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Biomedical subjects

J Lu

Publications and source records attributed to J Lu.

At least 217 records · Page 12Linked to original sources
PubMed2000

Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress.

Activation of the zinc-finger transcription factor early growth response (Egr)-1, initially linked to developmental processes, is shown here to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Chemokine, adhesion receptor, procoagulant and permeability-related genes are coordinately upregulated by rapid ischemia-mediated activation of Egr-1. Deletion of the gene encoding Egr-1 strikingly diminished expression of these mediators of vascular injury in a murine model of lung ischemia/reperfusion, and enhanced animal survival and organ function. Rapid activation of Egr-1 in response to oxygen deprivation primes the vasculature for dysfunction manifest during reperfusion. These studies define a central and unifying role for Egr-1 activation in the pathogenesis of ischemic tissue damage.

Animals↗
PubMed2000

M-ficolin is expressed on monocytes and is a lectin binding to N-acetyl-D-glucosamine and mediates monocyte adhesion and phagocytosis of Escherichia coli.

Ficolins are a group of multimeric proteins that contain collagen-like and fibrinogen-like (FBG) sequences. Three types of ficolins have been characterized: H-, L- and M-ficolins. Both H- and L-ficolins have demonstrated lectin activities. In the present study, the FBG domain of M-ficolin was expressed and shown to bind to N-acetyl-D-glucosamine. M-ficolin mRNA was expressed in monocytes but not in the more differentiated macrophages and dendritic cells. By flow cytometry, surface biotinylation and immunoprecipitation, we showed that M-ficolin was associated with the surface of promonocytic U937 cells. M-ficolin transiently expressed in COS-7 cells was also clearly detected on the cell surface by immunoprecipitation. By flow cytometry, M-ficolin was detected on peripheral blood monocytes but not on lymphocytes or granulocytes. Immobilized rabbit anti-M-ficolin F(ab')2 mediated U937 cell adhesion, and the antibody also inhibited phagocytosis of Escherichia coli K-12 by U937 cells. Therefore, M-ficolin might act as a phagocytic receptor or adaptor on circulating monocytes for micro-organism recognition and may potentially mediate monocyte adhesion.

Acetylglucosamine↗
PubMed2000

Two new acyclic diterpene-gamma-lactones from Salix matsudan.

Two new phytane-type diterpene-gamma-lactones named hanliuine I (1) and hanliuine II (2), were isolated from leaves of Salix matsudana (chinese name "hanliu", Berberidaceae). Their structures were deduced from 1D and 2D NMR techniques.

4-Butyrolactone↗
PubMed2000

Genetic expression by fetal chorionic villi during the first trimester of human gestation.

OBJECTIVE: The growth and differentiation of the embryo and the contiguous placental structures are fundamental to human reproduction and survival. Little is known, however, about the genetic control of these processes during early human development. Normal placentation is the result of a well-orchestrated sequence of events that consists of cellular adhesion and limited invasion controlled by relatively unknown genetic processes. We hypothesized that genes expressed by first-trimester chorionic villi constitute critical regulators of placentation and hence of early human development. Our objective was therefore to isolate and characterize genes, both known and unknown, expressed by the human placenta during the first trimester. STUDY DESIGN: Tissues collected consisted of placental material collected during first-trimester elective pregnancy terminations. Fetal chorionic villi were separated grossly from maternal decidual and quickly frozen in liquid nitrogen for ribonucleic acid preservation. Tissues from different gestational ages were kept separate. Total ribonucleic acid was extracted, messenger ribonucleic acid was isolated, and complementary deoxyribonucleic acid was synthesized. Complementary deoxyribonucleic acid was cloned into the ZAP Express lambda vector (Stratagene, La Jolla, Calif). Automated sequencing of random plaques was done. Sequence homology was searched for with the Basic Local Assignment Search Tool to search the Genbank database (National Center for Biotechnology Institute, Bethesda, Md). In the event that a known gene sequence was derived, no further workup was undertaken. If no homology was identified, the complete complementary deoxyribonucleic acid insert was sequenced in its entirety. Novel genes were further characterized by tissue-specific patterns, cellular localization, and chromosomal location. Expression by fetal villi was confirmed by reverse transcriptase polymerase chain reaction. RESULTS: We isolated a number of genes known to be expressed at the maternal-fetal interface. Seventeen of 186 random clones were >1 kilobase in length and did not display homology with known genes, and these may therefore constitute novel genes critical for placentation. One of the clones from a human chorionic villi complementary deoxyribonucleic acid library at 12 weeks' gestation is a 7-kilobase gene that is also abundantly expressed in human fetal brain, lung, liver, and kidney. In situ hybridization localized the transcript to the fetal renal glomerulus. CONCLUSIONS: Our findings indicate that the placenta serves as a rich source for potential novel gene expression. Seventeen clones were >1 kilobase in length and are potential novel genes involved in early first-trimester placentation. One of these 17 potential novel genes is expressed in abundance in several fetal tissues, which suggests a role in early human fetal development. Other potential novel genes are currently being characterized. The powerful molecular techniques that we used to isolate genes expressed by early fetal chorionic villi will lead us to a better understanding of the genetic control of normal human reproduction. They also may be used to study obstetric and other human disease.

