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Biomedical subjects

L Cheng

Publications and source records attributed to L Cheng.

At least 199 records · Page 11Linked to original sources
PubMed1999

Reversibility of prostatic intraepithelial neoplasia: implications for chemoprevention.

High-grade prostatic intraepithelial neoplasia is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence. It has a high predictive value as a marker for adenocarcinoma, and its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. Androgen deprivation therapy and radiation therapy decrease its prevalence and extent, suggesting a role in chemoprevention.

Adenocarcinoma↗
PubMed1999

Predicting cancer progression in patients with stage T1 bladder carcinoma.

PURPOSE: A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach. PATIENTS AND METHODS: The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer. RESULTS: The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P =.037). The 5-year progression-free survival rate for patients with depth of invasion of >/= 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P =.009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression. CONCLUSION: The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.

Aged↗
PubMed1999

Human mesenchymal stem cells promote human osteoclast differentiation from CD34+ bone marrow hematopoietic progenitors.

Interactions between osteoclast progenitors and stromal cells derived from mesenchymal stem cells (MSCs) within the bone marrow are important for osteoclast differentiation. In vitro models of osteoclastogenesis are well established in animal species; however, such assays do not necessarily reflect human osteoclastogenesis. We sought to establish a reproducible coculture model of human osteoclastogenesis using highly purified human marrow-derived MSCs (hMSCs) and CD34+ hematopoietic stem cells (HSCs). After 3 weeks, coculture of hMSCs and HSCs resulted in an increase in hematopoietic cell number with formation of multinucleated osteoclast-like cells (Ocls). Coculture of hMSCs with HSCs, transduced with a retroviral vector that expresses enhanced green fluorescent protein, produced enhanced green fluorescent protein+ Ocls, further demonstrating that Ocls arise from HSCs. These Ocls express calcitonin and vitronectin receptors and tartrate-resistant acid phosphatase and possess the ability to resorb bone. Ocl formation in this assay is cell contact dependent and is independent of added exogenous factors. Conditioned medium from the coculture contained high levels of interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), and macrophage-colony stimulating factor. IL-6 and LIF were present at low levels in cultures of hMSCs but undetectable in cultures of HSCs alone. These data suggest that coculture with HSCs induce hMSCs to secrete cytokines involved in Ocl formation. Addition of neutralizing anti-IL-6, IL-11, LIF, or macrophage-colony stimulating factor antibodies to the coculture inhibited Ocl formation. hMSCs seem to support Ocl formation as undifferentiated progenitor cells, because treatment of hMSCs with dexamethasone, ascorbic acid, and beta-glycerophosphate (to induce osteogenic differentiation) actually inhibited osteoclastogenesis in this coculture model. In conclusion, we have developed a simple and reproducible assay using culture-expanded hMSCs and purified HSCs with which to study the mechanisms of human osteoclastogenesis.

Acid Phosphatase↗
PubMed1999

Androgen receptor expression in prostate cancer lymph node metastases is predictive of outcome after surgery.

