Biomedical subjects

S Xue

Publications and source records attributed to S Xue.

At least 19 recordsLinked to original sources

PubMed2000

Central nervous system nitric oxide induces oropharyngeal swallowing and esophageal peristalsis in the cat.

BACKGROUND & AIMS: The functional role of brainstem nitric oxide (NO) in swallowing and esophageal peristalsis remains unknown. We examined the effects of blockade of central nervous system (CNS) NO synthase (NOS) on swallowing and on primary and secondary peristalsis. METHODS: (1) The effect of intravenous (IV) NOS inhibitor N(G)-nitro-L-arginine (L-NNA) on swallowing and swallowing-induced peristalsis was examined. (2) An NOS inhibitor (N(G)-monomethyl-L-arginine [L-NMMA]) was administered into the fourth ventricle intracerebroventricularly (ICV), and its effects on swallowing and primary and secondary peristalsis were examined. RESULTS: (1) IV L-NNA significantly reduced the number of oropharyngeal swallows and the induction of primary peristalsis in the smooth muscle portion of the esophageal body; the change was not significant within the striated muscle portion. (2) L-NMMA given ICV significantly reduced the number of oropharyngeal swallows and the incidence of primary peristalsis in both smooth and striated muscle, but the reduction in amplitude was significant only for the smooth muscle contraction. There was a significant reduction in both the amplitude and incidence of secondary peristalsis, only in the smooth muscle portion. CONCLUSIONS: CNS NO is an important neurotransmitter in the induction of oropharyngeal swallowing and esophageal peristalsis. The neural substrates mediating striated and smooth muscle peristalsis may be both anatomically and neurochemically distinct.

Animals↗

PubMed1999

Shock melting of the canyon diablo impactor: constraints from nickel-59 contents and numerical modeling

Two main types of material survive from the Canyon Diablo impactor, which produced Meteor Crater in Arizona: iron meteorites, which did not melt during the impact; and spheroids, which did. Ultrasensitive measurements using accelerator mass spectrometry show that the meteorites contain about seven times as much nickel-59 as the spheroids. Lower average nickel-59 contents in the spheroids indicate that they typically came from 0.5 to 1 meter deeper in the impactor than did the meteorites. Numerical modeling for an impact velocity of 20 kilometers per second shows that a shell 1.5 to 2 meters thick, corresponding to 16 percent of the projectile volume, remained solid on the rear surface; that most of the projectile melted; and that little, if any, vaporized.

Journal Article↗

PubMed1999

Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy.

Replication-incompetent viral vectors are being developed for the gene therapy of cancer. Although some of these may eventually be proven to have significant localized antitumoral activity, none to date have been shown to infect and cause regression of established tumors following i.v. administration. Because cancer is a systemic disease in almost all fatal cases, the lack of i.v. efficacy is a major limitation to treatment with replication-incompetent viral vectors. ONYX-015 (d11520) is an attenuated adenovirus that replicates in and causes selective lysis of cancer cells. We carried out i.v. efficacy and distribution studies in nude mice with s.c. and intraparenchymal tumor xenografts. ONYX-015 infected and replicated efficiently within tumors following i.v. administration. Viral titers in livers were relatively high 3 h after administration but decreased rapidly, becoming undetectable after 24 h. Effective antitumor doses were not associated with hepatic toxicity. Viral replication within tumors was associated with regressions in several tumor models. Selectively replicating viruses like ONYX-015 hold promise as agents to treat metastatic cancer.

Adenoviridae↗

PubMed1999

Effect of an o-raffinose cross-linked haemoglobin product on oesophageal and lower oesophageal sphincter motor function.

