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Biomedical subjects

Q Yi

Publications and source records attributed to Q Yi.

At least 37 records · Page 2Linked to original sources

Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells.

Multiple myeloma (MM) is a B-cell malignancy. The monoclonal immunoglobulin, secreted by myeloma plasma cells, carries unique antigenic determinants (idiotype [Id]) that can be regarded as a tumor-specific antigen. Id-based immunotherapy has been explored in myeloma patients for the purpose of enhancing or inducing Id-specific immune responses that might lead to tumor destruction. However, despite some evidence obtained from mouse plasmacytoma models, it is still unclear whether Id-specific immunity may play a role in the regulation of tumor cells in MM. In the current study, using dendritic cells (DCs) as antigen-presenting cells, autologous Id-specific cytotoxic T lymphocyte (CTL) lines containing both CD4+ and CD8+ T cells were generated from myeloma patients. The results show that Id-specific CTLs not only recognized and lysed autologous Id-pulsed DCs but also significantly killed the autologous primary myeloma cells. The cytotoxicity against the primary tumor cells was major histocompatibility complex (MHC) class I- and, to a lesser extent, class II-restricted, indicating that myeloma cells could process Id protein and present Id peptides in the context of their surface MHC molecules. Furthermore, the CTLs lysed the target cells mainly through the perforin-mediated pathway because Concanamycin A, but not Brefeldin A-the selective inhibitors for perforin- or Fas-mediated pathways-abrogated the cytolytic activity of the cells. These CTLs secreted predominantly interferon-gamma and tumor necrosis factor-alpha on antigen stimulation, indicating that they belong to the type-1 T-cell subsets. Taken together, these findings represent the first demonstration that Id-specific CTLs are able to lyse autologous tumor cells in MM and, thus, provide a rationale for Id-based immunotherapy in the disease.

Antigens, Neoplasm↗

Telomerase activity in plasma cell dyscrasias.

Activation of telomerase is essential for in vitro cellular immortalization and tumorigenesis. In the present study, we investigated telomerase activation and its implications in plasma cell dyscrasias including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plasma cell leukaemia (PCL). All 5 patients with MGUS exhibited normal levels of telomerase activity in their plasma cells. Elevated telomerase activity was found in the samples from 21/27 patients with MM and 4/4 with PCL. In addition, 4 myeloma cell lines all expressed high levels of telomerase activity. The expression of telomerase reverse transcriptase (hTERT) and telomerase RNA template (hTER) was positively associated with the levels of telomerase activity in MM/PCL. Tankyrase expression was upregulated, concomitant with the induction of hTERT and activation of telomerase in MM/PCL. The present findings indicate that MGUS cells may not be immortalized and that activation of telomerase plays a role in the malignant transformation from MGUS to MM.

Adult↗

Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE).

BACKGROUND: Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE), a substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial, was a prospective, double-blind, 3x2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients. METHODS AND RESULTS: A total of 732 patients >/=55 years of age who had vascular disease or diabetes and at least one other risk factor and who did not have heart failure or a low left ventricular ejection fraction were randomly assigned to receive ramipril 2.5 mg/d or 10 mg/d and vitamin E (RRR-alpha-tocopheryl acetate) 400 IU/d or their matching placebos. Average follow-up was 4.5 years. Atherosclerosis progression was evaluated by B-mode carotid ultrasound. The progression slope of the mean maximum carotid intimal medial thickness was 0.0217 mm/year in the placebo group, 0.0180 mm/year in the ramipril 2.5 mg/d group, and 0.0137 mm/year in the ramipril 10 mg/d group (P=0.033). There were no differences in atherosclerosis progression rates between patients on vitamin E and those on placebo. CONCLUSIONS: Long-term treatment with ramipril had a beneficial effect on atherosclerosis progression. Vitamin E had a neutral effect on atherosclerosis progression.

Aged↗

Biodegradation of quinoline by gel immobilized Burkholderia sp.

