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PubMed2005

BMI as a modifying factor in the relations between age at menarche, menstrual cycle characteristics, and risk of preeclampsia.

To examine the relations between age at menarche and menstrual cycle characteristics and preeclampsia risk, we analyzed data from a case-control study conducted from 1998 to 2002. Usual menstrual cycle characteristics among 286 preeclampsia cases and 471 normotensive controls were assessed using a structured interview during postpartum hospitalization. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for confounders. We also examined the influence of pre-pregnancy body mass index (BMI) on selected hypothesized relations. Among lean women (pre-pregnancy BMI < 25 kg/m(2)), preeclampsia risk was lower in those reporting cycles > or = 36 days in length (adjusted OR 0.78, CI 0.35-1.83) and menarche at > or = 14 years (adjusted OR 0.48, 95% CI 0.28-0.82). In contrast, among overweight or obese women, preeclampsia risk was higher in those with long cycles (OR 3.11, 95% CI 0.62-1.56, p(interaction) = 0.16) and late menarche (OR 1.53, 95% CI 0.59-3.97, p(interaction) = 0.03). These data suggest that adiposity influences the relations between usual menstrual cycle length, age at menarche, and preeclampsia. Overweight women with long cycles are at particularly high preeclampsia risk.

Age Factors↗
PubMed1995

Incubation temperature as a modifying factor on survival of Tenebrio molitor reared in selenium-containing media.

Newly emerged Tenebrio molitor were reared at 4, 25, and 37 degrees C in nutrient media supplemented with sodium selenate (0.0125, 0.0200, 0.0500, and 0.1000%). Ten insects comprised each group. Controls were maintained in unsupplemented medium at the same temperatures as the experimental groups. Survival percentages were determined. Survival curves were estimated at given times postincubation. Controls at 4 and 37 degrees C showed an increased lethality compared to those insects at 25 degrees C. Data indicate that 4 degrees C had a protective effect on survival for insects reared in media containing the three highest concentrations of selenium. For insects at 37 degrees C, killing was striking and equivalent for all groups, irrespective of media supplementation.

Animals↗
PubMed1968

Factors modifying host resistance to viral infection. 3. Effect of whole body x-irradiation on experimental encephalomyocarditis virus infection in mice.

The resistance of mice to encephalomyocarditis (EMC) virus was markedly decreased by prior exposure to whole body X-irradiation. In contrast to non-irradiated controls, the course of EMC virus infection in X-irradiated animals was characterized by (a) an enhanced mortality, (b) shortening of the incubation period, (c) higher levels of virus in the blood during the viremic phase and persistence of the viremia until death, (d) failure to develop detectable serum levels of neutralizing antibody, and (e) the earlier appearance and higher levels of virus in brain and heart tissue. The level of interferon in the serum during the course of infection was similar in both groups. The administration of relatively small quantities of anti-EMC virus neutralizing antibody to X-irradiated mice during the early phases of the infection with EMC virus restored their resistance to levels comparable to nonirradiated animals. An alteration of local organ defense mechanisms in the central nervous system could not be demonstrated. It is proposed that (a) the inability of the X-irradiated animal to elaborate specific neutralizing antibody was a critical determinant in their failure to clear the viremia, (b) this increase in the level and duration of the viremic phase resulted in the exposure of target organs to a greater inoculum of virus, and (c) the enhanced mortality observed in irradiated mice reflected this greater target organ involvement. The experimental model presented, therefore, suggests that the immunologic response is a critical determinant of host resistance during this primary systemic virus infection.

Animals↗
PubMed1980

Trypanosoma cruzi. Factors modifying ingestion and fate of blood form trypomastigotes.

Blood form trypomastigotes of the Y and CL strains of Trypanosoma cruzi were tested for their ability to enter and infect mouse peritoneal macrophages. Both strains failed to enter macrophages in appreciable numbers, whereas metacyclic trypomastigotes purified from acellular cultures were ingested with ease. Macrophage parasitization was enhanced manyfold after the removal of an antiphagocytic substance by trypsinization. This occurred without modification of parasite viability. Opsonization with hyperimmune mouse serum also enhanced the uptake of blood form trypomastigotes by macrophages. This effect was mediated by the macrophage Fc receptor. The effects of serum and trypsinization were additive at high parasite:cell ratios. Neither trypsin-mediated nor antibody-dependent opsonization of the organisms modified the fate of either strain within resident macrophages. However, lymphokine-activated macrophages were capable of destroying both strains, and antibody opsonization further enhanced this process.

Animals↗
PubMed1999

The impact of different presenilin 1 andpresenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain: evidence for other phenotype-modifying factors.