The present experiments evaluate the effects on oesophageal motility of an o-raffinose cross-linked haemoglobin-based oxygen carrier (HBOC) purified from outdated donated human blood cells (HemolinkTM), with attention to dose-response (0.6-2.4 g kg-1), oxygenation status and low molecular weight components (4.4-36.4% 64 kDa or less). In ketamine-anaesthetized cats, lower oesophageal sphincter (LES) function and oesophageal peristalsis were monitored 0.5 h before, during and up to 3.5 h after HBOC infusion, and in some cats at 24 h. (1) All products significantly inhibited LES relaxation and increased peristaltic velocity in the distal smooth muscle oesophagus, without consistently altering resting LES pressure. (2) Effects on peristaltic velocity reached a maximum at the smallest dose, whereas the effects on LES relaxation had a maximum effect at 1.2 g kg-1. (3) Effects were not significantly altered by the haemoglobin oxygenation status or presence of low molecular weight components. (4) Repetitive oesophageal contractions occurred. In the cat, an o-raffinose cross-linked human haemoglobin product produces changes in oesophageal body and LES function, which are independent of the HBOC oxygenation status and composition of the low molecular weight components tested. Changes may persist for at least 24 h. These motility changes are likely due to scavenging of nitric oxide by the haemoglobin.

Animals↗

PubMed1999

Depletion of blood-borne macrophages does not reduce demyelination in mice infected with a neurotropic coronavirus.

Mice infected with the neurotropic coronavirus mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating disease with symptoms of hindlimb paralysis. Histological examination of the brains and spinal cords of these animals reveals the presence of large numbers of activated macrophages/microglia. In two other experimental models of demyelination, experimental allergic encephalomyelitis and Theiler's murine encephalomyelitis virus-induced demyelination, depletion of hematogenous macrophages abrogates the demyelinating process. In both of these diseases, early events in the demyelinating process are inhibited by macrophage depletion. From these studies, it was not possible to determine whether infiltrating macrophages were required for late steps in the process, such as myelin removal. In this study, we show that when macrophages are depleted with either unmodified or mannosylated liposomes encapsulating dichloromethylene diphosphate, the amount of demyelination detected in MHV-infected mice is not affected. At a time when these cells were completely depleted from the liver, approximately equivalent numbers of macrophages were present in the spinal cords of control and drug-treated animals. These results suggest that blood-borne macrophages are not required for MHV-induced demyelination and also suggest that other cells, such as perivascular macrophages or microglia, perform the function of these cells in the presence of drug.

Animals↗

PubMed1999

Cortical activation during human volitional swallowing: an event-related fMRI study.

Functional magnetic resonance imaging (fMRI) provides a safe, noninvasive method for studying task-related cortical neuronal activity. Because the cerebral cortex is strongly implicated in the control of human swallowing, we sought to identify its functional neuroanatomy using fMRI. In 10 healthy volunteers, a swallow event-related paradigm was performed by injecting 5 ml water bolus into the oral cavity every 30 s. Whole brain functional magnetic susceptibility -weighted spiral imaging data were simultaneously acquired over 600 s on a 1.5-T magnetic resonance scanner, utilizing the blood oxygenation level-dependent technique, and correlation maps were generated using both >99% percentile rank and spatial extent thresholding. We observed areas of increased signal change consistently in caudal sensorimotor cortex, anterior insula, premotor cortex, frontal operculum, anterior cingulate and prefrontal cortex, anterolateral and posterior parietal cortex, and precuneus and superiomedial temporal cortex. Less consistent activations were also seen in posterior cingulate cortex and putamen and caudate nuclei. Activations were bilateral, but almost every region, particularly the premotor, insular, and frontal opercular cortices, displayed lateralization to one or the other hemisphere. Swallow-related cortical activity is multidimensional, recruiting brain areas implicated in processing motor, sensory, and attention/affective aspects of the task.

Adult↗

PubMed1999

Water pollution and human health in China.

China's extraordinary economic growth, industrialization, and urbanization, coupled with inadequate investment in basic water supply and treatment infrastructure, have resulted in widespread water pollution. In China today approximately 700 million people--over half the population--consume drinking water contaminated with levels of animal and human excreta that exceed maximum permissible levels by as much as 86% in rural areas and 28% in urban areas. By the year 2000, the volume of wastewater produced could double from 1990 levels to almost 78 billion tons. These are alarming trends with potentially serious consequences for human health. This paper reviews and analyzes recent Chinese reports on public health and water resources to shed light on what recent trends imply for China's environmental risk transition. This paper has two major conclusions. First, the critical deficits in basic water supply and sewage treatment infrastructure have increased the risk of exposure to infectious and parasitic disease and to a growing volume of industrial chemicals, heavy metals, and algal toxins. Second, the lack of coordination between environmental and public health objectives, a complex and fragmented system to manage water resources, and the general treatment of water as a common property resource mean that the water quality and quantity problems observed as well as the health threats identified are likely to become more acute.

