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At least 613 records · Page 34Linked to original sources
PubMed2004

Association of ampullary and colorectal malignancies.

BACKGROUND: Because of the similarities in terms of carcinogenesis and natural history between cancer of the ampulla of Vater and colorectal cancer, the authors examined whether ampullary and colorectal malignancies occur in the same individuals at increased rates. METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for the period from January 1973 through December 1999. Person-years of follow-up for patients with ampullary (or colorectal) cancer were used to calculate the expected number of cases of colorectal (or ampullary) cancer as a second primary malignancy. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated using Byar limits and assuming a Poisson distribution. RESULTS: The authors identified 2043 white patients with ampullary cancer who were included in the SEER registry between 1973 and 1999. Over an aggregate 5674 person-years of follow-up, 30 patients, compared with an expected 14, developed colorectal cancer, yielding an overall SIR of 2.14 (95% CI, 1.45-3.06). Similarly, 57 of 262,066 white patients with colorectal cancer developed ampullary cancer over an aggregate 1,270,255 person-years of follow-up, yielding an SIR of 2.18 (95% CI, 1.69-2.85). CONCLUSIONS: Patients with ampullary cancer are at increased risk for a second primary colorectal malignancy, and patients with colorectal cancer are at increased risk for a second primary ampullary malignancy. These findings suggest that ampullary and colorectal malignancies share common environmental and/or genetic risk factors.

Age Distribution↗
PubMed2005

Identifiability of models for fluorescence quenching in aqueous micellar systems.

The first deterministic identifiability analysis is presented for four commonly used kinetic models of fluorescence quenching of an excited probe in aqueous micelles: A) model with immobile quenchers, B) model with mobile quenchers, C) an extension of model B in which exchange of quenchers both via the aqueous phase and during micelle collisions is taken into account, and D) model with probe migration. It is shown that these specific models for fluorescence decay of an excited probe solubilized in a micelle and quenched by molecules or ions that are Poisson-distributed over the micelles, resulting in the generalized four-parameter equation f(t)=A(1) exp{-A(2)t-A(3)[1-A(4)t]}, are uniquely identifiable in terms of four descriptive A parameters. Moreover, each model also can be uniquely identified in terms of the underlying rate constants and micellar concentration or mean micellar aggregation number. This means that these parameters can be extracted in a unique way from time-resolved fluorescence quenching experiments on a probe in micelles. For each model the recommended analysis approach is given.

Journal Article↗
PubMed1993

Detection of rare cells at a frequency of one per million by flow cytometry.

In a model study we seeded the pre-B-cell line REH into 250 million peripheral blood mononuclear cells (PBMC) at frequencies of 10(-4), 10(-5), and 10(-6). By flow cytometry we could detect the REH cells and found a background of about one event per 100 million PBMC. This sensitivity was achieved by removing four sources of false positive events, including nonspecific immunofluorescence, autofluorescence, background particles from previous experiments, and bursts of events during acquisition. To overcome limits to rare event detection imposed by nonspecific staining and autofluorescence, we used positive and negative selection for the REH cells. Another fluorochrome was added to stain the background cells and particles. In order to remove particles and background from previous experiments, a cleaning technique was developed and event bursts were removed from the analysis by developing an algorithm that screens the list-mode data for events that were not Poisson distributed.

Algorithms↗
PubMed2007

Statistical considerations for enumeration of circulating tumor cells.

BACKGROUND: Circulating tumor cells (CTCs) in patients with carcinomas are extremely rare. In metastatic breast cancer, the presence of >or=5 CTCs in 7.5 ml of blood has been associated with short survival. As this threshold has clinical implications, it is important to recognize the limitations associated with the detection and enumeration of CTCs. METHODS: Statistical analyses were performed on data generated from a multi-center clinical trial that utilized the CellSearchtrade mark System to isolate and enumerate CTCs in 7.5 ml blood samples. The statistical issues associated with each step of the process, from blood collection to final image analysis and CTC enumeration, were determined and implemented into a model. RESULTS: A model describing the statistics of the different process steps that are needed for the isolation and detection of CTCs was developed. The model uses the Poisson distribution for blood collection and empirically determined distributions for the isolation and identification of CTCs. The variability between readers was identified as one of the main sources of errors responsible for the current threshold level of five CTCs. CONCLUSIONS: Elimination of the errors made in the identification of tumor cells isolated from 7.5 ml of blood could potentially reduce the CTC threshold for the identification of patients with a poor prognosis from the current value of five CTCs to one CTC per 7.5 ml of blood.

