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Biomedical subjects

Feng Lin

Publications and source records attributed to Feng Lin.

At least 91 records · Page 5Linked to original sources

Resource use for total and supracervical hysterectomies: results of a randomized trial.

OBJECTIVE: Hysterectomy is the most common major surgical procedure performed in the United States for nonobstetric reasons. Although most hysterectomies include removal of the cervix, the rate of supracervical procedures has increased in recent years. To provide evidence about the outcomes of both types of hysterectomy, we conducted a randomized clinical trial of total (TAH) or supracervical (SCH) hysterectomy (the "TOSH" trial). We report here an analysis of 24-month resource use by patients in this trial. METHODS: A randomized controlled trial was performed at 3 clinical centers to compare resources used by 120 patients who received a total or supracervical abdominal hysterectomy. Service use during a 24-month follow-up period was identified from medical and billing records and patient reports. Each service used was assigned a relative value, which was then converted into 2002 U.S. dollars. RESULTS: Overall resource use was similar in the 2 study groups in the first 12 months after randomization (TAH 5,870 US dollars; SCH 6,018 US dollars; 95% confidence interval for difference -960 US dollars, 1,255 US dollars; P <.79) and for the full 24 months (TAH 6,448 US dollars; SCH 7,479 US dollars; 95% confidence interval for difference -533 US dollars, 2,616 US dollars; P <.20). In exploratory multivariable analyses, resource use was significantly associated with baseline body mass index greater than or equal to 35 kg/m(2) (8,440 US dollars versus 6,398 US dollars, P =.02) and heavy bleeding (7,550 US dollars versus 5,368 US dollars, P =.02). CONCLUSION: We conclude that the use of medical care resources over a 24-month period is comparable for total and supracervical hysterectomy. The association of a woman's weight and bleeding pattern with subsequent resource use requires further investigation.

Adult↗

Retinoid X receptor regulates Nur77/TR3-dependent apoptosis [corrected] by modulating its nuclear export and mitochondrial targeting.

Retinoid X receptor (RXR) plays a central role in the regulation of intracellular receptor signaling pathways by acting as a ubiquitous heterodimerization partner of many nuclear receptors, including the orphan receptor Nur77 (also known as TR3 [corrected] or NGFI-B), which translocates from the nucleus to mitochondria, where it interacts with Bcl-2 to induce apoptosis. Here, we report that RXRalpha is required for nuclear export and mitochondrial targeting of Nur77 through their unique heterodimerization that is mediated by dimerization interfaces located in their DNA-binding domain. The effects of RXRalpha are attributed to a putative nuclear export sequence (NES) present in its carboxyl-terminal region. RXRalpha ligands suppress NES activity by inducing RXRalpha homodimerization or altering RXRalpha/Nur77 heterodimerization. The RXRalpha NES is also silenced by RXRalpha heterodimerization with retinoic acid receptor or vitamin D receptor. Consistently, we were able to show that the mitochondrial targeting of the RXRalpha/Nur77 heterodimer and its induction of apoptosis are potently inhibited by RXR ligands. Together, our results reveal a novel nongenotropic function of RXRalpha and its involvement in the regulation of the Nur77-dependent apoptotic pathway [corrected]

Active Transport, Cell Nucleus↗

[Microbial receptor competitive binding assay of basic macrolide antibiotics].

OBJECTIVE: To establish a biological method for determining the macrolide content in various matrices. METHODS Human serum, urine and tissue homogenate samples were diluted or extracted with MSU buffer, and the specimens of grain and premixed feed extracted with methanol-H(3)PO(4) buffer, before microbial receptor competitive binding assay was carried out on these various specimens, with the elimination of interference from methanol with the M8 buffer. RESULTS: The method was sensitive, class-specific and precise, and the recommended screening concentrations for specimens of the serum, urine, tissue and grains were 200, 200, 100 and 1 200 ng/g (ng/ml), respectively, with a relative standard deviation less than 8%. CONCLUSION: Microbial receptor competitive binding assay is accurate and rapid for efficient qualitative and quantitative assay of the total macrolide content in various matrices.

