Search PubMed⌕ Search

Biomedical subjects

M Xu

Publications and source records attributed to M Xu.

At least 397 records · Page 22Linked to original sources
PubMed1990

Parasite antigenemia in untreated and treated lymphatic filarial infections.

To evaluate the merit of antigen detection assays as a tool to monitor the efficacy of chemotherapy for lymphatic filariasis, we serially measured antigen levels in sera from jirds infected with Brugia malayi and from humans with bancroftian filariasis. Antigenemia was detected in all animals with parasitologically proven infection and was present in jirds with prepatent or occult filariasis. Antigen levels correlated with worm burdens, and progressively declined in drug-cured animals. Treatment with diethylcarbamazine (DEC) triggered a transient increase in serum levels of filarial antigens bearing the epitope recognized by the monoclonal antibody HC 11. All patients with bancroftian filariasis became amicrofilaremic within one week after DEC treatment. Antigenemia levels slowly declined over a period of several months in all but one treated individual. Forty-two months after treatment, progressively rising antigen levels are present in 10 patients. Six of these remain amicrofilaremic; in the other 4, elevated antigenemia levels preceded or were detected at the same time as recurrent parasitemia. Periodic monitoring of antigenemia levels after treatment of patients with lymphatic filariasis can be used to identify individuals who are likely to develop recurrent microfilaremia before the parasites become detectable in blood samples, thereby allowing timely retreatment.

Animals↗
PubMed1989

Expression of TAG-72 in normal colon, transitional mucosa, and colon cancer.

Monoclonal antibody (MAb) B72.3 detects an epitope carried by high-molecular-weight mucins (tumor-associated glycoprotein, TAG-72) recently identified as sialyl-Tn. B72.3 MAb has a restricted pattern of reactivity with normal tissues but it reacts with a high proportion of epithelial cancers. To determine the possible relationship between neoplastic transformation and reactivity with B72.3 MAb, we have analyzed samples of normal colon, colon cancer and transitional mucosa (mucosa adjacent to colorectal cancer) or reactive mucosa (mucosa adjacent to squamous carcinoma of the anal canal, or mucosa overlying lymphoma). B72.3 MAb reacted strongly with 21/21 specimens of transitional mucosa and with 17/21 specimens of adjacent colon cancer. Reactivity of B72.3 MAb with transitional mucosa was strong and homogeneous, whereas reactivity with cancer tissue was weaker and more heterogeneous. Reactive mucosa adjacent to squamous carcinoma or lymphoma was also reactive with B72.3 MAb. Our findings show that, in the colon, expression of TAG-72 antigen occurs during the process of epithelial cell transformation but is also regulated by factors unrelated to the process of carcinogenesis.

Antibodies, Monoclonal↗
PubMed1989

Immunoglobulin kappa gene expression after stable integration. I. Role of the intronic MAR and enhancer in plasmacytoma cells.

Rearranged MOPC41 immunoglobulin kappa gene constructs have been stably introduced into cultured S194 mouse plasmacytoma cells to investigate the effects of deleting the intronic enhancer and/or matrix association region (MAR) on gene expression. Intact single-copy kappa genes containing 1.5 kilobase pairs of upstream and 8.5 kilobase pairs of downstream flanking sequences exhibited sensitivity to chromosome position effects and were expressed at a mean level of 27% relative to the endogenous kappa gene expression or only 6% with respect to the MOPC41 kappa mRNA levels in the tumor. Deletion of the intronic MAR led to a 4-fold decrease in expression, while deletion of both the MAR and enhancer led to an 11-fold decline. These effects were dampened by preselecting for integration into a transcriptionally poised chromatin location as demonstrated by linkage to a selectable marker which lacked both a MAR and an enhancer. Significantly, we found that sequences downstream of the poly(A) addition site compensated 150-fold for deletion of the intronic enhancer.

Animals↗
PubMed1989

Immunoglobulin kappa gene expression after stable integration. II. Role of the intronic MAR and enhancer in transgenic mice.

