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Biomedical subjects

H Liu

Publications and source records attributed to H Liu.

At least 613 records · Page 34Linked to original sources
PubMed1999

Embolization of a giant torcular dural arteriovenous fistula in a neonate.

We treated a neonatal infant who presented with heart failure and a giant torcular dural arteriovenous fistula by staged transtorcular embolization with two guidewires, 95 platinum microcoils, and tissue glues through a needle-size craniotomy. Blood loss was minimal. The patient was stable without heart failure after a three-staged embolization. The lesion disappeared on the follow-up angiography done at the age of 3 years. This is the first documented case of neonatal giant torcular dural arteriovenous malformation cured by interventional neuroradiology. The dilemma and strategy in managing this patient will be presented and discussed.

Arteriovenous Fistula↗
PubMed1999

Comparison of stereotactic brain biopsy to interventional magnetic-resonance-imaging-guided brain biopsy.

Lesions within the brain are commonly sampled using stereotactic techniques. The advent of interventional magnetic resonance (MR) imaging now allows neurosurgeons to interactively investigate specific regions with exquisite visualization. We compared the safety and efficacy of this new surgical approach with stereotaxis. From February 1991 to June 1998, 134 stereotactic and 35 interventional MR-guided brain biopsies were performed. Stereotactic biopsies utilized preoperative scanning. Interactive scanning was used to confirm accurate positioning of the biopsy needle within the region of interest. Intraoperative pathologic examination of biopsy material was performed to verify the presence of diagnostic tissue in both biopsy groups. Intra- and postoperative MR imaging was obtained to exclude the presence of intraoperative hemorrhage. Recently, MR spectroscopic targeting has been utilized in 6 patients. In the stereotactic group, 129/134 (96%) biopsies were diagnostic. One patient had a transient hemiparesis after a brain stem biopsy and another suffered a fatal hemorrhage for a morbidity rate of 0.7% and a mortality rate of 0.7%. In reviewing 7,471 stereotactic biopsies, the morbidity was 3.5%, mortality 0.7% and diagnostic yield 91%. All 35 MR-guided brain biopsies were diagnostic (100%). MR spectroscopy was accurate in all cases in distinguishing recurrent tumor (5 cases) from radiation necrosis (1 case). One patient (3%) suffered a transient hemiparesis following a pontine biopsy and another patient (3%) developed a postoperative scalp cellulitis. No patient sustained a clinically or radiologically significant hemorrhage as determined by the immediate postbiopsy, intraoperative MR imaging. Interventional MR-guided brain biopsy is a safe and effective technique for evaluating lesions of the brain with morbidity and mortality rates comparable to those of stereotaxis. MR-guided biopsy appears to have a higher diagnostic yield than stereotaxis, which may reflect the ability to perform interactive, intraoperative scanning with that technique.

Biopsy↗
PubMed1999

Carbon monoxide stimulates the apical 70-pS K+ channel of the rat thick ascending limb.

We have investigated the expression of heme oxygenase (HO) in the rat kidney and the effects of HO-dependent heme metabolites on the apical 70-pS K+ channel in the thick ascending limb (TAL). Reverse transcriptase-PCR (RT-PCR) and Western blot analyses indicate expression of the constitutive HO form, HO-2, in the rat cortex and outer medulla. Patch-clamping showed that application of 10 microM chromium mesoporphyrin (CrMP), an inhibitor of HO, reversibly reduced the activity of the apical 70-pS K+ channel, defined by NPo, to 26% of the control value. In contrast, addition of 10 microM magnesium protoporphyrin had no significant effect on channel activity. HO involvement in regulation of the apical 70-pS K+ channel of the TAL, was further indicated by the addition of 10 microM heme-L-lysinate, which significantly stimulated the channel activity in cell-attached patches by 98%. The stimulatory effect of heme on channel activity was also observed in inside-out patches in the presence of 0.5-1 mM reduced nicotinamide adenine dinucleotide phosphate. This was completely abolished by 10 microM CrMP, suggesting that a HO-dependent metabolite of heme mediated the effect. This was further supported by exposure of the cytosolic membrane of inside-out patches to a carbon monoxide-bubbled bath solution, which increased channel activity. Moreover, carbon monoxide completely abolished the effect of 10 microM CrMP on the channel activity. In contrast, 10 microM biliverdin, another HO-dependent metabolite of heme, had no effect. We conclude that carbon monoxide produced from heme via an HO-dependent metabolic pathway stimulates the apical 70-pS K+ channel in the rat TAL.

