Differential response of cycling and noncycling cells to inducers of DNA synthesis and mitosis

The objective of this study was to determine whether cells in G(0) phase are functionally distinct from those in G(1) with regard to their ability to respond to the inducers of DNA synthesis and to retard the cell cycle traverse of the G(2) component after fusion. Synchronized populations of HeLa cells in G(1) and human diploid fibroblasts in G(1) and G(0) phases were separately fused using UV-inactivated Sendai virus with HeLa cells prelabeled with [(3)H]ThdR and synchronized in S or G(2) phases. The kinetics of initiation of DNA synthesis in the nuclei of G(0) and G(1) cells residing in G(0)/S and G(1)/S dikaryons, respectively, were studied as a function of time after fusion. In the G(0)/G(2) and G(1)/G(2) fusions, the rate of entry into mitosis of the heterophasic binucleate cells was monitored in the presence of Colcemid. The effects of protein synthesis inhibition in the G(1) cells, and the UV irradiation of G(0) cells before fusion, on the rate of entry of the G(2) component into mitosis were also studied. The results of this study indicate that DNA synthesis can be induced in G(0)nuclei after fusion between G(0)- and S-phase cells, but G(0) nuclei are much slower than G(1) nuclei in responding to the inducers of DNA synthesis because the chromatin of G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells differ from G(1) cells with regard to their effects on the cell cycle progression of the G(2) nucleus into mitosis. This difference between G(0) and G(1) cells appears to depend on certain factors, probably nonhistone proteins, present in G(1) cells but absent in G(0) cells. These factors can be induced in G(0) cells by UV irradiation and inhibited in G(1) cells by cycloheximide treatment.     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Targeted Sequencing for Studying Economically Useful Traits and Phylogenetic Diversity of Ancient Sheep

Russian Journal of Genetics - Sheep were one of the first animals to be domesticated. The history of sheep domestication and their widespread distribution dates to about ten thousand years ago,...     

KatG Ser3 15Thr mutation as the main reason of isoniazid resistance in Mycobacterium tuberculosis isolated in the Novosibirsk and Kemerovo Regions

KatG Ser3 15Thr mutation is one of the main reasons of resistance to isoniazid in Mycobacterium tuberculosis isolates. The frequency rate of the above mutation among isoniazid-resistant isolates made 94% in Novosibirsk Region and 93% in Kemerovo Region. The use of PCR-restriction fragment length polymorphism (PCR-RFLP) can be regarded as an adequate method for rapid screening of isoniazid resistance in Mycobacterium tuberculosis isolated in the West-Siberian Region.     

Function of hypothalamic-pituitary-adrenocortical system in hypertensive rats of ISIAH strain

Functional activity of hypothalamic-pituitary-adrenocortical axis has been studied under control and restraint stress conditions in rats with inherited stress-sensitive arterial hypertension (ISIAH strain) and in normotensive WAG (Wistar Albino Glaxo) strain. The levels of hypothalamic CRH-mRNA (in control and 2 hrs stress), pituitary and plasma ACTH and plasma corticosterone (in control and after 5, 15 or 30 min of restraint stress), were evaluated. Hypothalamic CRH-mRNA level was found to be approximately the same in the control rats of both strains. In control conditions, the pituitary and plasma ACTH content in ISIAH rats was significantly lower whereas the corticosterone level in the plasma differed from each other in both strain. The restraint stress resulted in a statistically significant increase of the CRH-mRNA in ISIAH rats and not in the WAG rats. Moreover, in spite of the lower ACTH level in stressed ISIAH rats, the corticosterone blood plasma concentration in hypetensive rats was significantly higher. The data obtained confirm the idea that the stress-dependent hypertension might be related to an enhanced sensitivity of the main endocrine links involved in the stress response organization.     

Expression of CYP1A in liver of A/Sn and CC57BR mice differing in sensitivity to hepatocarcinogenesis induced by o-aminoazotoluene

The induction of P450 cytochromes Cyp1a1 and Cyp1a2 in the liver of male mice differing in sensitivity to the carcinogenic effect of o-aminoazotoluene (OAT) has been studied. The level of Cyp1a1 and Cyp1a2 mRNA was assayed by quantitative competitive polymerase chain reaction (PCR). In both OAT-treated strains, the level of Cyp1a1 mRNA increased more than 1000-fold, while the amount of Cyp1a2 mRNA increased only two- or threefold. Interstrain differences in the Cyp1a mRNA level were revealed. The level of Cyp1a1 mRNA in liver of OAT-induced A/Sn mice was three times higher than in CC57BR mice. The amount of Cyp1a2 mRNA in control and OAT-treated mice was 7 and 13 times higher, respectively, than in CC57BR mice. The enzyme activities of cytochromes P450 1a were assayed. An increase in Cyp1a1 mRNA level in OAT-treated mice correlated with an enhancement of the benzo[a]pyrene hydrolase and 7-ethoxyresofurin o-deethylase activities; the correlation between the level of Cyp1a2 mRNA and 7-ethoxyresofurin o-demethylase activity was much less pronounced. Interstrain variation in Cyp1a1 and Cyp1a2 activities was also shown at the enzyme activity level. We suppose that quantitative differences in the Cyp1a2 mRNA level play a key role in OAT-induced hepatocarcinogenesis.     

Survival Rate and Enzyme Activities ofLactobacillus acidophilusFollowing Frozen Storage

The ability of two strains of Lactobacillus acidophilus, CRL 640 and CRL 800, to survive and retain their biological activities under frozen storage was determined. Freezing and thawing, as well as frozen storage, damaged the cell membrane, rendering the microorganisms sensitive to sodium chloride and bile salts. Both lactic acid production and proteolytic activity were depressed after 21 days at -20 degreesC, whereas beta-galactosidase activity per cell unit was increased. Cell injury was partially overcome after repair in a salt-rich medium. Copyright 1998 Academic Press.     

Effect of point substitutions in the <Emphasis Type="Italic">MnSOD,GPX1</Emphasis>, and <Emphasis Type="Italic">GSTP1</Emphasis> genes on the risk of familial and sporadic breast cancers in residents of Altai Krai

The frequencies of the polymorphic gene variants MnSOD Ala₉Val, GPX1 Pro₁₉₈Leu, and GSTP1 Ile₁₀₅Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T (rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58−0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05−2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.