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Biomedical subjects

D Wu

Publications and source records attributed to D Wu.

At least 325 records · Page 18Linked to original sources
PubMed1997

A case of presumptive monosomy 21 re-diagnosed as unbalanced t(5p;21q) by FISH and review of literature.

By using fluorescence in situ hybridization (FISH), we demonstrate a case of monosomy 21 to result from an unbalanced translocation involving the short arm of chromosome 5 and the long arm of chromosome 21. Our case is compared to 3 similar cases of t(5p;21q) reported recently, which were also originally diagnosed as monosomy 21. The breakpoint on chromosome 5 in these cases occurred in the p13-p15 region, whereas the breakpoint on chromosome 21 was in the q21-q22 region. Comparison of the clinical findings in these patients demonstrated great similarities. Furthermore, a strong correlation between the clinical manifestations of these patients with cridu-chat syndrome patients was also noted. We suggest that cases with unbalanced t(5p;21q) represent a distinct syndrome which can be grouped under a new category of "5p/21q deletion syndrome."

Chromosomes, Human, Pair 21↗
PubMed1997

Functional and pharmacokinetic properties of antibody-avidin fusion proteins.

In an attempt to produce broadly useful targeting agents, genetic engineering and expression techniques have been used to produce Ab-avidin fusion proteins. Chicken avidin has been fused to mouse-human chimeric IgG3 at the end of C(H)1 (C(H)1-Av), immediately after the hinge (H-Av), and at the end of C(H)3 (C(H)3-Av). Fusion heavy chains of the expected molecular mass were expressed, assembled with a co-expressed light chain, and secreted. The resulting molecules continued to bind Ag. They also bound biotinylated human serum albumin; C(H)3-Av had reduced affinity (K(A) = 5.13 x 10(9) M(-1)) compared with the tetrameric avidin (K(A) = 1 x 10(15) M(-1)), but greater affinity than monomeric avidin (K(A) = 1 x 10(7) M(-1)). Importantly, the avidin-IgG fusion proteins had a longer serum t1/2 in rats than avidin. The favorable pharmacokinetic parameters suggest that these avidin fusion proteins can be used effectively to deliver biotinylated ligands such as drugs and peptides to locales expressing any Ag recognized by the associated Ab.

Animals↗
PubMed1997

Functional magnetic resonance imaging in schizophrenia: initial methodology and evaluation of the motor cortex.

The purpose of the present study was to evaluate the differential activation of the motor cortex during finger tapping in patients with schizophrenia using the newly available imaging method of functional magnetic resonance imaging (fMRI). Nine patients with DSMIII-R schizophrenia and 9 well-matched healthy volunteer subjects underwent fMRI examination on a conventional MR unit; activation of the primary motor cortex was evaluated during performance of a finger motion task. Localized activation of the motor cortex was observed in 17 of 18 subjects during fMRI. Patients and controls were, however, indistinguishable with respect to signal intensity or area thereof within the motor cortex. fMRI did not reveal motor cortical dysfunction in schizophrenia. Despite its infancy, fMRI holds considerable promise to advance understanding of the neurodynamics of psychiatric disorders, particularly schizophrenia.

Adult↗
PubMed1997

Interaction and regulation of subcellular localization of CED-4 by CED-9.

The Caenorhabditis elegans survival gene ced-9 regulates ced-4 activity and inhibits cell death, but the mechanism by which this occurs is unknown. Through a genetic screen for CED-4-binding proteins, CED-9 was identified as an interacting partner of CED-4. CED-9, but not loss-of-function mutants, associated specifically with CED-4 in yeast or mammalian cells. The CED-9 protein localized primarily to intracellular membranes and the perinuclear region, whereas CED-4 was distributed in the cytosol. Expression of CED-9, but not a mutant lacking the carboxy-terminal hydrophobic domain, targeted CED-4 from the cytosol to intracellular membranes in mammalian cells. Thus, the actions of CED-4 and CED-9 are directly linked, which could provide the basis for the regulation of programmed cell death in C. elegans.