PURPOSE: Androgens mediate the growth of prostate cancer cells. The predictive value of androgen receptor immunostaining in patient outcome is controversial. We studied the expression of androgen receptors in a large series of patients with node positive cancer, and correlated the results with clinical progression and survival. MATERIALS AND METHODS: We evaluated 197 patients with a mean age of 65.5 years who had node positive adenocarcinoma, and who underwent bilateral pelvic lymphadenectomy and/or radical prostatectomy at our clinic between 1987 and 1992. Mean followup was 6.3 years. Immunohistochemical studies were performed using an antihuman androgen receptor monoclonal antibody. In each case 100 nuclei were counted from 3 separate areas (total 300 nuclei per diagnostic category) of benign epithelium, cancer and lymph node metastases. Mean androgen receptor expression was determined from the mean of the individual cases. The intensity of immunoreactivity was evaluated on a scale of 0-no staining to 3-strong staining. We assessed the correlation of androgen receptor immunoreactivity, deoxyribonucleic acid ploidy, Gleason score and preoperative serum prostate specific antigen (PSA) with clinical progression, all cause survival and cancer specific survival using the Cox proportional hazards model. Clinical progression was defined as a positive bone scan. RESULTS: There was heterogeneous staining in the majority of cells in benign and malignant prostatic epithelium. The mean number of immunoreactive nuclei was similar in all groups (56, 53 and 56% of benign epithelium, cancer and lymph node metastases, respectively). Pairwise comparisons revealed that the only significant difference was between benign epithelium and cancer (p = 0.001) with greater immunoreactivity in benign epithelium. Intensity was lower in benign epithelium than in cancer and lymph nodes (p <0.05). Androgen receptor expression in lymph node metastases was associated with all cause and cancer specific survival on univariate analysis (p = 0.03 and 0.04, respectively). The 7-year cause specific survival was 98, 94 and 86% in patients with 51 to 69, less than 50 and greater than 70% androgen receptor expression in lymph node metastases, respectively (p <0.05). The association of androgen receptor expression in lymph node metastases was significant on multivariate analysis for cancer specific survival (p = 0.021) but not all cause survival (p = 0.16) after controlling for Gleason score, deoxyribonucleic acid ploidy and preoperative PSA. Androgen receptor immunoreactivity in lymph nodes was not a significant univariate or multivariate predictor of clinical progression, while androgen receptor expression in the primary cancer was not predictive of clinical progression or survival (p >0.05). CONCLUSIONS: Androgen receptor expression was similar in benign epithelium, primary cancer and lymph node metastases with approximately half of the epithelial cell nuclei staining. Androgen receptor immunoreactivity in lymph node metastases was predictive of cancer specific but not all cause survival in univariate and multivariate models. Gleason score was the strongest predictor of all cause survival in this cohort of patients. Our results indicate that it may be clinically useful to determine lymph node androgen receptor expression in men with advanced prostate cancer when combined with Gleason score and PSA.

Adenocarcinoma↗
PubMed1999

Enzyme induction observed in healthy volunteers after repeated administration of rifapentine and its lack of effect on steady-state rifapentine pharmacokinetics: part I.

OBJECTIVE: To determine the effects of rifapentine on hepatic mixed function oxidase activity and to assess the effect of enzyme induction on the steady-state pharmacokinetics of rifapentine. STUDY DESIGN: Twenty-three healthy males were randomized to receive two of the following treatments in a two-period, four-treatment, incomplete block, crossover design: single daily oral rifapentine doses of 150 mg (group A), 300 mg (group B), or 600 mg (group C) on study days 1 and 4-10, or single oral rifapentine 600 mg doses given every 3 days for a total of four doses (group D). Serial blood samples were collected after the first and last rifapentine dose and assayed for rifapentine and its active metabolite, 25-desacetyl-rifapentine. Urine was collected for determination of cortisol and 6-hydroxycortisol concentrations. RESULTS: The ratio of 6beta-hydroxycortisol:cortisol increased during rifapentine administration (+229%, +317%, and +357% on day 10 for groups A, B, and C, respectively). Ratios returned to baseline 2 weeks after the last dose. The per cent increase in the ratio of 6beta-hydroxycortisol:cortisol following daily doses (+357%) was much higher compared with every 72-hour dosing (+236%). Single-dose and steady-state comparisons of AUCss(0-24) and AUC(0-->infinity) for both rifapentine and 25-desacetyl-rifapentine were similar (P = NS) at corresponding doses of rifapentine. Mean t(1/2) at steady-state was 84-98% of corresponding single-dose values. CONCLUSION: Rifapentine is a potent inducer of CYP3A activity. However, single-dose pharmacokinetics of rifapentine predict steady-state exposure, indicating no autoinduction of rifapentine metabolism with repeated administration. Enzyme activity returns to predose levels within 2 weeks of the last daily dose of rifapentine.

Adult↗
PubMed1999

Intravitreal toxicology in rabbits of two preparations of 1-O-octadecyl-sn-glycerol-3-phosphonoformate, a sustained-delivery anti-CMV drug.

PURPOSE: To determine intraocular toxicity and efficacy of the lipid prodrug of foscarnet, 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA), as a long-acting, nontoxic intravitreous injectable drug delivery system for cytomegalovirus (CMV) retinitis. METHODS: ODG-PFA was synthesized by coupling the phosphonate residue of PFA to the 3 hydroxyl of 1-O-octadecyl-sn-glycerol and formulated as micelles and liposomes at concentrations so that, after injection into the rabbit vitreous, the resultant intravitreal concentrations were 0.2 mM, 0.63 mM, and 2 mM in micellar formulation and 0.02 mM, 0.063 mM, 0.2 mM, and 0.63 mM for liposomal formulation. The compounds were injected, and toxicology evaluations were performed. RESULTS: Intravitreal injections of micellar ODG-PFA resulted in aggregation of the material in vitreous and variable local retinal damage. Intravitreal injections of the liposomal ODG-PFA revealed even dispersion of the compounds and a clear vitreous, using final concentration in the vitreous of 0.2 mM. No intraocular toxicity was found with the 0.632 mM final concentration. The 50% inhibitory concentration (IC50) for CMV of ODG-PFA was 0.43+/-0.27 microM, and the therapeutic index of ODG-PFA after intravitreal injection was estimated to be 1470:1. CONCLUSIONS: Lipid-derivatized foscarnet liposome formulations may be a useful long-acting delivery system for the therapy of CMV retinitis.