Animals↗
PubMed1999

O(2) deprivation inhibits Ca(2+)-activated K(+) channels via cytosolic factors in mice neocortical neurons.

O(2) deprivation induces membrane depolarization in mammalian central neurons. It is possible that this anoxia-induced depolarization is partly mediated by an inhibition of K(+) channels. We therefore performed experiments using patch-clamp techniques and dissociated neurons from mice neocortex. Three types of K(+) channels were observed in both cell-attached and inside-out configurations, but only one of them was sensitive to lack of O(2). This O(2)-sensitive K(+) channel was identified as a large-conductance Ca(2+)-activated K(+) channel (BK(Ca)), as it exhibited a large conductance of 210 pS under symmetrical K(+) (140 mM) conditions, a strong voltage-dependence of activation, and a marked sensitivity to Ca(2+). A low-O(2) medium (PO(2) = 10-20 mmHg) markedly inhibited this BK(Ca) channel open probability in a voltage-dependent manner in cell-attached patches, but not in inside-out patches, indicating that the effect of O(2) deprivation on BK(Ca) channels of mice neocortical neurons was mediated via cytosol-dependent processes. Lowering intracellular pH (pH(i)), or cytosolic addition of the catalytic subunit of a cAMP-dependent protein kinase A in the presence of Mg-ATP, caused a decrease in BK(Ca) channel activity by reducing the sensitivity of this channel to Ca(2+). In contrast, the reducing agents glutathione and DTT increased single BK(Ca) channel open probability without affecting unitary conductance. We suggest that in neocortical neurons, (a) BK(Ca) is modulated by O(2) deprivation via cytosolic factors and cytosol-dependent processes, and (b) the reduction in channel activity during hypoxia is likely due to reduced Ca(2+) sensitivity resulting from cytosolic alternations such as in pH(i) and phosphorylation. Because of their large conductance and prevalence in the neocortex, BK(Ca) channels may be considered as a target for pharmacological intervention in conditions of acute anoxia or ischemia.

Adenosine Triphosphate↗
PubMed1999

Reporting unethical research behavior.

Scientists, as professionals, have a responsibility to self-regulate. However, whistleblowing is rare. We investigated scientists' infrequent disclosure of unethical behavior by studying their responses to scenarios describing unethical research acts and compared their responses to those of research administrators. A cross-sectional survey was administered to National Science Foundation-funded principal investigators and their institutions' representatives (IRs) to the Office of Research Integrity. Both scientists and IRs proposed to respond to nearly all research behaviors that they rated as unethical. Scientists more often proposed responses limited to the research team (58% vs. 25% of cases, p < .001) whereas IRs more often proposed to inform an administrator or dean, journal editor, funding agency, professional society, or reporter. The prior behavior and academic rank of the scenario protagonist were associated with responses, but consequences of the unethical behavior were not. Scientists appear to perceive that they uphold their responsibility to respond to unethical behavior by disclosures within the research team, whereas administrators propose to report to externally accountable individuals, raising the question of whether scientists' behavior constitutes professional self-regulation or cover up.

Cross-Sectional Studies↗
PubMed1999

Functional analysis of a novel estrogen receptor-beta isoform.

