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PubMed2005

Is cervical dilatation during parturition at term associated with apoptosis?

AIMS: Cellular turnover may be involved in remodeling of the cervix during parturition. Therefore, the number and localization of apoptotic and proliferating cells during cervical dilatation at term were determined. METHODS: Biopsy specimens from the lower uterine segment of 36 women undergoing cesarean section with a cervical dilatation of < 2 cm (n = 10), 2- < 4 cm (n = 9), 4-6 cm (n = 8), and > 6 cm (n = 9) were examined for nuclear fragmentation by the TUNEL assay, and for cell survival by the apoptosis-blocking bcl-2. Proliferation was marked by Ki-67, epithelial cells by cytokeratin and leukocytes by CD 45. For quantification of apoptotic and proliferating cells, eight random fields of each specimen stained for TUNEL or Ki-67 were blindly counted by two investigators. For statistical evaluation, 90% confidence intervals based on a Poisson distribution were used; groups with non-overlapping intervals were considered significantly different. RESULTS: Apoptotic cells were found exclusively within the stromal compartment, while bcl-2 was expressed in epithelial cells and leukocytes. Proliferating cells were of stromal and epithelial origin. The number of apoptotic as well as proliferating cells ranged from 0 to 2 cells per high-power field (median number 0) in all groups. The confidence intervals were overlapping for all groups, showing no statistical difference between them. CONCLUSION: Apoptosis does not seem to play a decisive role in the process of cervical dilatation during parturition at term.

Apoptosis↗
PubMed2005

Gap-junctional coupling and absolute sensitivity of photoreceptors in macaque retina.

We investigated gap-junctional coupling of rods and cones in macaque retina. Cone voltage responses evoked by light absorption in neighboring rods were briefer and smaller than responses recorded in the rods themselves. Rod detection thresholds, calculated from noise and response amplitude histograms, closely matched the threshold for an ideal detector limited by quantal fluctuations in the stimulus. Surprisingly, cone thresholds were only approximately two times higher. Amplitude fluctuations in cones could be explained by a Poisson distribution of photoisomerizations within a pool of seven or more coupled rods. Neurobiotin coupling between rods and cones was consistent with our electrical recordings, with approximately six rods labeled per injected cone. The spatial distribution of tracer-coupled rods matched the light-evoked cone receptive field. The gap junction inhibitor carbenoxolone abolished both electrical and tracer coupling. Amplitude fluctuations in most rods were accounted for by the expected rate of light absorption in their outer segments. The fluctuations in some rods, however, were consistent with a summation pool of up to six rods. When single rods were injected with Neurobiotin, up to 10 rods were labeled. Rod-rod and rod-cone electrical coupling is expected to extend the range of scotopic vision by circumventing saturation at the rod to rod-bipolar cell synapse; however, because coupling also renders the rod synapse less effective at separating out photon signals from dark noise, coupling is expected to elevate the absolute threshold of dark-adapted observers.

Animals↗
PubMed2005

Kin selection is implicated in partial sib-mating populations with constant viability differences before mating.

The change in the frequency of a rare mutant allele under constant sex-differentiated viability selection in an infinite, partial full-sib mating population is studied. The diplo-diploid and haplo-diploid polygynous models are considered with a Poisson distribution for the number of offspring produced by every mated female. Reproduction is followed by weak selection among the offspring and then mating to form the next generation. It is shown that the rate of change with respect to the frequency of the mutant allele and the intensity of selection can be expressed in terms of costs or benefits of substituting the mutant type for the wild type, which correspond to average excesses in viability in females and males, multiplied by coefficients of relatedness to the individuals affected by such a substitution and reproductive values associated to the sexes of these individuals. This reveals hidden interactions between mated individuals and between males for mating, the former having positive effects on the reproductive success of related individuals and the latter having negative effects. Such interactions are the result of reproductive constraints when a fixed proportion of females must mate with a male sib and all females are fertilized as long as one mate is available. However, they affect the change in allele frequency because there is inbreeding or relatedness between mates and more generally relatedness between interacting individuals. Surprisingly, the effects of these interactions cancel out in a diploid population when the number of offspring is large enough so that the possibility for a female to have no male sib to mate with can be neglected and the viability differences are the same in both sexes.

Algorithms↗
PubMed2001

Incidence and prevalence of diabetes mellitus in the Americas.