Animals↗
PubMed1997

Coronary sinus stenosis as a late complication of catheter ablation in Wolff-Parkinson-White syndrome.

This report describes a patient who developed stenosis of coronary sinus and cardiac veins five years after application of electric shock currents to the posterior mitral annulus and posteroseptal region of the tricuspid annulus for ablation of a left posterior accessory pathway and a right posteroseptal accessory pathway. This is the first angiographic documentation of coronary sinus stenosis as a late complication of electric ablation of accessory pathway.

Adult↗
PubMed1997

Investigation on arteriosclerosis among population in a rare earth area in south China.

An ophthalmofunduscope was used to investigate arteriosclerosis among villagers aged 20-40 yr old in two rare earth areas in Ganzhou, Jiangxi Province. It was noted that the occurrence of arteriosclerosis of the fundus aculi was significantly high (P < 0.05-0.01), the detection of serum cholesterol (CHO) was remarkably increased (P < 0.01), and the level of IgM was also elevated. However, high-density lipoprotein (HDL) remained at a low level. The effect of taking rare earth elements (REE) could be direct or indirect, thus causing an increase in cholesterol and interfering with the synthesis of high-density lipoprotein. Furthermore, rare earth could also cause immunogenic damage to the vascular wall. All of these could facilitate the formation of arteriosclerosis.

Adult↗
PubMed1997

Bioelectrical activity of the central nervous system among populations in a rare earth element area.

Auditory brainstem electric response (ABR) and somatosensory evoked potential (SEP) of 21 subjects (41 ears) among villagers in a rare earth element (REE) area in Gan County, Jiangxi, China, were studied. No difference in ABR between the subjects from the REE area and the control group was noted. However, the conduction detected by SEP from the median nerve to the thalamus (P15) was shortened (P < 0.05), especially to the first-grade primary somatosensory responsive region (S1) (P < 0.01) and the amplitude of S1 decreased (P < 0.05), indicating that REE was difficult to accumulate in the brainstem, but it was susceptible to cerebral cortex, thus causing sub-clinical damage. This condition was confirmed in the animal experiment. It was suggested that the toxicity through long-term intake of small doses of REE might not be negligible, and the hazard of REE environments should be investigated.

Acetylcholinesterase↗
PubMed1997

Video-assisted thoracoscopic operation for interruption of patent ductus arteriosus in adults.

BACKGROUND: Patent ductus arteriosus (PDA) is a frequent congenital heart disease encountered in premature neonates, infants, and children. Video-assisted endoscopic techniques have been used in PDA interruption since 1993. Almost all the experiences are in pediatric patients. Applications in adults with PDA have been limited. METHODS: We report our experience of video-assisted thoracoscopic surgical ligation of PDA in adults. From August 1995 to January 1996, 60 patients with PDA were operated on with a video-assisted thoracoscopic technique. Twelve adults were identified with mean age of 30 years (range, 20 to 57 years). With the patient under general anesthesia and double-lumen endotracheal intubation, two 5-mm holes were made in the left lateral chest wall. Another 4-cm incision was made in the left third intercostal space for manipulation, dissection, and ligation. Conventional surgical instruments were used except an endoscopic grasper and an endoscopic tube that connected to a video camera. The surgical procedure was viewed on a video screen. Transesophageal echocardiography was used for monitoring during PDA ligation. RESULTS: All patients had successful ligation of the PDA. There was no surgical mortality, but there was one morbidity; transient recurrent nerve injury, which recovered 3 months later. Ten patients were extubated in operative room and 2 patients were extubated 2 hours after the operation. Tube thoracostomy was performed in the first 2 cases; it was omitted thereafter. No patients needed narcotic to control chest pain. Postoperative follow-up by echocardiography showed faint ductal flow in 1 patient without any murmur. All patients were discharged within 3 days after the operation. CONCLUSIONS: Our experience suggests that with refinement of instruments and surgical technique, video-assisted thoracoscopic surgical ligation can be safely applied not only in pediatric patients, but also in adults with PDA.