Agriculture↗

PubMed1999

Comparison of the effects of Apo(a) kringle IV-10 and plasminogen kringles on the interactions of lipoprotein(a) with regulatory molecules.

Lipoprotein(a) [Lp(a)] is associated with atherosclerosis and with disease processes involving thrombosis. Lp(a) contains apoprotein (a) [apo(a)], which has a sequence highly homologous to plasminogen. Hence, Lp(a) binds directly to extracellular matrix, cellular plasminogen receptors and fibrin(ogen) and competes for the binding of plasminogen to these regulatory surfaces. These interactions may contribute to the proatherothrombogenic consequences of high Lp(a) levels. These interactions are mediated by lysine binding sites (LBS). Therefore, we examined the role of apo(a) kringle IV-10 [the only apo(a) kringle demonstrated to exhibit lysine binding activity in the intact lipoprotein] in the interaction of Lp(a) with these regulatory molecules. We have compared directly apo(a) KIV-10 with plasminogen K4 to examine whether these highly structurally homologous kringle modules are also functionally homologous. Futhermore, because the plasminogen K5-protease domain (K5-PD) binds directly to fibrin, we have also examined the ability of this plasminogen fragment to inhibit the interaction of Lp(a) with these regulatory molecules and with extracellular matrix. Apo(a) KIV-10 competed effectively for the binding of 125I-Lp(a) to these surfaces but was less effective than either intact Lp(a), plasminogen K4 or plasminogen. Plasminogen KS-PD was a better competitor than apo(a) KIV-10 for 125I-Lp(a) binding to the representative extracellular matrix, Matrigel, and to plasmin-treated fibrinogen. In contrast, plasminogen K5-PD did not compete for the interaction of Lp(a) with cells, although it effectively competed for plasminogen binding. These results suggest that Lp(a) recognizes sites in all of the regulatory molecules that are also recognized by apo(a) KIV-10 and that Lp(a) recognizes sites in extracellular matrix and in plasmin-modified fibrinogen that also are recognized by plasminogen K5-PD. Thus, the interaction of Lp(a) with cells is clearly distinct from that with extracellular matrix and with plasmin-treated fibrinogen and the recognition sites within Lp(a) and plasminogen for these regulatory molecules are not identical.

Apolipoproteins A↗

PubMed1999

Linkage analysis and loss of heterozygosity for chromosome arm 1p in familial breast cancer.

We conducted linkage analysis of 64 multiple-case families with early-onset bilateral breast cancer using DNA markers on chromosome band 1p36. Evidence against tight linkage was obtained using a dominant model for transmission (summary LOD scores at recombination fraction theta = 0.000001 were -4.71 for D1S160 and -2.70 for D1S170). Similar results were obtained after excluding 20 families that were potentially attributable to BRCA1 or BRCA2. We also investigated loss of heterozygosity for a panel of markers on chromosome arm 1p using breast tumors from affected family members. The most common regions of allele loss were 1p36 (32% for D1S160, 35% for D1S243) and 1p32 (51% for MYCL). The frequency and location of 1p allele loss did not differ substantially from previous studies of sporadic breast cancer. We conclude that 1p36 probably does not contain a locus of susceptibility for a large proportion of breast cancer families, but a variety of loci on 1p may contribute to progression of familial and sporadic disease. Genes Chromosomes Cancer 25:354-361, 1999.

Breast Neoplasms↗

PubMed1998

Intracellular calcium distribution in apoptosis of HL-60 cells induced by harringtonine: intranuclear accumulation and regionalization.

