A syndrome resembling primary aldosteronism (Conn syndrome) in untreated HIV disease.
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HIV Infections↗
Biomedical subjects
C Hu
Publications and source records attributed to C Hu.
Proniosomes: a novel drug carrier preparation.
A procedure is described for producing a dry product which may be hydrated immediately before use to yield aqueous niosome dispersions similar to those produced by more cumbersome conventional methods. These 'proniosomes' minimize problems of niosome physical stability such as aggregation, fusion and leaking, and provide additional convenience in transportation, distribution, storage, and dosing. This report describes the preparation of dispersions of proniosome-derived niosomes, comparison of these niosomes to conventional niosomes, and optimization of proniosome formulations. In addition, conventional and proniosome-derived niosomes are compared in terms of their morphology, particle size, particle size distribution, and drug release performance in synthetic gastric or intestinal fluid. In all comparisons, proniosome-derived niosomes are as good or better than conventional niosomes.
Anti-Inflammatory Agents, Non-Steroidal↗
Decolorization and biodegradability of photocatalytic treated azo dyes and wool textile wastewater.
The photodegradation and biodegradability have been investigated for four non-biodegradable commercial azo dyes, Reactive YellowKD-3G, Reactive Red 15, Reactive Red 24, Cationic Blue X-GRL, an indicator. Methyl Orange, and one industrial wool textile wastewater, using TiO2 suspensions irradiated with a medium pressure mercury lamp. The color removal of dyes solution and dyeing wastewater reached to above 90% within 20-30 min. of photocatalytic treatment. Biochemical oxygen demand (BOD) was found to increase, while chemical oxygen demand (COD), total organic carbon (TOC) decreased, so that the ratio of BOD5/COD of the wastewater increased from original zero up to 0.75. The result implies that photocatalytic oxidation enhanced the biodegradability of the dye-containing wastewater and therefore relationship between decolorization and biodegradability exists. When the color disappeared completely, the wastewater biodegraded normally and could be discharged for further treatment. The experimental results demonstrate that it is possible to combine photocatalysis with conventional biological treatment for the remedy of wastewater containing generally non-biodegradable azo dyes.
Azo Compounds↗
On the use of survival analysis techniques to estimate medical care costs.
Measurement of treatment costs is important in the evaluation of medical interventions. Accurate cost estimation is problematic, when cost records are incomplete. Methods from the survival analysis literature have been proposed for estimating costs using available data. In this article, we clarify assumptions necessary for validity of these techniques. We demonstrate how assumptions needed for valid survival analysis may be violated when these methods are applied to cost estimation. Our observations are confirmed through simulations and empirical data analysis. We conclude that survival analysis approaches are not generally appropriate for the analysis of medical costs and review several valid alternatives.
Costs and Cost Analysis↗
Capability of serum to convert streptomycin to cytotoxin in patients with aminoglycoside-induced hearing loss.
Individual variations in sensitivity to the ototoxic effects of aminoglycoside antibiotics are well documented. Our research demonstrates that there is an apparent difference in serum from patients who are resistant or susceptible to aminoglycoside ototoxicity. In the first study, the cytotoxicity of sera from patients with and without hearing loss after various time periods following the discontinuation of aminoglycoside treatment was assayed using the isolated outer hair cell toxicity assay. The results indicate that sera from patients with hearing loss were significantly more toxic than sera from patients with normal hearing or minimal hearing loss. This toxicity may persist for up to 1 year after discontinuation of aminoglycoside therapy. In a second study, sera were obtained from patients who had received aminoglycoside therapy several years previously. None of these sera was toxic to isolated outer hair cells in vitro. Streptomycin was then incubated with the sera or a protein fraction isolated from sera, and the incubation mixtures were tested for toxicity. The percentage of damaged outer hair cells was significantly higher when streptomycin had been treated with sera or a serum protein fraction from patients with hearing loss (58+/-10% and 68+/-9%, respectively) than with sera or a serum protein fraction from a control group (10+/-5% and 17+/-4%, respectively). In addition, several incubation mixtures were analyzed using high performance liquid chromatography. A new chromatographic peak was only found in the incubations of streptomycin with serum protein from patients with hearing loss. The results suggest that sera from individuals sensitive to aminoglycoside antibiotics may metabolize these drugs to cytotoxins.
Adolescent↗
Inability of interleukin-12 to modulate T-helper 0 effectors to T-helper 1 effectors: a possible distinct subset of T cells.