Adult↗
PubMed1997

Macrophage prostaglandin production contributes to the age-associated decrease in T cell function which is reversed by the dietary antioxidant vitamin E.

The aging process is associated with a decline in T cell-mediated immunity, including decreased interleukin (IL)-2 production and mitogen-induced T cell proliferation. Because macrophages (M phi) from old mice have higher production of prostaglandin (PG) E2 than young mice, and PGE2 has been shown to suppress T cell-mediated function, we hypothesized that increased production of PGE2 would contribute to decreased T cell function with aging and that decrease in PGE2 production by dietary antioxidants would enhance T cell-mediated function. Experiments were conducted in which combinations of purified M phi and T cells (> 95% pure) from young or old C57BL/6N1A mice were cultured together. Co-cultures containing T cells and M phi from old mice had reduced ConA-stimulated proliferation and IL-2 secretion than those consisting of T cells and M phi from young mice. Addition of M phi from old mice suppressed proliferation and IL-2 secretion by T cells from young mice. Likewise, T cells from old mice secreted more IL-2 when cultured with M phi from young mice compared to those cultured with M phi from old mice. Addition of PGE2, at concentrations produced by old M phi, decreased proliferation and IL-2 production by young but not old T cells. Neither addition of H2O2 at physiological levels, nor catalase changed the response of cultures from young or old mice. However, addition of indomethacin and the antioxidant nutrient vitamin E, both of which decreased PGE2 production, improved T cell proliferation and IL-2 production. These experiments demonstrate that increased production of PGE2 by M phi contributes to the age-associated decline in T cell function. Vitamin E improves T cell responsiveness in old mice mostly by reducing M phi PGE2 production, although a direct effect of vitamin E on T cells was also observed.

Aging↗
PubMed1997

Determination of SR 49059 in human plasma and urine by LC-APCI/MS/MS.

SR 49059 ((2S 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3, 4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1 H-indole-2-carbonyl]-pyrrolidine-2-carboxamide) is an orally active non-peptide vasopressin V1a antagonist. A sensitive, selective, and robust LC-MS/MS method was developed to determine the plasma and urine concentrations of SR 49059 in support of clinical studies. Plasma samples were prepared based on a rapid extraction procedure using Chem Elut cartridges. The extracted samples were analyzed on a C18 HPLC column interfaced with a Finnigan TSQ 700 mass spectrometer. Positive atmospheric chemical ionization (APCI) was employed as the ionization source. The analyte and its internal standard (2H6-SR 49059) were detected by use of multiple reaction monitoring (MRM) mode. The plasma matrix had a calibration range 0.2-20 ng ml-1, with within and between run accuracy and precision both less than 10%. The chromatographic run time was approximately 3 min. Urine samples were prepared based on a simple dilution with water, followed by analysis under the same conditions as plasma. The calibration range for urine matrix was 20-5000 ng ml-1, with within and between run accuracy and precision less than 11%. The method has been successfully applied to the clinical sample analysis. The plasma assay was also evaluated on a Finnigan TSQ 7000 mass spectrometer. The performance based on precision and accuracy was virtually identical to that on the TSQ 700, with the exception of linearity in calibration curve (the TSQ 700 was linear, the TSQ 7000 was quadratic).

Antidiuretic Hormone Receptor Antagonists↗
PubMed1997

An automated multidimensional screening approach for rapid method development in high performance liquid chromatography.