Adult↗
PubMed2000

The metabolic availability of vitamin A is decreased at the onset of diabetes in BB rats.

Streptozotocin (STZ)-induced diabetic rats have been associated with an impaired metabolic availability of vitamin A (retinol). This study was undertaken to investigate whether Biobreeding (BB) rats, in which diabetes mellitus resembling human type I diabetes develops spontaneously, respond the same way at the onset of diabetes. Weaning diabetes-prone (BBdp) and normal (BBn) BB rats consumed NIH-07 nonpurified diet ad libitum until 120 d of age. Plasma and hepatic concentrations of retinol and its carriers, retinol-binding protein (RBP) and transthyretin (TTR) were lower in diabetic BB (BBd) rats than in BBn rats. In parallel with RBP, the abundance of mRNA was lower in the liver of BBd rats. Furthermore, the status of zinc, an important factor for the synthesis of RBP, was also disturbed in BBd rats, as indicated by lower circulatory levels and greater urinary excretion. To determine whether the biochemical evidence of vitamin A deficiency in BBd rats could be reversed, BBdp rats were fed a diet supplemented with vitamin A either alone or in combination with zinc. None of these treatments increased plasma vitamin A concentration. The hepatic abundance of RBP mRNA was significantly greater, whereas circulatory RBP concentrations were unaffected by vitamin A plus zinc supplementation. Overall, these results suggest that impaired metabolic availability of vitamin A, possibly caused by its decreased transport from hepatic stores, is another metabolic derangement associated with type I diabetes.

Animals↗
PubMed2000

Cervical intervertebral disc space narrowing and size of intervertebral foramina.

Computer-assisted simulation of C4-C5, C5-C6, and C6-C7 intervertebral disc space narrowing was performed on 16 anatomic specimen cervical spines to determine the relationship of the cross sectional foraminal areas with the degree of narrowing of the cervical intervertebral disc space. Compared with normal foraminal area values, reduction of 20% to 30% of the foraminal area was found after 1 mm narrowing of the intervertebral disc spaces; reduction of 30% to 40% of the foraminal area was found after 2 mm narrowing of the intervertebral disc space; and reduction of 35% to 45% of the foraminal area was found after 3 mm narrowing of the intervertebral disc space. Statistically significant differences were found among the remaining cross sectional foraminal areas after different degrees of intervertebral disc space narrowing. Compression of the nerve root within the intervertebral foramina after the collapse of the intervertebral disc space cannot be ignored, and an appropriate surgical procedure to maintain the normal height of the disc space is essential. The size of the intervertebral foramen is related directly to the height of the intervertebral disc space. A 3-mm vertical reduction of the intervertebral disc space is associated more frequently with severe narrowing of the neuroforamen.

Aged↗
PubMed2000

The structure of human aldose reductase bound to the inhibitor IDD384.