Breast Neoplasms↗
PubMed1986

Epstein-Barr virus-induced IgE production in limiting dilution cultures of normal human B cells.

The induction of in vitro IgE production in human B cells from normal, nonatopic donors has been difficult and somewhat controversial. We report that IgE production is consistently observed in limiting dilution cultures of in vitro Epstein-Barr virus (EBV)-infected normal human B lymphocytes. The frequency of IgE-committed, EBV-responsive cells ranged from 1/810 to 1/10 000 B lymphocytes, and it was similar in peripheral (blood, tonsil) and central (bone marrow) tissue sites. Poisson distribution analysis of these limiting dilution cultures suggested that IgE-committed B cells comprise 0.1-1% of all EBV-responsive B lymphocytes.

B-Lymphocytes↗
PubMed1987

Analysis of human lymphoblast mutation assays by using historical negative control data bases.

We describe here historical negative control data bases for gene locus mutation assays at the thymidine kinase locus and hypoxanthine-guanine phosphoribosyl transferase locus in TK6 and AHH-1 human lymphoblasts, respectively. Protocols have been designed which minimize the variability among independent experiments and thus facilitate the use of historical negative control data bases for assay analysis. The historical negative control data bases for both cell lines can be accurately modeled as gamma or Poisson distributions; confidence limits can be calculated from these distributions. We describe and justify a mutagenicity assay analysis procedure which uses a comparison to the concurrent negative control cultures via a t-test in conjunction with a comparison to the historical negative control data base. The incorporation of a comparison to the historical negative control data base allows the use of a higher confidence level without substantially sacrificing the sensitivity of the mutation assays. The analysis of the mutagenicity of saccharin in TK6 cells is presented as an example; saccharin was found to be nonmutagenic under the conditions tested.

Analysis of Variance↗
PubMed1989

Mutagenesis and mathematics: the allure of numbers.

This paper sets out the "formal," "empirical," and "mechanistic" equations that my colleagues and I have developed for the description and analysis of dose-response data on the lethal and genetic effects of mutagens in microorganisms. These three types of equations are interrelated inasmuch as they are all based ultimately on the use of the Poisson distribution in the formal definition of lethal and mutational hit functions. Explicit mathematical expressions for these functions can be written down in either empirical or mechanistic terms. The empirical equations are obtained simply by writing the hit functions as finite polynomials with adjustable coefficients. The mechanistic equations are based on the assumptions of the "DNA damage-repair hypothesis." The mathematical formulation of this hypothesis entails an important change in the definition of the word "hit" from that used in the classical hit/target theory of radiation biology. The theoretical and practical applications of these various equations in mutation research are summarized briefly and their merits are assessed in light of recent advances in our understanding of the biochemical basis of mutagenesis.

DNA Damage↗
PubMed1985

Confidence intervals and sample size calculations to compare variant frequencies.

Direct mutagenicity tests offer the opportunity of monitoring human populations to detect evidence of genetic damage that occurs in vivo. As such these tests offer the potential of linking earlier exposures to mutagenic agents to subsequent health effects. One such test detects mutant T-lymphocytes that arise in vivo in human peripheral blood. Statistical analysis of the value observed, the variant frequency (Vf), is the subject of this paper. We present and illustrate procedures for finding confidence intervals for a single variant frequency and for the ratio of two independent variant frequencies. We also derive formulae for required sample size to ensure adequate power to detect a specified change in a single variant frequency or a specified difference between two variant frequencies. Our approach is to exploit the approximate normality of the natural logarithm of a Poisson distributed variable. The procedures developed appear to be quite accurate even for the small (5-15) values often observed in the variant frequency assay. Moreover, the procedures are very easy to use and should prove valuable to investigators involved in direct mutagenicity testing.

Drug Resistance↗
PubMed1986

Statistical analyses for in vitro cytogenetic assays using Chinese hamster ovary cells.