Despite enormous advancements in the area of high performance liquid chromatography (HPLC) in recent years, method development remains a major challenge. This is primarily due to the unknown nature of the matrix material which sometimes is difficult to characterize (e.g. biological matrices). To improve the efficiency of method development a multidimensional screening approach was presented. This approach was based on two major steps: (1) a matrix spiked with drug was eluted from a large number of columns, each under different mobile phase compositions, to provide the preliminary selectivity-separation information; (2) this information was then used to compose column switching pairs (each pair consisted of a preparatory column followed by an analytical column) and the elution profile was evaluated to determine the suitable clean up and quantitation conditions. An example was provided using ethyl 3,5-bis(acetylamino)-2,4,6-triiodobenzoate (EEDA), an X-ray enhancement agent, in human plasma. Since the HPLC system was fully automated the data generation time, and consequently the method development time, can be significantly reduced.

Acetonitriles↗
PubMed1997

Successful radiofrequency ablation of idiopathic left ventricular tachycardia at a site away from the tachycardia exit.

OBJECTIVES: This study sought to assess the possibility of ablating verapamil-responsive idiopathic left ventricular tachycardia at a site distant from the tachycardia exit and thus to define the tachycardia circuit. BACKGROUND: The nature of the reentry circuit in idiopathic left ventricular tachycardia is unclear. If the circuit is of considerable size, then it should be possible to ablate the tachycardia at a site distant from the exit site. METHODS: Electrophysiologic studies and radiofrequency ablation were performed in 27 consecutive patients with verapamil-responsive idiopathic left ventricular tachycardia. In all 27 patients, the tachycardia exit site was defined as the site where the earliest Purkinje potential was recorded > or = 25 ms before the onset of the QRS complex during the tachycardia and where the pace map QRS complex resembled that during the tachycardia. A potential ablation site other than the exit site was then sought around the midseptum, proximal to the exit site. At such sites the tachycardia could be terminated transiently by pressure applied to the catheter tip, without induction of ventricular ectopic beats. RESULTS: The potential ablation site, other than the tachycardia exit site, was identified in seven male patients (mean [+/-SD] age 31 +/- 12 years, range 13 to 52). Application of the radiofrequency current at this site resulted in termination of the tachycardia within 1 to 5 s (mean 2.9 +/- 1.6), and successful ablation of the tachycardia was achieved in all seven patients (success rate 100%, 95% exact confidence interval 0.5898 to 1). The mean distance between the ablation site and the tachycardia exit site was 3.1 +/- 0.7 cm (range 2.0 to 4.0). A presystolic Purkinje spike was recorded 14 +/- 5 ms (range 8 to 20) before the onset of the QRS complex during the tachycardia. During the follow-up period of 24 +/- 11 months (range 12 to 39), there was no recurrence of tachycardia in these seven patients. CONCLUSIONS: Successful ablation of idiopathic left ventricular tachycardia can be achieved at sites away from the tachycardia exit site in some patients. This finding suggests that the reentry circuit is likely to be of considerable size, encompassing the middle, inferior and lower aspects of the left interventricular septum.

Action Potentials↗
PubMed1997

alpha-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor.

alpha-Latrotoxin is a potent stimulator of neurosecretion. Its action requires extracellular binding to high affinity presynaptic receptors. Neurexin I alpha was previously described as a high affinity alpha-latrotoxin receptor that binds the toxin only in the presence of calcium ions. Therefore, the interaction of alpha-latrotoxin with neurexin I alpha cannot explain how alpha-latrotoxin stimulates neurotransmitter release in the absence of calcium. We describe molecular cloning and functional expression of the calcium-independent receptor of alpha-latrotoxin (CIRL), which is a second high affinity alpha-latrotoxin receptor that may be the major mediator of alpha-latrotoxin's effects. CIRL appears to be a novel orphan G-protein-coupled receptor, a member of the secretin receptor family. In contrast with other known serpentine receptors, CIRL has two subunits of the 120 and 85 kDa that are the result of endogenous proteolytic cleavage of a precursor polypeptide. CIRL is found in brain where it is enriched in the striatum and cortex. Expression of CIRL in chromaffin cells increases the sensitivity of the cells to the effects of alpha-latrotoxin, demonstrating that this protein is functional in coupling to secretion. Syntaxin, a component of the fusion complex, copurifies with CIRL on an alpha-latrotoxin affinity column and forms stable complexes with this receptor in vitro. Interaction of CIRL with a specific presynaptic neurotoxin and with a component of the docking-fusion machinery suggests its role in regulation of neurosecretion.