To assess the influence of the presenilin 1 (PS1) and 2 (PS2) mutations on amyloid deposition, neurofibrillary tangle (NFT) formation and neuronal loss, we performed stereologically based counts in a high-order association cortex, the superior temporal sulcus, of 30 familial Alzheimer's disease cases carrying 10 different PS1 and PS2 mutations, 51 sporadic Alzheimer's disease cases and 33 non-demented control subjects. All the PS1 and PS2 mutations assessed in this series led to enhanced deposition of total Abeta and Abeta(x-42/43) but not Abeta(x-40) senile plaques in the superior temporal sulcus when compared with brains from sporadic Alzheimer's disease patients. Some of the PS1 mutations studied (M139V, I143F, G209V, R269H, E280A), but not others, were also associated with faster rates of NFT formation and accelerated neuronal loss in the majority of the patients who harboured them when compared with sporadic Alzheimer's disease patients. In addition, our analysis showed that dramatic quantitative differences in clinical and neuropathological features can exist even among family members with the identical PS mutation. This suggests that further individual or pedigree genetic or epigenetic factors are likely to modulate PS phenotypes strongly.

Age of Onset↗
PubMed2000

The chromo domain protein chd1p from budding yeast is an ATP-dependent chromatin-modifying factor.

CHD proteins are members of the chromo domain family, a class of proteins involved in transcription, DNA degradation and chromatin structure. In higher eukaryotes, there are two distinct subfamilies of CHD proteins: CHD1 and CHD3/4. Analyses carried out in vitro indicate that the CHD3/4 proteins may regulate transcription via alteration of chromatin structure. However, little is known about the role of CHD proteins in vivo, particularly the CHD1 subfamily. To understand better the cellular function of CHD proteins, we initiated a study on the Chd1p protein from budding yeast. Using genomic DNA arrays, we identified genes whose expression is affected by the absence of Chd1p. A synthetic-lethal screen uncovered genetic interactions between SWI/SNF genes and CHD1. Biochemical experiments using Chd1p purified from yeast showed that it reconfigures the structure of nucleosome core particles in a manner distinct from the SWI-SNF complex. Taken together, these results suggest that Chd1p functions as a nucleosome remodeling factor, and that Chd1p may share overlapping roles with the SWI-SNF complex to regulate transcription.

Adenosine Triphosphate↗
PubMed1987

Association between lipid peroxidation and life-modifying factors in rotifers.

The rate of lipid peroxidation (LP) was measured in rotifers reared under conditions of continuous darkness (D:D), dietary restriction, vitamin E supplementation, or elevated temperatures. D:D, diet restriction, and vitamin E supplementation increased life span and caused a significant decline in LP; elevated temperatures decreased life span and increased LP. The addition of physiological levels of malonaldehyde, a product of LP, did not alter life span. The dietary uptake of Paramecia, the food source for rotifers, did not change under the conditions of D:D, vitamin E supplementation, and elevated temperatures. These results suggest that the LP process is inversely related to longevity in the rotifer and that it appears to be involved in the aging process.

Aging↗
PubMed2004

Identification of modifiable factors that affect the genetic diversity of the transmitted HIV-1 population.

BACKGROUND: Our previous studies have shown that the majority of African women were infected with multiple HIV-1 genetic variants, while in the remaining women only a single viral genotype was detected early in infection. Infection with multiple viral variants was associated with higher plasma HIV-1 RNA levels and faster CD4 T-cell decline. METHOD: Socio-behavioral characteristics, use of hormonal contraceptives, and the presence of sexually transmitted diseases were prospectively assessed at approximately monthly intervals around the time of HIV-1 acquisition in female sex workers in Kenya. We assessed the relationship between these factors and HIV-1 genetic complexity early in infection. RESULTS: One hundred and fifty-six women were included in this analysis, of whom 89 had multiple viral genotypes and 67 had a single genotype at primary infection. Women with multiple variants were more likely to have a genital tract infection [odds ratio (OR), 4.7; 95% confidence interval (CI), 1.4-18.1] or to be using hormonal contraceptives (OR, 2.7; 95% CI, 1.3-5.6) at the time of their infection than those with a single variant. In multivariate analyses, these factors were independent predictors of early HIV-1 genetic complexity, and the presence of multiple viral variants early in infection remained significantly associated with a higher steady state plasma HIV-1 RNA level. CONCLUSION: The presence of genital tract infections and hormonal contraceptive use at the time of transmission were associated with the acquisition of multiple HIV-1 variants.

Adult↗
PubMed2005

The growing pre-mRNA recruits actin and chromatin-modifying factors to transcriptionally active genes.