OBJECTIVE: To present the incidence and prevalence of diabetes mellitus in the Americas as found through a thorough review of published information on the subject. METHODS: Data were obtained through a comprehensive review using the MEDLINE and BIREME bibliographical databases. In addition, government publications, conference reports, and meeting documents were identified by contacting government and nongovernmental organizations and other institutions. Incidence and prevalence rates were adjusted by age and sex, when possible, by the direct method using the world Segi population as the standard. The 95% confidence intervals were calculated using the Poisson distribution or the normal distribution. RESULTS: Diabetes mellitus represents a major public health problem in the Americas, and there is evidence that its prevalence is increasing in some countries. CONCLUSIONS: Given that most Latin American and Caribbean nations are experiencing a demographic transition, it is expected that the prevalence of diabetes will continue to increase rapidly in the near future. Despite the economic constraints faced by the countries of the Americas, there is a clear need for more efforts in the area of diabetes prevention and control.

Adolescent↗
PubMed2004

Impact of safety warnings on drug utilization: marketplace life span of cisapride and troglitazone.

STUDY OBJECTIVE: To evaluate the impact of safety alerts on the volume of cisapride and troglitazone usage. DESIGN: Retrospective database analysis. SETTING: University research center. MATERIAL: Idaho Medicaid claims data from January 1994--July 2000. MEASUREMENTS AND MAIN RESULTS: Monthly counts of total and new prescriptions filled for cisapride and troglitazone were analyzed graphically over time as a function of all prescriptions. New prescriptions were defined as those filled by patients who had not received the drug within the previous year. A binomial comparison of the 5 months before and after each safety alert was conducted by Poisson distribution. Overall and new cisapride usage increased after the first alert, which occurred in February 1995 (p<0.05). After the second alert, in September 1995, growth in new prescriptions ended but total prescriptions continued to grow (p<0.05). After the third alert, in June 1998, growth in total use ended and the number of new prescriptions declined (p<0.05). The final two alerts (June 1999 and January 2000) were met with significant declines (p<0.05 for both). Troglitazone was the subject of two alerts in October and December 1997. After these, overall usage increased (p<0.05), whereas the number o new prescriptions decreased (p<0.05). The third alert, in July 1998, caused no change as total prescription use continued to grow (p<0.05), whereas the number of new prescriptions decreased (p<0.05). A fourth alert, in June 1999, resulted in a decrease of overall usage and new prescriptions (p<0.05 for both). CONCLUSION: Numerous safety alerts were required for each drug before drug usage declined. The decline in overall use was slower than the decline in new prescriptions, possibly indicating a need for increased assessment of refilled prescriptions after the release of new safety data.

Chromans↗
PubMed2005

Impacts of soil moisture level on consumption and movement of three sympatric subterranean termites (Isoptera: Rhinotermitidae) in a laboratory assay.

Three subterranean termite species, Reticuliternes flavipes (Kollar), Reticulitermes tibialis Banks, and Reticulitermes virginicus (Banks), were collected from locations in northern Indiana and tested under laboratory conditions to determine whether preferential differences exist among species. Foraging behaviors and location of all three species were studied using a linear, three-dimensional assay with a soil moisture gradient (5, 15, 25, 35, 45, and 55% moisture by weight) and quantified by (1) consumption weights and (2) location counts. In a 7-d period, R. flavipes and R. tibialis consumed almost twice as much filter paper as R. virginicus. No significant difference in feeding was attributed to moisture level for R. tibialis, but there were differences for R. flavipes and R. virginicus. In terms of location of harborage, there were clear patterns associated with moisture level, as predicted using a Poisson distribution. Results from consumption and location data show unique patterns among species, and illustrate species-specific variation in feeding location and nesting preference in response to moisture. There are significant differences in movement patterns, consumption, and mortality among Indiana Reticulitermes according to the laboratory assay. These findings contribute to the overall understanding of midwestern Reticulitermes termites.

Animals↗
PubMed2006

Transformations of count data for tests of interaction in factorial and split-plot experiments.