The crystallographic structure of the complex between human aldose reductase (AR2) and one of its inhibitors, IDD384, has been solved at 1.7 A resolution from crystals obtained at pH 5.0. This structure shows that the binding of the inhibitor's hydrophilic head to the catalytic residues Tyr48 and His110 differs from that found previously with porcine AR2. The difference is attributed to a change in the protonation state of the inhibitor (pK(a) = 4.52) when soaked with crystals of human (at pH 5.0) or pig lens AR2 (at pH 6.2). This work demonstrates how strongly the detailed binding of the inhibitor's polar head depends on its protonation state.

Aldehyde Reductase↗
PubMed2000

Higher-order harmonics of limited diffraction Bessel beams

We investigate theoretically the nonlinear propagation of the limited diffraction Bessel beam in nonlinear media, under the successive approximation of the KZK equation. The result shows that the nth-order harmonic of the Bessel beam, like its fundamental component, is radially limited diffracting, and that the main beamwidth of the nth-order harmonic is exactly 1/n times that of the fundamental.

Journal Article↗
PubMed2000

Upregulation of tyrosine kinase TKT by the Epstein-Barr virus transactivator Zta.

The Zta protein is a key transactivator involved in initiating the Epstein-Barr virus (EBV) lytic cascade. In addition to transactivating many viral genes, Zta has the capacity to influence host cellular signals by binding to promoter regions or by interacting with several important cellular factors. Based on the observation that tyrosine kinases play central roles in determining the fate of cells, a kinase display assay was used to investigate whether cells expressing Zta have an altered pattern of kinase expression. The assay revealed that TRK-related tyrosine kinase (TKT) is expressed at significant levels in Zta transfectants but not in control cells. Additional evidence was obtained from Northern and Western blotting. Importantly, the upregulation of phosphorylated TKT and TKT downstream effector matrix metalloproteinase 1 in Zta transfectants hinted that TKT might initiate a signaling cascade in Zta-expressing cells. In addition, deletion analysis of the Zta protein revealed that the transactivation and dimerization domains were both essential for the upregulation of TKT transcription. Moreover, correlation of expression levels of Zta and TKT transcripts in nasopharyngeal carcinoma biopsy specimens was clearly demonstrated by quantitative PCR (Q-PCR), which provides the first evidence for an effect of Zta on cellular gene expression in vivo. These findings offer insight into the virus-cell interactions and may help us elucidate the role of EBV in tumorigenesis.

Cell Line, Transformed↗
PubMed2000

Compensatory sleep response to 12 h wakefulness in young and old rats.

There is a pronounced decline in sleep with age. Diminished output from the circadian oscillator, the suprachiasmatic nucleus, might play a role, because there is a decrease in the amplitude of the day-night sleep rhythm in the elderly. However, sleep is also regulated by homeostatic mechanisms that build sleep drive during wakefulness, and a decline in these mechanisms could also decrease sleep. Because this question has never been addressed in old animals, the present study examined the effects of 12 h wakefulness on compensatory sleep response in young (3.5 mo) and old (21.5 mo) Sprague-Dawley and F344 rats. Old rats in both strains had a diminished compensatory increase in slow-wave sleep (SWS) after 12 h of wakefulness (0700-1900, light-on period) compared with the young rats. In contrast, compensatory REM sleep rebound was unaffected by age. To assess whether the reduced SWS rebound in old rats might result from loss of neurons implicated in sleep generation, we counted the number of c-Fos immunoreactive (c-Fos-ir) cells in the ventral lateral preoptic (VLPO) area and found no differences between young and old rats. These findings indicate that old rats, similar to elderly humans, demonstrate less sleep after prolonged wakefulness. The findings also indicate that although old rats have a decline in sleep, this cannot be attributed to loss of VLPO neurons implicated in sleep.

Adaptation, Physiological↗
PubMed2000

Pulmonary expression of early growth response-1: biphasic time course and effect of oxygen concentration.

