Biomedical subjects

L Cheng

Publications and source records attributed to L Cheng.

At least 109 records · Page 6Linked to original sources

PubMed1999

Natural history of urothelial dysplasia of the bladder.

Urothelial dysplasia is the putative precursor of urothelial carcinoma in situ (CIS) and invasive urothelial carcinoma of the urinary tract. Urothelial dysplasia is frequently identified in patients with urothelial CIS and cancer. However, very little is known about the clinical presentation and natural history of urothelial dysplasia in the absence of urothelial CIS or invasive cancer. The authors studied 36 patients with isolated urothelial dysplasia at the Mayo Clinic between 1969 and 1984. None of these patients had previous or concurrent urothelial CIS or invasive cancer, and none received treatment for dysplasia. The histopathologic features of urothelial dysplasia were examined, and long-term clinical follow-up was obtained. Progression was defined as the development of urothelial CIS or carcinoma. The male-to-female ratio was 2.6:1, and the mean patient age at the time of diagnosis was 60 years (range 25-79). Urothelial dysplasia has a predilection for the posterior wall. Eleven patients had urinary irritative symptoms, 10 had hematuria, 3 had both irritative symptoms and hematuria, and 12 were found to have dysplasia incidentally. The mean follow-up was 8.2 years (range 0.1-25.5). Seven (19%) of 36 patients developed biopsy-proven progression, including 4 with CIS and 3 with invasive cancer, and 1 of them died of bladder cancer. The intervals from diagnosis to progression ranged from 6 months to 8 years (mean 2.5 years). One of the remaining 29 patients had positive cytologic results 2.5 years after the initial diagnosis of dysplasia. The authors conclude that urothelial dysplasia is a significant risk for the development of CIS and invasive urothelial carcinoma, and patients with urothelial dysplasia should be followed up closely.

Adult↗

PubMed1999

Villous adenoma of the urinary tract: a report of 23 cases, including 8 with coexistent adenocarcinoma.

Villous adenoma originating in the urinary tract is uncommon. We present the first study of a large number of cases of villous adenoma of the urinary tract with clinical follow-up. Our series consisted of 15 patients with isolated villous adenoma and 8 patients with coexistent adenocarcinoma. The tumors occurred in elderly patients and had a predilection for the urachus, dome, and trigone of the urinary bladder. The typical clinical presentation was hematuria and irritative symptoms, and endoscopic examination usually identified a tumor growth. There was no gender predominance. Light microscopic examination showed morphologic similarity to colonic villous adenoma in all cases. Each tumor was composed of pointed or blunt finger-like processes lined by pseudostratified columnar epithelium. The epithelial cells displayed nuclear stratification, nuclear crowding, nuclear hyperchromasia, and occasional prominent nucleoli and mitotic figures. There was intense carcinoembryonic antigen immunoreactivity on the luminal surfaces (89%). Most cases (78%) contained cytoplasmic acid mucin, demonstrated by Alcian blue periodic acid-Schiff stain. Cytokeratin 20 was positive in all cases, cytokeratin 7 was positive in 56% of cases, and epithelial membrane antigen was positive in 22% of cases. Recurrence or invasive adenocarcinoma did not develop in any patient with isolated villous adenoma during a mean follow-up of 9.9 years. Lung metastasis developed in one patient with coexistent adenocarcinoma and multiple recurrences in another (mean follow-up, 3 years). We conclude that the prognosis is excellent in patients with isolated villous adenoma, and complete surgical resection is curative. Patients with coexistent adenocarcinoma may experience recurrence or distant metastasis, and more aggressive treatment may be indicated.

Adenocarcinoma↗

PubMed1999

Prevalence and distribution of prostatic intraepithelial neoplasia in salvage radical prostatectomy specimens after radiation therapy.

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer. The effect of radiation therapy (RT) on the prevalence of PIN is uncertain. We studied 86 patients who underwent salvage radical prostatectomy after irradiation failure at the Mayo Clinic. The prevalence, volume, multicentricity, spatial proximity to cancer, and architectural patterns of PIN were evaluated. High-grade PIN was identified in 53 (62%) of 86 prostatectomy specimens. Multiple architectural patterns were usually observed, including tufting in 87%, micropapillary in 66%, cribriform in 38%, and flat in 17%. The mean volume of PIN was 0.12 cm3 (range, 0.05-1.20 cm3). PIN was usually multicentric (70%), with a mean number of PIN foci of 2.5 (range, 1-10). Ninety-four percent of PIN foci were located within 2 mm of invasive cancer. There was no correlation between PIN and pathologic stage, surgical margin, tumor size, DNA ploidy, post-RT Gleason score, time interval from RT to biopsy-proven recurrence, postoperative prostate-specific antigen level, distant metastasis-free survival, or cancer-specific survival. Our examination of salvage radical prostatectomy specimens indicated that the prevalence and extent of PIN appeared to be reduced after RT compared to published studies of prostatectomies without prior RT.

Aged↗

PubMed1999

Diagnosis of prostate cancer in needle biopsies after radiation therapy.

