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PubMed1985

Factors modifying cytotoxicity induced by 5-FU and hydroxyurea.

Pretreatment of exponentially growing 9L cells for 24 hours with a nontoxic (0.77 microM) or moderately toxic (7.7 microM) concentration of 5-FU (5-FUra) enhanced cell kill induced by a subsequent 6-hour treatment with 1.3 mM hydroxyurea (HU) by a magnitude of 1 log. In confluent 9L cultures or 9L cells treated in serum-free medium that decreased the cycling population, however, the 5-FUra-HU combination did not enhance the cell kill. No recovery from potentially lethal damage was observed for up to 24 hours after treatment of 9L cells with 7.7 microM 5-FUra alone or with 0.77 or 7.7 microM 5-FUra followed by 1.3 mM HU. These results show that 5-FUra and HU in combination kill cycling cells effectively and that cytotoxicity is fixed on completion of the treatment. Although the number of sister chromatid exchanges per metaphase increased significantly with increasing length of exposure to a nontoxic (0.77 microM) or moderately toxic (7.7 microM) concentration of 5-FUra, subsequent treatment with HU that resulted in cell kills of 70%-80% and 99%, respectively, did not increase the number of sister chromatid exchanges per metaphase beyond that expected from 5-FUra treatment alone. Thus, the enhanced cell kill does not appear to be a result of direct DNA damage.

Animals↗
PubMed1998

Factors modifying the prognosis in men with asymptomatic carotid artery disease.

OBJECTIVES: Carotid artery stenosis is associated with an increased prevalence and incidence of ischaemic heart disease (IHD). The aim of this study has been to assess whether, in men with carotid artery stenosis, survival and incidence of stroke and myocardial infarction is different in men with and men free from IHD; and to characterize probands with incident cerebrovascular (CBV) event in terms of smoking, hypertension and leg artery disease. DESIGN: Population-based cohort study, 'Men born 1914'. SETTING: Malmö, a city in southern Sweden. SUBJECTS: A total of 478 of 621 men born in 1914, who in 1982 participated in ultrasound examination of the carotid arteries. MAIN OUTCOME MEASURES: Morbidity and mortality during 10 years of followup. RESULTS: Asymptomatic carotid artery stenosis was, in men free from IHD, associated with reduced survival and an increased incidence of serious CBV events that occurred, on average, 3.6 years after the examination. In men with prevalent IHD, there was no relationship between carotid artery stenosis and incidence of CBV events. The main explanation to the lack of association seems to be the high vascular mortality rate in that group. CONCLUSIONS: It's our conclusion that in patients with asymptomatic carotid artery stenosis there is a great heterogeneity with regard to severity of disease and prognosis. Survival and incidence of stroke and myocardial infarction depends on whether patients have concomitant IHD.

Aged↗
PubMed2004

[Health-promoting education in nutrition as a factor modifying dietary habits in menopausal women].

The study was aimed at evaluating effects of health-promoting education in nutrition on changes in incorrect dietary habits and on effects of those changes on blood parameters regarded as diagnostic for medical purposes. The study, carried out in 1991-2003, involved 1648 women aged 45-54 years with Body Bass Index (BMI) higher than 30 and 40, i.e., indicative of second and third degree obesity. The women participated in a 4-month-long nutrition course. The classes, held once a week and two 45-minute periods each, were taught to groups of 20-22 individuals. The curriculum encompassed information on: fundamentals of alimentary tract function; physiological role and sources of as well as demand for basic nutrients, vitamins, micro- and macroelements; the role of water and acid-base equilibrium in nutrition; nutrition-based prophylaxis of circulatory diseases, insulin-independent diabetes, and diet-depending cancers; and numerous other problems of physiology and dietetics. The 4-month-long period of health-promoting education in nutrition was found to result in significant improvement of dietary habits (increased consumption of dairy products, whole-meal grain products, pulses, fruits, vegetables, and fluids, accompanied by a reduced intake of meat products, sugar, and sweets). The changes gave rise to a slow, but consistent body weight reduction and normalisation of contents of hormones and blood biochemical components analysed.

Body Mass Index↗
PubMed1999

Possible factors modifying the surgically induced astigmatism in cataract surgery.