Hypoxia induces complex adaptive responses. In this report, induction of early growth response-1 (Egr-1) transcripts in lungs of mice subjected to hypoxia is shown to be dose and time dependent. Within 30 min of hypoxia, Egr-1 transcripts were approximately 20-fold elevated in 6% oxygen, approximately 5.2-fold increased by 10% oxygen, and returned to the normoxic baseline by 12% oxygen. Time course studies up to 48 h showed a biphasic profile with an initial steep rise in Egr-1 transcripts after 0.5 h of hypoxia and a second elevation beginning after 20-24 h. Hypoxic induction of Egr-1 was paralleled by enhanced expression of the downstream target gene tissue factor. Egr-1 and tissue factor antigen were visualized in bronchial and vascular smooth muscle and in alveolar macrophages. Egr-1 has the capacity to modulate expression of genes involved in the remodeling of the extracellular matrix and properties of smooth muscle, thus possibly contributing to the pulmonary response to chronic hypoxia.

Animals↗
PubMed2000

Anatomical and radiological considerations of the fifth metatarsal bone.

Twenty cadaver fifth metatarsals were harvested from cadaver feet. They were then sectioned coronally in three locations. The cortical thickness (medial, lateral, dorsal, and plantar) and the intra-medullary canal diameter (dorsoplantar and mediolateral) were measured at the three sectional sites. The intra-medullary canal of six specimens was outlined with radiopaque solder wire. The canal was then examined radiographically with the lateral and dorsoplantar views. A lateral bow on the dorsoplantar view was observed in some specimens, which could contribute to surgical complications. On lateral view the intramedullary canal appeared straight in all specimens. The canal projects at least partially into the fifth metatarsal cuboid joint. When considering intra-medullary fixation a surgeon must take into account quality of bone stock and bowing of the canal. A bowed intra-medullary canal lends to vulnerability of the medial cortex at roughly mid-shaft of the fifth metatarsal. The canal has a narrower diameter in the dorsoplantar dimension than the mediolateral dimension. The cortical thickness was found to be less in the dorsal and plantar areas of the fifth metatarsal when compared to medial and lateral cortex. All of these findings lead to causes for complication in intra-medullary fixation of the fifth metatarsal.

Aged↗
PubMed2000

Survival advantage from higher-dose radiation therapy for clinically localized prostate cancer treated on the Radiation Therapy Oncology Group trials.

PURPOSE: We evaluated the effect of external-beam radiation therapy on disease-specific survival (death from causes related to prostate cancer) and overall survival in men with clinically localized prostate cancer. METHODS: From 1975 to 1992, 1,465 men with clinically localized prostate cancer received radiation therapy on four Radiation Therapy Oncology Group phase III randomized trials and were pooled for this analysis. No one received androgen-deprivation therapy with his initial treatment. All original histology had central pathologic review for grading using the Gleason classification system. Total delivered radiation dose ranged from 60 to 78 Gy (median, 68.4 Gy). The median follow-up time was 8 years. RESULTS: A Cox regression model revealed that Gleason score was an independent predictor of disease-specific survival and overall survival. The 10-year disease-specific survival rates by Gleason score were as follows: score of 2 through 5, 85%; score of 6, 79%; score of 7, 62%; and score of 8 through 10, 43%. Stratifying outcome by this important prognostic factor revealed that higher radiation dose was a significant predictor for improved disease-specific survival and overall survival only for those patients whose cancers had Gleason scores of 8 through 10 (P <.05). After adjusting for clinical T stage, nodal status, and age, treating with a higher radiation dose was associated with a 29% lower relative risk of death from prostate cancer and 27% reduced mortality rate (P <.05). CONCLUSION: These data demonstrate that higher-dose radiation therapy can significantly reduce the risk of dying from prostate cancer in men with clinically localized disease. This survival benefit is restricted to men with poorly differentiated cancers.

Aged↗
PubMed2000

Occipital screws in occipitocervical fusion and their relation to the venous sinuses: an anatomic and radiographic study.

