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Biomedical subjects

E Huang

Publications and source records attributed to E Huang.

At least 19 recordsLinked to original sources
PubMed2007

DNA methylation and histone modification regulate silencing of epithelial cell adhesion molecule for tumor invasion and progression.

Epithelial cell adhesion molecule (Ep-CAM) is believed to have a critical role in carcinogenesis and cell proliferation. However, the association of Ep-CAM with cancer invasion and progression is less clear. We found that Ep-CAM was highly expressed on low-invasive cells compared with highly invasive cells. Forced expression of Ep-CAM decreased cancer invasiveness, and silencing Ep-CAM expression elevated cancer invasiveness. Ep-CAM expression was associated with promoter methylation. Treatment with a demethylating agent, and/or the histone deacetylase inhibitor reactivated Ep-CAM expression in Ep-CAM-negative cells and inhibited cancer invasiveness. Using a promoter-reporter construct, we demonstrated methylation of the promoter fragment drive Ep-CAM-silenced transcription. Additionally, silenced Ep-CAM gene in cancer cells was enriched for hypermethylated histone 3 lysine 9. When unmethylated and active, this promoter was associated with acetylated histone 3 lysine 9. Furthermore, we observed an increased association of Ep-CAM promoter with repression components as tumor invasiveness increased. In cancer tissues, Ep-CAM expression significantly correlated with tumor progression and associated with promoter methylation. Our data support the idea that modulation of Ep-CAM plays a pivotal role in tumor invasion and progression. Moreover, aberrant DNA methylation of Ep-CAM is implicated in enhancing invasive/metastatic proclivity of tumors.

Antigens, Neoplasm↗
PubMed2004

Distribution of divalent metal transporter-1 in the monkey basal ganglia.

An accumulation of iron occurs in the brain with age, and it is thought that this may contribute to the pathology of certain neurodegenerative diseases, including Parkinson's disease. In this study, we elucidated the distribution of divalent metal transporter-1 (DMT1) in the monkey basal ganglia by immunocytochemistry, and compared it with the distribution of ferrous iron in these nuclei by Turnbull's Blue histochemical staining. We observed a general correlation between levels of DMT1, and iron staining. Thus, regions such as the caudate nucleus, putamen, and substantia nigra pars reticulata contained dense staining of DMT1 in astrocytic processes, and were also observed to contain large numbers of ferrous iron granules. The exceptions were the globus pallidus externa and interna, which contained light DMT1 staining, but large numbers of ferrous iron granules. The thalamus, subthalamic nucleus, and substantia nigra pars compacta contained neurons that were lightly stained for DMT1, but few or no iron granules. The high levels of DMT1 expression in some of the nuclei of the basal ganglia, particularly the caudate nucleus, putamen, and substantia nigra pars reticulata, may account for the high levels of iron in these regions.

Animals↗
PubMed2004

Neuronal localization and association of Niemann Pick C2 protein (HE1/NPC2) with the postsynaptic density.

Niemann-Pick disease type C (NP-C) is an inherited disorder that is characterized biochemically by cellular cholesterol and glycolipid storage, and clinically by progressive neurodegeneration. Most cases of NP-C are caused by inactivating mutations of the npc1 gene, but about 5% are linked to npc2, which encodes a soluble cholesterol binding protein, previously identified as epididymal secretory glycoprotein 1 (HE1). The present study was carried out to investigate the immunocytochemical localization of HE1/NPC2 protein in the mouse brain. Using an antibody against recombinant HE1/NPC2, we found HE1/NPC2 to be localized predominantly in neurons in the brain. Immunoreactivity for HE1/NPC2 was observed in pyramidal or projection neurons in the cerebral cortex and amygdala, and Purkinje neurons in the cerebellum. Neurons in the thalamus, hypothalamus, and globus pallidus were lightly labeled, or unlabeled. This regional pattern of expression of HE1/NPC2 is similar to our previous findings with NPC1, with a low level of expression of both NPC1 and HE1/NPC2 proteins in regions derived from the diencephalon, such as the thalamus and hypothalamus. In contrast to NPC1, however, which is predominantly in astrocytes, HE1/NPC2 was observed mainly in neurons. Electron microscopic immunocytochemistry showed that HE1/NPC2 is present in the cytosol of dendrites and on post-synaptic densities (PSD). The occurrence of HE1/NPC2 in the PSD was confirmed by Western blots of PSD-enriched brain subcellular fractions that showed the presence of HE1/NPC2 together with the PSD-associated protein, PSD-95. These results suggest that NPC1 and HE1/NPC2 are differentially enriched in astrocytes and neurons, respectively, and that HE1/NPC2 may function in supporting the integrity of the PSD of neurons.