PURPOSE: To investigate possible modifiers of the surgically induced astigmatism with special reference to age, gender, preoperative astigmatism, and the intraocular pressure. METHODS & PATIENTS: Data for one hundred and one cataract patients operated on with extracapsular cataract extraction and intraocular lens implantation were prospectively recorded and followed for six years. Different explanatory variables like age, gender, preoperative astigmatism and postoperative intraocular pressure (IOP) were considered. Astigmatic changes were calculated as Naeser's polar values. RESULTS: The surgically induced astigmatism was not significant at one year, but was significantly increased 3- and 6-years postoperatively. At the same time the keratometric axis made a shift toward against-the-rule astigmatism. The postoperative mean-IOP was lower at all controls. Multiple regression analysis showed that a large preoperative astigmatism, a low postoperative IOP, and high age resulted in more surgically induced astigmatism against-the-rule. CONCLUSION: The length and the architecture of the incision are known to have an influence on the surgically induced astigmatism in cataract surgery. In the present study we used a multiple regression analysis model to show a significant correlation between the surgically induced astigmatism and age, preoperative astigmatism, and postoperative IOP.

Adult↗
PubMed1982

Both genetic background and environmental factors modify the phenotypic expression of H-2 associated genes participating in the polygenic control of antibody responsiveness to Salmonella antigens.

The genetic control of responsiveness to flagellar (f) and somatic (s) antigens of Salmonellae was studied in high (H) and low (L) lines of mice selected for the character 'antibody response to sheep erythrocytes'. The minimal immunogenic dose was, for the two antigens, lower in H than in L mice and the dominance of the responder phenotype was then greater in F1 hybrid females than in males. Genes associated with H-2 locus intervene in the responses to each antigen. Their expression was found to vary according to the conditions of immunization and to the sex. The quantifiable H-2 effect was measured in interline hybrids, i.e. on an heterogeneous genetic background equivalent to that of F2. In the case of the flagellar (f) antigen, the H-2 locus was responsible in secondary response for about 50% of the interline difference in the two sexes. In the primary response, the H-2 effect was only observed in females. It was smaller (25% of the interline difference) and independent of the antigen dose. In contrast, with somatic (s) antigen the H-2 locus did not intervene in the control of secondary response. The H-2 effect in the primary response was again only found in females. Unexpectedly, the allele linked to the H-2 phenotype of L mice had a more favourable effect on hybrid responsiveness than that linked to the phenotype of H mice.

Animals↗
PubMed1995

Factors modifying the risk of IDDM in offspring of an IDDM parent.

Offspring of mothers with insulin-dependent diabetes mellitus (IDDM) have a much lower risk of IDDM than do offspring of diabetic fathers, and this risk is particularly low for offspring born to diabetic mothers over the age of 25 years. To determine whether increasing maternal age also protects the offspring of IDDM fathers from IDDM, we surveyed 367 IDDM fathers (IDDM onset before age 35) who first came to the Joslin Clinic (Boston, MA) between 1945 and 1969. Of the 840 offspring of these men, IDDM developed in 28 before the age of 20, giving a cumulative risk of 5.1 +/- 1.0% (means +/- SE). Because this is similar to the result of our earlier study of IDDM fathers, the two groups were combined to give 1,084 offspring, 39 having IDDM (cumulative risk of IDDM 5.4 +/- 0.9% by age 20), for comparison with our cohort of 1,391 offspring of 739 IDDM mothers. In that cohort, IDDM developed in 20 offspring before the age of 20 years, giving a cumulative risk of 2.1 +/- 0.5%. The risk of diabetes in offspring was higher if the parent's IDDM was diagnosed before age 11 than if it was diagnosed later: 9.3 compared with 4.0% (P = 0.006) for the offspring of IDDM fathers and 2.7 compared with 1.8% for the offspring of IDDM mothers (P = 0.06). In the families in which the father's IDDM was diagnosed after age 11, a protective effect of maternal age > or = 25, similar to that in families of IDDM mothers, seems to be present.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMed1968

Factors modifying renal tubular bicarbonate reabsorption in the dog.

