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Increase of inflammatory state in overweight adults with combined hyperlipidemia.

BACKGROUND AND AIM: Elevated levels of acute phase reactants are found in patients with cardiovascular disease. It is suggested that adipose tissue is a determinant of a low level of inflammatory state in overweight persons. The aim of the study was to determine, whether combined hyperlipidemia, which is an important factor of atherosclerosis, has influence on the inflammatory response in overweight adults. METHODS AND RESULTS: Levels of soluble cell adhesion molecules sICAM-1, sE-selectin and sP-selectin, PAI-1 Ag (by Elisa test), orosomucoid (ORM) and transferrin (TRF) (by microturbidimetry) and fibrinogen (FBG) according to Clauss were examined in peripheral blood of overweight adults (n 33, body mass index 27.1 +/- 1.8 kg/m2) with combined hyperlipidemia and in equal numbers of age, sex and BMI matched non-hyperlipidemic group. Overweight adults with combined hyperlipidemia had significantly higher plasma levels of sICAM-1 (376.5 +/- 107.4 ng/mL vs 239.3 +/- 60.4 ng/mL; p < 0.001), sE-selectin (70.4 +/- 20.2 ng/mL vs 48.5 +/- 25.6 ng/mL; p = 0.005), sP-selectin (228.2 +/- 88.6 ng/mL vs 123.1 +/- 45.3 ng/mL; p < 0.001) and positive acute phase proteins ORM (0.82 +/- 0.16 g/L vs 0.64 +/- 0.20 g/L; p = 0.005), FBG (3.42 +/- 0.54 g/L vs 2.74 +/- 0.57 g/L; p = 0.037) and PAI-1 Ag (97.9 +/- 40.6 ng/mL vs 56.4 +/- 25.6 ng/mL; p < 0.05), and a decrease of negative acute phase protein TRF (2.14 +/- 0.40 g/L vs 2.77 +/- 0.45 g/L; p < 0.001) compared to the results in overweight non-hyperlipidemic controls. CONCLUSIONS: It is suggested that overweight adults have an increase of inflammatory response dependent on hyperlipidemia. It was apparent from the elevation of sE--selectin, sP--selectin and sICAM-1 and from an increase of systemic inflammatory response according to the increase of "positive" acute phase proteins (APRs) and the decrease of "negative" APR protein levels in these patients.

Acute-Phase Proteins↗

Telomere binding of the Rap1 protein is required for meiosis in fission yeast.

Telomeres are essential for chromosome integrity, protecting the ends of eukaryotic linear chromosomes during cell proliferation. Telomeres also function in meiosis; a characteristic clustering of telomeres beneath the nuclear membrane is observed during meiotic prophase in many organisms from yeasts to plants and humans, and the role of the telomeres in meiotic pairing and the recombination of homologous chromosomes has been demonstrated in the fission yeast Schizosaccharomyces pombe and in the budding yeast Saccharomyces cerevisiae. Here we report that S. pombe Rap1 is a telomeric protein essential for meiosis. While Rap1 is conserved in budding yeast and humans, schemes for telomere binding vary among species: human RAP1 binds to the telomere through interaction with the telomere binding protein TRF2; S. cerevisiae Rap1, however, binds telomeric DNA directly, and no orthologs of TRF proteins have been identified in this organism. In S. pombe, unlike in S. cerevisiae, an ortholog of human TRF has been identified. This ortholog, Taz1, binds directly to telomere repeats [18] and is necessary for telomere clustering in meiotic prophase. Our results demonstrate that S. pombe Rap1 binds to telomeres through interaction with Taz1, similar to human Rap1-TRF2, and that Taz1-mediated telomere localization of Rap1 is necessary for telomere clustering and for the successful completion of meiosis. Moreover, in taz1-disrupted cells, molecular fusion of Rap1 with the Taz1 DNA binding domain recovers telomere clustering and largely complements defects in meiosis, indicating that telomere localization of Rap1 is a key requirement for meiosis.

Amino Acid Sequence↗

Four-year follow-up of teacher-reported problem behaviours.

This study investigated the stability and change in teacher-reported problem behaviours across a four-year period. An epidemiological sample of 811 children aged 4-12 at the initial assessment was assessed twice with the Achenbach Teacher Report Form (TRF). We found medium stability in the level of TRF total problem scores. Highest stability was found for aggressive and other externalizing behaviours. Stability was higher for girls than for boys. Of the girls who could be regarded as disturbed at base line, 50% could still be so regarded four years later, whereas only 23% of the boys could be considered persistently disturbed across the study interval. Girls' scores on the Externalizing syndrome were especially stable.