Interleukin-12 (IL-12) strongly favours the development of T-helper 1 (Th1)-type cells through its ability to induce interferon-gamma (IFN-gamma) production by natural killer cells and T cells. In the present work we analysed the effects of IL-12 on the synthesis and secretion of IFN-gamma and IL-4 by human T-cell clones. Several previously described human T-cell clones exhibiting Th1, Th2 or Th0 phenotypes were used for these analyses. We demonstrated, by enzyme-linked immunosorbent assay (ELISA) and intracytoplasmic staining, that, in Th0 clones, IL-12 up-regulated the production of both IFN-gamma and IL-4 and was unable to modulate these cells to Th1-type. The up-regulation of cytokine gene expression was transcriptionally regulated and was not due to differences in mRNA stability. In Th1 cells, IL-12 up-regulated only IFN-gamma and not IL-4. However, in Th2 cells, both IFN-gamma and IL-4 were up-regulated by IL-12. This suggests that Th2 cells may be less stable than Th1 cells. We also observed that human Th2 cells expressed the IL-12beta2 receptor, in contrast to murine Th2, which lacks this receptor. The observed differences in the effects of IL-12 on the three T-cell subsets may have important ramifications for IL-12-based therapies.
Blotting, Northern↗
Regulation of alpha1-antitrypsin gene expression in human intestinal epithelial cell line caco-2 by HNF-1alpha and HNF-4.
There is still relatively limited information about mechanisms of gene expression in enterocytes and mechanisms by which gene expression is regulated during enterocyte differentiation. Using the human intestinal epithelial cell line Caco-2, which spontaneously differentiates from a cryptlike to a villouslike enterocyte, we have previously shown that there is a marked increase in transcription of the well-characterized alpha1-antitrypsin (alpha1-AT) gene during enterocyte differentiation. In this study we examined the possibility of identifying the cis-acting elements and trans-acting DNA-binding proteins responsible for expression of the alpha1-AT gene in Caco-2 cells during differentiation. Footprint analysis and electrophoretic mobility shift assays showed that hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta, and HNF-4 from nuclear extracts of Caco-2 cells specifically bound to two regions in the proximal promoter of the alpha1-AT gene. Cotransfection studies showed that HNF-1alpha and HNF-4 had a synergistic effect on alpha1-AT gene expression. RNA blot analysis showed that HNF-1alpha and HNF-4 mRNA levels and electrophoretic mobility shift assays showed that HNF-1alpha binding activity increase coordinately with alpha1-AT mRNA levels during differentiation of Caco-2 cells. Finally, overexpression of antisense ribozymes for HNF-1alpha in Caco-2 cells resulted in a selective decrease in endogenous alpha1-AT gene expression. Together, these results provide evidence that HNF-1alpha and HNF-4 play a role in the mechanism by which the alpha1-AT gene is upregulated during enterocyte differentiation in the model Caco-2 cell system.
Base Sequence↗
Population pharmacokinetics. A regulatory perspective.
The application of population approaches to drug development is recommended in several US Food and Drug Administration (FDA) guidance documents. Population pharmacokinetic (and pharmacodynamic) techniques enable identification of the sources of inter- and intra-individual variability that impinge upon drug safety and efficacy. This article briefly discusses the 2-stage approach to the estimation of population pharmacokinetic parameters, which requires serial multiple measurements on each participant, and comprehensively reviews the nonlinear mixed-effects modelling approach, which can be applied in situations where extensive sampling is not done on all or any of the participants. Certain preliminary information, such as the compartment model used in describing the pharmacokinetics of the drug, is required for a population pharmacokinetic study. The practical design considerations of the location of sampling times, number of samples/participants and the need to sample an individual more than once should be borne in mind. Simulation may be useful for choosing the study design that will best meet study objectives. The objectives of the population pharmacokinetic study can be secondary to the objectives of the primary clinical study (in which case an add-on population pharmacokinetic protocol may be needed) or primary (when a stand-alone protocol is required). Having protocols for population pharmacokinetic studies is an integral part of 'good pharmacometric practice'. Real-time data assembly and analysis permit an ongoing evaluation of site compliance with the study protocol and provide the opportunity to correct violations of study procedures. Adequate policies and procedures should be in place for study blind maintenance. Real-time data assembly creates the opportunity for detecting and correcting errors in concentration-time data, drug administration history and covariate data. Population pharmacokinetic analyses may be undertaken in 3 interwoven steps: exploratory data analysis, model development and model validation (i.e. predictive performance). Documentation for regulatory purposes should include a complete inventory of key runs in the analyses undertaken (with flow diagrams if possible), accompanied by articulation of objectives, assumptions and hypotheses. Use of diagnostic analyses of goodness of fit as evidence of reliability of results is advised. Finally, the use of stability testing or model validation may be warranted to support label claims. The opinions expressed in this article were revised by incorporating comments from various sources and published by the FDA as 'Guidance for Industry: Population Pharmacokinetics' (see the FDA home page http:/(/)www.fda.gov for further information).