In applied entomological experiments, when the response is a count-type variable, certain transformation remedies such as the square root, logarithm (log), or rank transformation are often used to normalize data before analysis of variance. In this study, we examine the usefulness of these transformations by reanalyzing field-collected data from a split-plot experiment and by performing a more comprehensive simulation study of factorial and split-plot experiments. For field-collected data, significant interactions were dependent upon the type of transformation. For the simulation study, Poisson distributed errors were used for a 2 by 2 factorial arrangement, in both randomized complete block and split-plot settings. Various sizes of main effects were induced, and type I error rates and powers of the tests for interaction were examined for the raw response values, log-, square root-, and rank-transformed responses. The aligned rank transformation also was investigated because it has been shown to perform well in testing interactions in factorial arrangements. We found that for testing interactions, the untransformed response and the aligned rank response performed best (preserved nominal type I error rates), whereas the other transformations had inflated error rates when main effects were present. No evaluations of the tests for main effects or simple effects have been conducted. Potentially these transformations will still be necessary when performing these tests.

Analysis of Variance↗
PubMed2003

Adherent cells generated during long-term culture of human umbilical cord blood CD34+ cells have characteristics of endothelial cells and beneficial effect on cord blood ex vivo expansion.

Hematopoiesis depends on the association of hematopoietic stem cells with stromal cells that constitute the hematopoietic microenvironment. The in vitro development of the endothelial cell from umbilical cord blood (UCB) is not well established and has met very limited success. In this study, UCB CD34(+) cells were cultured for 5 weeks in a stroma-free liquid culture system using thrombopoietin, flt3 ligand, and granulocyte-colony stimulating factor. By week 4-5, we found that firmly adherent fibroblast-like cells were established. These cells showed characteristics of endothelial cells expressing von Willebrand factor, human vascular cell adhesion molecule-1, human intracellular adhesion molecule-1, human CD31, E-selectin, and human macrophage. Furthermore, when comparing an ex vivo system without an established endothelial monolayer to an ex vivo system with an established endothelial monolayer, better expansion of total nucleated cells, CD34(+) cells, and colony-forming units (CFUs)-granulocyte-macrophage and CFUs-granulocyte-erythroid-megakaryocyte-macrophage were found during culture. This phenomenon was in part due to the fact that a significant reduction of apoptotic fractions was found in the CD34(+) cells, which were cultured on the adherent monolayer for up to 5 weeks. To gather quantitative data on the number of endothelial cells derived from a given number of CD34 cells, we performed limiting dilution assay by using Poisson distribution: the number of tested cells (linear scale) producing a 37% negative culture (logarithmic scale) is the number of cells containing one endothelial cell. By this method, one endothelial cell may be found from 314 CD34(+) cells after 5 weeks of culture. These results suggest that the UCB CD34(+) cell fraction contains endothelial cell precursors, establishing the hematopoietic microenvironment and providing the beneficial effects through downregulating apoptosis on UCB expansion protocols. These observations may provide insight for future cellular therapy or graft engineering.

Antibodies↗
PubMed2001

Long-term genomic instability in human lymphocytes induced by single-particle irradiation.

Recent evidence suggests that genomic instability, which is an important step in carcinogenesis, may be important in the effectiveness of radiation as a carcinogen, particularly for high-LET radiations. Understanding the biological effects underpinning the risks associated with low doses of densely ionizing radiations is complicated in experimental systems by the Poisson distribution of particles that can be delivered. In this study, we report an approach to determine the effect of the lowest possible cellular radiation dose of densely ionizing alpha particles, that of a single particle traversal. Using microbeam technology and an approach for immobilizing human T-lymphocytes, we have measured the effects of single alpha-particle traversals on the surviving progeny of cells. A significant increase in the proportion of aberrant cells is observed 12-13 population doublings after exposure, with a high level of chromatid-type aberrations, indicative of an instability phenotype. These data suggest that instability may be important in situations where even a single particle traverses human cells.

Cations, Divalent↗
PubMed2004

Genetics of osteochondral disease and its relationship with meat quality and quantity, growth, and feed conversion traits in pigs.