MOPC41 immunoglobulin kappa gene constructs have been stably introduced into the mouse germ line to investigate the effects of deleting the conserved intronic sequences on gene expression. Intact kappa genes containing 1.5 kilobase pairs of upstream and 8.5 kilobase pairs of downstream flanking sequences were highly expressed tissue-specifically, raising the total level of kappa mRNA in spleens severalfold in most transgenic animals. This high expression was often accompanied by marked suppression of endogenous kappa gene activity. Transgenes containing a deletion of the matrix association region (MAR) or both the MAR and enhancer were expressed tissue-specifically at mean levels only 2- and 3-fold lower, respectively, than that of intact transgenes. Therefore, while the intronic enhancer and MAR appear to play a quantitative role in gene expression, these sequences are not absolutely essential for transcriptional activation of rearranged kappa genes in a normal developmental environment.

Animals↗
PubMed1989

Differential effects of M1- and M2-muscarinic drugs on striatal dopamine release and metabolism in freely moving rats.

A dialysis loop cannula was implanted into rat striatum under anesthetized condition, and the area was perfused with Ringer's solution under freely moving condition after 3 days for surgical recovery. Dopamine (DA) and 3,4-dihydroxyphenylacetic acid recovered in the dialysate were measured by high-performance liquid chromatography with electrochemical detection. The effects of M1- and M2-muscarinic receptor agents, which were perfused continuously into the striatum through the dialysis membrane, were investigated. Continuous perfusion of AF102B, an M1-selective agonist, and oxotremorine, a non-selective agonist, resulted in a dose-dependent increase in the striatal DA release. Pirenzepine (10(-5) and 10(-7) M), an M1-selective antagonist, decreased the release of DA, and the stimulatory effect of AF102B (10(-5) M) was completely inhibited by 10(-5) and 10(-7) M pirenzepine, while the stimulatory effect of oxotremorine (10(-4) M) was only partly inhibited by 10(-5) M pirenzepine. AF-DX116 (10(-5) M), an M2-selective antagonist, increased the DA release, and showed an additive effect on the DA release evoked by AF102B (10(-5) M), whereas it produced no significant effect on oxotremorine (10(-5) M)-evoked DA release. These results suggest that in vivo DA release in the rat striatum is modulated by different subtypes of muscarinic receptors; i.e., the stimulatory effect is mainly mediated by M1-sites and inhibitory effect is mainly mediated by M2-sites. The changes in the DA release induced by the various drugs were prevented by pretreatment with tetrodotoxin (TTX). Since action potential-dependent DA release (exocytosis) is blocked by the pretreatment with TTX, those drugs affect DA release by means of action potential-dependent processes.

Animals↗
PubMed1986

Transcription termination and chromatin structure of the active immunoglobulin kappa gene locus.

To investigate the chromatin surrounding an active gene, we have determined the distribution of RNA polymerase molecules, the intactness of nucleosomal structure, and the subnuclear compartmentalization along 15 kilobase pairs (kb) of the mouse kappa immunoglobulin locus of MPC-11 plasmacytoma cells. Hybridization of in vitro nuclear transcripts to probes specific for the template strand reveals that transcription terminates within the region between 1.1 and 2.3 kb downstream from the poly(A) addition site. Ten different short sequences (8-13 base pairs) reside within 460 base pairs of this termination region that exhibit homology with sequences found in the termination regions of mouse beta-globin and chicken ovalbumin genes. Transcription of the nontemplate strand occurs on either side of this termination region. We find that both within the transcription unit and 6.5 kb downstream of the termination region of the kappa gene, the canonical nucleosomal structure is perturbed, the chromatin exhibits pronounced insolubility, and the nucleosomes liberated by micrococcal nuclease appear to lack histone H1. The insolubility is characterized by interactions that are disrupted by 0.3 to 0.6 M NaCl treatment. We conclude that the active chromatin phenotype spreads a considerable distance along the kappa locus, well beyond the region of transcription termination.

Animals↗
PubMed1986

The active immunoglobulin kappa chain gene is packaged by non-ubiquitin-conjugated nucleosomes.