A new level of complexity has recently been added to estrogen signaling with the identification of a second estrogen receptor, ERbeta. By screening a rat prostate cDNA library, we detected ERbeta as well as a novel isoform that we termed ERbeta2. ERbeta2 contains an in-frame inserted exon of 54 nucleotides that results in the predicted insertion of 18 amino acids within the ERbeta hormone-binding domain. We also have evidence for the expression of both ERbeta1 and ERbeta2 in human cell lines. Competition ligand binding analysis of bacterially expressed fusion proteins revealed an 8-fold lower affinity of ERbeta2 for 17beta-estradiol (E2) [dissociation constant (Kd approximately 8 nM)] as compared with ERbeta1 (Kd approximately 1 nM). In vitro transcribed and translated ERbeta1 and ERbeta2 bind specifically to a consensus estrogen responsive element in a gel mobility shift assay. Furthermore, we show heterodimerization of ERbeta1 and ERbeta2 with each other as well as with ERalpha. In affinity interaction assays for proteins that associate specifically with the hormone-binding domain of these receptors, we demonstrate that the steroid receptor coactivator SRC-1 interacts in an estrogen-dependent manner with ERalpha and ERbeta1, but not with ERbeta2. In cotransfection experiments with expression plasmids for ERalpha, ERbeta1, and ERbeta2 and an estrogen-responsive element-containing luciferase reporter, the dose response of ERbeta1 to E2 was similar to that of ERalpha although the maximal stimulation was approximately 50%. In contrast, ERbeta2 required 100- to 1000-fold greater E2 concentrations for maximal activation. Thus, ERbeta2 adds yet another facet to the possible cellular responses to estrogen.

Alternative Splicing↗
PubMed1999

Therapeutic drug concentration monitoring using saliva samples. Focus on anticonvulsants.

In the last 30 years there has been great interest in the use of saliva in therapeutic drug monitoring. Numerous investigators have suggested that saliva be used as an alternative body fluid for the therapeutic drug monitoring of anticonvulsant drugs. Not only can saliva be obtained easily on multiple occasions with minimal discomfort to the patient but, more importantly, useful relationships exist between the saliva and blood concentrations of the most commonly used anticonvulsant drugs. The measurement of anticonvulsant drug concentrations in saliva has been applied to pharmacokinetic and pharmacodynamic studies, and for therapeutic drug monitoring in a variety of seizure disorders. However, this simple and non-invasive method is not widely accepted in clinical practice. Several recent developments in sample collection and analytical methods, and the growing interest in free drug concentrations, provide a renewed impetus for saliva sampling for therapeutic drug monitoring of anticonvulsant drugs. Salivary flow rates vary significantly both between individuals and under different conditions. The use of stimulated saliva has several advantages over resting saliva. The salivary flow rate and pH, sampling conditions, contamination and many other pathophysiological factors may influence the concentrations of the medication in saliva. However, under standardised and well-controlled sampling condition, therapeutic drug monitoring of anticonvulsant drugs in saliva can be useful for determining compliance with medication in paediatric patients, for analysing the concentration of free drug and in situations where repeated sampling is necessary. Saliva is an alternative matrix for the therapeutic drug monitoring of carbamazepine, phenytoin, primidone and ethosuximide because the concentrations of these medications in saliva reflect the concentrations of the drug in serum. This is not the case for valproic acid (valproate sodium) and some controversy exists for phenobarbital. Further studies are required to assess the clinical value of monitoring anticonvulsant drugs and their metabolites in saliva, to examine the influence of pathophysiological factors on salivary drug concentrations, to improve the design of special devices to reproducibly and conveniently collect saliva samples, and to develop and use new analytical methods to achieve more sensitive and accurate results.

Anticonvulsants↗
PubMed1999

Functional magnetic stimulation: a new modality for enhancing systemic fibrinolysis.