It is a widely held view that objective statistical criteria are needed for the evaluation of genetic toxicity assays. This paper presents statistical methods for the analysis of data from in vitro sister chromatid exchange (SCE) and chromosome aberration tests that use Chinese hamster ovary cells. For SCEs, an extensive study of solvent control results demonstrated that there is a substantial interday component of variability in the data, and that a Poisson sampling model is applicable to data generated via the protocol of Galloway et al [1985]. Consequently, a trend test for evidence of a dose response is proposed for such SCE data. As an illustration of this statistical method, analysis of data previously considered to be negative [Gulati et al, 1985] indicates that di(2-ethyl-hexyl) phthalate induces a weak, but reproducible, SCE dose response in CHO cells. Monte Carlo methods are used to show that the trend test is more sensitive than four other statistical procedures considered for the analysis of Poisson-distributed SCEs. A similar trend test for dose response in proportions is proposed for chromosome aberration data, where the percent of cells with chromosome aberrations is the response of interest. Sensitivity (or power) studies indicate that three doses and a control with 50 cells/dose point is a reasonable design for an in vitro SCE study that uses the Galloway et al protocol. For in vitro chromosome aberrations, however, three doses and a control with 100 cells/dose point appears to produce too insensitive an assay; an increase to 200 cells/dose point in the Galloway et al protocol seems worthy of serious consideration.

Animals↗
PubMed1992

Precursor frequency analysis of human cytolytic T lymphocytes directed against autologous melanoma cells.

Limiting numbers of peripheral-blood mononuclear cells (PBMC) from melanoma patients were stimulated with irradiated autologous tumor cells in the presence of interleukins-2 and -4 and in the absence of feeder cells. The responder cells were restimulated every week. After 2 to 4 weeks, the microcultures were tested for their lytic activity against the autologous tumor cells. Significant lysis of the tumor cells was observed with a fraction of these microcultures, whereas no lysis was observed with control microcultures seeded without stimulator melanoma cells. Because our aim was to measure the precursor frequency of CTL showing specificity for the tumor, and not that of NK-like effectors that were also capable of lysing the melanoma cells, we used cold-target inhibition with an excess of NK target K562 to inhibit the NK-like activity. Microcultures whose lysis on the tumor cells was not abolished by K562 competition were observed. The specificity of these CTL clones was confirmed by the absence of lytic activity on autologous T-cell blasts. The numbers of microcultures with anti-tumor CTL activity fitted the zero-order of the Poisson distribution equation, indicating that they resulted from the activity of single T-cell clones. The frequency of anti-tumor CTL precursor cells (CTL-P) of 7 melanoma patients ranged from 1/900 to 1/33,000. Frequencies of anti-tumoral CTL-P were higher and NK-like effectors were less frequent when sorted CD8+ T lymphocytes were used as responder cells.

CD4-CD8 Ratio↗
PubMedDate not supplied

Analysis of human sperm function following exposure to the ionophore A23187. Comparison of normospermic and oligozoospermic men.

Time exposure photomicrography and interspecific in vitro fertilization techniques have been used to compare the responses to the divalent cation ionophore A23187 of spermatozoa from normal fertile and oligozoospermic men. The fertilizing capacity of spermatozoa from the fertile controls produced a bell-shaped dose response curve when assessed in the presence of ionophore. The optimal responses occurred in the presence of 50 and 100 microM A23187. At this concentration, a mean penetration rate of about 75%, in association with multiple polyspermy, was observed without significant changes in motility patterns. At higher doses of A23187, there was a decline in fertilization rates, an independent reduction in sperm motility, and a significant decrease in the amplitude of lateral sperm head displacement. In contrast to the fertile controls, spermatozoa recovered from patients with oligozoospermia failed to exhibit a significant change in their fertilizing potential following exposure to A23187. Calculations based on the Poisson distribution theory indicated that this lack of responsiveness was not related to any differences in the motility of the spermatozoa from the oligozoospermic patients compared to the controls. These results suggest that calcium ionophores may be of value in providing a rapid and sensitive indicator of the functional competence of human spermatozoa, which circumvents problems concerning the rate and efficiency of sperm capacitation encountered with conventional protocols.

Adult↗
PubMed2005

Evaluation of a standardized procedure for [corrected] microscopic cell counts [corrected] in body fluids.

