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Biomedical subjects

B Lu

Publications and source records attributed to B Lu.

At least 109 records · Page 6Linked to original sources
PubMed2000

Evaluation of electron beam tomographic coronary arteriography with three-dimensional reconstruction in healthy subjects.

In this study, the authors evaluated the performance characteristics of contrast-enhanced electron-beam tomography (EBT) with three-dimensional reconstruction in defining the coronary artery lumen in healthy subjects. Thirty patients with normal coronary angiograms by selective coronary arteriography (SCA) underwent contrast-enhanced EBT examination. Measured parameters included degree of luminal enhancement, intravascular contrast-to-noise ratio (CNR), and diameter and length of visualized lumen. Ventricular cavity, aortic blood pool, and coronary artery attenuation were found to be significantly different before and after intravenous injection of contrast material (p < 0.001). CNR decreased from proximal to distal segments within each vessel (p < 0.001), with a peak of 11.2 +/- 2.3 occurring in the proximal left anterior descending coronary artery (LAD) to a low of 4.8 +/- 2.0 in the distal left circumflex (LCX). Luminal diameters visualized by EBT had no significant difference with that of SCA (p > 0.05). Therefore, EBT angiography with three-dimensional reconstruction allows for noninvasive coronary arteriography revealing long segments of the major coronary arteries in normal subjects.

Adult↗
PubMed2000

BMP-binding modules in chordin: a model for signalling regulation in the extracellular space.

A number of genetic and molecular studies have implicated Chordin in the regulation of dorsoventral patterning during gastrulation. Chordin, a BMP antagonist of 120 kDa, contains four small (about 70 amino acids each) cysteine-rich domains (CRs) of unknown function. In this study, we show that the Chordin CRs define a novel protein module for the binding and regulation of BMPs. The biological activity of Chordin resides in the CRs, especially in CR1 and CR3, which have dorsalizing activity in Xenopus embryo assays and bind BMP4 with dissociation constants in the nanomolar range. The activity of individual CRs, however, is 5- to 10-fold lower than that of full-length Chordin. These results shed light on the molecular mechanism by which Chordin/BMP complexes are regulated by the metalloprotease Xolloid, which cleaves in the vicinity of CR1 and CR3 and would release CR/BMP complexes with lower anti-BMP activity than intact Chordin. CR domains are found in other extracellular proteins such as procollagens. Full-length Xenopus procollagen IIA mRNA has dorsalizing activity in embryo microinjection assays and the CR domain is required for this activity. Similarly, a C. elegans cDNA containing five CR domains induces secondary axes in injected Xenopus embryos. These results suggest that CR modules may function in a number of extracellular proteins to regulate growth factor signalling.

Amino Acid Sequence↗
PubMed2000

Insurance decisions about obesity surgery: a new type of randomization?

BACKGROUND: Studies of obesity surgery are frequently criticized for lack of an appropriate non-operative control arm. Additionally, insurance approval for coverage of these procedures can be difficult to obtain by patients and caregivers. This retrospective study tested the hypothesis that the insurance preapproval process would yield well-matched operative and non-operative treatment groups which could simulate a randomization process. METHODS: Of 466 patients deemed to be appropriate candidates for surgery, 58% ultimately received surgical therapy. Roux-en-Y gastric bypass (RYGBP) was performed on 244 patients who were compared with 187 patients who did not undergo surgery (NonOP). RESULTS: The groups were similar in gender (81% female), age (39 yr), and Body Mass Index (52 kg/m2). The percentage of African Americans in the NonOP group was greater. The distribution of comorbid conditions among the groups were similar. CONCLUSIONS: The insurance approval process results in a reasonable control group for parameters except race.

Adult↗
PubMed2000

Functional characteristics of a novel murine estrogen receptor-beta isoform, estrogen receptor-beta 2.