Animals↗
PubMed1999

Expression in normal human tissues of five nucleotide excision repair genes measured simultaneously by multiplex reverse transcription-polymerase chain reaction.

DNA repair is central to the integrity of the human genome. Reduced DNA repair capacity has been linked to genetic susceptibility to cancer. An adequate expression level of DNA repair genes is essential for normal DNA repair activities. Although there is tissue specificity in the expression, searching for a surrogate tissue is needed for molecular epidemiological studies. In this study, the relative expression levels of five selected human nucleotide excision repair (NER) genes (ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6, and XPC) in 20 different types of human normal tissue were simultaneously measured by a new multiplex reverse transcription (RT)-PCR assay using the expression level of the beta-actin gene as an internal control. Transcripts of each of the five NER genes were detectable, but the levels varied in these normal tissues. Both mitogen (phytohemagglutinin)-stimulated and unstimulated human peripheral lymphocytes showed similar expression patterns for the five NER genes. In general, the expression levels of stimulated lymphocytes were also similar to most of the rapidly proliferating tissues, such as the skin, breast, intestine, liver, testis, ovary, placenta, or prostate, but was relatively higher than that of the slowly proliferating or nonproliferating tissues such as adipose, brain, hippocampus, muscle, spleen, or lung. The data suggested that although the five NER genes were expressed at different levels in the normal tissues examined, PHA-stimulated peripheral lymphocytes may be used as a surrogate tissue for estimating expression levels of these genes in proliferating tissues. This new multiplex RT-PCR assay may help detect aberrant expression of these NER genes in both normal and tumor tissues.

Cell Line↗
PubMed1999

Cell proliferation in prostate cancer patients with lymph node metastasis: a marker for progression.

The biological aggressiveness of lymph node-positive prostate cancer is closely linked to cancer volume in nodal metastases. We evaluated MIB-1 (Ki-67) labeling index and bcl-2 expression in primary cancer and matched nodal metastases from 138 node-positive patients treated with radical prostatectomy and bilateral pelvic lymphadenectomy between 1987 and 1992 at the Mayo Clinic. One hundred twenty-eight patients (93%) received androgen deprivation therapy within 90 days after radical prostatectomy. Mean patient age was 66 years (range, 51-78). The median follow-up was 6.7 years (range, 0.03-11). MIB-1 (Ki-67) labeling index was determined by digital image analysis, and nodal cancer volume was determined by the grid method. Systemic progression, defined as the presence of distant metastasis documented by biopsy or radiographic examination, was used as an outcome end point in the Cox proportional hazard models. MIB-1 labeling index in nodal metastases was predictive of systemic progression-free survival (P = 0.001). The 8-year systemic progression-free survival was 100% for those with MIB-1 labeling index <3.5% compared with 78% for those with MIB-1 labeling index > or =7.8%. MIB-1 labeling index correlated with Gleason score, DNA ploidy, and nodal cancer volume (P<0.001, 0.04, and <0.001, respectively). After controlling for nodal cancer volume, MIB-1 labeling index remained significant in predicting systemic progression-free survival (P = 0.047). bcl-2 expression in the primary cancer and lymph node metastasis was associated with systemic progression-free survival in univariate analysis (P = 0.027 and 0.048, respectively) but was not significant after adjusting for nodal cancer volume (P = 0.52 and 0.17, respectively). Our data indicate that assessment of cell proliferation in nodal metastasis is predictive of clinical outcome in prostate cancer patients with regional lymph node metastasis.

Aged↗
PubMed1999

A new photoisomerization of bilirubin.