In the dipteran Chironomus tentans, actin binds to hrp65, a nuclear protein associated with mRNP complexes. Disruption of the actin-hrp65 interaction in vivo by the competing peptide 65-2CTS reduces transcription drastically, which suggests that the actin-hrp65 interaction is required for transcription. We show that the inhibitory effect of the 65-2CTS peptide on transcription is counteracted by trichostatin A, a drug that inhibits histone deacetylation. We also show that actin and hrp65 are associated in vivo with p2D10, an evolutionarily conserved protein with histone acetyltransferase activity that acts on histone H3. p2D10 is recruited to class II genes in a transcription-dependent manner. We show, using the Balbiani ring genes of C. tentans as a model system, that p2D10 is cotranscriptionally associated with the growing pre-mRNA. We also show that experimental disruption of the actin-hrp65 interaction by the 65-2CTS peptide in vivo results in the release of p2D10 from the transcribed genes, reduced histone H3 acetylation, and a lower level of transcription activity. Furthermore, antibodies against p2D10 inhibit run-on elongation. Our results suggest that actin, hrp65, and p2D10 are parts of a positive feedback mechanism that contributes to maintaining the active transcription state of a gene by recruiting HATs at the RNA level.

Acetyltransferases↗
PubMed1978

Factors modifying equilibrium between activated and non-activated forms of steroid-receptor complexes.

Steroid-receptor complexes formed in concentrated cytosol at low temperature, low ionic strength and neutral pH are unable to bind to nuclei. Various procedures are known to promote their 'activation'. In the present work it is shown that an increase in temperature only enhances the rate of the reaction whereas no change in the equilibrium between activated and non-activated complexes is observed. On the contrary an increase in ionic strength or pH, as well as a removal of a low-molecular-weight inhibitor, not only accelerate the reaction but also increase the concentration of activated complexes at equilibrium. Using two steroids differing 3-fold in their affinity for the receptor, no difference was seen in the effect of the bound steroid on receptor activation. When combining various activation procedures it was observed that they acted independently of each other and additively. In all cases they retained their property of either modifying only the rate of the reaction or both its rate and equilibrium. Using changes in pH, it was also possible to induce shifts in the equilibrium between activated and non-activated complexes. After activation at pH 6.5, a first equilibrium was attained. When the pH was increased to 8 the equilibrium was displaced towards higher concentrations of activated complexes. A lowering of the pH resulted in a reversal of steroid-receptor complexes from the activated to the non-activated state. To clearly establish that this was not due to irreversible damage of the receptor, which would render it unable to bind to nuclei, it was shown that the complexes which had reverted to the non-activated state were still susceptible to activation. Regulatory events may thus exist which, for a given level of hormone and receptor, modulate the concentration of activated steroid-receptor complexes.

Adrenalectomy↗
PubMed2001

Accuracy and modifying factors of the sonographic estimation of fetal weight in a high-risk population.

There have been a number of reviews assessing the accuracy of different methods of sonographic estimation of fetal weight, without identifying any clearly superior equation. In order to optimise accuracy in a high-risk population, we decided to compare some of the most popular early equations with the newer volume-based equations, and to try and identify factors that affect the ability of these equations to estimate fetal weight accurately We collected the scan and delivery details of 192 fetuses born within one week of a sonographic estimation of fetal weight. We then applied three of the most popular equations and two newer volume-based equations to the recorded fetal biometric parameters to assess the performance of each equation overall, and under varying maternal, fetal, and scan conditions. The equations of Shepard, Hadlock A, Hadlock B and Combs produced similar results with systematic (mean) errors in the range 1.2-1.9% and random error characterised by one standard deviation in the range of 8.6-9.5%. Dudley's volume-based equation produced a significant systematic error in the form of a mean error of 7.4%, which corresponds to a mean birthweight (BW) which is 7.4% above the mean estimated fetal weight (EFW). When we stratified the study group by birthweight, Combs' equation produced significant differences in the mean error, (p < 0.00001), that ranged from a mean overestimation in fetal weight of 8.5% for babies with BW < 1000 g to a mean underestimation in fetal weight of 6.2% for babies with BW > 3000 g. Oligohydramnios resulted in a trend towards an increased mean error for all equations which was only statistically significant for Hadlock B. The equations Shepard and Hadlock A performed best in our high-risk population. They produced the smallest systematic errors across the entire study group and were not adversely affected by variations in birthweight, liquor volume, or fetal presentation. The newer, volume-based equations were disappointing, producing large systematic errors. Large random errors in all equations continue to be the Achilles' heel that limit the value of sonographic EFW.

Biometry↗
PubMed1981

Factors modifying the toxicity of organophosphorus compounds including dichlorvos.

The effect of repetitive doses of organophosphorus agents in experimental animals has been studied. The cumulative LD50 dose depended upon the time interval between injections of toxic agent. From these data it was possible to obtain the rate of detoxification of these agents. In the case of soman and sarin TOCP pretreatment, an inhibitor of plasma aliesterase, modified both the acute LD50 and the rate of detoxification. The results therefore suggest that recovery of plasma aliesterase contributes to a large extent in detoxification of chronically administered soman and sarin. In contrast, tolerance to chronically administered dichlorvos can not be correlated to recovery of plasma aliesterase, but correlates well with a rapid spontaneous reactivation of acetylcholinesterase.

Acetylcholinesterase↗