We have isolated a highly expressed splice variant mRNA of murine estrogen receptor-beta (ERbeta), mERbeta2, containing an in-frame 54 nucleotide insertion between exons 5 and 6 of wild-type mERbeta1. The predicted ERbeta2 protein contains 18 amino acids inserted in the ligand binding domain of mERbeta1. Recombinant protein generated by in vitro transcription/translation showed that mERbeta2 had markedly reduced ligand binding (K(D)=17.7+/-4.7 nM, mean+/-s.e.m., n=3) compared with mERbeta1-bound (3)H-estradiol (K(D)=0.56+/- 0.19 nM, mean+/-s.e.m., n=3). Both receptors bound similarly to palindromic estrogen responsive elements (EREs) in vitro and in vivo, and similarly bent DNA. Transcriptional activity was assessed using transient transfection analysis into a homologous murine cell line, NIH 3T3 cells. mERbeta1 transactivated ERE-tk-CAT reporter genes similarly to mERalpha, whereas mERbeta2 had little activity except at high ligand concentrations. However, under conditions in which mERbeta2 is unlikely to be ligand saturated, co-transfected mERbeta2 inhibited activity of mERalpha and possibly mERbeta1 on ERE-tk-CAT genes. Using a 'novel raloxifene responsive' gene reporter system (TGF-beta3-CAT), we found the ability of estradiol and LY117018 to activate both mERalpha and mERbeta1 on this promoter was identical, and mERbeta2 activity in the presence of either estradiol or LY117018 was only slightly less than that observed with either mERbeta1 or mERalpha. Both mERbeta1 and mERbeta2 when liganded with LY117018 inhibited transcription at a classical ERE-regulated promoter under these transfection conditions, which was in marked contrast to their stimulatory effect at the transforming growth factor-beta3 promoter. These data suggest that responsiveness of gene expression to a relatively highly expressed variant murine ERbeta isoform, mERbeta2, is both ligand and promoter specific. Determination of the relative level of expression of mERbeta1 mRNA and mERbeta2 mRNA in mouse tissues indicated predominance of mERbeta2 mRNA in some but not all tissues. These data suggest that the mERbeta2 may have some tissue-specific and promoter-specific modulatory effects.

3T3 Cells↗
PubMed2000

Effect of sterilization method and other modifications on the wear resistance of acetabular cups made of ultra-high molecular weight polyethylene. A hip-simulator study.

BACKGROUND: Wear of ultra-high molecular weight polyethylene acetabular cups in hip prostheses produces billions of submicrometer wear particles annually that can cause osteolysis and loosening of the components. Thus, substantial improvement of the wear resistance of ultra-high molecular weight polyethylene could extend the clinical life span of total hip prostheses. It has become apparent that the conditions under which ultra-high molecular weight polyethylene cups have been sterilized can markedly affect their long-term wear properties, and new sterilization methods and other modifications have been developed to minimize the negative effects. METHODS: In the present study, a hip-joint simulator was used to assess whether it is preferable to sterilize ultra-high molecular weight polyethylene cups without gamma irradiation, to avoid radiation-induced oxidative degradation, or to sterilize with gamma irradiation while the cups are packaged in a suitable low-oxygen atmosphere to minimize oxidation while retaining the increased wear resistance conferred by the radiation-induced cross-linking. Ion-implanted cups and cups made of a highly crystalline polyethylene (Hylamer) also were investigated. Cups made of each material were subjected to wear-testing prior to and after artificial thermal aging to accelerate oxidative degradation. RESULTS: The results of the present study demonstrated that the cross-linking induced by gamma irradiation improves the wear resistance of ultra-high molecular weight polyethylene, while oxidation reduces it. Without thermal aging, the two types of cups that were sterilized with gamma irradiation while in low-oxygen packaging exhibited about a 50 percent lower rate of wear than did either the nonsterilized cups or the nonirradiated cups sterilized with gas plasma. There was a comparable advantage in the rate of wear after fourteen days of thermal aging. However, after thirty days of aging, the cups sterilized with gamma irradiation in low-oxygen packaging wore several times faster than did the nonirradiated cups. Ion-implanting improved the wear resistance without thermal aging, but after extensive thermal aging the oxidation and wear were greater than those of the controls. Hylamer cups (that is, those that were sterilized with gas plasma) exhibited wear properties very close to those of the nonsterilized ultra-high molecular weight polyethylene cups (the controls) with or without aging. CONCLUSIONS: Sterilizing an ultra-high molecular weight polyethylene acetabular cup without radiation (for example, with ethylene oxide or gas plasma) avoids immediate and long-term oxidative degradation of the implant but does not improve the inherent wear resistance of the polyethylene. Sterilizing with use of gamma irradiation with the implant packaged in a low-oxygen atmosphere avoids immediate oxidation and cross-links the polyethylene, thereby increasing its wear resistance, but long-term oxidation of the residual free radicals may markedly reduce the wear resistance. Ideally, cross-linking with gamma irradiation to reduce wear should be done in a manner that avoids both immediate and long-term oxidation.