Anti-Bacterial Agents↗

[Short-term effects of chemotherapy with combination of hydroxycamptothecine and oxaliplatin in the treatment of advanced digestive tract cancers].

OBJECTIVE: To evaluate the short-term therapeutic effects and side effects of combined hydroxycamptothecine and oxaliplatin in the treatment of advanced digestive tract cancers. METHODS: Thirty patients suffering from advanced digestive tract tumors including gastric cancer 8, colorectal cancer 20, cholecystic cancer 1 and malignant fibroadenoma 1 were studied. They were treated with hydroxycamptothecine plus oxaliplatin for 2 cycles with interval of 21 days. RESULTS: The complete response, partial response, stable disease and progressive disease rates were 3.3% (1/30), 36.7% (11/30), 53.3% (15/30) and 6.7% (3/30) respectively with an overall response rate (CR + PR) of 40.0% (12/30). In the whole 77 cycles, leukocytopenia was observed in 34 cycles (44.2%) and 19 cycles (55.9%) at grades III and IV. Diarrhea developed in 42 cycles (54.5%) and 20 cycles (47.6%) grades III and IV. The other side effects were fever, alopecia, nausea and vomiting, constipation, hepatic and renal function abnormity and neuritis. CONCLUSION: Satisfactory response rate is obtainable in advanced colorectal cancer as treated by hydroxycamptothecine plus oxaliplatin. The toxicity consists of severe leukocytopenia and diarrhea.

Adenocarcinoma↗

Recurrent genetic alterations in 26 colorectal carcinomas and 21 adenomas from Chinese patients.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The incidence of CRC in the Chinese population has increased dramatically during the last two decades; however, nonrandom chromosomal alterations in Chinese patients have not been described. In the present study, comparative genomic hybridization (CGH) was applied to detect recurrent chromosome alterations in 26 primary colorectal carcinomas and 21 colorectal adenomas from Chinese patients. In CRC, several recurrent chromosomal changes were found, including gains of 8q (14/26 cases, 54%), 20q (54%), 3q (50%), 13q (50%), 5p (46%), 7p (42%), 7q (42%), and 12p (38%) and losses of 18q (65%) and 17p (42%). From comparison with previous CGH studies, the frequent gains of 3q and 12p might be distinctive occurrences in Chinese patients. The distribution of frequently found chromosomal alterations in different locations was studied. The gain of 20q was more frequently found in colon cancer (P<0.01) and the gain of 12p was more frequently found in rectal cancer. Chromosomal alterations were found in 19/21 of adenomas; the most frequent chromosomal alteration was the loss of 18q (9/21 cases, 43%). These recurrent alterations provide several starting points for the isolation of candidate oncogenes and tumor suppressor genes.

Adenoma↗

Regulation of retinoic acid receptor beta expression by peroxisome proliferator-activated receptor gamma ligands in cancer cells.

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor family member that can form a heterodimeric complex with retinoid X receptor (RXR) and initiate transcription of target genes. In this study, we have examined the effects of the PPAR gamma ligand ciglitazone and the RXR ligand SR11237 on growth and induction of retinoic acid receptor (RAR) beta expression in breast and lung cancer cells. Our results demonstrated that ciglitazone and SR11237 cooperatively inhibited the growth of ZR-75-1 and T-47D breast cancer and Calu-6 lung cancer cells. Gel shift analysis indicated that PPAR gamma, in the presence of RXR, formed a strong complex with a retinoic acid response element (beta retinoic acid response element) in the RAR beta promoter. In reporter gene assays, RXR ligands and ciglitazone, but not the PPAR gamma ligand 15d-PGJ(2), cooperatively promoted the transcriptional activity of the beta retinoic acid response element. Ciglitazone, but not 15d-PGJ(2), strongly induced RAR beta expression in human breast and lung cancer cell lines when used together with SR11237. The induction of RAR beta expression by the ciglitazone and SR11237 combination was diminished by a PPAR gamma-selective antagonist, bisphenol A diglycidyl ether. All-trans-retinoic acid or the combination of ciglitazone and SR11237 was able to induce RAR beta in all-trans-retinoic acid-resistant MDA-MB-231 breast cancer cells only when the orphan receptor chick ovalbumin upstream promoter transcription factor was expressed, or in the presence of the histone deacetylase inhibitor trichostatin A. These studies indicate the existence of a novel RAR beta-mediated signaling pathway of PPAR gamma action, which may provide a molecular basis for developing novel therapies involving RXR and PPAR gamma ligands in potentiating antitumor responses.