Burkholderia sp, a gram-negative, rod-shaped, aerobe, capable of degrading quinoline was immobilized in calcium alginate gel beads and used for degradation of quinoline in aqueous solution in the reactor. The optimal conditions for immobilization of the microorganism, such as alginate concentration, calcium ion concentration, initial cell loading, hardening time and bead size, were determined with a view to improving the quinoline degradation rate. The characteristics of quinoline degradation by immobilized microbial cells were investigated. The repeated use of immobilized cells for quinoline degradation was performed and the results revealed that the bioactivity of immobilized cells was stable over 100 h in the repeated batch cultivation for quinoline degradation.

Biodegradation, Environmental↗

Myeloma-reactive allospecific cytotoxic T lymphocytes lyse target cells via the granule exocytosis pathway.

Accumulating evidence indicates that a graft-vs.-myeloma effect (GVM) and its associated clinical remission of the disease can be induced by donor lymphocyte infusion in myeloma patients who have relapsed after allogeneic bone marrow transplantation. Although it is believed that GVM is induced by allospecific T cells, T-cell subsets and the mechanisms involved in the killing of myeloma cells by donor T cells have not been studied. In this study, we generated allospecific cytotoxic T lymphocyte (CTL) lines against three different myeloma cell lines, ARK, ARP-1 and U266, from unmatched healthy donors and examined their cytotoxicity against the target cells. Our results demonstrate that the allospecific CTLs efficiently lysed myeloma cells. The observed cytotoxicity was mediated mainly by CD8+ T cells and inhibited by MHC class I-blocking antibody. Furthermore, the CTLs lysed the target cells via the perforin-mediated pathway, as concanamycin A, but not brefeldin A (the selective inhibitors for perforin- or Fas-mediated pathways respectively) or tumour necrosis factor-alpha (TNF-alpha)-blocking antibody, abrogated the cytolytic activity of the cells. These CTLs expressed and produced predominantly TNF-alpha and interferon-gamma (IFN-gamma), indicating that they belong to the type 1 T-cell subsets. Taken together, these results indicate that CD8+ allospecific T cells may be responsible for mediating GVM and that the granule-mediated lysis of target cells is the major pathway in the CD8+ T-cell response against myeloma cells.

Adoptive Transfer↗

Cytotoxic T-lymphocyte antigen-4 microsatellite polymorphism is associated with multiple myeloma.

Multiple myeloma (MM) is a B-lineage malignancy with unknown aetiology. It has been considered that predisposing genetic factors might be implicated in the disease. In this study, the microsatellite polymorphism in the exon 3 of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene was analysed in patients with MM and monoclonal gammopathy of undetermined significance (MGUS), together with ethnically matched healthy controls. The results showed that frequencies of the genotype 86/86 and of the allele 86 were significantly decreased in MM and MGUS compared with matched healthy controls, indicating that the CTLA-4 microsatellite polymorphism might represent a susceptibility locus for MM and MGUS.

Abatacept↗

Trends in health service delivery for cataract surgery at a large Australian ophthalmic hospital.

PURPOSE: To evaluate trends in health service delivery for cataract surgery at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. METHODS: A retrospective study was conducted of computerized hospital admissions for cataract surgery from July 1994 through June 1999. Main outcome measures included the annual number of cataract surgeries, waiting time, percentage of patients hospitalized overnight, length of overnight hospitalization, type of cataract surgery, surgery duration and total time in the operating theatre. RESULTS: Although the annual number of patients undergoing cataract surgery increased from 3395 to 4796 over the 5-year study interval, there was a 13-day reduction in mean waiting time for public patients, a 30% reduction in overnight hospitalizations and a half-day reduction in length of hospitalization for all patients. There was also an increasing trend in use of phacoemulsification cataract extraction. CONCLUSIONS: The health-care delivery for cataract surgery appears to have improved during the past 5 years at the Royal Victorian Eye and Ear Hospital.

Aged↗

Controlled study of the use of autologous serum in dry eye patients.