Acetabulum↗
PubMed2000

Interferon-gamma receptor signaling is dispensable in the development of autoimmune type 1 diabetes in NOD mice.

There have been two previous conflicting reports that the development of T-cell-mediated autoimmune diabetes (type 1 diabetes) was respectively unaffected or inhibited in NOD mice genetically deficient in the T-helper (Th) 1 cytokine interferon (IFN)-gamma or the alpha-chain subunit of its receptor. Our goal was to resolve this conundrum by congenically transferring, from a 129 donor strain to the NOD background, a functionally inactivated gene for the beta-chain signaling (located on chromosome 16) rather than the alpha-chain ligand binding domain (located on chromosome 10) of the IFN-gamma receptor. These NOD.IFNgammaRBnull mice were characterized by normal patterns of leukocyte development and T-cells that produced greatly enhanced levels of the putatively type 1 diabetes-protective Th2 cytokine interleukin (IL)-4. However, despite being unable to respond to the primary Thl cytokine IFN-gamma and having T-cells that produce greatly enhanced levels of IL-4, NOD.IFNgammaRBnull mice remained highly susceptible to type 1 diabetes. This result indicated that the previously reported inhibition of type 1 diabetes in NOD mice carrying a functionally inactivated IFN-gamma receptor alpha-chain gene may have been due to a closely linked and previously unidentified diabetes resistance allele. Furthermore, our results indicate that the pathogenicity of diabetogenic T-cells in NOD mice is not dampened by an inability to respond to IFN-gamma and a concurrent shift to greatly enhanced Th2 cytokine production. This finding calls into question whether clinical protocols designed to shift beta-cell autoreactive T-cells from a Thl to Th2 cytokine production profile will truly be safe and efficacious in blocking the development of type 1 diabetes in humans.

Animals↗
PubMed2000

Detection and analysis of intracoronary artery stent after PTCA using contrast-enhanced three-dimensional electron beam tomography.

We evaluated several three-dimensional methods of contrast-enhanced electron beam tomography (EBT) for evaluation of intracoronary stent characteristics after percutaneous transluminal coronary angioplasty (PTCA). Twenty-six patients who had undergone PTCA and stenting (31 stents) were investigated by using contrast-enhanced, electrocardiographically (ECG) triggered EBT scanning. EBT results were compared with conventional selective coronary arteriography (SCA). Overall, 27 intracoronary stents had been identified on EBT images (87.1%), while 4 stents could not be evaluated because of impaired image quality. EBT correctly identified the only case in which there was a residual stenosis at the distal portion of the stent. As compared with SCA results, EBT showed an over-estimation of intracoronary stent diameter (p < 0.001) and accurate measurement on the visualized length of the stents (p > 0.05). Fifty Hu, 100 Hu and 150 Hu were used as the observed window levels on three-dimensional (3-D) images; the accuracy for stent assessment increased with ascending window levels. EBT can reliably characterize coronary artery stents and may become a useful non-invasiveive method for patency evaluation of stented coronary segments after PTCA.

Adult↗
PubMed2000

Electron beam tomography with three-dimensional reconstruction in the diagnosis of aortic diseases.