A standardized urinalysis and manual microscopic cell counting system was evaluated for its potential to reduce intra- and interoperator variability in urine and cerebrospinal fluid (CSF) cell counts. Replicate aliquots of pooled specimens were submitted blindly to technologists who were instructed to use either the Kova system with the disposable Glasstic slide (Hycor Biomedical, Inc., Garden Grove, CA) or the standard operating procedure of the University of California-Irvine (UCI), which uses plain glass slides for urine sediments and hemacytometers for CSF. The Hycor system provides a mechanical means of obtaining a fixed volume of fluid in which to resuspend the sediment, and fixes the volume of specimen to be microscopically examined by using capillary filling of a chamber containing in-plane counting grids. Ninety aliquots of pooled specimens of each type of body fluid were used to assess the inter- and intraoperator reproducibility of the measurements. The variability of replicate Hycor measurements made on a single specimen by the same or different observers was compared with that predicted by a Poisson distribution. The Hycor methods generally resulted in test statistics that were slightly lower than those obtained with the laboratory standard methods, indicating a trend toward decreasing the effects of various sources of variability. For 15 paired aliquots of each body fluid, tests for systematically higher or lower measurements with the Hycor methods were performed using the Wilcoxon signed-rank test. Also examined was the average difference between the Hycor and current laboratory standard measurements, along with a 95% confidence interval (CI) for the true average difference. Without increasing labor or the requirement for attention to detail, the Hycor method provides slightly better interrater comparisons than the current method used at UCI.

Cell Count↗
PubMed1982

Concentration of mast-cell progenitors in bone marrow, spleen, and blood of mice determined by limiting dilution analysis.

When hematopoietic cells of congenic +/+ mice were injected into the skin of genetically mast-cell-depleted (WB X C57BL/6)F1-W/Wv mice, mast cells appeared at the injection site. The donor origin of developing mast cells was confirmed by using giant granules of C57BL/6-bgl/bgl mice as a marker. When the number of injected cells was decreased, the proportion of injection sites at which mast cells did not appear increased according to the expected frequency of null response in a Poisson distribution. Therefore, such proportions were used to calculate the concentration of mast-cell precursors in the bone marrow, spleen, and peripheral blood. The relative concentration of mast-cell precursors in these tissues was similar to that of spleen-colony-forming cells. The present method seems useful as a semiquantitative in vivo assay for a population of progenitor cells which are committed to differentiate into mast cells.

Animals↗
PubMed1985

Effects of adhesion on mixing homogeneity. II: Highest attainable degree of mixing of a polydisperse ingredient and a monodisperse diluent.

The highest attainable degree of mixing of a polydisperse ingredient adherent to a monodisperse diluent was derived from the Poisson distribution and found to equal the quality of the noninteractive random mixture. The derivation assumes the arrangement of the ingredient particles onto the surface of the diluent to be random in the equilibrium situation. To produce ordered mixtures of a higher degree of homogeneity should require an ordering mechanism which must enforce the arrangement of the adherent particles to become ordered.

Chemistry, Pharmaceutical↗
PubMed2005

Reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women.

OBJECTIVES: The objective of this study was to establish a reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women. This test is needed for future prenatal Rh prophylaxis. METHODS: A novel real-time PCR-based assay targeting RHD exon 7 combined with a published assay for RHD exon 10 were used to determine the fetal RHD status in DNA extracted from plasma, sampled from 56 pregnant RhD negative women in 15th-36th week of gestation. Thirty-eight samples were from ongoing pregnancies of Danish women and 21 samples from 18 pregnant women were stored anonymized samples from the International Blood Group Reference Laboratory, Bristol, United Kingdom. Prediction of fetal RhD type was compared with the serological result obtained after birth. RESULTS: The prediction of the fetal RhD type was in 100% concordance with the serological RhD type from the 16th week of gestation. One sample from the 15th week of gestation was inconclusive. The number of copies of fetal RHD DNA was found to increase with gestational age. Low levels of DNA were found to follow the Poisson distribution (p = 1.0000). CONCLUSION: Our set-up was very reliable for determination of fetal RhD genotype, and thus will be of value in prenatal Rh prophylaxis and in the management of immunized women.