Apoptosis↗

Solution structure of a functionally active fragment of decay-accelerating factor.

The second and third modules of human decay accelerating factor (DAF) are necessary and sufficient to accelerate decay of the classical pathway (CP) convertase of complement. No structure of a mammalian protein with decay-accelerating activity has been available to date. We therefore determined the solution structure of DAF modules 2 and 3 (DAF approximately 2,3). Structure-guided analysis of 24 mutants identified likely contact points between DAF and the CP convertase. Three (R96, R69, and a residue in the vicinity of L171) lie on DAF approximately 2,3's concave face. A fourth, consisting of K127 and nearby R100, is on the opposite face. Regions of module 3 remote from the semiflexible 2-3 interface seem not to be involved in binding to the CP convertase. DAF thus seems to occupy a groove on the CP convertase such that both faces of DAF close to the 2-3 junction (including a positively charged region that encircles the protein at this point) interact simultaneously. Alternative pathway convertase interactions with DAF require additional regions of CCP 3 lying away from the 2-3 interface, consistent with the established additional requirement of module 4 for alternative pathway regulation.

Binding Sites↗

Protection of epidermal cells against UVB injury by the antioxidant selenium-containing single-chain Fv catalytic antibody.

The antioxidant effect of selenium-containing single-chain Fv catalytic antibody (Se-scFv2F3), a new mimic of glutathione peroxidase, was confirmed using a model system in which cultured rat skin epidermal cells were injured by ultraviolet B (UVB). The cell damage was characterized in terms of lipid peroxidation of the cells, cell viability, and cell membrane integrity. The injury effects of UVB and protection effects of Se-scFv2F3 on the cells were studied using the model system. UVB can damage the cells severely. Upon precultivation of the cells with 0.4U/ml Se-scFv2F3, however, the damage was significantly reduced as shown by the increase in cell viability, the decrease in the malondialdehyde and hydrogen peroxide levels, and the normalization of lactate dehydrogenase activity. In addition, a novel finding that Se-scFv2F3 can stimulate cultured epidermal cells to proliferate under certain conditions was observed.

Animals↗

Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Randomized trials of postmenopausal hormone therapy have found differing effects on fasting glucose levels. No trial has evaluated the effect of hormone therapy on diabetes incidence. OBJECTIVE: To evaluate the effect of hormone therapy on fasting glucose level and incident diabetes. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 20 U.S. clinical centers. PARTICIPANTS: 2763 postmenopausal women with coronary heart disease who were followed for 4.1 years. At baseline, 734 women had diabetes, 218 women had impaired fasting glucose, and 1811 women were normoglycemic; the 2029 women without diabetes were followed for incident diabetes. INTERVENTION: 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily, or placebo. MEASUREMENTS: Fasting glucose level was measured at baseline, at year 1, and at the end of the trial. Incident diabetes was defined by self-report of diabetes or disease complication, fasting glucose level of 6.9 mmol/L or greater (> or =126 mg/dL), or initiation of therapy with diabetes medication. RESULTS: Fasting glucose levels increased significantly among women assigned to placebo but did not change among women receiving hormone therapy. The incidence of diabetes was 6.2% in the hormone therapy group and 9.5% in the placebo group (relative hazard, 0.65 [95% CI, 0.48 to 0.89]; P = 0.006). The number needed to treat for benefit to prevent one case of diabetes was 30 (CI, 18 to 103). Changes in weight and waist circumference did not mediate this effect. CONCLUSIONS: In women with coronary disease, hormone therapy reduced the incidence of diabetes by 35%. This observation provides important insights into the metabolic effects of postmenopausal hormones but is insufficient to recommend the use of hormones for secondary prevention of heart disease.