BACKGROUND: This study was performed to evaluate the protocols of electron beam tomographic angiography and three-dimensional reconstruction for assessing the diagnostic value of aortic diseases. METHODS EXPERIMENTAL DESIGN: Retrospective and comparative study. SETTINGS: University hospital. PATIENTS: Between 1996 and 1998, 189 cases who underwent electron beam tomographic angiography and diagnosed with aortic diseases were analyzed retrospectively. The results were compared with surgical and pathological findings in 68 cases. Electron beam tomographic angiography was used single-slice-scanning with ECG-triggering for screening of the thoracic aorta, continuous-volume-scanning, permitted by continuous X-ray exposure with table incremention, was performed for the abdominal aorta scanning without ECG-triggering. Three-dimensional reconstructions were performed with shaded-surface display, multiplanar reformatting and/or maximum intensity projection methods. RESULTS: Electron beam tomography angiography with ECG-triggered sections of single-slice-scanning improved the image quality of the ascending aorta without motion artifacts. Continuous-volume-scanning was suitable for screening of the abdominal aorta because of minimizing exposure time (10-14 sec) and saving contrast media (total contrast material of 45.5+/-6.6 ml was needed). One hundred eighty-nine cases were diagnosed with aortic dissection (97 cases), aortic aneurysm (26 cases), pseudoaneurysm (8 cases), Marfan's syndrome (39 cases), Takayasu's arteritis (5 cases) and congenital aortic malformations (14 cases). Electron beam tomography results were compared with the findings of surgery (as gold standard) in 68 cases, the diagnostic accuracy was 97% (2 cases with aortic aneurysm were erroneously diagnosed with pseudoaneurysm). CONCLUSIONS: Electrocardiographically triggered, contrast-enhanced electron beam tomography is feasible for the diagnosis of all kinds of aortic diseases, with excellent three-dimensional images competitive in quality with conventional selective aortic angiography or digital subtraction angiography.

Adolescent↗
PubMed2000

[Treatment of intrauterine growth retardation with magnesium sulfate].

OBJECTIVE: To study the relationship between magnesium level in umbilical vein and mother's peripheral blood with intrauterine growth retardation (IUGR) and fetal weight. METHODS: 39 pregnant women with IUGR were randomly divided into 3 groups: Group 1 (n = 14): The patients were treated with 10% glucose 500 ml + danshen compound 14 ml + low molecular weight dextran 500 ml i.v.; Group 2 (n = 14): in addition to the same treatment as in group 1, 25% magnesium sulfate 20 ml in 5% glucose 500 ml i.v. was given; Group 3 (n = 11): no treatment was given; and another 12 normal term delivery women were served as control. Magnesium concentration levels were determined in both maternal peripheral blood and their fetal umbilical vein. RESULTS: Maternal serum magnesium level was higher in Group 2 (1.06 +/- 0.09) mmol/L than that in Group 1 (0.69 +/- 0.05) mmol/L (P < 0.05), while there was no significant difference between Group 1 and Group 3. The serum magnesium levels in both mother and fetal umbilical vein of normal pregnancy and of Group 2 were significantly higher than those of Group 1 and 3 (P < 0.01), so did the birth weight of their newborns (P < 0.05). CONCLUSION: Magnesium deficiency might be one of the causes of IUGR, and magnesium sulfate treatment was effective.

Adult↗
PubMed2000

[The acute effect of tetrandrine pulmonary targeting microspheres on hypoxic pulmonary hypertension in rats].

OBJECTIVE: To investigate the effect of tetrandrine (Tet) pulmonary targeting microspheres on hypoxic pulmonary hypertension and its selective role on pulmonary circulation. METHODS: Tet pulmonary targeting microspheres were synthesized by spraying desiccation, the content of tetrandrine in pulmonary targeting microspheres is 32%. Twenty Wistar rats were exposed to hypoxia for three weeks, the rats were given Tet pulmonary targeting microspheres and Tet aqueous solution respectively and another 10 rats were as normal control. The mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization, mean systemic blood pressure (mSBP) was measured by left femoral catheterization. RESULTS: At the end of hypoxic treatment, rats developed pulmonary hypertension. mPAP in the rats receiving Tet pulmonary targeting microspheres decreased more obviously than the rats receiving Tet aqueous solution (P < 0.05), and the effects maintained for 60 min after administration. However, the mSBP remained normal in rats receiving Tet pulmonary targeting microspheres. CONCLUSION: Tet pulmonary targeting microspheres can improve the effect of Tet on the hypoxic pulmonary hypertension and Tet has the selective role on the pulmonary circulation.

Alkaloids↗
PubMed1999

Estrogen receptor-alpha mRNA variants in murine and human tissues.