To elucidate the molecular features of active chromatin, we have mapped, by two-dimensional electrophoresis, the protein composition of nucleosomes that package the immunoglobulin kappa chain gene of mouse plasmacytoma cells. Nucleoprotein particles that possess the active kappa chain gene comigrate with bulk mononucleosomes that contain high mobility group proteins HMG-14 or -17 but lack histone H1. High electrophoretic resolution of the underlying core particles, after removal of ubiquitin by isopeptidase treatment, reveals that these nucleosomes are nonubiquitinated, even though they coincidently migrate with bulk ubiquitinated particles. This distinctive electrophoretic behavior may be correlated with the presence of histone H2A.X. Nucleosomes exhibiting these unusual properties appear to span at least 10 kilobases, in both transcribed and nontranscribed regions, suggesting that mechanisms independent of transcription exist to initiate, maintain, and propagate a common chromatin phenotype over long distances along the kappa chain locus.

Animals↗
PubMedDate not supplied

Evaluation of efficacy and plasma concentrations of ropivacaine in continuous axillary brachial plexus block: high dose for surgical anesthesia and low dose for postoperative analgesia.

BACKGROUND AND OBJECTIVES: Ropivacaine is a potent local anesthetic that, experimentally at low concentrations, produces an effective block of pain conducting nerve fibers. Therefore, it was hypothesized that 0.1% and 0.2% ropivacaine would provide clinically adequate postoperative analgesia in continuous axillary plexus block. METHODS: Sixty patients (ASA I-II) scheduled for elective hand or forearm surgery received 5 mg/kg of 0.75% ropivacaine for axillary block using nerve stimulator technique. One hour later, in random order, a continuous infusion of either 0.1% ropivacaine (0.125 mg/kg/h), 0.2% ropivacaine (0.25 mg/kg/h) or saline 6 to 11 mL/h was started. RESULTS: The mean total ropivacaine dose for the surgical block was 5.1 to 5.2 mg/kg with the supplementation. All patients were pain free for the first 12 to 15 hours after the block. The need for postoperative analgesics during the infusion was similar in all groups. After the initial block, the maximum plasma concentrations (mean 2.5 microg/mL) were measured at 45 or 60 minutes after injection. The highest individual plasma concentration was 4.2 microg/mL. Despite the high venous peak concentration, no toxic reactions were observed. The mean peak plasma concentration (Cmax) was 2.2+/-0.5 microg/mL for saline, 2.6+/-0.8 microg/mL for 0.1% ropivacaine, and 2.6+/-0.7 microg/mL for 0.2% ropivacaine. During the continuous infusion of 24 hours, the ropivacaine concentration declined steadily. CONCLUSIONS: Ropivacaine is safe and effective for axillary brachial plexus block. The continuous infusion of 0.1% or 0.2% ropivacaine was no more beneficial than an infusion of saline in relieving postoperative pain in patients having elective hand surgery. None of the infusions were sufficient to adequately treat the patients' pain without the addition of adjunct agents.

Adult↗
PubMedDate not supplied

MHC class II allosteric site drugs: new immunotherapeutics for malignant, infectious and autoimmune diseases.

The discovery of the interactions of the 'Ii-Key' segment of the Ii protein with the major histocmpatibility complex (MHC) Class II allosteric site, which is adjacent to the antigenic peptide-binding site, creates therapeutic opportunities by regulating the antigenic peptide binding to MHC class II molecules. The binding of Ii-Key to the MHC class II allosteric site loosens the hold of the MHC Class II 'clamshell' on antigenic peptides and leads to highly efficient antigenic peptide charging to or releasing from the MHC class II antigenic peptide-binding groove. Ii-Key peptide-induced spilling of bound antigenic peptide, or replacement with inert blockers, leads to 'inert immunosuppression'. Highly efficient replacement of ambient with vaccine peptides by Ii-Key permits 'active immunosuppression' for antigen-specific control of autoimmune diseases in the absence of cytokines or adjuvants. On the other hand, active immunization against cancer or infectious disease can result from epitope replacement mediated by Ii-Key and accompanied by cytokines or other adjuvants. Finally, linking the Ii-Key peptide through a simple polymethylene bridge to an antigenic sequence vastly increases the potency of MHC Class II peptide vaccines. In summary, the discovery of the MHC class II allosteric site allows one to increase the efficiency of MHC class II-related, antigenic epitope-specific therapy for malignant, infectious, and autoimmune diseases. The focus of this review is on the mechanism and potential clinical use of such novel allosteric site-directed, Ii-key drugs.