OBJECTIVE: To investigate whether functional magnetic stimulation (FMS) of the leg muscles could enhance systemic fibrinolysis. DESIGN: A within-subject analysis of systemic fibrinolysis before and after 60 minutes of FMS. SETTING: The Functional Magnetic Stimulation and Special Coagulation Laboratories in the Spinal Cord Injury Service at a Veterans Administration health care facility. PARTICIPANTS: Twenty healthy volunteers were recruited. The exclusion criteria were: (1) personal or family history of venous or arterial thrombosis, (2) personal or family history of cardiac arrythmias, (3) current use of medication, and (4) the presence of a cardiac pacemaker or other metallic implants. MAIN OUTCOME MEASURES: Whole blood clot lysis time (WBCLT) and tissue plasminogen activator (t-PA) antigen determined at baseline and 10 and 60 minutes after FMS. RESULTS: A significant decrease was observed in the mean WBCLT after FMS. The WBCLT decreased from 17+/-1.3 h before FMS to 12+/-1.0 h and 11+/-0.8 h at 10 and 60 minutes post-FMS, respectively. The mean t-PA antigen levels did not show a significant change (p = .6701) from pre-FMS (6.7+/-0.91 ng/mL) to 10 min post-FMS (6.8+/-0.91 ng/mL) and 60 min post-FMS (7.0+/-1.02 ng/mL). Several patterns of fibrinolytic response to FMS were observed. They differed in relation to the degree of enhancement, the period at which maximum enhancement occurred, and the corresponding t-PA antigen levels observed. CONCLUSIONS: The FMS-induced contractions of the leg muscles enhanced systemic fibrinolysis ex vivo. The improvement in fibrinolysis occurred immediately after FMS and was also observed at 60 minutes post-FMS. FMS appears to produce a sustained enhancement of systemic fibrinolysis that may prove useful in deep-vein thrombosis prophylaxis.

Adult↗
PubMed1999

[Relationship between the expression of transforming growth factor beta type I receptor (T beta R I) and prognosis of hepatocellular carcinoma (HCC)].

OBJECTIVE: To study the expression of T beta R I in HCC tissues and its clinical significance. METHODS: Expressions of T beta R I in HCC tissues (HT, n = 30) and surrounding liver tissues(HST, n = 30) as well as four normal control liver tissues (CIT, n = 4) were determined by radioligand binding assay with 125I TGF beta 1 as the ligand. Relationships between some clinicopathological parameters of HCC and the relative expression rates of T beta R I in HCC were studied. RESULTS: Compared with that in HST, the expression of T beta R I HT was significantly lower than in HST and CIT (P < 0.01). The expression of T beta R I in HST is similar to that in CIT. T beta R I relative expression rates in the group of no capsule or capsule invaded and in the group of tumor embolus were markedly decreased (P < 0.05). No close relationships were found between the T beta R I relative expression rate and age, sex, HBV infection, liver cirrhosis, AFP concentration, tumor diameter, tumor number, tumor differentiation as well as tumor embolus. CONCLUSIONS: The low expression of T beta R I in HT may be one of the key event which promote the HCC malignant growth by protecting them against the growth inhibition effect of active TGF beta. The T beta R I relative expression rate may be related to the prognosis of HCC.

Activin Receptors, Type I↗
PubMed1999

Reduced expression of beta-subunit of Na,K-ATPase in human clear-cell renal cell carcinoma.

PURPOSE: Multiple subtypes of renal cancer have been identified. Clear-cell renal cell carcinoma (RCC) is the most common subtype of RCC and one of the more aggressive. The goal of this study was to investigate in RCC the levels of Na,K-ATPase, an abundant enzyme in the kidney which is crucial for various kidney functions. Na,K-ATPase is a heterodimer consisting of a catalytic a-subunit and a glycosylated beta-subunit whose function is still not well-defined. MATERIALS AND METHODS: Fourteen clear-cell RCC specimens were studied. The levels of the Na,K-ATPase alpha and beta-subunits in normal kidney and RCC tissues were determined by immunoblot analysis. The localization of the alpha and beta-subunits was studied by immunofluorescence and laser scanning confocal microscopy. Na,K-ATPase activity was determined using a coupled-enzyme spectrophotometric assay. RESULTS: In normal kidney, the cells demonstrate an epithelial morphology with distinct basolateral plasma membrane localization of the alpha and beta-subunits. Conversely, the cells of the clear-cell RCC have lost their epithelial phenotype and the alpha and beta-subunits show a diffuse intracellular staining. Clear-cell RCC tumor cell lysates showed a consistent 95.6+/-2.8% (mean +/- SD) reduction in protein levels of beta-subunit relative to the levels in normal kidney. The alpha-subunit level in RCC lysates was generally near or above the levels relative to normal kidney. The reduced beta-subunit expression was accompanied by a significant reduction in the Na,K-ATPase activity in RCC membranes. CONCLUSIONS: These results suggest that the beta-subunit may regulate the Na,K-ATPase activity in vivo. Diminished Na,K-ATPase activity in conjunction with the reduced beta-subunit level is associated with the clear-cell RCC phenotype.