This study examined the safe zone for placement of occipital screws without endangering the sinuses. In the first part of the study, 10 cadaveric skulls were exposed. The borders of the confluences and the transverse sinuses were located on the outer table of the occiput. In the second part of the study, six cadaveric skulls were used and screws were placed in different sites and angiography of the venous sinuses was performed. The exact location of the venous sinuses on the outer table of the occiput were analyzed. The examination of the relationship between occipital screws placed at different sites and the venous sinuses clearly demonstrated that whenever the screws were inserted at the level of the external occipital protuberance, or 1 cm below it, sinus injury could rarely be avoided. To enhance the safety of the occipitocervical fusion, the external occipital protuberance should be avoided, and occipital screws should be placed at least 2 cm below the superior nuchal line.

Atlanto-Occipital Joint↗
PubMed2000

Anterior approach to the cervical spine: surgical anatomy.

While performing the anterior approach to the cervical vertebral bodies, injury to important anatomic structures in the vicinity of the dissection represents a serious risk. The midportion of the recurrent laryngeal nerve and the external branch of the superior laryngeal nerve are encountered in the anterior approach to the lower cervical spine. The recurrent laryngeal nerve is vulnerable to injury on the right side, especially if ligation of inferior thyroid vessels is performed without paying sufficient attention to the course and position of the nerve, and the external branch of the superior laryngeal nerve is vulnerable to injury during ligature and division of the superior thyroid artery. Avoiding injury to the recurrent laryngeal nerve (especially on the right side) and superior laryngeal nerve is a major consideration in the anterior approach to the lower cervical spine. The sympathetic trunk is situated in close proximity to the medial border of the longus colli at the C6 level (the longus colli diverge laterally, whereas the sympathetic trunk converges medially). The damage leads to the development of Horner's syndrome with its associated ptosis, meiosis, and anhydrosis. Awareness of the regional anatomy of the sympathetic trunk may help in identifying and preserving this important structure while performing anterior cervical surgery or during exposure of the transverse foramen or uncovertebral joint at the lower cervical levels. Finally, the spinal accessory nerve (embedded in fibroadipose tissue in the posterior triangle of the neck) is prone to injury. Its damage will result in an obvious shoulder droop, loss of shoulder elevation, and pain. Prevention of inadvertant injury to the accessory nerve is critical in the neck dissection.

Cadaver↗
PubMed2000

Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH) is a common genetic lipid disorder with a frequency of 1-2% in the population. In addition to the hypercholesterolemia and/or hypertriglyceridemia that affected individuals exhibit, small, dense LDL particles and decreased HDL-cholesterol levels are traits frequently associated with FCH. Recently, we reported that families with FCH and families enriched for coronary artery disease (CAD) share genetic determinants for the atherogenic lipoprotein phenotype (ALP), a profile presenting with small, dense LDL particles, decreased HDL-cholesterol levels, and increased triglyceride levels. Other studies in normolipidemic populations have shown that the hepatic lipase (HL) gene is linked to HDL-cholesterol levels and that a polymorphism within the HL promoter (-514C-->T) is associated with increased HDL-cholesterol levels as well as larger, more buoyant LDL particles. In the present study, we tested whether the HL gene locus also contributes to ALP in a series of Dutch FCH families using nonparametric sibpair linkage analysis and association analysis. Evidence for linkage of LDL particle size (P < 0.019), HDL-cholesterol (P < 0.003), and triglyceride levels (P < 0.026) to the HL gene locus was observed. A genome scan in a subset of these families exhibited evidence for linkage of PPD (LOD = 2.2) and HDL-cholesterol levels (LOD = 1.2) to the HL gene locus as well. The -514C-->T promoter polymorphism was significantly associated (P < 0.0001) with higher HDL-cholesterol levels in the unrelated males of this population, but not in unrelated females. No association was observed between the polymorphism and LDL particle size or triglyceride levels. Our results provide support that ALP is a multigenic trait and suggest that the relationship between small, dense LDL particles, HDL-cholesterol, and triglyceride levels in FCH families is due, in part, to common genetic factors.

Adult↗