Animals↗
PubMed2002

Rupture of the renal pelvis associated with intravenous fluid bolus.

Previously reported cases of spontaneous rupture of the kidney or ureter reflect underlying renal pathology and have been reported both spontaneously and in relationship to delivery, but not in relation to other operative procedures. A 27-year-old woman at 19 weeks' gestation developed severe right flank pain in the operating room immediately prior to cerclage placement. Postoperative renal ultrasound examination and intravenous pyelogram performed to evaluate persistent flank pain demonstrated renal pelvis rupture. No other renal abnormality was present. We postulated that increased urine flow from the fluid bolus for the spinal anesthetic precipitated the rupture.

Adult↗
PubMed2002

Closure of the subcutaneous dead space and wound disruption after Cesarean delivery.

OBJECTIVE: To determine whether suture closure of subcutaneous dead space decreases wound disruption after Cesarean delivery. METHODS: All patients undergoing Cesarean delivery at the New England Medical Center from September 1995 to June 1997 were eligible. One group (162 patients) was randomly assigned to have the subcutaneous fat layer closed with a running 3-0 plain suture. The other group (165 patients) had this layer left unclosed. Both groups had careful hemostasis of this layer with cautery and copious irrigation. All laboring and ruptured patients received prophylactic antibiotics. The patients were followed for 6 weeks after delivery for wound disruption. RESULTS: No significant differences were noted between the two groups with respect to demographic, obstetric, or surgical characteristics or loss to follow-up. Excluding those lost to follow-up (27 closed vs. 22 unclosed), there was no difference in wound infection (11 (8.1%) closed vs. 13 (9.1%) unclosed, RR 0.90, 95% CI 0.14, 2.08). There were decreases in risk of skin separation (three (2.2%) vs. six (4.2%), RR 0.53, 95% CI 0.42, 1.93) and seroma or hematoma formation (two (1.5%) vs. seven (4.9%), RR 0.30, 95% CI 0.06, 1.43) that were not statistically significant. Decreases that were not statistically significant were also noted for any wound disruption (14 (10.4%) vs. 21 (14.7%), RR 0.71, 95% CI 0.37, 1.33) and non-infected wound complication (three (2.2%) vs. eight (5.6%), RR 0.40, 95% CI 0.11, 1.47). Increasing gravidity and parity, and Cesarean delivery performed for failure to progress were independent risk factors for any wound complication. Controlling for these factors did not alter the effect of subcutaneous closure. CONCLUSIONS: Closure of the subcutaneous space does not increase and may protect against wound complications in patients undergoing Cesarean delivery.

Adult↗
PubMed2001

Predicting the clinical status of human breast cancer by using gene expression profiles.

Prognostic and predictive factors are indispensable tools in the treatment of patients with neoplastic disease. For the most part, such factors rely on a few specific cell surface, histological, or gross pathologic features. Gene expression assays have the potential to supplement what were previously a few distinct features with many thousands of features. We have developed Bayesian regression models that provide predictive capability based on gene expression data derived from DNA microarray analysis of a series of primary breast cancer samples. These patterns have the capacity to discriminate breast tumors on the basis of estrogen receptor status and also on the categorized lymph node status. Importantly, we assess the utility and validity of such models in predicting the status of tumors in crossvalidation determinations. The practical value of such approaches relies on the ability not only to assess relative probabilities of clinical outcomes for future samples but also to provide an honest assessment of the uncertainties associated with such predictive classifications on the basis of the selection of gene subsets for each validation analysis. This latter point is of critical importance in the ability to apply these methodologies to clinical assessment of tumor phenotype.

Bacillus anthracis↗
PubMed2001

Spatial shaping of cochlear innervation by temporally regulated neurotrophin expression.