Photoirradiation of solutions of natural (4Z,15Z)-bilirubin-IX alpha in chloroform with approximately 366 nm UV light leads rapidly to a new photoisomer that has been characterized by NMR spectroscopy and by its (ground-state reaction) adducts with methanol and other protic nucleophiles. Unlike the previously described Z-->E geometric isomerization important in phototherapy of neonatal jaundice, the new photoisomerization involves regiospecific photoautomerization to afford 2-ethenyl-18-ethylidene- 1,10,19,22,24-pentahydro-2,7,13,17-tetramethyl-1,19- dioxo-21H-biline-8,12-dipropanoic acid.

Bilirubin↗
PubMed1999

[The study on the role of apoptosis suppressive gene bcl-2 in the pathogenesis of hemangioma].

OBJECTIVE: To elucidate the relationship between bcl-2 and hemangioma. METHODS: We investigated the expression of bcl-2 in 38 samples of hemangioma (19 cases of capillary hemangioma, 10 cases of cavernous hemangioma, 9 cases of racemose hemangioma) and 6 samples of normal skin by immunohistochemical SP method. RESULTS: The results showed that the expression of bcl-2 was higher in cavernous and racemose hemangioma than in the controls, the expression of bcl-2 was lower in capillary hemangioma than in the controls. The differences were statistically significant. CONCLUSION: It can be deduced from the results that there is an intimate relationship between bcl-2 and the growth of cavernous and racemose hemangioma, and the lower expression of bcl-2 in capillary hemangioma shows that capillary hemangioma may disappear naturally.

Adolescent↗
PubMed1999

Blocking L-calcium current by l-tetrahydropalmatine in single ventricular myocyte of guinea pigs.

AIM: To study the effect of l-tetrahydropalmatine (l-THP) on L-type calcium channel. METHODS: Patch clamp technique (whole cell recording) was used to record L-Ca2+ current in single cardiac myocyte. RESULTS: 1) l-THP 1, 10, and 100 micromol.L-1 reduced ICa-max from (999 +/- 93) pA to (700 +/- 111) pA, (582 +/- 66) pA, and (420 +/- 112) pA (n = 6, P < 0.01), respectively. 2) l-THP reduced the voltage at half-maximal inactivation (V1/2) of L-Ca2+ channel to more negative potentials by 9 mV (n = 5, P < 0.05). 3) l-THP caused both tonic and use-dependent reduction of Ca2+ current. Tonic block of l-THP on Ca2+ current was 46% +/- 8% (n = 6, P < 0.01). The degree of use dependent blocking was 13.5% +/- 2.4% (n = 6, P < 0.05) at 1 Hz, the degree increased to 44% +/- 5% (n = 6, P < 0.01) at 3 Hz. 4) l-THP delayed half-recovery time of Ca2+ channel recovery from inactivity from (94 +/- 39) ms to (170 +/- 42) ms(n = 6, P < 0.01). CONCLUSION: l-THP has a moderate inhibitory effect on L-Ca2+ current.

Animals↗
PubMed1999

[Termination of 10-16 weeks's gestation with mifepristone plus misoprostol: a multicentre randomized clinical trial].

OBJECTIVES: To find out the optimal regimen of mifepristone in combination with misoprostol for termination of 10-16 week's gestation. METHODS: A randomized comparative study in 2,007 women requesting medical abortion at 10-16 week's gestation from 24 hospitals was conducted in Shanghai. Women were randomly divided into 4 groups. In group I (n = 511) women took mifepristone 75 mg orally per day for 2 days (total dose 150 mg), and 48 hours later misoprostol 0.6 mg orally every 3-4 hours for 3 times; group II (n = 491) mifepristone 100 mg orally per day for 2 days (total dose 200 mg) and 48 hours later same dose of misoprostol were taken as in group I; group III (n = 519) same dose of mifepristone as in group I and 48 hours later misoprostol given vaginally every 12 hours for 3 times; group IV (n = 486) same dose of mifepristone as in group II and 48 hours later same dose of misoprostol vaginally as in group III. RESULTS: The successful abortion rate from group I to group IV were 88.6%, 89.4%, 90.9% and 94.0% respectively. The successful abortion rate of group IV was higher than that in group I and II with significant differences (P < 0.05). The average dose of misoprostol by vaginal route in successful case was much lower than that by oral (P < 0.01), and the rate of side effects was much lower by vaginal too. CONCLUSION: Mifepristone taken 200 mg orally plus misoprostol vaginally is an optimal method for termination of 10-16 week's gestation.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

[Low doses of mifepristone for emergency contraception].