A side-by-side comparison of several normal mouse and human tissues was undertaken in order to determine if exon-deleted variant ER-alpha mRNAs are expressed in the mouse. The data showed that the complex pattern of ER-alpha alternative splicing that is detected in multiple human tissues was not apparent in murine tissues. Only low levels of an exon-4 deleted ER-alpha transcript were detected in murine tissues, although multiple relatively abundant exon-deleted ER-alpha transcripts were detected in human tissues. The data support a species-specific difference in the expression of ER-alpha variant mRNAs between mouse and human.

Alternative Splicing↗
PubMed1999

Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila.

The sensory bristles of the fruit fly Drosophila are organized in a polarized fashion such that bristles on the thorax point posteriorly. These bristles are derived from asymmetric division of sensory organ precursors (SOPs). The Numb protein, which is localized asymmetrically in a cortical crescent in each SOP, segregates into only one of the two daughter cells during cell division, thereby conferring distinct fates to the daughter cells [1] [2]. In neuroblasts, establishment of apical-basal polarity by the protein Inscuteable is crucial for orienting asymmetric division, but this is not the case for division of SOPs [3]. Instead, the Frizzled (Fz) protein mediates a planar polarity signal that controls the anteroposteriorly oriented first division (pl) of SOPs [4]. Here, we report that Flamingo (Fmi), a seven-transmembrane cadherin [5], controls the planar polarity of sensory bristles and the orientation of the SOP pl division. Both the loss of function and overexpression of fmi disrupted bristle polarity. During mitosis of the SOP, the axis of the pl division and the positioning of the Numb crescent were randomized in the absence of Fmi activity. Overexpression of Fmi and Fz caused similar effects. The dependence of proper Fmi localization on Fz activity suggests that Fmi functions downstream of Fz in controlling planar polarity. We also present evidence suggesting that Fz also functions in the Wingless pathway to pattern sensory organs.

Animals↗
PubMed1999

Neurotrophins and hippocampal synaptic transmission and plasticity.

Neurotrophins are traditionally thought to be secretory proteins that regulate long-term survival and differentiation of neurons. Recent studies have revealed a previously unexpected role for neurotrophins in synaptic development and plasticity in diverse neuronal populations. In this review, we focus on the synaptic function of brain-derived neurotrophic factor (BDNF) in the hippocampus. Although a variety of in vitro experiments have shown the ability of BDNF to acutely modulate synaptic transmission, whether BDNF truly potentiates basal synaptic transmission in hippocampal neurons remains controversial. More consistent evidence has been obtained for the role of BDNF in long-term potentiation (LTP), a cellular model for learning and memory. BDNF also potentiates high frequency transmission by modulating the number of docked vesicles and the levels of the vesicle protein synaptobrevin and synaptophysin at the CA1 synapses. Both pre- and postsynaptic effects of BDNF have been demonstrated. Recent studies have begun to address the role of BDNF in late-phase LTP and in the development of hippocampal circuit. BDNF and other neurotrophins may represent a new class of neuromodulators that regulate neuronal connectivity and synaptic efficacy. J. Neurosci. Res. 58:76-87, 1999. Published 1999 Wiley-Liss, Inc.

Animals↗
PubMed1999

Cloning, structural characterization, and chromosomal localization of the gene encoding the human prostaglandin E(2) receptor EP2 subtype.

Northern blot analysis of human placental RNA using a probe to the 5' end of the human prostaglandin E(2) (PGE(2)) EP2 receptor subtype coding region revealed the existence of a high abundance, low molecular weight transcript. To investigate the origin of this transcript, and its possible relationship to the human EP2 mRNA, we have cloned and characterized the gene encoding the human PGE(2) EP2 receptor subtype, identified transcriptional initiation and termination sites in two tissues (spleen and thymus), and determined its chromosomal localization. The human EP2 gene consists of two exons separated by a large intron, utilizes a common initiation site in both spleen and thymus at 1113 bp upstream of the translation initiation site, and has 3' transcript termini at 1140 bp and 1149 bp downstream of the translation stop site in spleen and thymus respectively. Southern and fluorescence in situ hybridization analysis demonstrated the human EP2 gene to be a single copy gene located in band 22 of the long arm of chromosome 14 (14q22). Though our initial interest in this gene was to investigate potential differential splicing of the human EP2 gene in placenta, this work demonstrates that the atypical transcript observed in placenta probably arises from a distinct, yet related, gene. Knowledge of the sequence, structure, and transcription events associated with the human EP2 gene will enable a broader understanding of its regulation and potential role in normal physiology and disease.