Harringtonine (HT), an anticancer drug with high chemotherapeutic efficiency to human chronic granulocytic/myelomonocytic leukemia, has been reported to rapidly induce apoptosis in HL-60 cells in a wide scope/range of dosage by investigators from our lab and others. In the present studies, by using video enhancement contrast (VEC) microscopy, we dynamically analyzed changes in intracellular calcium distribution in a single HL-60 cell over the period from the initiation of apoptosis to the obvious appearance of chromatin condensation. The results from this paper demonstrated the striking distinction of intracellular calcium distribution at different time points after treatment with HT. Before treatment in normal HL-60 cells the highest [Ca2+]i accumulation was observed in the peri-nuclear area and the lowest was observed in the nucleus; after treatment with 1 microg/ml HT for 30 min intracellular calcium diffused all over the cell compartments, while intranuclear calcium increased comparatively and significantly. The phenomenon of intranuclear calcium accumulation was further confirmed by using laser scanning confocal microscopy (LSCM). In addition, co-localization of the highest calcium region with condensed chromatin in apoptotic HL-60 cells was also observed by LSCM. Our results suggest that two sequential alterations of intracellular calcium distribution occurred in apoptotic HL-60 cells induced by HT, i.e. (a) accumulation of calcium in the nucleus and (b) regionalization in a specific nuclear region.

Antineoplastic Agents↗

PubMed1998

Infection with cytotoxic T-lymphocyte escape mutants results in increased mortality and growth retardation in mice infected with a neurotropic coronavirus.

C57BL/6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis several weeks after inoculation. Previously, we showed that mutations in the immunodominant CD8 T-cell epitope (S-510-518) could be detected in nearly all samples of RNA and virus isolated from these mice. These mutations abrogated recognition by T cells harvested from the central nervous systems of infected mice in direct ex vivo cytotoxicity assays. These results suggested that cytotoxic T-lymphocyte (CTL) escape mutants contributed to virus amplification and the development of clinical disease in mice infected with wild-type virus. In the present study, the importance of these mutations was further evaluated by infecting naive mice with MHV-JHM variants isolated from infected mice and in which epitope S-510-518 was mutated. Compared to mice infected with wild-type virus, variant virus-infected animals showed higher mortality and morbidity manifested by decreased weight gain and neurological signs. Although a delay in the kinetics of virus clearance has been demonstrated in previous studies of CTL escape mutants, this is the first illustration of significant changes in clinical disease resulting from infection with viruses able to evade the CD8 T-cell immune response.

Animals↗

PubMed1997

Antigen specificity of CD4 T cell response in the central nervous system of mice infected with mouse hepatitis virus.

Previously, we showed that the transmembrane (M) and surface (S) glycoproteins were recognized by splenic CD4 T lymphocytes harvested from mice infected intraperitoneally with mouse hepatitis virus, strain JHM (MHV-JHM), whereas only the S protein was recognized by splenocytes derived from mice with MHV-induced chronic demyelination. From these results, it could not be determined which proteins were recognized by T cells localized in the infected central nervous system (CNS). Herein, we show that CD4 T cells responding to both the M and S proteins can be detected in the CNS of mice with either acute encephalitis or the chronic demyelinating disease. As part of these analyses, two CD4 T cell epitope regions encompassing residues 328-347 and 358-377 within the S protein were identified. Both epitopes, as well as a previously identified M-specific epitope, were recognized by the CNS-derived lymphocytes. Finally, viral RNA harvested from mice with chronic demyelination was analyzed for mutations in the S specific CD4 T cell epitopes since changes resulting in escape from CD8 T cell surveillance were previously identified in these samples. A mutation in epitope region S(328-347) (ala to thr at position 337) was detected in a minority of samples but this change did not abrogate recognition of the epitope and therefore was unlikely to contribute to virus persistence. In conclusion, these studies identify epitopes recognized by MHV-specific CD4 T cells in the infected CNS and show that these cells are preferentially located at the site of infection in mice with clinical disease.

Animals↗

PubMed1997

Changes in activity of cytosolic phospholipase A2 in human amnion at parturition.

