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At least 289 records · Page 16Linked to original sources

Morphometric grading of breast cancer: thresholds for tubular differentiation.

We evaluated the degree of tubular differentiation in 172 samples of invasive ductal breast cancer in order to determine numerical thresholds for histological breast cancer grading. The tubular differentiation in each sample was defined as the fraction of fields showing tubular differentiation (FTD). The analysis was based on Kaplan-Meier curves reflecting survival and recurrence of disease, univariate and multivariate analyses of Cox's regression, and maximum efficiencies of ROC analysis. The minimum P-value cut-off for FTD was determined at 59%. The practical interpretation is that tubular differentiation in the neoplasm observed in at least 60% of microscopical fields in the tumour area indicates favourable prognosis of disease. The relative risks for breast cancer death for patients with FTD below 59% as compared with those with FTD above 59% were 6.7--and 6.3-fold (univariate and multivariate analyses respectively). Another threshold could be determined at FTD 23%, although this threshold was associated with clearly lower statistical significancies. The paper introduces two possible solutions for application of the thresholds to the morphometric breast cancer grading system. The study also emphasizes the clinical relevance of the evaluation of tubular differentiation in breast cancer. The consistent morphometric evaluation method was vital in allowing the full weight of the biological significance of tubular differentiation to emerge.

Adenocarcinoma↗

T cell priming by dendritic cells: thresholds for proliferation, differentiation and death and intraclonal functional diversification.

The variables that influence priming of human naive CD4+ T cells by dendritic cells (DC) were dissected in vitro by analyzing the response to the bacterial superantigen toxicshock syndrome toxin or to alloantigens. We show that under conditions that force DC-T cell interactions a single DC can prime up to 20 naive T cells. Moreover, the strength of antigenic stimulation, as determined by DC numbers, antigen dose, TCR avidity and duration of DC-T cell interactions, drives the progressive differentiation of proliferating T cells from a non-effector CCR7+ stage, to an effector CCR7- stage and, eventually, to cell death. We also show that the proliferating CCR7+ and CCR7- populations share clonotypic sequences, demonstrating that the two cell fates can be generated within a single clone. Taken together these results indicate that the strength of antigenic stimulation regulates T cell progression through thresholds of proliferation, differentiation and death. However, the random nature of DC-T cell encounters introduces a critical stochastic element in T cell stimulation, which leads to the generation of cells endowed with distinct homing potentials and effector functions within a given T cell clone.

Bacterial Toxins↗

[Status of the sensory sphere in schizophrenic patients with a cenestopathic-hypochondriacal syndrome].

The state of and interrelations between the kinesthetic and visual sensitivity were studied in 70 patients and 24 normal subjects by using the technique of parallel-sequential sensometry suggested by A. V. Zavyalov. At 30 sec intervals at the constant baseline irritation, 16 thresholds of weight differentiation and 16 thresholds of brightness differentiation were registered. The results were subjected to the correlational and informational analysis. It was established that hyposensitivity of the sensory systems studied was accompanied with the weakening of direct and strengthening of the inverse optical-kinesthetic correlation, the absence of the functional predominance of the kinesthetic analyzer over the visual one, low orderliness of the parameters of the interanalyzer relationship and a sharp liability of the intersensory correlation to the effect of the heterosensory irritant. Changes in the systemic organization of the sensory sphere seem to be responsible for various cenesthopathies.

Adult↗

Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis.

Despite the potential of the inhibitor of apoptosis proteins (IAPs) to block cytochrome c-dependent caspase activation, the critical function of IAPs in regulating mammalian apoptosis remains unclear. We report that the ability of endogenous IAPs to effectively regulate caspase activation depends on the differentiation state of the cell. Despite being expressed at equivalent levels, endogenous IAPs afforded no protection against cytochrome c-induced apoptosis in naive pheochromocytoma (PC12) cells, but were remarkably effective in doing so in neuronally differentiated cells. Neuronal differentiation was also accompanied with a marked reduction in Apaf-1, resulting in a significant decrease in apoptosome activity. Importantly, this decrease in Apaf-1 protein was directly linked to the increased ability of IAPs to stringently regulate apoptosis in neuronally differentiated PC12 and primary cells. These data illustrate specifically how the apoptotic pathway acquires increased regulation with cellular differentiation, and are the first to show that IAP function and apoptosome activity are coupled in cells.

