and proton release are speculated to be involved in the rate-limiting step for N-OH oxidation.

Acetaminophen↗

Modulation of respiratory motor output by cerebellar deep nuclei in the rat.

The present study was undertaken to determine what roles the various cerebellar deep nuclei (CDN) play in modulation of respiration, especially during chemical challenges. Experiments were carried out in 12 anesthetized, tracheotomized, paralyzed, and ventilated rats. The integrated phrenic nerve activity (integralPN) was recorded as an index of respiratory motor output. A stimulating electrode was sequentially placed into the fastigial nucleus (FN), the interposed nucleus, and the lateral nucleus. Only stimulation of the FN significantly altered respiration, primarily via increasing respiratory frequency associated with a pressor response. The evoked respiratory responses persisted after blocking the pressor response via pretreatment with phenoxybenzamine or use of transient stimulation (<2 s) but were abolished by microinjection of kainic acid into the FN. To test the involvement of FN neurons in respiratory chemoreflexes, ventilation with hypercapnic gases mixture and intravenous injection of sodium cyanide were applied before and after CDN lesions induced by kainic acid. CDN lesions did not significantly alter eupneic breathing, but FN lesions attenuated the respiratory response to hypercapnia and sodium cyanide. We conclude that, with respect to the CDN in the rat, FN neurons uniquely modulate respiration independent of cardiovascular effects and facilitate respiratory responses mediated by activation of CO(2) and O(2) receptors.

Animals↗

Relative potency of cellular and humoral immune responses induced by DNA vaccination.

DNA vaccines can prime broad-based immune responses in small animal models. In the present study, we sought to evaluate the relative ability of DNA vaccines to induce humoral and cellular immune responses. Using a DNA vaccine encoding HIV gag in mice, we observed that CD8+ T cell responses were primed more readily than were antibody responses, particularly at low doses of DNA. These CD8+ T cell responses were detected in spleen cells, as well as at local sites such as the lung and draining lymph nodes. The potency of the HIV gag DNA vaccine used was sufficient to prime strong CTL responses in macaques, but only low to undetectable antibody responses. Therefore, DNA vaccines appear able to prime strong, broad CTL but only modest antibody responses. These results may have implications on the development of vaccines against infectious diseases where both CTL and antibody responses are desired, such as HIV.

AIDS Vaccines↗

Primary meningeal rhabdomyosarcoma in a child with hypomelanosis of Ito.

Intracranial rhabdomyosarcomas are rare neoplasms, and those thought to be primary meningeal tumors are even more rare. Hypomelanosis of Ito is a neurocutaneous disorder believed to involve a defect in cells of neural crest origin. We report the case of a 15-month-old boy with hypomelanosis of Ito who developed a primary meningeal rhabdomyosarcoma. The patient initially presented with hydrocephalus and 2 months later developed neurologic signs localizing to the spinal cord. Radiologic studies revealed widespread leptomeningeal enhancement with compression of the spinal cord at C5-C7. A brain biopsy revealed a tumor diffusely involving the meninges. Microscopically, the tumor was composed of rhabdomyoblasts, many of which showed prominent cross-striations on routine hematoxylin-eosin staining. To the best of our knowledge, this is the first reported case of meningeal rhabdomyosarcoma in a patient with hypomelanosis of Ito and the fourth reported case of a primary meningeal rhabdomyosarcoma reported in the world literature.

Actins↗

Identification of a cell type-specific silencer in the first exon of the His-1 gene.

The His-1 gene is developmentally expressed in the murine choroid plexus but is silenced in the adult brain. To test the hypothesis that the gene contains cis-acting elements that contribute to this repression, we have analyzed segments of the proximal promoter for negative regulatory sequences by transient transfection analysis. The activity of the proximal promoter was moderately influenced by positively and negatively acting sequences located from -335 to -168 and -617 to -335, respectively. A strong His-1-positive regulatory element (HPRE, +18 to +29) was essential for maximal promoter activity and could also enhance the activity of the heterologous SV40 promoter in an orientation-dependent manner. The HPRE contains homology to the neuronal restrictive silencer element (NRSE) but interacted with nuclear proteins that were distinct from the NRSE-binding factor (NRSF). By contrast, a potent negative regulatory sequence (HNRE) was identified in the first exon that repressed either the His-1 or SV40 promoters by greater than 80%. This negative regulatory sequence interacted with nuclear proteins from cells that contain a silent His-1 gene but showed no interaction with nuclear proteins from cells that actively transcribe the endogenous gene. HNRE-mediated repression was orientation independent; most of this activity was mapped to a minimal 26-bp sequence. These findings suggest that the first exon of the His-1 gene contains a cell type-specific silencer that contributes to the regulation of His-1 transcription.