1. Acute experiments were carried out on anaesthetized dogs during metabolic alkalosis produced by I.V. administration of NaHCO(3). Partial constriction of one ureter led to a significant rise in the HCO(3) (-) threshold, beyond the simultaneous value for the other kidney. The magnitude of the increase was not correlated with the reduction of glomerular filtration.2. Stop-flow analysis, following complete unilateral obstruction of urine flow, demonstrated proximal as well as distal tubular reabsorption of bicarbonate. At any given plasma P(co2) the detailed configuration of the concentration changes which developed depended on (a) the presence and concentration of mannitol, (b) the duration of urinary stasis, and (c) the plasma concentration of HCO(3) (-).3. If a solution containing 15% (w/v) mannitol was infused I.V., the HCO(3) (-) concentration in free flow urine was lower than in plasma, and it fell further during arrest of flow in the entire column of trapped fluid. If less mannitol was infused, or none at all, interruption of urine flow led to a striking increase of HCO(3) (-) concentration in the distal portion of the occluded column, and to a fall in the fluid arrested in the proximal segments.4. It was demonstrated that the HCO(3) (-) concentration attained after 2(1/2), 6, or 15 min of urinary stasis at any point in the trapped fluid column was due to the combined effects of water reabsorption and HCO(3) (-) reabsorption which proceeded independently, and with a different time course.5. If mannitol was administered the lowest urinary HCO(3) (-) concentration in the series moved progressively to a more distal location with increasing duration of urinary stasis. When HCO(3) (-) concentration peaks were present in distal fluid they were conspicuous only after short interruptions of urine flow; during extended stop-flow periods they became attenuated, or disappeared. If no mannitol was administered this did not occur.6. Provided the plasma level of HCO(3) (-) was sufficiently elevated, mannitol (15%, w/v) was administered, and the time available for reabsorption was lengthened by ureter obstruction, much larger concentration differences between plasma and trapped fluid developed than the largest that are ever found between the plasma and freely draining urine. The magnitude of the largest plasma-urine (P-U) concentration difference for HCO(3) (-) increased with intratubular ;contact time', and no limiting value was found.7. Potassium concentration in distal occluded fluid fell with prolonged duration of stasis. This was related to the slow and progressive diminution of distal HCO(3) (-) concentration. But if instead of bicarbonate a nonreabsorbable anion, such as phosphate, was the dominant distal anion, K(+) concentration in distal fractions remained high and rose further with time.

Absorption↗
PubMed1994

Silicosis surveillance in Ontario: detection rates, modifying factors, and screening intervals.

The Province of Ontario has had a surveillance program for workers in dusty industries for almost 70 years. This paper reports the detection rates of silicosis among 68,701 silica-exposed individuals who were first exposed to dust in 1950 or later, and who were still employed in 1979 or later. The detection rate varied strongly with latency, being less than two new cases per 10,000 examinations during the first two decades from first exposure, reaching two new cases per 1,000 examinations at 27 years from first exposure, and averaging between two and four new cases per 1,000 examinations thereafter. The silicosis incidence rate among miners was only about half that among foundry workers. Cigarette smoking was also found to be a risk factor for the diagnosis of silicosis. These data were used to model the detection rate of new cases of silicosis as a function of the time interval between examinations, and results are presented for examination cycles between 2 and 10 years.

Humans↗
PubMed1980

Polymorphism at the G6pd and 6Pgd loci in Drosophila melanogaster. IV. Genetic factors modifying enzyme activity.

Different homozygous lines of similar genotype with respect to G6pd and 6Pgd were shown to have different enzyme activities for G6PD and 6PGD. Crosses between high and low lines suggested that there were modifying genes present on the autosomes, while others were probably located on the X chromosome. Allelic variation within each electrophoretic class of G6pd and 6Pgd might, however, also have contributed to this variation. An experiment on adaptation to sodium octanoate demonstrated that in adapted flies selection for lower enzyme activity had occurred, which provided further evidence for the existence of genetic differences in activity. Furthermore, a strong positive correlation between the activities of G6PD and 6PGD was found for each genotype. Since no correlation was found between MDH and the two enzymes G6PD and 6PGD, it could be concluded that this correlation was probably rather specific for G6PD and 6PGD. Interaction between genotypes with respect to activity was also found. It was shown that the variation at 6Pgd influenced the activity of G6PD within a genotype. The data are discussed in relation to fitness differences presented in foregoing articles.

Adaptation, Physiological↗
PubMed1977

Factors modifying radiation induced stimulation in plants: pre-irradiation seed moisture content.

The effect of moisture content of seeds at the time of irradiation in relation to radiation-induced stimulation was investigated on rice (Oryza sativa c.v. D-6-2-2). The optimum moisture content was 8% for stimulation measured as seedling height. It is concluded that seed moisture at the time of irradiation plays an important role in the expression of stimulation and its reproducibility.

Cobalt Radioisotopes↗