Interpretation of postirradiation needle biopsies is a major diagnostic challenge for the pathologist because of substantial radiation-induced changes in benign and malignant prostatic tissue. Reports that have systematically evaluated the histopathologic findings in postirradiation needle biopsies are limited. In this study, we evaluated 46 histologic features in 29 postirradiation needle biopsy specimens from 29 patients. All patients had recurrent cancer on needle biopsies after external beam radiation, and all subsequently underwent salvage radical prostatectomy and bilateral pelvic lymphadenectomy. Patient age ranged from 57 to 78 years (mean, 61 years). The interval from radiation therapy to biopsy ranged from 1.0 to 17 years (mean, 3.9 years). Histologic features that were helpful in the diagnosis of cancer after radiation therapy included infiltrative growth, perineural invasion, intraluminal crystalloids, blue mucin secretions, the absence of corpora amylacea, and the presence of coexistent high-grade prostatic intraepithelial neoplasia. Benign glands usually showed nuclear enlargement (86%) and prominent nucleoli (50%), and therefore, these cytologic features alone were not reliable for the diagnosis of cancer after irradiation. Postirradiation needle biopsies underestimated the prostatectomy Gleason grade in 35% of cases and overestimated it in 14% of cases; these results were similar to published reports from patients not receiving radiation therapy. There was a major discrepancy in degree of radiation effect between radical prostatectomy and biopsies. Moderate or severe radiation effect on cancer was present in 48% of needle biopsy specimens, whereas 94% of radical prostatectomy specimens had no or minimal radiation effect on cancer when the areas with the least amount of radiation effect were chosen for quantification. These findings indicate that quantification of radiation effect in needle biopsy specimens was inaccurate and potentially misleading. Conversely, Gleason grade in postirradiation needle biopsy specimens appeared to provide useful predictive information and should be reported.

Adenocarcinoma↗

PubMed1999

Treatment of herpes retinitis in an animal model with a sustained delivery antiviral drug, liposomal 1-O-octadecyl-SN-glycerol-3-phosphonoformate.

PURPOSE: To evaluate the clinical treatment efficacy of a long-lasting intravitreous injectable anti-cytomegalovirus (CMV) liposomal drug, 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA). METHODS: Sixty-four pigmented rabbits were used for evaluation of the potency and duration of action of ODG-PFA after intravitreal injection using a herpes simplex virus (HSV)-1 retinitis model. For the potency evaluation, liposomal ODG-PFA was injected into rabbit vitreous at the same time that HSV-1 virus was inoculated onto the retina (simultaneous treatment). For the duration evaluation, ODG-PFA was injected days or weeks before inoculation (pretreatment). Retinitis was clinically graded by indirect ophthalmoscopy, and the retinitis scores were compared across the treatment and control groups. RESULTS: Simultaneous treatment study revealed that ODG-PFA was much more potent than its parent compound, foscarnet (P = 0.0027). Pretreatment study indicated that ODG-PFA possesses a much longer antiviral effect (at least 2 weeks) than foscarnet after a single intravitreal injection. CONCLUSION: Liposomal ODG-PFA is a potent long-lasting intravitreal injectable antiviral compound that may be an ideal alternative for treatment of CMV retinitis in patients with acquired immunodeficiency syndrome.

Animals↗

PubMed1999

Cell cycle regulation of DNA replication initiator factor Dbf4p.

The precise duplication of eukaryotic genetic material takes place once and only once per cell cycle and is dependent on the completion of the previous mitosis. Two evolutionarily conserved kinases, the cyclin B (Clb)/cyclin-dependent kinase (Cdk/Cdc28p) and Cdc7p along with its interacting factor Dbf4p, are required late in G1 to initiate DNA replication. We have determined that the levels of Dbf4p are cell cycle regulated. Dbf4p levels increase as cells begin S phase and remain high through late mitosis, after which they decline dramatically as cells begin the next cell cycle. We report that Dbf4p levels are sensitive to mutations in key components of the anaphase-promoting complex (APC). In addition, Dbf4p is modified in response to DNA damage, and this modification is dependent upon the DNA damage response pathway. We had previously shown that Dbf4p interacts with the M phase polo-like kinase Cdc5p, a key regulator of the APC late in mitosis. These results further link the actions of the initiator protein, Dbf4p, to the completion of mitosis and suggest possible roles for Dbf4p during progression through mitosis.

Aldehyde Oxidoreductases↗

PubMed1999

Differential microvascular response to disuse in rat hindlimb skeletal muscles.

The aim of the study was to address discrepant findings in the literature regarding coupling between decreased functional demand during disuse and reduced capillarity. We previously reported [K. Tyml, O. Mathieu-Costello, and E. Noble. Microvasc. Res. 49: 17-32, 1995] that severe disuse of rat extensor digitorum longus (EDL) muscle caused by a 2-wk application of tetrodotoxin (TTX) on the sciatic nerve is not accompanied by capillary loss. Using the same animal model, the present study examined whether this absence of coupling could be explained in terms of 1) too short a duration of disuse and 2) muscle-specific response to disuse. Fischer 344 rats were exposed to either no treatment (control) or to 2- or 8-wk TTX applications. Fiber size, capillary density per fiber cross-sectional area, and capillary-to-fiber (C/F) ratio were determined by morphometry in the EDL muscle (control, 2- and 8-wk groups) and in the superficial portion of medial gastrocnemius (Gas) muscle (control, 2 wk). In both muscles, microvascular blood flow was evaluated by intravital microscopy [red blood cell velocity in capillaries (V(RBC))] and by laser Doppler flowmetry (LDF). Regardless of duration of TTX application or muscle type, TTX-induced disuse resulted in a significant reduction of fiber area (44-71%). However, capillary density increased in EDL muscle (both at 2 and 8 wk) but not in Gas muscle. C/F ratio decreased in EDL muscle at 8 wk (18%) and in Gas muscle (39%). This indicates that the effect on capillarity depended on duration of disuse and on muscle type. V(RBC) and LDF signal were significantly larger in EDL than in Gas muscle. Analysis of change in capillarity vs. V(RBC) suggested that the outcome of disuse may be modulated by blood flow. We conclude that the duration of skeletal muscle disuse per se does not dictate capillary loss, and we hypothesize that discrepant findings of coupling between functional demand and capillarity could be due to the presence/absence of flow-related angiogenesis superimposed on the capillary removal process during disuse.

Animals↗

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↗