Previous work suggested qualitatively different effects of neurotrophin 3 (NT-3) in cochlear innervation patterning in different null mutants. We now show that all NT-3 null mutants have a similar phenotype and lose all neurons in the basal turn of the cochlea. To understand these longitudinal deficits in neurotrophin mutants, we have compared the development of the deficit in the NT-3 mutant to the spatial-temporal expression patterns of brain-derived neurotrophic factor (BDNF) and NT-3, using lacZ reporters in each gene and with expression of the specific neurotrophin receptors, trkB and trkC. In the NT-3 mutant, almost normal numbers of spiral ganglion neurons form, but fiber outgrowth to the basal turn is eliminated by embryonic day (E) 13.5. Most neurons are lost between E13.5 and E15.5. During the period preceding apoptosis, NT-3 is expressed in supporting cells, whereas BDNF is expressed mainly in hair cells, which become postmitotic in an apical to basal temporal gradient. During the period of neuronal loss, BDNF is absent from the basal cochlea, accounting for the complete loss of basal turn neurons in the NT-3 mutant. The spatial gradients of neuronal loss in these two mutants appear attributable to spatial-temporal gradients of neurotrophin expression. Our immunocytochemical data show equal expression of their receptors, TrkB and TrkC, in spiral sensory neurons and thus do not relate to the basal turn loss. Mice in which NT-3 was replaced by BDNF show a qualitative normal pattern of innervation at E13.5. This suggests that the pattern of expression of neurotrophins rather than their receptors is essential for the spatial loss of spiral sensory neurons in NT-3 null mutants.

Afferent Pathways↗
PubMed2001

Myc requires distinct E2F activities to induce S phase and apoptosis.

Previous work has shown that the Myc transcription factor induces transcription of the E2F1, E2F2, and E2F3 genes. Using primary mouse embryo fibroblasts deleted for individual E2F genes, we now show that Myc-induced S phase and apoptosis requires distinct E2F activities. The ability of Myc to induce S phase is impaired in the absence of either E2F2 or E2F3 but not E2F1 or E2F4. In contrast, the ability of Myc to induce apoptosis is markedly reduced in cells deleted for E2F1 but not E2F2 or E2F3. From this data, we propose that the induction of specific E2F activities is an essential component in the Myc pathways that control cell proliferation and cell fate decisions.

Adenoviridae↗
PubMed2001

Prophylactic use of antibiotics for nonlaboring patients undergoing cesarean delivery with intact membranes: a meta-analysis.

OBJECTIVE: We performed a meta-analysis to examine the role of antibiotic prophylaxis in preventing postoperative infections among nonlaboring women undergoing cesarean delivery with intact membranes. STUDY DESIGN: A computerized literature search was performed with MEDLINE. Studies were included if they contained data on patients undergoing cesarean delivery in the absence of labor and ruptured membranes. Only randomized trials with a placebo control group were included. RESULTS: Seven studies were found. Use of antibiotics decreased the risk of all infectious outcomes reported. When the results of 4 studies were pooled, prophylactic antibiotic use was associated with a significant reduction in postoperative fever (relative risk, 0.25; 95% confidence interval, 0.14-0.44). A similar reduction was noted for endometritis in 4 studies (relative risk, 0.05; 95% confidence interval, 0.01-0.38). Two studies reported on wound infection and showed a trend toward a protective effect (relative risk, 0.59; 95% confidence interval, 0.24-1.45). CONCLUSION: The prophylactic use of antibiotics reduces the risk of postoperative infectious complications after cesarean delivery even in the population at lowest risk.

Antibiotic Prophylaxis↗
PubMed2001

Role for E2F in control of both DNA replication and mitotic functions as revealed from DNA microarray analysis.

We have used high-density DNA microarrays to provide an analysis of gene regulation during the mammalian cell cycle and the role of E2F in this process. Cell cycle analysis was facilitated by a combined examination of gene control in serum-stimulated fibroblasts and cells synchronized at G(1)/S by hydroxyurea block that were then released to proceed through the cell cycle. The latter approach (G(1)/S synchronization) is critical for rigorously maintaining cell synchrony for unambiguous analysis of gene regulation in later stages of the cell cycle. Analysis of these samples identified seven distinct clusters of genes that exhibit unique patterns of expression. Genes tend to cluster within these groups based on common function and the time during the cell cycle that the activity is required. Placed in this context, the analysis of genes induced by E2F proteins identified genes or expressed sequence tags not previously described as regulated by E2F proteins; surprisingly, many of these encode proteins known to function during mitosis. A comparison of the E2F-induced genes with the patterns of cell growth-regulated gene expression revealed that virtually all of the E2F-induced genes are found in only two of the cell cycle clusters; one group was regulated at G(1)/S, and the second group, which included the mitotic activities, was regulated at G(2). The activation of the G(2) genes suggests a broader role for E2F in the control of both DNA replication and mitotic activities.