3T3 Cells↗

Synergistic interaction between anti-p185HER-2 ricin A chain immunotoxins and radionuclide conjugates for inhibiting growth of ovarian and breast cancer cells that overexpress HER-2.

Radionuclide conjugates or ricin A chain (RTA) immunotoxins that target pl85HER-2 have partially inhibited the growth of human ovarian cancer xenografts in athymic mice but generally have not cured mice bearing human tumor transplants. The present study was undertaken to explore whether a combination of ionizing radiation and an immunotoxin could exert additive or synergistic cytotoxicity in culture and in vivo against cancer cells that overexpress p185HER-2. In cell culture, treatment with 200-2000 cGy external beam irradiation followed by incubation with TA1-anti-pl85mHER2-RTA immunotoxin (TA1-RTA) produced synergistic inhibition of clonogenic growth of ovarian and breast cancer cells that expressed > 10(6) pl85HER-2 receptors/cell. The effect on cell survival correlated with an inhibition of DNA repair. A prior study (F. J. Xu et al, Nucl. Med. Biol., 24: 451-460, 1997) compared the biodistribution of radionuclide conjugates prepared with monoclonal antibodies that bind to different epitopes on the extracellular domain of pl85HER-2 and found optimal tumor uptake with the 520C9 antibody, which did not compete with TA1 for binding to the receptor. In this report, the TA1-RTA immunotoxin and the 131I-labeled 520C9 radionuclide conjugate could each inhibit the growth of clone-9002-18 xenografts in athymic mice but did not yield long-term survivors using maximally tolerated doses of each agent. When TA1-RTA and 131I-labeled 520C9 were used in combination, a greater inhibition of tumor growth was obtained than with either single agent. Similarly, survival with the combined treatment was significantly prolonged (P = 0.004) relative to treatment with immunotoxin or radionuclide conjugate alone. After treatment with an optimal combination of immunotoxin and radionuclide conjugate, 50% of mice survived >300 days, whereas controls succumbed with a median survival of 36 days. These results suggest that combinations of immunotoxins and radionuclide conjugates deserve further evaluation for the treatment of cancers that overexpress pl85HER-2.

Animals↗

[Expression of vascular endothelial growth factor receptor kinase inser domain containing receptor in human cervical carcinoma].

OBJECTIVE: To observe the expression of vascular endothelial growth factor receptor (KDR) in human cervical carcinomas, to clarify the relationship between the expression and invasion, metastasis, prognostic value in human cervical carcinoma. METHODS: KDR was stained immunohistochemically in 80 cases of human cervical carcinoma. RESULTS: The expression of KDR in the endothelial cells of tumor vasculature is: the high KDR expression rate of clinical cancer stages < or = I b and II a-III a was 21.4% and 60.6% (P < 0.01). The high KDR expression rate of the high, middle and low pathohistologic grading was 7.7%, 27.8% and 84.1% respectively (P < 0.01). The high KDR expression rate of adenocarcinoma and squamous-cell carcinoma was 0/5 and 57.3% (P < 0.05). The high KDR expression rate of the cases with lymphonodus metastasis and without lymphonodus metastasis was 77.8% and 46.8% respectively (P < 0.05). The survival rate of patients with high KDR expression tumors was significantly lower than that of patients with low KDR expression (P < 0.05). CONCLUSION: KDR is highly related to growth, invasion and metastasis of human cervical carcinoma, it may be one of the predictors for the biological behavior of human cervical carcinoma.

Adenocarcinoma↗