Affective Symptoms↗

Inter- and intraspecific resolution of nrDNA TRFLP assessed by computer-simulated restriction analysis of a diverse collection of ectomycorrhizal fungi.

An assessment of the inter- and intraspecific resolution of 5' nrDNA ITS TRFLP was conducted by computer-simulated restriction analysis of 316 ectomycorrhizal GenBank sequences. Generally, sequences with a similarity of < 90 % could be distinguished with two to three independent enzyme digests, although sequences with similarity > 95 % were likely to remain unresolved. Choice of restriction enzyme strongly influenced resolution, especially when less than three enzymes were used. Although our results showed that 5' nrDNA ITS TRFLP is a powerful tool for distinguishing between species of ectomycorrhizal fungi, closely related species, including species of Rhizopogon, Dermocybe, Hebeloma, and Lactarius produced indistinguishable 5' nrDNA ITS TRFLP--profiles. 5' nrDNA ITS TRFLP may also split a species, and the probability of this occurring reflected intraspecific sequence variation. For groups of closely related species, the use of 3' nrDNA ITS in conjunction with 5' nrDNA ITS produced improved resolution comparable with RFLP analyses. Overall, our results show that nrDNA ITS TRFLP is a valuable addition to the array of molecular tools available to ectomycorrhizal ecologists. However, simple assessments of ectomycorrhizal species diversity based on numbers of unique TRF created with a single restriction enzyme must be viewed with caution, as for each enzyme we examined, identical TRF common to groups of unrelated species were observed. In addition, to maximize the effectiveness of TRFLP in surveys of ectomycorrhizal fungi it will be useful to combine information from at least two independent enzyme digests in order to distinguish and track species in the field.

Basidiomycota↗

Aggression and threat perception abnormalities in children with learning and behavior problems.

The current study investigated the connection between aggression and the perception of threat in a group of children with learning and behavior problems (N = 103). Aggression was assessed by means of the aggressive behavior subscales of the Child Behavior Checklist (CBCL), Teacher Report Form (TRF), and Youth Self-Report (YSR). Perception of threat was measured by studying children's reactions to a series of stories depicting ambiguous social situations. Results demonstrated small but significant correlations between self-reported aggression (as indexed by the YSR) and threat perception abnormalities. That is, high levels of aggression were associated with a high frequency of threat perception, high ratings of threat, high levels of negative feelings and cognitions, and an early detection of threat. Furthermore, no substantial connections emerged between children's level of aggression as rated by parents (CBCL) and teachers (TRF) and threat perception indices. Finally, regression analyses revealed that in particular YSR social problems was a better predictor of most threat perception abnormalities than YSR aggressive behavior. Implications of these findings are briefly discussed.

Adolescent↗

Individual differences in aggression: genetic analyses by age, gender, and informant in 3-, 7-, and 10-year-old Dutch twins.

Aggression in humans is associated with substantial morbidity and mortality. In this study we report on the aggressive behavior syndrome (AGG) in young children as defined by the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF). We assessed aggression in a large sample of Dutch twins at ages 3, 7, and 10 years. The purpose of this study was three-fold. First, we determined the number of children who are "clinically deviant" on the AGG scale. Second, we assessed the genetic and environmental contributions to AGG for the maternal, paternal, and teacher ratings at each age, for boys and girls. Third, we explored issues of rater bias by analyzing parental and teacher data simultaneously. CBCL data were available from mothers on 6436 three-year-old, 5451 seven-year-old, and 2972 ten-year-old twin pairs and CBCL data from fathers on 4207 three-year-old, 4269 seven-year-old, and 2295 ten-year-old twin pairs. Teacher report data from the TRF were collected for 1036 seven-year-old and 903 ten-year-old twin pairs from the Netherlands Twin Registry. Structural equation modeling was employed to obtain genetic and environmental estimates at each age. Analyses were conducted separately by age and informant, as well as simultaneously, for all informants. Differences in raw scores across gender were found, with boys being rated as more aggressive than girls by all informants. Mothers reported more symptoms than fathers, who reported more symptoms than teachers. Evidence for moderate to high genetic influence (51%-72%) was seen for AGG by all three informants at all ages with only small sex differences in heritability estimates. Best fitting models for AGG by parent reports also included a small contribution of common environment. The largest sex differences in heritabilities were seen at age 10. Contributions of common (13%-27%) and unique (16%-31%) environment were small to moderate. There was some evidence of genetic dominance by teacher report for 10-year-old girls.