Amino Acid Sequence↗
PubMed1997

Effect of pyridine on the expression of cytochrome P450 isozymes in primary rat hepatocyte culture.

In vivo administration of pyridine has been shown to increase the activity and content of several forms of cytochrome P450 by transcriptional and posttranscriptional mechanisms. The effect of pyridine on CYP1A and CYP2E1 isozymes was studied in a rat hepatocyte culture model. Hepatocytes were isolated from non-induced rats and seeded onto matrigel-coated dishes and incubated in William's medium E containing 10% fetal calf serum, hormones, and essential metals. Cultures were treated with 0, 10 or 25 mM pyridine for 1-3 days and microsomes were isolated to determine catalytic activity and for immunoblot analysis, and total RNA was isolated for mRNA determinations. CYP2E1 content, CYP2E 1 mRNA, and CYP2E1 catalyzed oxidation of p-nitrophenol declined during culture to values of 3, 30 and 19% that of initial, non-cultured controls by day 3 of culture. Pyridine prevented this decline of CYP2E1 protein and activity such that 60-80% original activity remained after 3 days of culture in the presence of 25 mM pyridine. However, pyridine did not prevent the fall in CYP2E1 mRNA levels, nor did pyridine increase the content or activity of CYP2E1 above initial values of microsomes from freshly isolated hepatocytes. Pyridine increased the content of CYP1A2 and the oxidation of ethoxyresorufin 2-4 fold compared to cultures incubated without pyridine over the 3 day culture period. CYP1A1 levels, which rapidly declined, were induced and maintained in the presence of pyridine. Pyridine increased CYP1A content and activity 2-3 fold over initial values of freshly isolated hepatocytes. These increases were associated with corresponding increases in CYP1A mRNA levels. CYP1A2, but not CYP1A1, mRNA levels increased in the cultures incubated in the absence of pyridine. These results indicate that pyridine has different effects on CYP1A and CYP2E1 in this hepatocyte culture model. Pyridine appears to modulate CYP2E1 levels by posttranscriptional mechanisms as CYP2E1 activity and content were maintained in the presence of pyridine under conditions in which CYP2E1 mRNA levels declined. These mechanisms may involve increased translational efficiency of existing CYP2E1 mRNA or stabilization of CYP2E1 protein against degradation. Pyridine increased CYP1A1 and CYP1A2 content, activity and mRNA levels, either inducing CYP1A transcription or stabilizing CYP1A mRNA. Hepatocyte cultures may be a useful model to study the interaction of pyridine with P450 isozymes and their associated drug-mediated toxicity.

Animals↗
PubMed1997

Molecular cloning and gene expression analysis of PSP94 (prostate secretory protein of 94 amino acids) in primates.

Prostate secretory protein of 94 amino acids (PSP94) has shown the potential to be a diagnostic biomarker and a therapeutic agent for prostate cancer. Primates have been the main animal models for studying the biology of this molecule. We have cloned and analyzed the cDNA and promoter region of PSP94 from baboon (Papio anubis). Sequence divergence among baboon, monkey, pig, and human, in both the exons and 5'-flanking region indicates rapid evolution of the PSP94 gene. There are conserved steroid hormone response elements (SHRE) in the promoter region of all three primate species. Multiple, alternative transcripts starting near these SHREs and upstream to the TATA box were identified by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of 5'-cDNA ends (5' RACE) in primate prostatic tissues. This differential transcription initiation may be linked to androgen regulation of PSP94 gene expression. PSP94 transcripts were detected by RT-PCR in a wide variety of mucus-secreting tissues. However, the alternative transcripts were found only in the prostate. The distribution of the PSP94 protein in baboon secretory tissues was also examined by Western blot analysis using a polyclonal antibody against the human homolog. A positive immunoreactive band was detected, but it was weak, due probably to epitope divergence between the two species. In all young, healthy primate animals tested, the level of immunoreactive PSP94 in prostate tissues was lower than expected. In addition, RT-PCR combined with Southern blot analysis on prostate tissues in these animals failed to detect the PSP57 mRNA produced by alternative splicing of PSP94 primary transcript. These observations can be explained by the sexual immaturity and incomplete prostate development in these young primates. This explanation was supported by histological examination of their prostate during PSP94 immunohistochemistry.

