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At least 811 records · Page 45Linked to original sources

Alpha-catenin expression has prognostic value in local and locally advanced prostate cancer.

Normally functioning cell-cell adhesion plays an important role in the maintenance of tissue architecture and cell cohesion. E-cadherin is an important adhesion molecule of epithelial cells. In many types of cancer the expression of E-cadherin is reduced leading to increased risk of disease progression. alpha-Catenin is one of the intracellular elements of the E-cadherin-catenin complex. The abnormalities in the expression of alpha-catenin seem to associate with malignant cellular features and disease progression in prostate cancer. To further analyse the significance of alpha-catenin expression, we studied 215 cases of prostate cancer by immunohistochemistry and the results were related to other known prognostic factors and patient survival during a mean follow-up period of 13 years. alpha-Catenin expression was down-regulated in 19% of the cases and 3% of the tumours were totally alpha-catenin-negative. The abnormal alpha-catenin expression and cytoplasmic signal were significantly linked with high T-category, metastatic disease, high Gleason score, perineural growth, high mitotic rate, high S phase fraction and DNA aneuploidy (P < 0.05 for all). In the survival analysis, reduced alpha-catenin expression (P = 0.06) and cytoplasmic signal (P = 0.04) were related to unfavourable patient outcome. In the multivariate analysis, including TM-classification and Gleason score, alpha-catenin expression had independent prognostic value in T1-2 M0 tumors. In the M0 tumours, abnormal alpha-catenin signal was independently associated with recurrence-free survival as well. The results indicate that down-regulation of alpha-catenin is related to several malignant cellular features, and it seems to have prognostic significance in the early phases of cancer progression. We suggest that alpha-catenin expression can provide prognostic information in early prostate cancer.

Adult↗

To succeed globally, disperse locally: effects of local pollen and seed dispersal on tetraploid establishment.

Newly formed tetraploid plants in sympatry with their diploid progenitors should face significant obstacles to persistence and population establishment because of low-fitness triploids formed by cross-ploidy pollinations. Prior models have found restrictive conditions for a minority tetraploid subpopulation to persist. A stochastic spatial model, parameterized using snow buttercups (Ranunculus adoneus), was used to examine the influence of limited seed and pollen dispersal distances on the success of minority tetraploids and the interaction of these factors with different rates of self-pollination and tetraploid advantage. Higher rates of self-pollination and increased tetraploid advantage increase the probability of tetraploid persistence. Limiting the dispersal of seeds and pollen further increases the positive impact of any given level of self-pollination and tetraploid advantage. Taxa with short-distance seed and pollen dispersal should face much less stringent barriers to sympatric polyploid speciation than taxa with long-distance dispersal patterns. With short-distance seed and pollen dispersal, polyploid speciation should be possible in the absence of ecological differentiation or recurrent polyploid formation through unreduced gametes.

Crosses, Genetic↗

Investigating the clinical utility of the percent of positive prostate biopsies in predicting PSA outcome following local therapy for patients with clinically localized prostate cancer.

The clinical utility of the percent of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome following radical prostatectomy (RP), or external beam radiation therapy (RT), for men with PSA detected, or clinically palpable prostate cancer was investigated. After accounting for the established prognostic significance of the PSA level, biopsy Gleason score and the clinical T-stage, the percent of positive prostate biopsies added clinically significant information regarding time to PSA failure following RP. These findings were validated in the intermediate risk patients using an independent surgical and radiation data set. Prostate Cancer and Prostatic Diseases (2000) 3, 259-264

Journal Article↗

Subcellular localization of prostaglandin H synthase-2 in a human amnion cell line: implications for nuclear localized prostaglandin signaling pathways.

We have determined that prostaglandin H synthase-2 localises strongly to the nuclear membrane as well as being found in the endoplasmic reticulum in human amnion-derived WISH cells which have been stimulated with interleukin 1beta and phorbol ester. This is consistent with findings in cells of non-reproductive origin. There is strong evidence that prostaglandin J2 derivatives, which in other tissues exhibit tumour suppressing, antiproliferative and/or differentiation promoting activities, act through binding of intracellular receptors which then enter the nucleus. In addition, some arachidonic acid derivatives are clearly generated by enzymes at the nuclear envelope and localise to sites in nuclei or bind sites in nuclei. The WISH cell line will make an excellent system for studying these perinuclear intracellular prostanoid signaling mechanisms.

Amnion↗

Community-level firearm injury surveillance: local data for local action.

In the United States, firearms are used to commit homicide more frequently than all other methods combined. According to the US Department of Justice, firearms are used to commit more than 1 million crimes each year. Despite the magnitude of this problem, little is known about the epidemiology of firearm crimes and assaults. Many states require medical personnel to report all nonfatal shootings to law enforcement, but the rate of compliance with this requirement is unknown. To enhance cooperation between community emergency departments and law enforcement agencies, we created a unified firearm injury notification system for the City of Atlanta, Georgia, and 5 surrounding counties: Fulton, DeKalb, Cobb, Gwinnett, and Clayton. Our findings are reported here.

Emergency Service, Hospital↗

Cellular and subcellular localization of 1,25-(OH)2-vitamin D3 in rat kidney: comparison with localization of parathyroid hormone and estradiol.