Animals↗
PubMed2001

Selective inhibition of the renal angiotensin type 2 receptor increases blood pressure in conscious rats.

The angiotensin II type 2 (AT(2)) receptor is present in rat kidney; however, its function is not well understood. The purpose of this study was to evaluate the role of the AT(2) receptor in blood pressure (BP) regulation. The effects of selective inhibition of the renal AT(2) receptor with phosphorothioated antisense oligodeoxynucleotide (AS-ODN) were examined in conscious uninephrectomized rats. Oligodeoxynucleotides (AS-ODN or scrambled [S-ODN]) were infused directly into the renal interstitial space by using an osmotic pump at 1 microL/h for 7 days. Texas red-labeled AS-ODN was distributed in renal tubules in the infused but not the contralateral kidney of normal rats. Continuous renal interstitial infusion of the AS-ODN, but not S-ODN, caused a significant (P<0.01) increase in BP 1 to 5 days after the initiation of the infusion. AS-ODN-treated rats experienced an increase in systolic BP from 109+/-4 to 130+/-4 mm Hg (n=8, P<0.01), whereas S-ODN-treated (n=8) and vehicle-treated (n=8) rats did not show any significant change in BP. On day 5 of the oligodeoxynucleotide infusion, AS-ODN-treated rats exhibited a greater pressor response to systemic angiotensin II infusion (30 ng/kg per hour) than did S-ODN-treated rats (P<0.01). Renal interstitial fluid cGMP decreased from 11.9+/-0.8 to 3.6+/-0.5 pmol/mL (P<0.001), and bradykinin decreased from 0.05+/-0.05 to 0.18+/-0.03 ng/mL (P<0.001) in response to AS-ODN, but they were not significantly changed in response to S-ODN. To evaluate the effects of AS-ODN and S-ODN on AT(2) receptor expression, Western Blot analysis was performed on treated kidneys. Kidneys treated with AS-ODN had approximately 40% less expression of AT(2) receptor than did kidneys treated with S-ODN or vehicle (P<0.05). These results suggest that AS-ODN directed selectively against the renal AT(2) receptor decreased receptor expression and caused an increase in BP. We conclude that the renal AT(2) receptor plays an important role in the regulation of BP via a bradykinin/cGMP vasodilator signaling cascade.

Actins↗
PubMed2001

Novel fungal metabolites as cell wall active antifungals: fermentation, isolation, physico-chemical properties, structure and biological activity.

Two novel antifungal compounds, 1 (SCH 466457), and 2 (SCH 466456), active in a "cell wall" assay, were isolated from the fermentation broth of an unidentified fungus. The active compounds were separated from the broth filtrate by adsorption on a macroreticular resin and were purified on reverse phase HPLC. Detailed mass spectrometric and NMR experiments and degradative studies helped in elucidating the structures of these compounds. The compounds were identified to be peptides containing amino acids such as alanine, aminoisobutyric acid, proline, leucine, valine, glycine and a previously identified beta-keto acid, 2-methyl 3-oxotetradecanoic acid. (5) Both compounds were active against Candida, dermatophytes and Aspergillus (Geometric Mean MIC's, 8.9, 20 and 16 microg/ml, and 64, 128 and 23 microg/ml, respectively for 1 and 2).

Anti-Bacterial Agents↗
PubMed2000

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗
PubMed2000

Self-assessed health-related quality of life in men who have completed radiotherapy for prostate cancer: instrument validation and its relation to patient-assessed bother of symptoms.