Adult↗
PubMed1999

Induction of apoptosis in CD34+ cells by sera from patients with aplastic anemia.

To investigate the pathogenesis of aplastic anemia (AA), the apoptosis of CD34+ cells was assayed with annexin V-fluorescein 24 hr and 48 hr after incubation with the serum of normal controls (n = 10), patients with non severe AA (NSAA, n = 13) and severe AA (SAA, n = 10). The CD34+ progenitors from the bone marrow of normal donors contained a significantly greater proportion of apoptotic cells after incubation with serum from SAA patients than that incubated with serum from normal controls and NSAA. Moreover, the percent apoptosis of CD34+ cells after 24 hr incubation with serum from NSAA was slightly higher than that of normal controls. This appears to be related to clinical severity. No significant difference was found in the percent apoptosis of CD34+ cells between incubation for 24 hr and 48 hr with the same serum. To further explore the mechanism of increased apoptosis induced by the serum of AA patients, the expression of the Fas receptor was measured after incubation with serum from the normal controls and AA patients using flow cytometry. After incubation with serum from the AA patients, the Fas receptor was overexpressed, correlating with the increased apoptosis induced by the same serum from AA patients. In addition, the induction of apoptosis and Fas expression on CD34+ cells by serum from the SAA patients was blocked partly by preincubation of the serum with anti-gamma-IFN neutralizing MoAb. These findings suggested that some aberrant components of the serum in the AA patients, which was confirmed partly to be gamma-IFN, can induce CD34+ progenitors apoptosis through the Fas signaling pathway. This may contribute to understanding the decreased number of stem cells characteristic of aplastic anemia.

Adolescent↗
PubMed1999

Incorporation of an (125)I-labeled hexa-iodinated diglyceride analog into low-density lipoprotein and high specific uptake by cells of cervical carcinoma cell lines.

The feasibility of using low-density lipoprotein (LDL) to deliver cytotoxic drugs to tumor cells has been explored since the 1980s, when cells of a number of cancer cell lines were found to have higher LDL receptor activity than normal cells. Such differential uptake between tumor and normal cells may provide a unique opportunity to use LDL as a tumor-specific carrier of radiopharmaceuticals for the clinical management of cancer. In this study, an (125)I-labeled hexa-iodinated diglyceride analog, 1, 3-dihydroxypropan-2-one 1,3-diiopanoate (DPIP), was synthesized and incorporated into LDL using a fusion technique. It was found that approximately 500 [(125)I] DPIP molecules were incorporated into each LDL particle. Cells of three human cervical tumor cell lines, HeLa, SiHa and C-33A, were used to examine the cellular uptake of the [(125)I]DPIP-LDL conjugate. It was shown that the [(125)I]DPIP-LDL conjugate was specifically bound to and taken up by cervical tumor cells through an LDL receptor-mediated endocytosis pathway. The results suggest that LDL may be a selective carrier for delivering hydrophobic radiopharmaceuticals to cancer cells and particularly for the diagnosis of cervical tumors.

Binding Sites↗
PubMed1999

Effects of microgravity on urinary osteopontin.

Increased risk of renal stone formation during space flight has been linked primarily to increased calcium excretion from bone demineralization induced by space flight. Other factors contributing to increased risk include increased urinary calcium oxalate supersaturation, while urinary citrate, magnesium and volume are all decreased. The aim of this study was to increase the predictive value of stone risk profiles for crew members during space flight by evaluating the excretion of urinary protein inhibitors of calcium crystallization so that more comprehensive stone risk profiles could relate mineral saturation to the concentrations of inhibitor proteins. Levels of urinary osteopontin (uropontin) are reported in a series of 14 astronauts studied before, during, and after space flights. During space flight, a compensatory increase in uropontin excretion was not observed. However, the uropontin excretion of a majority of astronauts was increased during the period after space flight and was maximal at 2 wk after landing. The downward shift in the molecular size of uropontin observed in samples obtained during space flight was shown to result from storage at ambient temperature during flight, rather than an effect of microgravity on uropontin synthesis.