Data Interpretation, Statistical↗
[Cloning and sequencing of variable region genes of HAb25 McAb against hepatocellular carcinoma].
OBJECTIVE: To clone the variable genes of HAb25 McAb against hepatocellular carcinoma. METHODS: The HAb25 variable region genes were isolated by RT-PCR technique from the HAb25 hybridoma, and its nucleic acid sequences were analyzed by the sanger's dideoxy-mediated chain-termination method. RESULTS: The gene of VH was 360 bp long encoding 120 amino acids and the gene of VL was 330 bp long encoding 110 amino acids. Only one open reading frame could be found in each of the variable genes. A comparison of the sequences of VH and VL domatins derived from the HAb25 antibody with those of the published mouse Ig genes in GenBank by computer revealed that the VH gene was homologous to the VH186.2 germline gene family (84.00%) and VL gene was homologous to the MMIgGKAVAG(82.00%). CONCLUSION: Both of the two genes are rearranged variable region genes, which are VHDJH3 for the VH and VK J K4 for the VL.
Amino Acid Sequence↗
Th2-specific protein/DNA interactions at the proximal nuclear factor-AT site contribute to the functional activity of the human IL-4 promoter.
IL-4 is a pleiotropic immunoregulatory cytokine secreted by activated Th2, but not Th1, cells. The proximal IL-4 promoter contains MARE, C/EBP, P0, octamer-like, P1, and activating protein-1 elements. The half c-Maf binding site (MARE), P0, and P1 sites were previously shown to be involved in Th2-specific transcriptional activity. Except the MARE and P1 site, the molecular basis for Th2 specificity of the P0 site has not been analyzed. Here, we provide the first detailed analysis of the P0 binding factors and show that in Th2, but not in Th1, cells, NF-AT and proteins of the activating protein-1 family are involved in cooperative binding to the P0 and the adjacent octamer-like site. In the mouse Th2 D10 cells, Oct-1/Oct-2 are also found to participate in formation of the P0-binding complexes. Mutation, deletion, and methylation interference analysis demonstrate that both the P0 and the octamer-like sequence are required for inducible binding. Furthermore, we provide the first report of the functional relevance of each site in the human IL-4 promoter by mutagenesis/transfection analysis and demonstrate that the octamer-like, P0 and P1 sites are important for the biologic function of the IL-4 promoter. The MARE site, although it was shown to be critical for the function of the murine IL-4 promoter, does not appear essential for human IL-4 promoter activity in Jurkat T cells. These findings suggest that besides c-Maf, another Th2-specific factor(s) may be involved in tissue-specific expression of the IL-4 gene.
Animals↗
Transforming growth factor-alpha and insulin-like growth factor-I, but not epidermal growth factor, elicit autocrine stimulation of mitogenesis in endometrial cancer cell lines.