OBJECTIVE: The purpose of this study was to determine whether increased cytosolic phospholipase A2 activity mediated arachidonic acid mobilization for prostaglandin synthesis in amnion at parturition. STUDY DESIGN: Amnion was collected immediately after delivery from four groups of patients: preterm (<37 weeks) with no labor or labor and term (>37 weeks) with no labor or labor and stored at -70 degrees C. Tissues were homogenized and centrifuged for 1 hour at 100,000 g, and cytosol was assayed for cytosolic phospholipase A2 activity with use of carbon 14-labeled 1-stearoyl-2 arachidonyl phosphatidylcholine plus 10 micromol/L unlabeled substrate and 5 mmol/L calcium in 10 mmol/L N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid, pH 7.4. Incubations were performed in duplicate +/- 10 micromol/L arachidonyl trifluoromethyl ketone, a specific inhibitor of cytosolic phospholipase A2 activity, at 30 degrees C for 45 minutes. RESULTS: Total cytosolic phospholipase A2 activity (in picomoles of arachidonic acid per minute per milligram of protein) calculated as the difference between the activity in the presence and absence of arachidonyl trifluoromethyl ketone was (mean +/- SE) as follows: preterm no labor (n = 7) 8.94 +/- 3.08, preterm with labor (n = 6) 6.79 +/- 2.31, term no labor (n = 7) 14.85 +/- 1.66, and term with labor (n = 5) 5.51 +/- 1.52. Enzyme activity increased with gestational age and was highest in the term no labor group. A significant decrease in cytosolic phospholipase A2 activity occurred with labor (p < 0.05). The greatest decrease in activity was in the term group (p < 0.05). CONCLUSION: Total cellular cytosolic phospholipase A2 activity in amnion is highest in anticipation of labor but during labor total activity is depleted, resulting in the low activity measured after delivery of the placenta. The substrate specificity and changes in amnion total cytosolic phospholipase A2 activity with labor strongly suggests a role in mediation of arachidonic acid mobilization and prostaglandin synthesis at labor.

Amnion↗

PubMed1997

Microstimulation of auditory nerve for estimating cochlear place of single fibers in a deaf ear.

Multielectrode cochlear prostheses seek to approximate the cochlea's normal frequency-place mapping through spatial segregation of stimulus currents. Various electrode configurations have been employed to achieve such segregation. Direct measurements of stimulation regions among single auditory nerve (AN) fibers has been possible only when normal hearing is preserved, such that each fiber's cochlear place can be inferred from its tuning curve. This precludes measurements in deafened ears, or ears compromised by implantation of the electrodes. Data presented here demonstrate that the cochlear place of an AN fiber can be estimated without acoustic sensitivity, using electrical microstimulation through a recording pipette in the AN bundle. The procedure exploits cochleotopic projection to isofrequency laminae within the contralateral inferior colliculus (IC). Microstimulation excites a small group of fibers neighboring the recorded fiber, generating centrally propagated volleys along a narrow frequency-specific pathway. Evoked potential recordings at varying depths are made to identify the ICC lamina where the response to AN microstimulation is greatest. Preliminary data are also presented for an alternative method of identifying the lamina using a frequency domain measure of binaural interactions within the IC.

Animals↗

PubMed1997

Superior laryngeal nerve stimulation in the cat: effect on oropharyngeal swallowing, oesophageal motility and lower oesophageal sphincter activity.

Superior laryngeal nerve (SLN) stimulation can activate the brainstem swallowing mechanism to produce a complete swallowing sequence consisting of oropharyngeal, oesophageal and lower oesophageal sphincter (LOS) components. However, little is known of the effect of SLN stimulation (peripheral-sensory input from the pharynx) on the characteristics of oesophageal motor activity, especially in the smooth muscle portion. The present study examined the effect of varying stimulus train length and frequency on each of the three components of the reflex. Acute studies were performed in urethane anaesthetized cats. Oesophageal motility was monitored using conventional manometric techniques, and oropharyngeal swallowing by the mylohyoid electromyogram. SLN stimulus train length (1-10 sec) and frequency (5-30 Hz) were varied independently. Increased train length or frequency resulted in (1) an increase in oropharyngeal swallowing and incidence of the complete swallowing response, (2) an increase in latency to onset of the oesophageal peristaltic wave, (3) reduction of the amplitude of the evoked peristaltic contraction in the smooth muscle portion, without altering its velocity, (4) increased LOS relaxation, and increased LOS after-contraction. The LOS contraction was abolished by atropine (100 micrograms kg-1). Therefore, increased SLN stimulation not only results in excitation of the central swallowing program and the oropharyngeal stage of swallowing, but has major effects on the oesophageal and LOS stages of swallowing. Afferent SLN stimuli can impact on the control mechanisms for each stage, to inhibit or excite the stages in different ways.

Animals↗

PubMed1997

Cytotoxic T-cell-resistant variants arise at early times after infection in C57BL/6 but not in SCID mice infected with a neurotropic coronavirus.