Gravitation↗
PubMed1999

Cloning and expression of truncated PTHrP receptor in Escherichia coli.

To evaluate the effects of recombinant soluble parathyroid hormone related protein receptor(sPTHrPR), the RNA prepared from renal cell carcinoma was reverse-transcribed and amplified by a polymerase chain reaction(PCR). A 543 base pair fragment corresponding to extracellular domain of PTHrPR was obtained and cloned. Sequencing was performed by the dideoxy chain-termination method. Comparison of the nucleic acid sequence with the published data revealed that only one nucleotide had changed. A high level expression vector referred to as pET-3a/sPTHrPR was constructed. The binding specificity of the expression products was proved by indirect ELISA. Our preliminary experiment also showed that the expression products can block the biological activity of PTHrP.

Amino Acid Sequence↗
PubMed1999

Computer modeling of fluid dynamics related to a myocardial bridge in a coronary artery.

Fluid mechanics associated with blood flows induced by the so-called myocardial bridge (MB) has been studied systematically using a computational fluid dynamic modeling of the Newtonian, incompressible, two-dimensional, unsteady flow in a channel with a time-dependently flushing in/out indentation. During each cycle, a train of vortex wave flow was observed downstream of the phasic stenosis and both upper and lower walls suffer severely from consistently high, oscillating wall shear stresses (WSS). Extensive studies were conducted on the influence of the Reynolds number, the geometry and the Strouhal number of the MB movement on the nature of the vortex flow and the time-dependent wall shear stress distribution. Special attention was drawn to the relationship between the vortex wave and the pressure distribution. It was found that the pressure gradient changed markedly during one cycle, which was apparently dominated by the dynamics of the indentation. A steep, adverse pressure gradient was observed when the indentation was flushing out, which corresponded to the existence of the most developing vortices. It implies the possibility that the MB in a coronary artery can produce an extremely low pressure region immediately downstream of the phasic stenosis, where elastic choking or collapse of the coronary artery might occur.

Computational Biology↗
PubMed1999

Experimental study of sagittal fracture of the mandibular condyle.

OBJECTIVE: To observe the healing of sagittal fracture of the mandibular condyle (SFMC) and its effect on the temporomandibular joint in immature miniature pigs. METHODS: Twenty-seven immature miniature pigs were randomly chosen and divided into three groups. Twelve immature miniature pigs underwent sagittal fracture of the mandible condyle; 12 underwent transverse fracture, and 3 were maintained as a normal control. Three-phase scintigraphy, computed tomography (CT) imaging, and histological tests were conducted at 3 weeks, 6 weeks, 12 weeks, and 24 weeks. RESULTS: The data showed the value of the time-activity curve of blood-flow image increased and blood-flow arriving time was postponed after condylar fracture. The alpha/beta ratio was the highest at 2 weeks after SFMC. The count of blood-pool image and static image were higher than nonfractured sides. Peaks were seen at 2 weeks postfracture. Disc and condyle adhesion was found in all sagittal fractures of the mandibular condyle and bifid mandibular condyle was formed. Adhesive tissues between condyle and disc were fibro-connective tissues, which connected the disc directly to cartilage or bone tissue. A large number of fibroblasts and sparse chondrocytes were seen in the adhesive tissue. Blood vessels and adipose cells were seen in the disc, whereas there were no distinguishable changes in transverse fracture. CONCLUSION: Bifid mandibular condyle was found in most SFMC in childhood. The mechanism of bifid condyle deformity is related to secondary injuries to the disc, adhesions between the condyle and disc, and displacement of the medial split fragment. The age when SFMC occurs is an important factor in bifid condyle formation.

Animals↗