OBJECTIVES: Endometrial carcinoma cell lines were evaluated for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factor I (IGF-1) production and for autocrine stimulation. METHODS: Conditioned, serum-free media (CM) from cell lines RL95-2, KLE, HEC, and Ishikawa (ISH) were concentrated radioimmunoassayed (RIA). Samples for the IGF-1 assay were extracted with acid-ethanol to remove IGF-1 binding protein. Polymerase chain reaction (PCR) was used to validate the presence of mRNA for growth factors and receptors. Cells were incubated with Ab528, an antibody blocking EGF receptors, and alphaIR3, an antibody blocking IGF-1 receptors. Proliferation was quantified using [3H]thymidine incorporation. RESULTS: TGF-alpha was detected in CM: RL95-2 (0.4 +/- 0.001 ng/ml), KLE (0.7 +/- 0.003 ng/ml), HEC (0.8 +/- 0.01 ng/ml), ISH (1.2 +/- 0.05 ng/ml). No EGF was detected in CM. In extracted samples, IGF-1 was detected in CM: RL95-2 (0.8 +/- 0. 03 ng/ml), KLE (1.25 +/- 0.02 ng/ml), HEC (1.6 +/- 0.01 ng/ml), ISH (1.6 +/- 0.08 ng/ml). Unconditioned media served as the control. EGF, TGF-alpha, and IGF-1 mRNA was identified in all cell lines, as was the mRNA for EGF and IGF-1 receptors. Incubation with Ab528 or alphaIR3 resulted in significant inhibition of DNA synthesis in HEC 1A, KLE, and ISH. No inhibition was detected in the RL95-2 cell line. A control antibody did not inhibit the cell lines. CONCLUSION: Autocrine production and stimulation of endometrial carcinoma cell lines by TGF-alpha and IGF-1 are demonstrated in three of four endometrial cancer cell lines. No measurable EGF was produced by any of the cell lines.
Autocrine Communication↗
Bcl-xL is expressed in ovarian carcinoma and modulates chemotherapy-induced apoptosis.
OBJECTIVE: To investigate the role of Bcl-xL in resistance to chemotherapy-induced apoptosis in ovarian carcinoma. METHODS: Two human ovarian carcinoma cell lines were used in this study: A2780 and SKOV3. A2780 cells were transfected with human Bcl-xL or control plasmid alone. Expression of Bcl-xL in single cell clones was analyzed by flow cytometry and protein expression was confirmed by Western blot. For in vitro chemotherapy-induced death assays, cisplatin and Taxol were used. The percentage of apoptotic cells was determined by nuclear propidium iodide staining followed by flow cytometric analysis. Human ascites samples were used to make tumor lysates which were then analyzed for expression of Bcl-xL protein by Western blot. RESULTS: A2780 cells express low levels of endogenous Bcl-xL while SKOV3 cells express high amounts as determined by Western blot. In addition, A2780 cells are sensitive to chemotherapy-induced cell death while SKOV3 cells are resistant. To determine if chemoresistance is mediated by expression of Bcl-xL, A2780 cells were transfected with Bcl-xL or control plasmid. Cells were incubated with either cisplatin or Taxol to induce apoptosis. Bcl-xL-expressing cells were highly resistant to cisplatin and Taxol compared with controls (P < 0.05). All samples of malignant ascites analyzed expressed high levels of Bcl-xL on Western blot. CONCLUSIONS: The results of these studies indicate that Bcl-xL is expressed in ovarian carcinoma, and in A2780 cells functions in a manner analogous to Bcl-2 by inhibiting chemotherapy-induced apoptosis. This may have prognostic significance; previous studies have demonstrated that patients with breast cancer that overexpress Bcl-2 have low-grade, hormonally responsive tumors. In ovarian carcinoma, another Bcl-2 family member, Bcl-xL may be responsible for modulating resistance to chemotherapy-induced apoptosis.
Antineoplastic Agents↗
Detection of hepatocellular carcinoma cells in peripheral venous blood and its significance.
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Aged↗
[Innominate osteotomy in the treatment of subluxation of hip in adult].
The symptomatic subluxation of hip is not uncommon in adults, and several kinds of surgical options are available. Twenty-six patients (26 hips) suffering from residual symptomatic subluxation of the hip were treated with innominate osteotomy during 1985 to 1991. The patients were followed-up for 4 to 9 years. The ages of the patients ranged from 22 to 38 years with an average of 26 years and 6 months. The duration of symptoms ranged from 3 to 6 years with an average of 3 years and 5 months. The pertinent prior diseases were the congenital dislocation of hip in 12 cases, Perthes disease in 10 cases, and in the remaining 4 cases, the causes were not identified. The indications for operative intervention were that presence of a reasonable articular cartilaginous space, a reasonable range of motion preserved and particularly a reasnable joint congruity must exist. A new method of re-alignment of the acetabulum was used to placing the ipsilateral foot on the contralateral thigh. The result was evaluated by the symptoms, the function of the hip and the radiographic findings. According to these criteria, the excellent results were obtained in 11 cases and the good result in 15 cases. It was suggested that the innominate osteotomy were also suitable for the treatment of residual symptomatic subluxation of hip in carefully selected adults and the new method of re-alignment of acetabulum was simple and effective.