PURPOSE: To determine the efficacy and safety of topical autologous serum as a treatment of dry eye patients. METHODS: A 2-month, prospective, single-masked, placebo-controlled study was conducted in patients with bilateral severe dry eye. One eye was randomized to receive the patient's own serum as a tear substitute, and the fellow eye received unpreserved normal saline solution as a placebo. Subjective symptoms and clinical parameters of dry eye including conjunctival impression cytology were assessed at baseline and 1 week, 1 month, and 2 months after treatment. RESULTS: Twelve dry eye patients were enrolled. Both subjective symptoms (discomfort, foreign-body sensation, dryness, and photophobia), objective signs (fluorescein and rose bengal staining and conjunctival impression cytology) improved significantly in treated eyes compared with baseline. Control eyes also had improvement in symptoms, signs, and rose bengal staining compared with baseline. Neither Schirmer test results nor tear break-up time improved in either group. The means score of all parameters were improved in both groups, and the results of conjunctival impression cytology were better in treated eyes; however, these results are not significantly different. There were no serious adverse effects observed in this study. CONCLUSIONS: There was a trend toward improvement in symptoms and signs of dry eye including cytologic changes after application of autologous serum in severe dry eye patients. However, this trend was not statistically significant. A larger scale study is warranted.

Administration, Topical↗

Soy intake and the maintenance of peak bone mass in Hong Kong Chinese women.

Our previous study on bone health among premenopausal women showed that bone mass consolidation is attained by the early 30s, and small loss of spinal bone mineral density (SBMD) occurs soon after peak bone mass attainment. Recent interest has been shown in the potential beneficial effects of phytoestrogens on bone health. However, data are lacking, particularly in Asian women. This study aims to investigate the effect of soy isoflavones intake on the maintenance of peak bone mass in a cohort of 132 women aged 30-40 years who were followed up for 3 years. Baseline measurements of SBMD (L2-L4) were obtained using dual-energy X-ray densitometry, and dietary intake of soy foods and other key nutrients, including dietary calcium, were obtained through a quantitative food frequency method. Information on body measurements; physical activity (PA), weight-bearing activity in particular; age of menarche; and number of pregnancies were obtained at baseline. Repeated measurements of SBMD were obtained yearly for a further 3 years with an average follow-up time of 38 months. Analyses were performed on 116 subjects with at least three SBMD measurements (at baseline, 3-year follow-up, and at least one measurement during follow-up). The individual SBMD regression slope was computed for each of the subjects. Soy isoflavones consumption was categorized as quartiles of intake. We observed a significant difference in the SBMD individual regression slopes between women belonging to the fourth and first soy isoflavones intake quartiles. The positive effect of soy isoflavones on SBMD remained after adjusting for age and body size (height, weight, and bone area). Multiple linear regression analysis including the other known covariates (lean body mass, PA, energy adjusted calcium, and follow-up time) showed that soy isoflavones, together with these variables, accounted for 24% of the variances of the SBMD individual regression slope. This longitudinal study shows that soy intake had a significant effect on the maintenance of SBMD in women aged 30-40 years. The effects of phytoestrogens on bone health should be explored further in a population with habitual dietary soy but low calcium intake.

Absorptiometry, Photon↗

[A comparison between a submerged membrane bioreactor and a conventional activated sludge process].

A comparison between a submerged membrane bioreactor (MBR) and a conventional activated sludge process (CAS) was carried out under similar operational conditions. MBR demonstrated a more stable and excellent effluent quality than CAS. Its effluent COD concentration was 55.5 mg/L on average, much lower than that of CAS (79.7 mg/L). Soluble microbial products accumulated in the MBR during the first 120 days in operation due to membrane interception of macromolecules, but these accumulated substances were degraded at last with microbial acclimation. No similar phenomenon was observed in the CAS system. Compositions of the CAS effluent, MBR supernatant and membrane permeate were found quite different. In the CAS effluent and MBR supernatant, both macromolecules with MW > 60,000 and small molecules with MW < 3,000 were dominant and macromolecules had a much larger occupation in the MBR supernatant. In the membrane permeate, however, small molecules with MW < 3,000 were the major component. The relatively small floc size in the MBR was proved favorable to improve oxygen transfer rate.