OBJECTIVE: To investigate the efficacy of three different low doses of mifepristone for emergency contraception, the side effects and the influence to the next menstruation. METHODS: A randomized multicentre trial was conducted in Shanghai. 639 women with regular cycles and history of unprotected intercourse within 120 h of attendance were recruited, and they were randomly assigned to three groups. Group I (n = 214) mifepristone 50 mg was given, group II (n = 214) 25 mg and group III (n = 211) 10 mg. RESULTS: There were eight pregnancies totally, 2 cases in group I, 1 in group II and 5 in group III. After correction for method failure there was only 1 pregnancy in each group and the contraceptive effectiveness rate were 93.4%, 93.3% and 93.8% respectively. The side effects of mifepristone were slight and tolerable and there was significant difference between the 50 mg group and the lower doses (25 mg and 10 mg) groups (P < 0.05) in women with no complaints. There were about 12%-14% women had a early onset of menses and about 25%-28% had a late one, but no significant differences were found among the 3 groups. The average days of delayed onset of next menstruation were significant longer in group I than that in group III (P < 0.05). CONCLUSION: All the 3 doses of mifepristone could be used as an effective emergency contraception.

Adolescent↗
PubMed1999

[Investigation on the fruit output and ecological environment of Caesalpinia in China].

OBJECTIVE: To estimate the fruit output of Caesalpinia in China and understand its ecological environment. METHOD: On-the-spot investigation in the producing area. RESULT: The output of 8 species of Caesalpinia was estimated and their ecological environment was described. CONCLUSION: The natural resources of Chinese Caesalpinia, especially C. decapetala and C. minax, are rich, and thus worth exploring and developing.

Caesalpinia↗
PubMed1999

[Epidemiological survey on orchard pollinosis].

OBJECTIVE: To investigate the prevalence of Orchard Pollinosis in China. METHOD: From 1995 to 1998, an epidemiological survey on orchard pollinosis was carried on among 1,660 primary and middle school students and 2,167 university students, including questionnaire investigation, nasal inspection and scratch test. From April to June of 1998, a clinical investigation of orchard pollinosis was adopted among 30 patients of allergic rhinitis including scratch test and nasal mucosa test. RESULT: 1. The total positive rate of orchard pollen scratch test was 6.7%, and the prevalence of orchard pollinosis was 0.37%. 2. 5 cases (16.7%) were hypersensitive to orchard pollen clinically in allergen test. CONCLUSION: Orchard pollinosis is one kind of important pollinosis and should be paid high attention to.

Adolescent↗
PubMed1999

[A clinical study on sudden deafness in juveniles].

OBJECTIVE: To understand the clinical characteristics, treatment efficacy and the main factors affecting the prognosis of sudden deafness in juveniles. METHOD: Clinical data of thirty-four cases about juvenile with sudden deafness were respectively analysesed. RESULT: 1) The number of male cases is as about four times as that of female cases, nearly one-third of the cases had a history of virus infection. 2) The total effective rate was 52.4%. The significantly differences among the different modalities were not found. 3) An association was found between the prognosis and the sex, the type of primary audiogram, the course of disease and the degree of hearing loss. The threshold of hearing at 4,000 Hz. was found valuable to judge the prognosis of sudden deafness in juveniles. The influence of the vertigo and tinnitus was not remarkable. CONCLUSION: Some aspects of sudden deafness in juvenile were similar to that in adult, however, there are also some special characteristics about it.

Adolescent↗
PubMed1999

[Determination of resveratrol in grape wine by high performance liquid chromatography].

Resveratrol is a microactive factor for preventing human cancer. A reversed phase high performance liquid chromatographic method for the determination of resveratrol in grape wine was developed. Samples were extrated by ethyl acetate and washed with 3% NaHCO3; after dehydrated with Na2SO4 and dried in vacunm at 40 degrees C, dissovled in acetonitrile. The conditions of HPLC analysis were as follows: the maximum absorptions of trans-resveratrol and cis-resveratrol were at 306 nm and 280 nm respectively. Separation was achieved by the use of mu-Bondapak C18 column (3.9 mm x 300 mm). The mobile phase was V(acetonitrile):V(water) = 40:60. The retention times of trans- and cis-resveratrol were 7.7 min and 8.9 min respectively. The recovery rates were 90.0%-97.8% and the CV was 3.3%. Detection limit was 10 micrograms/L. Eleven kinds of red and white grape wine made in China were detected. All of them contained resveratrol, but the quantity, from 10.0 to 920.0 micrograms/L, were quite different.

Anticarcinogenic Agents↗