The main objective of this research was to estimate heritabilities of seven osteochondrosis (OC) lesions in station-tested pigs and their genetic and phenotypic correlations with four meat quality (MQ) traits, the percentage of premium cuts (PPC), daily weight gain (DWG), and feed conversion ratio (FCR). Observed OC lesions were on the head of humerus (HK), condylus medialis humeri (CMH), condylus lateralis humeri (CLH), radius and ulna proximal (RUP), distal epiphyseal cartilage of ulna (DEU), head of femur (FK), and condylus medialis femoris (CMF). Meat quality traits were i.m. fat (IMF), muscle pH at 1 h after slaughter (pH1), muscle pH at 30 h after slaughter (pH30), and light reflectance on muscle (H30). The data set comprised 2,710 animals, of which 1,291 animals had OC records. All traits were analyzed by multiple-trait linear mixed model, with the animal's genetic and common litter effects as random. Fixed effects in the model varied between traits. Each OC lesion was further analyzed by a univariate generalized linear mixed model or, equivalently, "threshold models," assuming logistic, probit (normal), and Poisson distributions of the underlying "liability" to the disease. For OC lesions, estimates of heritability were low on the original "incidence" scale (0.06 for HK to 0.16 for CLH) and moderate to high on the liability scale (0.08 to 0.42). Genetic correlations (r(g)) between OC lesions and most MQ traits and PPC were generally unfavorable. Significant r(g) were -0.44 for DWG-CMH, 0.31 for DWG-CMF, 0.40 for FCR-HK, 0.21 for PPC-CLH, 0.32 for PPC-RUP, 0.30 for PPC-CMF, -0.54 for pH1-CLH, 0.47 for pH1-DEU, -0.34 for pH30-CMH, 0.58 for pH30-DEU, -0.50 for H30-HK, -0.31 for H30-DEU, and 0.31 for H30-CMF. Genetic susceptibilities to some OC lesions within the front leg were positively related to each other (r(g) range = 0.57 to 0.69), but r(g) between front and hind leg OC lesions were mostly negative (range = -0.21 to -0.40). Estimated h2 was 0.60 for PPC, and ranged from 0.12 to 0.66 for MQ traits, 0.28 for DWG, and 0.42 for FCR. Genetic correlations among meat quality and quantity traits ranged from -0.66 to 0.37. This is the first study to report genetic and phenotypic correlations between OC lesions and several meat quality and quantity traits in pigs. These findings will be useful to pig industry, especially in designing breeding programs for robust pigs.

Aging↗
PubMed1991

Measurement of sensitivity to adriamycin in hybrid spheroids.

Using the newly developed hybrid spheroid system, we have been able to measure sensitivities to adriamycin in two sublines of LoVo cells (a human colon adenocarcinoma line). Hybrid spheroids are composed of coagglomerated LoVo cells, and nonproliferating HeLa "feeder" cells, mimicking a population of minitumors. Spheroids of uniform size, but containing different numbers of LoVo cells, were incubated with various concentrations of adriamycin and after washing, plated for colony formation. Binomial counting statistics were achieved by marking surface-attached spheroids soon after plating, and scoring colonies one week later. From the fraction of noncolony formers, the average number of clonogens per spheroid (clonogenicity) was calculated using the zero term of the Poisson distribution. The effect of treatment with adriamycin was evaluated from the decrease in clonogenicity in parallel series of hybrid spheroids. Response to treatment was found to be independent of cellular clonogenicity in the control, untreated series. Dose-response curves were obtained for each of the two sublines after treatment for 1.5 h with various concentrations of adriamycin. The difference in the response to adriamycin between the two sublines amounted to a factor of 27 (deduced from D0 ratios; these are the same as isosurvival dose ratios).

Adenocarcinoma↗
PubMed1986

Jamestown Canyon virus (California serogroup) is the etiologic agent of widespread infection in Michigan humans.

In a sample population of 780 Michigan residents tested for neutralizing antibodies to California serogroup viruses, 216 (27.7%) had specific neutralizing antibody to Jamestown Canyon virus. An additional eight (1.0%) had specific neutralizing to trivittatus virus; none had specific neutralizing antibody to La Crosse virus. Significantly more male residents than female residents of the Lower Peninsula had antibody to Jamestown Canyon virus. The frequency of neutralizing antibody titers fits the Poisson distribution, suggesting that Jamestown Canyon virus infections occur endemically in residents of Michigan. Among 128 sera with specific neutralizing antibody to Jamestown Canyon virus, only two (1.6%) were found to have significant hemagglutination-inhibiting antibody titers with La Crosse virus, while 23 of 44 (52%) had significant titers with Jamestown Canyon virus; a single serum had significant antibody by complement fixation tests with both La Crosse and Jamestown Canyon viruses. This study confirms earlier speculation that complement fixation and hemagglutination-inhibition tests with La Crosse virus (the only tests for California serogroup virus infections performed by most state diagnostic laboratories) fail to detect antibody to Jamestown Canyon virus. ASPEX computer-drawn maps demonstrated that the distribution of persons with antibody to Jamestown Canyon virus and residing in Michigan's Lower Peninsula is closely correlated with the estimated distribution of white-tailed deer in that part of the state, further supporting the hypothesis that white-tailed deer are the primary vertebrate host for Jamestown Canyon virus.