Results of thaw-mount autoradiographic studies of kidney obtained 1--3 hr after a single injection of 1,25-(OH)2-[3H]vitamin D3 to rats showed strong nuclear concentration of radioactivity in podocytes and cells of distal tubules, including the pars convoluta, macula densa, and pars recta. Intermediate nuclear concentration was found in cells of the thin limb of Henle's loops, whereas weak or no nuclear uptake was seen in cells of the proximal tubules. In contrast, after injection of 3H-labeled parathyroid hormone or [3H]estradiol, mainly cells of the proximal tubules were labeled; after 3H-labeled parathyroid hormone, apical cytoplasmic uptake of radioactivity was seen most strongly in the proximal part of the proximal tubules, whereas, after [3H]estradiol, weak nuclear concentration was seen in cells throughout the proximal tubules. The results are consistent with the concept that synthesis of 1,25-(OH)2-vitamin D3 occurs in the proximal tubules under stimulation of parathyroid hormone or estradiol (or other hormones) and that the major site of action of 1,25-(OH)2-vitamin D3 is in the distal tubules.

Animals↗

Reelin immunoreactivity in the adult primate brain: intracellular localization in projecting and local circuit neurons of the cerebral cortex, hippocampus and subcortical regions.

Reelin is a large secretable protein which is widely expressed by specific neuronal populations. In the embryonic brain, Reelin plays a signaling role critical for the correct positioning of migrating neuroblasts. Reelin is also expressed in the adult mammalian brain, including humans; however, its function/s there remain poorly understood. To gain insight into which neuronal populations and specific circuits may be influenced by Reelin in the adult, we have conducted a light and electron microscope analysis of Reelin-immunoreactive neuron types in the cerebral cortex and subcortical regions of adult macaque monkeys. Results show that the great majority of brain neurons, including interneurons and projection neurons, are immunoreactive for Reelin although some neuronal populations do not contain Reelin. The immunoreactive protein is located intracellularly, mainly in neuronal somata. Reelin is also present in gray matter neuropil as well as in some long axonal pathways and their terminal arborizations, suggesting that it can be axonally transported over long distances. The staining patterns in the labeled neurons are remarkably diverse. Our observations reveal a wider distribution of Reelin in the adult macaque brain than in any other species investigated to date. The data show that Reelin is in a position to influence most brain circuits in the adult primate brain.

Animals↗

Relationship between local oxygen consumption and local and external cardiac work: effect of tachycardia.

This study was designed to determine the extent of coupling between regional myocardial segment work and corresponding regional oxygen consumption, and to examine whether tachycardia induced changes in regional work are translated into corresponding changes in external cardiac work. In the open chest anaesthetised dog, the heart was paced at frequencies of 120-270 beats.min-1. Global and regional myocardial O2 supply, consumption, and balance were evaluated at each heart rate, and correlated with corresponding functional changes. Global cardiac function was evaluated from aortic flow, blood pressure, and left ventricular pressure. Coronary sinus flow and O2 saturation were used to calculate O2 consumption. The integrated multiple of myocardial shortening (ultrasonic dimension crystals) by corresponding force (strain gauge arch) during an averaged beat was used to express regional segment work. Regional coronary blood flow was measured with radioactive microspheres, and microspectrophotometry was used to evaluate O2 saturation in small arteries and veins. These indices were used to calculate regional myocardial oxygen consumption. NADH redox levels were recorded by surface fluorometry, and were found to increase with heart rate by up to 67%. Increasing heart rate from 120 to 180 beats.min-1 increased regional work from 3040(SEM 220) to a peak of 4290(280) mm.g-1.min-1, whereas external cardiac work did not increase [67.0(2.6) to 65.3(4.4) mm Hg.litre-1.min-1] and fell further at the highest rates. Regional oxygen consumption increased from 6.16(0.47) to 8.29(0.53) ml O2.min-1.100 g-1 and was linearly related to regional work at all heart rates (r = 0.971, p less than 0.05). External cardiac work fell by about 26% whereas global myocardial oxygen consumption increased by 49% during tachycardia. It is concluded that myocardial oxygen consumption is more closely related to regional segment work than to external work, and that tachycardia significantly raises the oxygen cost of external work of the heart.

Animals↗

Local UV-induced DNA damage in cell nuclei results in local transcription inhibition.

UV-induced DNA damage causes cells to repress RNA synthesis and to initiate nucleotide excision repair (NER). NER and transcription are intimately linked processes. Evidence has been presented that, in addition to damaged genes, undamaged loci are transcriptionally inhibited. We investigated whether RNA synthesis from undamaged genes is affected by the presence of UV damage elsewhere in the same nucleus, using a novel technique to UV irradiate only part of a nucleus. We show that the basal transcription/repair factor TFIIH is recruited to the damaged nuclear area, partially depleting the undamaged nuclear area. Remarkably, this sequestration has no effect on RNA synthesis. This result was obtained for cells that are able to carry out NER and for cells deficient in NER. We conclude that cross talk between NER and transcription occurs only over short distances in nuclei of living cells.

Cell Nucleus↗