Acetabulum↗
Differential ability of T cell subsets to undergo activation-induced cell death.
Human T cell clones were analyzed for their susceptibility to activation-induced cell death (AICD) in response to CD3/T cell receptor ligation. AICD was observed only in Th1 clones and was Fas-mediated, whereas Th2 clones resisted AICD. Analysis of a panel of Th0 clones, characterized by their ability to secrete both Th1 and Th2 cytokines, revealed that this subset included both AICD-sensitive (type A) and -resistant (type B) clones. Resistance to AICD by Th2 and Th0-type B clones was not due to lack of expression of either Fas receptor or its ligand. Paradoxically, the AICD-resistant clones were susceptible to apoptosis when Fas receptor was directly ligated by anti-Fas antibodies. However, prior activation of the resistant clones by monoclonal antibodies to CD3/TCR complex induced resistance against Fas-mediated apoptosis. Thus, the Fas-FasL pathway is critical for the induction of AICD in T cells, and moreover this pathway can be negatively regulated in the AICD-resistant clones by signals that are generated from ligation of the CD3/TCR complex.
Antigen-Presenting Cells↗
Characterization of constitutive and inducible transcription factors binding to the P2 NF-AT site in the human interleukin-4 promoter.
Interleukin-4 (IL-4) is a pleiotropic immunomodulatory cytokine secreted by T helper 2 cells. The IL-4 promoter contains multiple sites with DNA sequences homologous to the IL-2 NF-AT binding site. One of these sites--the P2 site--located between -173 and -150 was previously found to be flanked by two octamer-like motifs. NF-ATp/c and octamer proteins were suggested to bind to this region and to cooperatively activate the promoter activity (Chuvpilo et al., 1993). To precisely analyze the P2-binding factors we used antibodies against NF-ATp, NF-ATc, Fos, Jun, Oct-1 and Oct-2 in EMSA. We show here that nuclear extracts from T-cells form two P2-binding complexes--a PMA/ionomycin-inducible and a constitutive one. The PMA/ionomycin-inducible complex contains NF-ATp/c, Fos and Jun. No octamer binding factors could be detected in either of the two complexes. Analysis of the precise DNA contact points of the two complexes showed that both complexes are formed in the center of the NF-AT consensus site. No DNA contact points could be detected in the octamer-like motif site. Furthermore, purified recombinant POU domains of Oct-1 and Oct-2 failed to bind to the P2 site, suggesting that this site is not an independent octamer-binding site. Therefore, the DNA sequence at -173 to -150 of the IL-4 promoter is a binding site for NF-ATp/c and AP-1. Octamer proteins are unlikely to cooperate with NF-ATp/c at this site.
Cells, Cultured↗
Differential interaction of nuclear factors with the PRE-I enhancer element of the human IL-4 promoter in different T cell subsets.
The immunomodulatory cytokine IL-4 affects cells of most hemopoietic lineages. IL-4 is secreted by activated Th2 but not Th1 cells and plays a major role in the immune response by modulating the differentiation of naive Th cells toward the Th2 phenotype. We have previously identified an enhancer element, PRE-I, that is essential for the function of the human IL-4 promoter. To investigate the mechanisms responsible for tissue-specific expression of the IL-4 gene, we analyzed nuclear factors binding to the PRE-I site and compared the binding activities of these factors to the IL-4 promoter of Th1 and Th2 cells. We show that PRE-I interacts with PMA- and PMA/ionomycin-inducible, cyclosporin A-sensitive nuclear factors. Using anti-C/EBPbeta (NF-IL6), anti-C/EBPdelta (NF-IL6beta), anti-NF-ATc, anti-NF-ATp, anti-Fos, and anti-Jun Abs we demonstrate that the previously identified PRE-I binding factor POS-1 is composed of different transcription factors in different Th cell subsets. In the IL-4-producing Th0-like human Jurkat and mouse EL-4 cells, POS-1 (designated POS-1a) contains NF-IL6beta and Jun. In the mouse Th2 D10 cells and in the human Th2 clones, POS-1 (designated POS-1b) contains NF-IL6beta, Jun, and NF-ATc/p. In contrast, POS-1 was not found in nuclear extracts of human Th1 clones. These findings suggest that PRE-I may play a role in the differential regulation of IL-4 gene expression levels.
Animals↗
T cell help and antiphospholipid antibody immunogenesis.
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Animals↗