Aged↗

Lipid changes on hormone therapy and coronary heart disease events in the Heart and Estrogen/progestin Replacement Study (HERS).

BACKGROUND: Despite the effect of lowering low-density lipoprotein cholesterol (LDL-C) levels and raising high-density lipoprotein cholesterol (HDL-C) levels, combination hormone therapy did not reduce the incidence of coronary heart disease (CHD) events in the Heart and Estrogen/progestin Replacement Study (HERS). To explore possible mechanisms, we examined the association between lipid changes and CHD outcomes among women assigned to hormone therapy. METHODS: HERS participants were postmenopausal women with previously diagnosed CHD who were randomly assigned to receive conjugated estrogens and medroxyprogesterone or identical placebo and then followed-up for an average of 4.1 years. Among women assigned to hormone therapy, associations between baseline-to-year-1 lipid level changes and CHD events were compared with the associations observed for baseline lipids using multivariate proportional hazards models. RESULTS: Among women assigned to hormone therapy, CHD events were independently predicted by baseline LDL-C levels (relative hazard [RH] 0.94 per 15.6 mg/dL decrease, 95% CI 0.88-1.01) and HDL-C levels (RH 0.89 per 5.4 mg/dL increase, 95% CI 0.81-0.99), but not by triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.97-1.06). CHD events were marginally associated with first-year reductions in LDL-C levels (RH 0.95 per 15.6 mg/dL decrease, 95% CI 0.86-1.04), and were not associated with increases in HDL-C levels ( RH 1.03 per 5.4 mg/dL increase, 95% CI 0.91-1.16) or triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.98-1.05). CONCLUSION: Changes in lipid levels with hormone therapy are not predictive of CHD outcomes in women with heart disease in the HERS trial.

Aged↗

Stress urinary incontinence surgery in the United States.

OBJECTIVE: To describe the prevalence, regional rates and demographic characteristics, morbidity, and mortality of stress urinary incontinence surgeries in the United States. METHODS: We used data from the 1998 National Hospital Discharge Survey and the 1998 National Census to calculate rates of surgeries for stress urinary incontinence by age, race, and region of the United States. From these data we estimated morbidity and mortality associated with incontinence surgery. RESULTS: In 1998, approximately 135000 women had inpatient surgery for stress urinary incontinence in the United States. The mean age of these women was 54.0 (+/-13.3) years. The South had the highest rate of surgery (14.8 per 10000 women), whereas the Northeast had the lowest (9.8 per 10000). In the 79% of discharges for which race was stated, the surgery rate for whites (11.6 per 10000) was almost five times greater than for blacks (2.6 per 10000), whereas the perioperative complication rate for blacks was twice that for whites (20.6% compared with 9.7%). Almost 70% of incontinence surgeries were done in combination with other major gynecologic procedures. For all incontinence surgeries, approximately 18% had complications, and mortality was rare (0.01%). CONCLUSION: Stress urinary incontinence surgery is common, especially among white women. Differences in regional and racial surgical rates may represent differences in physician practice, patient expectations, and access to or utilization of care.

Adult↗

A randomized comparison of total or supracervical hysterectomy: surgical complications and clinical outcomes.