Animals↗

Frequency discrimination in the chinchilla.

Chinchillas were trained with shock-avoidance procedures to discriminate or detect pure-tone frequency differences. Inital attempts at determining frequency-difference thresholds utilized a complex discrimination paradigm and a go-no-go response. Although discriminations of large frequency differences were obtained from chinchillas after considerable training, discriminations of small frequency differences could not be trained. Therefore, determinations of frequency-difference thresholds could not be made with the complex discrimination paradigm and the go-no-go response task. A simple detection paradigm, involving the detection of frequency alternation in an ongoing train of tone bursts proved to be a more successful technique. Frequency-alternation detection was quickly learned by six chinchillas, and frequency-difference thresholds were obtained with an adaptive sequential procedure. Psychometric functions were reconstructed from the threshold tracking data of chinchillas, and comparisons were made with differential frequency thresholds from cats and humans obtained by previous investigators. Differential frequency thresholds from chinchillas paralleled those from cats and were about twice as large. Differential frequency thresholds from humans were considerably smaller than from chinchillas, especially for low-frequency tones. When a constant detectability index was used to specify differential frequency sensitiviy in chinchillas, chinchilla and human differential sensitivity functions paralleled one another. Human differential sensitivity was about ten times better than that of the chinchilla.

Animals↗

A Bayesian determination of threshold for identifying differentially expressed genes in microarray experiments.

The original definitions of false discovery rate (FDR) and false non-discovery rate (FNR) can be understood as the frequentist risks of false rejections and false non-rejections, respectively, conditional on the unknown parameter, while the Bayesian posterior FDR and posterior FNR are conditioned on the data. From a Bayesian point of view, it seems natural to take into account the uncertainties in both the parameter and the data. In this spirit, we propose averaging out the frequentist risks of false rejections and false non-rejections with respect to some prior distribution of the parameters to obtain the average FDR (AFDR) and average FNR (AFNR), respectively. A linear combination of the AFDR and AFNR, called the average Bayes error rate (ABER), is considered as an overall risk. Some useful formulas for the AFDR, AFNR and ABER are developed for normal samples with hierarchical mixture priors. The idea of finding threshold values by minimizing the ABER or controlling the AFDR is illustrated using a gene expression data set. Simulation studies show that the proposed approaches are more powerful and robust than the widely used FDR method.

BRCA1 Protein↗

Motion perception deficits in glaucomatous optic neuropathy.

The mechanisms mediating impaired motion perception in glaucoma were investigated. Direction discrimination thresholds for low (4.2 deg/sec) and high (12.5 deg/sec) velocity random-dot kinematograms were measured in controls and patients with glaucoma or ocular hypertension. Thresholds were elevated significantly in glaucoma patients and individual ocular hypertensives. Threshold elevations were not due to blur or pupil size. After compensating for motion reversals, high but not low velocity thresholds remained elevated. Only high velocity thresholds correlated with differential luminance sensitivity. A hypothesis that different mechanisms mediate glaucoma-induced deficits at high and low velocities is presented.

Adult↗

[Differential light perception threshold of the visual field and ERG following operatively attached retinal detachment].

After surgical treatment of retinal detachment with a spontaneously pigmented demarcation line the visual fields of twelve patients were tested. The increment threshold of all positions (determined with the Octopus automatic perimeter system) was compared with the reduction in the scotopic and photopic ERG amplitudes (determinated with the CEMIDA system). This reduction in the ERG amplitudes was evaluated using the difference between the amplitude of the ERG waves of the eye with cured retinal detachment and of the healthy fellow eye. No great correlation between the two parameters was found, but it appeared that a reduced mean increment threshold correlated with a reduction in the a-wave amplitude.