Bioreactors↗

NMR characterization of residual structure in the denatured state of protein L.

Triple-resonance NMR experiments were used to assign the (13)C(alpha), (13)C(beta), (15)N and NH resonances for all the residues in the denatured state of a destabilized protein L variant in 2 M guanidine. The chemical shifts of most resonances were very close to their random coil values. Significant deviations were observed for G22, L38 and K39; increasing the denaturant concentration shifted the chemical shifts of these residues towards theory random coil values. Medium-range nuclear Overhauser enhancements were detected in segments corresponding to the turn between the first two strands, the end of the second strand through the turn between the second strand and the helix, and the turn between the helix and the third strand in 3D H(1), N(15)-HSQC-NOESY-HSQC experiments on perdeuterated samples. Longer-range interactions were probed by measuring the paramagnetic relaxation enhancement produced by nitroxide spin labels introduced via cysteine residues at five sites around the molecule. Damped oscillations in the magnitude of the paramagnetic relaxation enhancement as a function of distance along the sequence suggested native-like chain reversals in the same three turn regions. The more extensive interactions within the region corresponding to the first beta-turn than in the region corresponding to the second beta-turn suggests that the asymmetry in the folding reaction evident in previous studies of the protein L folding transition state is already established in the denatured state.

Amino Acid Sequence↗

Microbial degradation of phthalic acid esters under anaerobic digestion of sludge.

The microbial degradation by anaerobic sludge of three phthalates, priority pollutants, listed by both China National Environmental Monitoring Center and the U.S.EPA, namely, dimethyl (DMP), di-n-butyl (DBP) and di-n-octyl (DOP) phthalates was investigated. The experimental results indicated that the biodegradation rate and the biodegradability of three phthalates under anaerobic conditions appeared to be related to the length of the alkyl-side chains. More than 90% of DMP and DBP with the short alkyl-side chain phthalates can be degraded, whereas the DOP degradation appeared to be relatively slow under the same experimental conditions. The quantity of methane produced was measured and the results showed that both the ester groups and the phthalate ring were mineralized at a significant rate. The kinetics study demonstrated that the biodegradation of three phthalates conformed to the first-order model with respect to their concentrations.

Bacteria, Anaerobic↗

Interleukin 6, tumour necrosis factor alpha, interleukin 1beta and interleukin 1 receptor antagonist promoter or coding gene polymorphisms in multiple myeloma.

Proinflammatory cytokines such as interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha) and IL-1beta are considered to be involved in the pathogenesis of multiple myeloma (MM). In the present study, we examined a G/C polymorphism at position -174 in the promoter region of IL-6, a biallelic polymorphism at position -308 in the promoter region of TNF-alpha, the TaqI restriction fragment length polymorphism in exon 5 of IL-1beta and a variable number of identical tandem repeat polymorphisms in intron 2 of IL-1 receptor antagonist (IL-1Ra) genes. The alleles of these loci are known to influence the level of production of the cytokines and the IL-1Ra. Seventy-three patients with MM, 27 with monoclonal gammopathy of undetermined significance (MGUS) and 129 healthy individuals were included. No difference was found between patients and healthy controls or between MM and MGUS patients in the distributions of genotypes and frequencies of alleles of the IL-6 (-174), TNF-alpha (-308), IL-1beta TaqI and IL-1Ra gene polymorphisms. No associations between the polymorphisms at the loci under study and clinical factors such as age, sex, clinical stage at onset and M-protein type were observed. Our results indicate that the cytokine (IL-6, TNF-alpha and IL-1beta) and IL-Ra gene polymorphisms do not confer susceptibility to the development of MM.