Adolescent↗
PubMed1999

Water vole (Arvicola terrestris scherman) density as risk factor for human alveolar echinococcosis.

Concern is growing in Europe about alveolar echinococcosis (AE) with the increase in grassland rodent and red fox populations, intermediate and definitive hosts for Echinococcus multilocularis, respectively. The objective of this study was to assess the influence of rodent densities on human AE distribution. Spatial Poisson regression analyses were performed with geomorphologic features, landscape composition, climatic characteristics, and water vole density as independent variables. The outcome consisted of AE cases diagnosed over the period 1980-1992. High vole density yielded a 10-fold risk (relative risk [RR] = 10.34, 95% confidence interval [CI] = 2.78-38.39), and the first plateau (400-700 m altitude) compared with the plain (200-400 m) was associated with a large increase in risk (RR = 7.10, 95% CI = 1.30-38.63). These results confirm that human AE is strongly influenced by the densities of arvicolid species. Foxes feeding almost exclusively on grassland rodents when the latter expand could mediate this relation.

Altitude↗
PubMed2003

Rate coding: neurobiological network performing detection of the difference between mean spiking rates.

We propose a network of model neurones that "reads" the information encoded as a mean spiking rate by mechanisms relevant to the organism. The streams of independent irregular spiking activity with a Poisson distribution enters the network in parallel via two inputs. The network integrates both synaptic inputs and at the same time acts as a counter allowing their continuous comparison. Detection of the mean spiking rate difference is signalled by spikes emitted at the output. The exactness of the mean-rate discrimination was quantified by the probability of theoretically best comparison.

Action Potentials↗
PubMed2006

[Examination of PET image evaluation experimentation method aiming at improved accuracy of data acquisition].

Multiple data evaluation is desirable for data obtained by positron emission tomography (PET), as the data follow the Poisson distribution. Such evaluation, however, tends to be very complicated, since the count- rates change with nuclide decay. To solve this problem, we propose a new data scan protocol in this communication. With this method, the true+scatter coincidence counts were computed during the initial one-minute scanning, which was fixed as the standard. A dynamic scan was then performed with the fixed counts from the high count-rate region. Regions with +/-2.5% of the image noise of the standard image was chosen to provide the data for evaluation. These were found to be the regions of 16.5-25.5 kcps (2D) and 81.1-138.5 kcps. Image quality was found to be affected by noise (2D) and random coincidence. Using this method, multiple data could be obtained by a single experiment, and very reliable image evaluation could be done.

Positron-Emission Tomography↗
PubMedDate not supplied

[An epidemiological study of workers exposed to vinyl chloride in the plants of Ferrara, Rosignano and Ravenna].

The aim of the present study is to investigate cause-specific mortality among male workers employed in vinyl chloride manufacture and polymerization in three Italian plants located in Ferrara, Rosignano and Ravenna. The cohorts include all workers hired between start of operation and, respectively 1985, 1978 and 1985, amounting to 418, 206 and 635 subjects followed up for mortality until 1996 (Ferrara and Rosignano) and 1997 (Ravenna). Cause specific SMRs (Standardized mortality ratios) were computed. Expected figures were obtained from mortality rates for the population resident in the region where the plant was located, for each SMR value a 90% confidence interval (CI) was calculated on the assumption of a Poisson distribution. The study detected an increased mortality for primary liver cancer in all three plants; SMR values were 444 in Ferrara (4 Obs. 90% CI 160-1069), 200 in Rosignano (1 Obs. 90% CI 10-869) and 375 in Ravenna (3 Obs. 90% CI 110-1038). In the pooled cohort liver cancer SMR was equal to 364 (8 Obs. 90% CI 108-390). In one plant, Ferrara, observed mortality was above the expected for lung cancer, SMR = 146 (14 Obs. 90% CI 89-229) and for larynx cancer, SMR = 500 (4 Obs. 90% CI 174-1167). One death from pleural cancer was observed in Rosignano (SMR = 1000 90% CI 47-4331). A non significant increase was detected for liver cirrhosis, in Ferrara (SMR 108, 6 Obs. 90% CI 73-332) and Rosignano (SMR 129, 3 Obs. 90% CI 35-332). The study results are confirming the carcinogenic action of vinyl chloride on the liver, they are pointing to its possible role in lung cancer development, as already shown for workers employed in Porto Marghera; an increased risk for larynx cancer is also shown.