Amino Acid Sequence↗
PubMed1999

Differential expression and cross-regulatory function of RANTES during mycobacterial (type 1) and schistosomal (type 2) antigen-elicited granulomatous inflammation.

The role of RANTES in Th1 and Th2 cell-mediated immune responses has been enigmatic. To approach this question, we analyzed RANTES expression and function in murine models of types 1 and 2 cell-mediated pulmonary granulomas elicited with Mycobacterium bovis or Schistosoma mansoni egg Ag-coated beads, respectively. Compared with type 2, type 1 lesions had up to 4-fold greater RANTES protein and mRNA production. Type 1 draining lymph nodes also produced up to 7-fold higher levels of RANTES. Anti-RANTES Ab treatments had opposite effects, decreasing type 1 lesion area by 25% and augmenting type 2 lesions by 50%. The latter was associated with increased IL-4, IL-5, IL-10, and IL-13 production by lymph nodes. Infusion of rRANTES (1 mg/kg/day) did not affect type 1 lesions, but reduced type 2 lesion area by 27% and eosinophils by 40%. Lymph node cultures from RANTES-treated mice had augmented type 1 and impaired type 2 responses. In vitro, RANTES caused selective, dose-related inhibition of IL-4 that was largely dependent on CCR1 receptors. In conclusion, RANTES plays different roles in types 1 and 2 granuloma formation, promoting the former and mediating cross-regulatory inhibition of the latter. Moreover, RANTES may have therapeutic potential in the treatment of established type 2 hypersensitivity.

Adjuvants, Immunologic↗
PubMed1999

Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice.

Brain-derived neurotrophic factor (BDNF) promotes long-term potentiation (LTP) at hippocampal CA1 synapses by a presynaptic enhancement of synaptic transmission during high-frequency stimulation (HFS). Here we have investigated the mechanisms of BDNF action using two lines of BDNF knockout mice. Among other presynaptic impairments, the mutant mice exhibited more pronounced synaptic fatigue at CA1 synapses during high-frequency stimulation, compared with wild-type animals. Quantitative analysis of CA1 synapses revealed a significant reduction in the number of vesicles docked at presynaptic active zones in the mutant mice. Synaptosomes prepared from the mutant hippocampus exhibited a marked decrease in the levels of synaptophysin as well as synaptobrevin [vesicle-associated membrane protein (VAMP-2)], a protein known to be involved in vesicle docking and fusion. Treatment of the mutant slices with BDNF reversed the electrophysiological and biochemical deficits in the hippocampal synapses. Taken together, these results suggest a novel role for BDNF in the mobilization and/or docking of synaptic vesicles to presynaptic active zones.

Animals↗
PubMed1999

The substance P receptor is necessary for a normal granulomatous response in murine schistosomiasis mansoni.

Immune cells within the granulomas of murine schistosomiasis mansoni make the neuropeptide substance P (SP) and express neurokine 1 receptor, which is the specific receptor for substance P (SPr). It was determined if mice with deletion of the SPr (SPr-/-) would develop a normal granulomatous response to schistosome ova during the course of natural infection. Mean liver granuloma size was smaller in SPr-/- mice compared with that of wild-type control animals. Although flow analysis revealed little difference in the cellular composition of the granulomas, both splenocytes and granuloma cells from SPr-/- mice produced much less IFN-gamma and IgG2a and less IgE. The expression of Th2 cytokines (IL-4/IL-5) and IgG1 was comparable to the wild-type control. The mouse with targeted disruption of its SPr had the nonmammalian gene encoding the enzyme beta-galactosidase inserted in exon 1 of the SPr gene. There was beta-galactosidase activity in many mononuclear cells scattered throughout the schistosome granulomas of SPr-/- mice. Also, a granuloma T cell line derived from this transgenic mouse produced beta-galactosidase. These results provide further evidence that in murine schistosomiasis SPr is displayed commonly on granuloma inflammatory cells and is important for granuloma development and expression of IFN-gamma circuitry in this natural infection.

Animals↗