Adult↗

Cataract extraction in a major ophthalmic hospital: day-case or overnight stay?

PURPOSE: Cataract surgery is increasing in Australia and represents a significant burden on limited health resources. This study examines the frequency and outcomes of cataract surgery for patients who were hospitalized overnight compared with those treated as day surgery cases. METHODS: Medical records of 671 consecutive admissions for cataract surgery at the Royal Victorian Eye and Ear Hospital were reviewed. Data analysed included demographic features, insurance status, length of hospitalization, ophthalmic conditions, medical conditions, social problems and planned surgical technique. Ophthalmic and anaesthetic complications, active ophthalmic and medical interventions were also studied. RESULTS: Of the 671 patient admissions for cataract during the study period, 226 (33.4%) were hospitalized overnight. Factors significantly associated with overnight hospitalization in univariate analyses include older age, female sex, country residence, Veterans' Affairs insurance, monocular vision status, pre-existing ischaemic heart disease, pre-existing asthma/chronic obstructive lung disease, absence of carer, transportation problems, planned extra-capsular cataract extraction technique, ophthalmic complications and active ophthalmic and/or medical interventions. After adjusting for possible confounding factors using backwards stepwise multivariate logistic regression models all except pre-existing ischaemic heart disease and ophthalmic complications were significantly associated with overnight admission for cataract surgery. In total, 14 cases (2.1%) needed active ophthalmic and/or medical interventions, 13 overnight cases and one day case. CONCLUSIONS: These data suggest that many patients who are hospitalized overnight for cataract surgery could be safely treated as day cases. Such a shift in the pattern of care for cataract surgery could provide a significant potential for health care savings.

Adult↗

Evidence for involvement of the epidermal platelet-activating factor receptor in ultraviolet-B-radiation-induced interleukin-8 production.

Ultraviolet B radiation has been shown to generate cutaneous inflammation in part through inducing oxidative stress and cytokine production in human keratinocytes. Amongst the proinflammatory cytokines synthesized in response to ultraviolet B radiation is the potent chemoattractant interleukin-8. Though the lipid mediator platelet-activating factor (PAF) is synthesized in response to oxidative stress, and keratinocytes express PAF receptors linked to cytokine biosynthesis, it is not known whether PAF is involved in ultraviolet-B-induced epidermal cell cytokine production. These studies examined the role of the PAF system in ultraviolet-B-induced epidermal cell interleukin-8 biosynthesis using a novel model system created by retroviral-mediated transduction of the PAF-receptor-negative human epidermal cell line KB with the human PAF receptor. Treatment of PAF-receptor-expressing KB cells with the metabolically stable PAF receptor agonist carbamoyl-PAF resulted in increased interleukin-8 mRNA and protein, indicating that activation of the epidermal PAF receptor was linked to interleukin-8 production. Ultraviolet B irradiation of PAF-receptor-expressing KB cells resulted in significant increases in both interleukin-8 mRNA and protein in comparison to ultraviolet-B-treated control KB cells. Pretreatment with PAF receptor antagonists inhibited both carbamoyl-PAF-induced and ultraviolet-B-induced interleukin-8 production in the PAF-receptor-positive cells, but not in control KB cells. Similarly, treatment of the PAF-receptor-expressing primary cultures of human keratinocytes or the human epidermal cell line A-431 with carbamoyl-PAF or ultraviolet B radiation resulted in interleukin-8 production that was partially inhibited by PAF receptor antagonists. These studies suggest that the epidermal PAF receptor may be a pharmacologic target for ultraviolet B radiation in skin and thus may act to augment ultraviolet-B-mediated production of cytokines such as interleukin-8.

Cells, Cultured↗

Regression method to estimate provisional TLV/WEEL-equivalents for non-carcinogens.