Amino Acid Sequence↗
PubMed1997

Effect of vitamin E supplementation on prostaglandin concentrations in aspirin-induced acute gastric injury in aged rats.

Nonsteroidal antiinflammatory drugs (NSAIDs), such as aspirin, frequently cause gastric mucosal injury in the elderly. Impairment of prostaglandin synthesis is a crucial step by which aspirin attenuates mucosal defense capacity. Vitamin E has been shown to decrease prostanoid concentrations, which implies an ulceropermissive effect of vitamin E. To assess the effect of vitamin E on aspirin-induced gastric injury and mucosal prostanoid concentrations, 20 male rats aged 20 mo were divided into two groups and fed diets containing either 30 (physiologic requirement) or 500 mg all-rac-alpha-tocopheryl acetate/kg. After 6 wk, all rats received two intragastric doses of aspirin (1.4 mumol/kg body wt). A third group of six animals fed the high-vitamin E diet received a vehicle solution without aspirin. Mucosal samples for vitamin E and prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane A2 measurements were collected. The prevalence and degree of mucosal lesions were not significantly different among all groups. Rats fed the high-vitamin E diet had significantly higher mucosal vitamin E concentrations than rats fed the low-vitamin E diet. Mucosal concentrations of all three prostanoids were 95% lower in aspirin-treated rats than in controls (P = 0.0001 in all instances). The high-vitamin E diet group had significantly lower mucosal 6-keto-prostaglandin F1 alpha concentrations (P = 0.02) than the low-vitamin E diet group, indicating decreased prostacyclin formation, whereas concentrations of prostaglandin E2 and thromboxane A2 were similar in the aspirin-treated groups. Aspirin markedly reduced mucosal prostanoid concentrations in rats, without apparent effects on gastric injury, whereas vitamin E supplementation significantly reduced mucosal 6-keto-prostaglandin F(1 alpha) concentrations. Nevertheless, vitamin E supplementation did not result in more gastric injury in aspirin-treated rats than in controls.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Induced current and SAR distributions for a worker model exposed to an RF dielectric heater under simulated workplace conditions.

We have used the finite-difference time-domain method to calculate the distributions of absorbed energy for a 1.34 x 1.34 x 1.4 cm resolution anatomically based model of the human body for exposure to leakage electromagnetic fields of a radiofrequency dielectric heater operating at 40.68 MHz. To simulate workplace conditions, the dielectric heater is assumed to be placed in a screen room and different operator postures, such as standing or sitting on a wooden or metal stool with hands on sides or extended toward the radiofrequency heater, are considered. To obviate the problem of having to model a fairly large volume of the screen room of assumed dimensions 2.13 x 3.05 x 2.13 m, we have used a uniform finer grid of points for the finite-difference time-domain method for the closely coupled region consisting of the front region of the heater and the human model, while a newly developed expanding-grid finite-difference time-domain formulation is used elsewhere. This results in a saving of both the memory and computation times by almost a factor of four. The average rates of energy absorption are given for the whole body, selected parts of the body, and various organs. As expected, the foot currents and the rates of energy absorption are higher with the screen room for sitting postures where the upper parts of the body are in higher electromagnetic fields, and for hands extended toward the heater.

Electromagnetic Fields↗