Adolescent↗

[Working conditions and functional body stress of operators in the television video recording centers].

In order to determine the ways for prevention of operators' overstrain, the working conditions and functional body stress were dynamically studied during the 12-hour shift by means of TV video-recording. The majority of operators experienced some neurologic disorders, high rates of situational and personality anxiety and an elevated level of neurotism. Mean rate of potential systoles was 75 +/- 2 per min, systolic arterial pressure 114 +/- 2, diastolic AP 74 +/- 2 mm of mercury column. No renewable dynamics of the above indicators was noted. The Kerdau vegetative index experienced a decline from + 6.0 +/- 2.5 to -6.5 +/- 3.0 arbitrary units during the shift. The regulatory system strain index in the half of the examined workers reached 300AU. The speed of data processing remained stable during the shift. To its end the critical fusion frequency on the peripheric visual field and remote visual thresholds decreased and differentiated achromatic thresholds increased. The level of operators' functional body strain could be regarded as admissible. The above characteristics of load response of some physiologic systems were assumed to be variants of an adaptable norm. The proposed preventive measures assisted in decreasing operators' functional body strain.

Hemodynamics↗

The influence of refraction accuracy on automated perimetric threshold measurements.

The effect of refraction accuracy on the differential light threshold of a Goldmann size III (0.43 degrees diameter) stimulus was evaluated in the right eyes of five normal subjects with randomly ordered sequence of plano, +1.00-, +2.00-, +3.00-, +4.00-, +5.00-, and +6.00-diopter (D) spherical overcorrections. Threshold measurements were performed at 0 degree, 5 degrees, 10 degrees, 15 degrees, 20 degrees, and 25 degrees eccentricity nasally along the 180 degrees meridian with the F4 program on the Octopus 201 perimeter. The +1.00- through +6.00-D overcorrections decreased the threshold values by an average of 1.4, 2.9, 4.2, 5.6, 6.7, and 7.6 dB, respectively, compared with the plano overcorrection. The depression of the differential light threshold was of similar magnitude at all eccentricities within the central 25 degrees.

Adult↗

Regulation of WNT signaling molecules by retinoic acid during neuronal differentiation in NT2 cells: threshold model of WNT action (review).

NT2/NTera2 cells, derived from human embryonal tumor, differentiate into neuronal cells after treatment with all-trans-retinoic acid (ATRA). We have cloned and characterized 13 out of 19 human WNT genes, and also 9 out of 10 human Frizzled (FZD) genes encoding seven-transmembrane-type WNT receptors, which are potent targets for pharmacogenomics in the post-genomic era, especially in the field of regenerative medicine and clinical oncology. Because WNT signals are implicated in morphogenesis of neural tissues, regulation of 19 WNT genes and 10 FZD genes during the early phase of neuronal differentiation in NT2 cells is reviewed. Multiple WNTs and FZDs are expressed in NT2 cells. WNT2B/WNT13 gene encode 2 isoforms due to alternative splicing of alternative promoter type, and WNT2B isoform 2 (WNT2B2) rather than WNT2B isoform 1 (WNT2B1) is expressed in NT2 cells. WNT3A, WNT8A, WNT8B, WNT10B and WNT11 are down-regulated in NT2 cells after ATRA treatment, while WNT2, WNT7B and WNT14B are up-regulated. FZD4 and FZD10 are up-regulated in NT2 cells after ATRA treatment. Expression of multiple WNT signaling molecules are dramatically changed during the early phase of neuronal differentiation in NT2 cells. Each WNT activates the beta-catenin - TCF pathway, the JNK pathway or the Ca2+-releasing pathway in NT2 cells, and summed effects of multiple WNTs might determine the fate of NT2 cells (self-renewal or differentiation) through switching intracellular WNT signaling pathways. The author proposes the threshold model of WNT action.

Cell Differentiation↗