The purpose of this study was to develop a psychometrically reliable and valid questionnaire to assess the disease-specific dimensions of health-related quality of life (HRQOL) in the urinary function (UF), bowel function (BF), and sexual function (SF) domains of prostate cancer (PCa) patients treated with radiation therapy. Patients were given a six-page questionnaire using Likert-type questions assessing three HRQOL dimensions during their follow-up visits after completing radiotherapy. Scales created from an earlier study were utilized and tested for reliability and validity. In addition, we assessed the relationship between these dimensions and the degree to which a decreased HRQOL increases the degree to which patients feel bothered about their symptoms. There are two scales within each dimension: BF, Urgency and Daily Living; UF, Urgency and Weakness of Stream; SF, Interest/Satisfaction and Impotence. Internal-consistency reliability coefficients (Cronbach's alpha) for the proposed scales range from 0.48 to 0.92, and all item-scale correlations and divergence correlations validate the use of the scales, ranging from 0.49 to 0.89. The validity of these scales is also confirmed by the rising median scores with rising reported levels of patient-perceived "bother." The different dimensions have differing quantitative influences on patients. We have developed a prostate-specific HRQOL instrument that is an adequate and suitable tool for measuring HRQOL along three distinct dimensions for patients who have completed radiotherapy for PCa. Psychometric standards for reliability and validity were met for the proposed scales. Moreover, positive correlations were found between these dimensions and how bothered patients were by their symptoms, suggesting important relationships that should be followed in PCa patients after radiotherapy. Certain scales have strong influences on patient-perceived "bothersomeness" of symptoms, such as loss of control of BF, urgency of BF, urgency of urination, and level of interest/satisfaction in sex. Compared to our earlier study on patients being treated with radiotherapy for PCa, this study produced very similar results. With some modification, the same questionnaire could be used for both groups of patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 163-172 (2000).

Adult↗
PubMed2000

Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes.

Notch proteins regulate many developmental processes. Notch1 is highly expressed on thymocytes, but its role in regulating their development is not known. We show that activation of Notch1 signaling in CD4+CD8+ double positive thymocytes promotes the maturation of both CD4+ and CD8+ single positive thymocytes and that this occurs in the absence of interactions between the T cell receptor and MHC molecules expressed on thymic epithelial cells. We have also identified several genes that are transcriptionally regulated by Notch1 in T cells and show that they are upregulated during maturation into both single positive lineages. These observations suggest that Notch1 signaling plays a role in promoting maturation into both the CD4 and CD8 T cell lineages.

ADAM Proteins↗
PubMed2000

Dexamethasone pharmacokinetics in the inner ear: comparison of route of administration and use of facilitating agents.

There is growing otologic interest in treating inner ear disorders, such as sudden sensorineural hearing loss and acute or unremitting Meniere's disease, with intratympanic dexamethasone (IT-DEX). Although anecdotally reported, there are no scientific clinical papers and few prior laboratory research publications on the subject. This study compares perilymph dexamethasone concentrations after systemic and intratympanic administration and assesses the role of 3 potential transport facilitators of IT-DEX into perilymph. Forty guinea pigs (79 ears) were randomly separated into 5 groups. Dexamethasone levels were measured by radioimmunoassay. IT-DEX resulted in higher perilymph steroid levels than intravenous dexamethasone (P < 0.05). Histamine facilitator resulted in significantly higher perilymph steroid levels than IT-DEX alone (P < 0.05). Neither hyaluronic acid nor dimethylsulfoxide was a potent facilitator. This study demonstrates that IT-DEX administration results in superior perilymph levels within 1 hour of administration and does not result in systemic absorption. Histamine is a potent facilitating agent. The clinical implications are considerable.

Administration, Topical↗
PubMed2000

Regulation of renal epithelial cell affinity for calcium oxalate monohydrate crystals.

The binding and internalization of calcium oxalate monohydrate (COM) crystals by tubular epithelial cells may be a critical step leading to kidney stone formation. Exposure of MDCK cells to arachidonic acid (AA) for 3 days, but not oleic or linoleic acid, decreased COM crystal adhesion by 55%. Exogenous prostaglandin PGE(1) or PGE(2) decreased crystal binding 96% within 8 h, as did other agents that raise intracellular cAMP. Actinomycin D, cycloheximide, or tunicamycin each blocked the action of PGE(2), suggesting that gene transcription, protein synthesis, and N-glycosylation were required. Blockade of crystal binding by AA was not prevented by the cyclooxygenase inhibitor flurbiprofen, and was mimicked by the nonmetabolizable AA analog eicosatetryanoic acid (ETYA), suggesting that generation of PGE from AA is not the pathway by which AA exerts its effect. These studies provide new evidence that binding of COM crystals to renal cells is regulated by physiological signals that could modify exposure of cell surface molecules to which the crystals bind. Intrarenal AA, PGs, and/or other agents that raise the intracellular concentration of cAMP may serve a protective function by preventing crystal adhesion along the nephron, thereby defending the kidney against crystal retention and stone formation.

5,8,11,14-Eicosatetraynoic Acid↗