Under certain conditions, C57BL/6 mice persistently infected with mouse hepatitis virus strain JHM (MHV-JHM) develop clinical disease and histological evidence of demyelination several weeks after inoculation with virus. In a previous report, we showed that mutations in the RNA encoding an immunodominant CD8 T-cell epitope within the surface glycoprotein (epitope S-510-518) were present in all persistently infected animals and that these mutations abrogated recognition by virus-specific cytotoxic T cells (CTLs) in direct ex vivo cytotoxicity assays. To obtain further evidence that these mutations were necessary for the development of clinical disease, the temporal course of their appearance was determined. Mutations in the epitope were identified by 10 to 12 days after inoculation, and in some mice, virus containing mutated epitope was the dominant species detected by 15 days. In addition, most mice that remain asymptomatic at 80 days after inoculation, a time after which clinical disease almost never develops, were infected with only wild-type virus. Finally, analysis of virus isolated from mice with severe combined immunodeficiency (SCID) revealed the presence only of wild-type epitope S-510-518. These results, by showing that mutations are not selected in SCID mice and occur at early times after inoculation in C57BL/6 mice, support the view that they result from immune pressure and contribute to virus persistence and demyelination in mice infected persistently with MHV-JHM.

Amino Acid Sequence↗

PubMed1996

Induction of both cytosolic phospholipase A2 and prostaglandin H synthase-2 by interleukin-1 beta in WISH cells in inhibited by dexamethasone.

In previous studies we have shown that IL-1 beta induced both PGE2 release and total cellular cPLA2 activity and cPLA2 protein synthesis in human amnion-derived WISH cells. In this study, the effect of IL-1 beta on cPLA2 and PGHS-2 mRNA expression was investigated. Using RT-PCR, we found that IL-1 beta (0.1 ng/ml) coordinately induced both cPLA2 and PGHS-2 mRNA expression within 2 hours. The synthetic glucocorticoid dexamethasone (10(-10)-10(-6)M) inhibited IL-1 beta-induced cPLA2 and PGHS-2 mRNA expression activity and protein synthesis and PGE2 release in a concentration dependent manner. In the absence of IL-1 beta, dexamethasone alone (10(-6)M) inhibited basal cPLA2 activity, mRNA expression and protein synthesis. In addition, cycloheximide (5 micrograms/ml) apparently superinduced, but actinomycin D (2 micrograms/ml) inhibited IL-1 beta-induced cPLA2 and PGHS-2 mRNA expression suggesting that both are immediate early genes and a transcriptional mechanism is involved in the induction of both cPLA2 and PGHS-2 mRNA by IL-1 beta.

Amnion↗

PubMed1996

Effects of nitric oxide synthase blockade on esophageal peristalsis and the lower esophageal sphincter in the cat.

The present study explores the role of nitric oxide (NO) in control of esophageal peristalsis and lower esophageal sphincter (LES) function in the cat. Studies were performed on 20 ketamine-anesthetized cats with manometric recording at the LES, 0, 2, 4, and 6 cm above the LES (smooth muscle section), and 12 and (or) 14 cm above the LES (striated muscle section). L-Ng-Nitro-arginine (L-NNA, 10(-6)-10(-4) mol/kg) was given intravenously, and the effects on swallow-induced esophageal peristalsis were assessed. (i) L-NNA increased the velocity of swallow-induced peristalsis in the smooth muscle esophagus; the effect was dose dependent, more prominent distally, and completely reversed by L-arginine (10(-3) mol/kg). (ii) L-NNA decreased the amplitude of peristaltic contraction in the very distal esophagus; the decrease also was dose dependent but not returned to normal by L-arginine. (iii) L-NNA inhibited LES relaxation (reversed by L-arginine) and decreased the LES "after-contraction" amplitude (unaffected by L-arginine). (iv) L-NNA was associated with the appearance of repetitive contractions. Basal LES tone was unaffected by L-NNA. In conclusion, NO is an important mediator for the timing of peristalsis in the distal smooth muscle esophagus and for LES relaxation in the cat, a species whose contraction amplitude is largely determined by cholinergic excitation. The role of NO in controlling esophageal body and LES contraction amplitude, and in preventing repetitive contractions, requires further study.

Animals↗