OBJECTIVE: To compare surgical complications and clinical outcomes after total versus supracervical abdominal hysterectomy for control of abnormal uterine bleeding, symptomatic uterine leiomyomata, or both. METHODS: We conducted a randomized intervention trial in four US clinical centers among 135 patients who had abdominal hysterectomy for symptomatic uterine leiomyomata, abnormal uterine bleeding refractory to hormonal treatment, or both. Patients were randomly assigned to receive a total or supracervical hysterectomy performed using the surgeon's customary technique. Using an intention-to-treat approach, we compared surgical complications and clinical outcomes for 2 years after randomization. RESULTS: Sixty-eight participants were assigned to supracervical hysterectomy (SCH) and 67 to total abdominal hysterectomy (TAH). Hysterectomy by either technique led to statistically significant reductions in most symptoms, including pelvic pain or pressure, back pain, urinary incontinence, and voiding dysfunction. Patients randomly assigned to (SCH) tended to have more hospital readmissions than those randomized to TAH, but this difference was not statistically significant. There were no statistically significant differences in the rate of complications, degree of symptom improvement, or activity limitation. Participants weighing more than 100 kg at study entry were twice as likely to be readmitted to the hospital during the 2-year follow-up period (relative risk [RR] 2.18, 95% confidence interval [CI] 1.06, 4.48, P=.034). CONCLUSION: We found no statistically significant differences between (SCH) and TAH in surgical complications and clinical outcomes during 2 years of follow-up.

Aged↗

Medroxyprogesterone acetate treatment of abnormal uterine bleeding: factors predicting satisfaction.

OBJECTIVE: This study was undertaken to identify the determinants of patient satisfaction with a cyclic regimen of medroxyprogesterone acetate (MPA) for abnormal uterine bleeding. STUDY DESIGN: A prospective cohort study of 413 premenopausal women were treated for 3 to 5 months with oral MPA 10 to 20 mg per day for 10 to 14 days per month. We assessed satisfaction with and willingness to continue MPA. Baseline characteristics hypothesized to predict treatment satisfaction were entered into logistic regression analysis. RESULTS: Sixty-five percent of subjects (271) completed at least 3 months of MPA, 79% (215) filled out a satisfaction survey, and 57% (123) expressed satisfaction with MPA. Satisfaction was predicted by age 35 years or older (odds ratio [OR] 2.67, CI 1.07-6.7), desire for uterine conservation (OR 1.36, CI 1.11-1.66), perceived importance of stopping bleeding (OR 0.69, CI 0.54-0.87), and tubal sterilization (OR 0.52, CI 0.28-0.96). Neither bleeding history nor parity predicted MPA satisfaction. CONCLUSION: These findings underscore the importance of considering patient age, fertility status, attitudes about uterine conservation, and desire for definitive resolution of bleeding when deciding whether to use MPA versus other treatments for abnormal uterine bleeding.

Adult↗

Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States.

Black Americans experience a disproportionate burden of ESRD compared with whites. Whether this is caused by the increased prevalence of chronic renal insufficiency (CRI) among blacks or by their increased progression from CRI to ESRD was investigated. A birth cohort analysis was performed using data from the Third National Health and Nutrition Examination Survey and the United States Renal Data System. It was assumed that those who developed ESRD in 1996 aged 25 to 79 yr came from the source population with CRI aged 20 to 74 yr that was sampled in the Third National Health and Nutrition Examination Survey (midpoint 1991). GFR was estimated using the Modification of Diet in Renal Disease study equation. The prevalence of CRI (GFR 15 to 59 ml/min per 1.73 m(2)) was not different among black compared with white adults (2060 versus 2520 per 100,000; P = 0.14). For each 100 blacks with CRI in 1991, five new cases of ESRD developed in 1996, whereas only one case of ESRD developed per 100 whites with CRI (risk ratio, 4.8; 95% confidence interval, 2.9 to 8.4). The increased risk for blacks compared with whites was only modestly affected by adjustment for age, gender, and diabetes. Blacks with CRI had higher systolic (147 versus 136 mmHg; P = 0.001) and diastolic (82 versus 77 mmHg; P = 0.02) BP and greater albuminuria (422 versus 158 micro g urine albumin/mg urine creatinine; P = 0.01). The higher incidence of ESRD among blacks is not due to a greater prevalence of CRI among blacks. The key to understanding black-white differences in ESRD incidence lies in understanding the extreme differences in their progression from CRI to ESRD.

Adult↗