Adult↗
PubMed1999

[Influence of specific clinical lessons in the Dutch Journal of Medicine on clinical management].

OBJECTIVE: To establish whether publication of an article propagating a laboratory test leads to measurable increase of the number of requests for that test. DESIGN: Retrospective. METHOD: From volume 138 (1994) of the Dutch Journal of Medicine (NTvG), three clinical lessons were selected that contained an unequivocal clinical message and a recommendation to request a specific laboratory test for particular patients. All laboratories performing the test in question were asked to report the number of requests per month in the months before, after and during publication of the article in question and during the same months of 1993. The difference between the number of requests in the period after publication of the article in 1994 and in the same period in 1993 was determined and tested postulating a Poisson distribution. RESULTS: Regarding two clinical lessons (one about determination of Coxsackie virus in neonates and one about examining arthritis patients for parvovirus B19) no significant difference in the numbers of requests before and after the publication was found, particularly also because the laboratories could not supply itemized data so that relevant information was lost in a flood of other data. The third clinical lesson (about determination of antibodies against Onchocerca in patients complaining of itching after a trip to the tropics) was followed by a significant increase of the number of requests (from 50 to 90; p < 0.001) in the 3 months following publication. CONCLUSION: Publication of a clinical lesson about a recommended laboratory test for onchocerciasis in the NTvG resulted in a significant rise of the number of requests for that test.

Family Practice↗
PubMed1978

Long-term antibody synthesis in vitro. VI. Anti-allotype sera as probes of clonal products in affinity maturation.

A new experimental system is described for measuring the allotypic product of rabbit B cells during long-lasting in vitro antibody responses. The immunoenzymatic assays described allow determination of several parameters mapping in different regions of the same molecule, which can be measured and combined to yield a multidimensional picture of the time-course dynamics of antibody synthesis. The rabbit immune system responding to Escherichia coli beta-D-galactosidase was sample and disassembled by (a) culturing lymph node microfragments and (b) sorting out from among all anti-enzyme antibodies only those activating a mutant enzyme, AMEF, which bore the b4 or b9 allotype. A considerable simplification of the response was achieved in the microcultures as documented by cultures of heterozygous cells which produced only one allotype and by the fact that each culture showed a distinctive pattern when antibody titre, association constant, heterogeneity index, L-chain type, and k-chain allotype were considered together. This array of patterns was not an artifact but the result of disassembling a representative sample of the rabbit immune system into small components, since the b4/b9 ratio obtained by averaging the results of all cultures from a heterozygous rabbit lymph node was the same as the serum ratio. Despite the Poisson distribution of the responder microcultures, none of them was monoclonal; i.e. no antibodies homogeneous by all parameters tested were observed, This finidng supports the notion that in normal lymphoid tissue in its native tridimensional arrangement, one T cell can trigger several B cells clustered in one antibody-forming unit. This natural arrangement would ensure the monospecificity of the cluster (dictated by the T cell) while allowing for variation in affinity (depending upon the array of B cells in the unit). Accordingly our findings would results from the fact that as the size of the microfragments was reduced, the cells diluted out first were T cells, but as long as one of them was present, several B-cell clones were triggered. The b4/b9 pattern of any given culture remained constant over several months, but the ratio kappa/lambda underwent changes. An increase in molecules with non kappa-chains (which could not be reacted with anti-kappa-chain allotype antisera) was usually associated with a parallel decrease in antibody affinity. This occurred by the end of the antibody cycle and might be related to the regulation of antibody synthesis by T-cell suppressor factors.

Animals↗