Adolescent↗

Teacher-reported problem behaviour in Turkish immigrant and Dutch children: a cross-cultural comparison.

OBJECTIVE: To compare problem behaviour in Turkish immigrant children living in the Netherlands versus problem behaviour in Dutch children from the general population as reported by teachers. METHOD: Teacher's Report Forms (TRF) were filled out by Dutch teachers, and for a subsample also by Turkish immigrant teachers, concerning 524 Turkish immigrant children selected randomly from the immigrant population in two large cities in the Netherlands. TRFs completed for Turkish immigrant children were compared with TRFs filled out for 1625 children selected randomly from the Dutch general population. RESULTS: No significant differences were revealed between children from both cultures on the TRF total problems, internalizing, externalizing and specific syndrome scales. Turkish immigrant teachers, however, reported higher total problems, internalizing and anxious/depressed scores for immigrant children than did Dutch teachers for the same immigrant children. CONCLUSION: No significant differences were found in the levels of behavioural and emotional problems reported by Dutch teachers for Turkish immigrant versus Dutch children. However, Turkish immigrant teachers reported high levels of anxiety and depression in immigrant children which go largely undetected by their Dutch teachers.

Adolescent↗

Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy.

Telomerase activity and telomere length in mononuclear cells (MNCs) and granulocytes from peripheral blood (PB) and bone marrow (BM) specimens were studied in pediatric acute leukemia (ALL, n = 15; AML, n = 11) and pediatric solid tumor (ST) patients (n = 9) at diagnosis, during and after chemotherapy. In four ST patients, tumor tissue was also available. For comparative analysis, MNCs from healthy donors (n = 53) were analyzed. Telomerase was evaluated using a modified telomeric repeat amplification protocol (TRAP) assay, and telomere length by terminal restriction fragment (TRF) analysis. At diagnosis, high telomerase activity was detected in MNCs from all leukemia patients, which was similar to the activity from ST biopsy specimens. This exceeded by 10- to 20-fold the activity in PB MNCs from ST patients and healthy donors (P < 0.05). Granulocyte fractions lacked telomerase activity in all groups. BM MNCs in leukemia patients revealed a four-fold higher telomerase activity than PB (P = 0.005). After induction chemotherapy and response to treatment, telomerase activity decreased to borderline or undetectable levels in PB MNCs in leukemia (P < 0.01). Average telomeres in PB MNCs from pediatric patients were significantly longer (n = 25; 10.9 kbp) than telomeres in PB and BM MNCs from adult healthy donors (7.45 kbp) (P < 0.0001). At diagnosis, telomeres were shorter from BM compared to PB specimens in leukemia (P < 0.05), and two peak TRFs were observed corresponding to the malignant and normal cell clones. With the attainment of remission, the lower TRF peak, reflecting the leukemic population, was lost. In leukemia patients, mean TRFs increased on average 2.2 kbp after induction chemotherapy, but decreased thereafter on consolidation and maintenance chemotherapy (1 kbp). This was comparable to an average telomere loss of 1.2 kbp in PB specimens from ST patients after chemotherapy. In all patients, telomere loss in granulocytes as compared to MNCs was more pronounced with 1.8 vs 1 kbp, respectively (P = 0.014). Our results demonstrate that at diagnosis, telomerase was consistently and highly upregulated in BM and PB specimens in leukemia, decreased after induction therapy, and correlated with remission. BM specimens in leukemia had higher telomerase activity, probably due to the greater leukemic burden than in PB. Telomeres were significantly longer in children than in adults, but shortened as a consequence of chemotherapy with repeated cycles of hematopoietic regeneration. In acute leukemia, with the loss of the leukemic burden after induction chemotherapy, longer mean TRFs were found, a reflection of the repopulation with normal cells. Our findings suggest that telomerase activity may be useful in the management of childhood malignancies. The significance of telomere length shortening in pediatric patients undergoing chemotherapy and possible telomere regeneration after myelosuppressive treatment remain to be determined.

Adolescent↗

Receptor-mediated endocytosis of asialoglycoproteins and diferric transferrin is independent of second messengers.