There is a huge and changing number of chemicals in commerce for which workplace exposure criteria have not been assigned. Assigning an exposure criterion by an expert committee is resource-intensive-not soon available for the large majority of chemicals in current use. In the absence of assigned criteria, we have provided a regression method to estimate a first-screen estimate of a 'TLV/WEEL-equivalent' inhalation time-weighted average exposure criterion for a pure chemical (or chemical group) from a measure of a non-stochastic toxic exposure to elicit a chronic or sub-chronic health effect, known as a lowest observable adverse effect level (LOAEL) or a (highest) no observable adverse effect level (NOAEL). Results are presented for six data sets for which both a threshold limit value (TLV) or workplace environmental exposure level (WEEL) exposure criterion is presently assigned, and a LOAEL or NOAEL measure of toxic health effect was available from the United States Environmental Protection Agency Integrated Risk Information System data base. The results can be applied as a first estimate of exposure to substances for which no TLV or WEEL (TLV/WEEL) exists, and also serve as a mechanism for identifying substances for potential re-evaluation of their exposure limit, based on their relative position about the prediction models.

Air Pollutants, Occupational↗

Menopausal symptoms and symptom clustering in Chinese women.

OBJECTIVES: this paper aims to report the prevalence of symptoms in the Hong Kong Chinese perimenopausal women; to construct reported symptoms into symptom groupings; and to clarify whether the symptom groups are associated with menopausal status. METHODS: a random telephone survey of perimenopausal women aged 44-55 years was conducted in 1996. Eligible subjects were identified through telephone dialing of a random sample of the numbers listed in the residents' telephone directory. Standardized questionnaire, including a 22-item symptom check list, was administered over the telephone. The principal component analysis method followed by varimax rotation was used to examine the relations among the symptoms. RESULTS: differences in the prevalence of menstrual problems across the menopausal status were noted with perimenopausal women having the most complaints. Musculoskeletal conditions were the top complaints reported by the respondents, followed by headaches and psychological symptoms. About 10% of the women complained of hot flushes, and less than 5% of cold sweats. Five symptom clusters, namely psychological, musculoskeletal/gastrointestinal, non-specific somatic, respiratory, and vasomotor, have been identified. After adjustment for age, the analysis of variance showed that psychological, non-specific somatic and vasomotor symptoms were significantly associated with menopausal status, while musculoskeletal and respiratory were of borderline statistical significance. CONCLUSIONS: compared with pre- and post-menopausal women, perimenopausal women had the highest reports of symptom complaints. Musculoskeletal complaints were the most prevalent complaints, followed by psychological symptoms. While vasomotor symptoms were significantly associated with menopausal status, their prevalence was comparatively lower than that reported in Caucasian populations.

Adult↗

T-cell-epitope mapping of the idiotypic monoclonal IgG heavy and light chains in multiple myeloma.

The idiotypic structures of the myeloma protein might be regarded as tumor-specific antigens. The present study was designed to map T-cell epitopes of the idiotypic myeloma protein to prove the existence of naturally occurring major-histocompatibility-complex-dependent idiotype (peptide)-specific T cells in multiple myeloma. The fine specificity of idiotype-reactive, interferon-gamma-producing blood T cells of a patient with multiple myeloma stage I was characterized by identification of idiotype (heavy and light chains)-derived MHC-restricted T-cell epitopes. T cells specifically reacting with peptides corresponding to each of the 3 complementarity-determining regions (CDRs) of the heavy-chain variable part (V(H)) of the autologous idiotype were found. In contrast, none of the peptides corresponding to the 3 CDRs of the light chain (V(L)) induced a specific T-cell response. The idiotype amino-acid sequence corresponding to the junction of the V(H), diversity (D), and joining (J) gene segments of the VH appeared to be an important target for T cells, since the sequence expressed MHC-class-I- as well as MHC-class-II-restricted epitopes. The study provides further support for the existence of MHC-restricted idiotype-specific T cells, which may target immunogenic CDR peptides in multiple myeloma. Such T cells could be an important part of the specific anti-tumor immune responses induced in idiotype vaccination protocols.

Aged↗