Allosteric Site↗
PubMedDate not supplied

Radiosensitization of heat resistant human tumour cells by 1 hour at 41.1 degrees C and its effect on DNA repair.

The present study was undertaken to determine if short duration (1-2 h), moderate hyperthermia (41.1 degrees C) could radiosensitize human tumour cells. It was found that moderate hyperthermia (41.1 degrees C), for as little as 1 h, can radiosensitize heat resistant human adenocarcinoma cells, NSY42129 (NSY), provided the cells are irradiated 15 min prior to the end of the heat exposure. Analysis of the survival data showed a 2.5-3-fold increase in the alpha parameter with no significant change in the beta parameter of the survival curve, implying that the cells had become more susceptible to killing by single radiation energy deposition events as opposed to lethal events that require an interaction between two separate energy deposition events. 41.1 degrees C hyperthermia did not affect the induction or repair of alkaline labile DNA damage in a way that correlated with radiosensitivity. In contrast, heat-induced changes in the induction of micronuclei by radiation correlated with changes in cell killing. Therefore, the effect of 41.1 degrees C hyperthermia on the intracellular localization of the DNA double strand break repair protein, Mre11, was measured using in situ immunofluorescence and immunoblotting of soluble and insoluble cellular fractions. The results showed that Mre11 delocalizes from the nucleus as a function of time at 41.1 degrees C. It was then determined if 41.1 degrees C hyperthermia altered the association of Mre11 with its functional partner, Rad50. A significant decrease in the amount of Rad50 recovered with Mre11 occurred under the experimental conditions that produced significant radiosensitization. These results are consistent with the possibility that the heat-induced perturbation in Mre11 localization and its radiation-induced association with Rad50 contributes to an increase in radiosensitivity.

Cell Nucleus↗
PubMedDate not supplied

Thermal radiosensitization of human tumour cell lines with different sensitivities to 41.1 degrees C.

While much work on radiosensitization by hyperthermia in the 43 degrees C and higher temperature range has been done, relatively little work has been done at temperatures in the 41-42 degrees C range. In this moderate hyperthermia range there are dramatic differences in the resistance of mammalian cells to hyperthermia. Therefore, thermal radiosensitization was measured in two human colon adenocarcinoma cell lines, one that expresses chronic thermotolerance and proliferates at 41.1 degrees C, NSY 42129 (NSY) cells and one that is slowly killed at 41.1 degrees C, HCT15 cells. Heat-resistant NSY cells were found to be more radioresistant than heat-sensitive HCT15 cells. Hyperthermia at 41.1 degrees C enhanced the radiation sensitivity in NSY cells, but no significant induction of heat-induced radiosensitization was observed in HCT15 cells. The radiation sensitivity induced by 41.1 degrees C in NSY cells appeared to be related to both intrinsic heat-induced radiosensitization (HIR) and cell-cycle redistribution at 41.1 degrees C. Incidentally, cells incubated at 41.1 degrees C for between 8-16 h displayed an identical radiosensitivity to those heated for 24 h. This result implies that modest hyperthermia for 2 h or more can have a radiosensitizing effect in heat-resistant cells.

Adenocarcinoma↗
PubMedDate not supplied

Optical imaging of turbid media using independent component analysis: theory and simulation.

A new imaging approach for 3-D localization and characterization of objects in a turbid medium using independent component analysis (ICA) from information theory is developed and demonstrated using simulated data. This approach uses a multisource and multidetector signal acquisition scheme. ICA of the perturbations in the spatial intensity distribution measured on the medium boundary sorts out the embedded objects. The locations and optical characteristics of the embedded objects are obtained from a Green's function analysis based on any appropriate model for light propagation in the background medium. This approach is shown to locate and characterize absorptive and scattering inhomogeneities within highly scattering medium to a high degree of accuracy. In particular, we show this approach can discriminate between absorptive and scattering inhomogeneities, and can locate and characterize complex inhomogeneities, which are both absorptive and scattering. The influence of noise and uncertainty in background absorption or scattering on the performance of this approach is investigated.

Biopolymers↗