DNA↗
PubMed2004

ProteomeGRID: towards a high-throughput proteomics pipeline through opportunistic cluster image computing for two-dimensional gel electrophoresis.

The quest for high-throughput proteomics has revealed a number of critical issues. Whilst improved two-dimensional gel electrophoresis (2-DE) sample preparation, staining and imaging issues are being actively pursued by industry, reliable high-throughput spot matching and quantification remains a significant bottleneck in the bioinformatics pipeline, thus restricting the flow of data to mass spectrometry through robotic spot excision and protein digestion. To this end, it is important to establish a full multi-site Grid infrastructure for the processing, archival, standardisation and retrieval of proteomic data and metadata. Particular emphasis needs to be placed on large-scale image mining and statistical cross-validation for reliable, fully automated differential expression analysis, and the development of a statistical 2-DE object model and ontology that underpins the emerging HUPO PSI GPS (Human Proteome Organization Proteomics Standards Initiative General Proteomics Standards). The first step towards this goal is to overcome the computational and communications burden entailed by the image analysis of 2-DE gels with Grid enabled cluster computing. This paper presents the proTurbo framework as part of the ProteomeGRID, which utilises Condor cluster management combined with CORBA communications and JPEG-LS lossless image compression for task farming. A novel probabilistic eager scheduler has been developed to minimise make-span, where tasks are duplicated in response to the likelihood of the Condor machines' owners evicting them. A 60 gel experiment was pair-wise image registered (3540 tasks) on a 40 machine Linux cluster. Real-world performance and network overhead was gauged, and Poisson distributed worker evictions were simulated. Our results show a 4:1 lossless and 9:1 near lossless image compression ratio and so network overhead did not affect other users. With 40 workers a 32x speed-up was seen (80% resource efficiency), and the eager scheduler reduced the impact of evictions by 58%.

Algorithms↗
PubMed1989

A surveillance system based on a short memory scheme.

A surveillance system is proposed to detect an increase in the mean of a Poisson distribution of cases of a disease. This system, called short memory (SM), is based on conditional binomial tests which are performed sequentially at fixed time intervals. The probability of rejection at each test defines the run length distribution which has a geometric tail. A standard SM scheme outperforms other SM schemes. The CUSUM outperforms the SM schemes when the baseline mean is specified correctly. This type of misspecification does not affect the SM scheme.

Data Interpretation, Statistical↗
PubMed1994

A quantitative assay that evaluates the capacity of human stromal cells to support granulomonopoiesis in situ.

We describe an assay that makes possible the observation of granulomonocytic colonies grown on allogeneic stromal layers and the quantification of the stroma-adherent colony-forming cells (CFC). Stromal layers were generated from Stro-1 positive cells isolated from adherent layers of primary long-term marrow cultures using magnetic beads coated with the Stro-1 antibody. The stromal layers consisted mainly of myofibroblastic cells. Marrow fractions depleted of cells bearing receptors for soybean agglutinin (SBA) and enriched in CD34+ cells were obtained by panning. SBA-, CD34+ marrow cells were seeded onto stromal cells grown in 96-well plates. After four weeks, a mixture of cytokines was added (granulocyte-macrophage colony-stimulating factor [GM-CSF]: 25 U/ml, interleukin [IL]-3: 4 ng/ml, Steel factor: 5 ng/ml and growth factors provided by 3% conditioned medium from the 5637 cell line). Wells with large colonies (containing 10(3) to 10(4) cells) were scored after 14 days. Limiting dilution analysis of data revealed a Poisson distribution of the stroma-adherent CFC. There was an average of one stroma-adherent CFC per 167 CD34+ enriched marrow cells, which gave an estimated frequency of one CFC per 10(5) unfractionated bone marrow cells. Colonies contained cells that gave rise to CFU-GM after replating in agar (5-40 CFU-GM were provided per each stroma-adherent CFC), but not cells with self-renewal ability (as indicated by negative results after replating single colonies onto secondary adherent layers). Colonies usually formed from a cobblestone-area and developed in intimate contact with alpha SM actin positive stromal cells. Some of the stromal cells were located above granulocytic cells, corresponding to the description of "blanket cells." This assay should allow the study of colony-formation on marrow stroma without disrupting the hemopoietic niche.

Antibodies, Monoclonal↗