The intracellular concentrations of cyclic AMP, polyphosphoinosides and free Ca2+ were unaffected during receptor-mediated endocytosis of the neoglycoprotein beta-D-galactosyl-bovine serum albumin (D-Gal-BSA) by isolated hepatocytes. Elevation of either intracellular cyclic AMP by glucagon or inositol phosphates and Ca2+ by vasopressin were without effect on the binding and internalization of D-Gal-BSA. The normal response of this cell to glucagon- and vasopressin-mediated mobilization of these second messengers was not modified in the presence of saturating concentrations of D-Gal-BSA. Receptor-mediated endocytosis of diferric transferrin (Fe3+-TRF) by both hepatocytes and HL60 cells was also shown to be independent of second messengers, although the unequivocal expression of the transferrin receptor by hepatocytes could not be satisfactorily demonstrated. The results of the present study are at variance with a suggested regulatory role for second messengers in receptor-mediated endocytosis of serum-derived ligands such as asialoglycoproteins and Fe3+-TRF. Receptor phosphorylation by protein kinase C in particular has been proposed to regulate the distribution and recycling of these receptors in actively endocytosing cells. We would suggest that if receptor phosphorylation has a regulatory role during endocytosis, it is likely to be mediated by a second-messenger-independent protein kinase analogous to casein kinase II. An alternative interpretation is that phosphorylation has no physiological significance and receptor-mediated endocytosis is a constitutive event coupled to membrane turnover.

Animals↗

Speech reception in reverberation related to temporal resolution.

In this study, the influence of temporal properties of the auditory system on speech recognition, either in noise or in both noise and reverberation, has been investigated. Temporal resolution parameters consisted of both the temporal resolution factor (TRF) and the minimum detectable gap (MDG). TRFs were measured for probe-tone frequencies of 500, 1000, and 3000 Hz; MDGs were measured for octave-band noises centered at 500, 1000, and 3000 Hz and for a wideband noise. TRF and MDG proved to be rather independent parameters of temporal resolution. For both temporal-resolution parameters, there was considerable overlap between the performance of the normal-hearing and hearing-impaired listeners. A correlation analysis shows that MDG for wideband noise is related to speech recognition in reverberation. However, there is a mutual dependence of speech recognition and MDG on the pure-tone audiogram.

Adolescent↗

The socioemotional behaviors of children with SLI: Social Adaptation or Social Deviance?

Two models of the relationship between socioemotional behavior and verbal abilities are compared: Social Adaptation and Social Deviance. The socioemotional integrity of 17 children with specific language impairment (SLI) and 20 unaffected children who were age-matched (AM) was examined using the Child Behavior Checklist (CBCL) and the Teacher's Report Form (TRF) at kindergarten and first grade. All CBCL and TRF syndrome scale means for both groups were within normal limits. Significant group x respondent interaction effects were observed; teachers, and not parents, rated the children with SLI as having more social and internalizing behavioral problems than their AM peers. Significant differences between groups were restricted to internalizing, social, and attention problems. Very little congruence or stability over time was observed in the clinical ratings. The outcomes support a Social Adaptation Model of socioemotional behavior and language impairment. Implications for the clinical management of children with SLI are discussed.

Adaptation, Psychological↗

Genetic variation of Der p 2 allergens: effects on T cell responses and immunoglobulin E binding.

BACKGROUND: Der p 2 is a highly polymorphic allergen that shows a distinct pattern of sequence divergence. The effect of the variations on T cell and antibody responses has not been compared. OBJECTIVES: To compare IgE antibody binding and T cell proliferation and cytokine release induced by variants of Der p 2. METHODS: Peripheral blood mononuclear cells (PBMC) from 19 allergic and 15 non-allergic people were stimulated with recombinant variants of Der p 2. IL-5, IL-10, IL-13 and IFN-gamma were measured by a time resolved fluorescence (TRF) assay. Serum IgE antibody was measured using a solid-phase TRF assay. RESULTS: Overall the most prevalent variant of Der p 2 (Der p 2. 0101) was the highest or approximately equal highest inducer of T cell proliferation and IL-5, IL-10, IL-13 and IFN-gamma release. The most divergent variant 0104 induced the next highest responses. The variants 0107 and 0108 showed interesting changes especially when the allergic status was considered. Responses to 0107 showed poor Th1/Th2 polarization and, except for IL-10 release, cytokine responses to 0108 were low for non-allergic subjects. The variant 0101 showed similar monoclonal antibody binding but moderately less IgE binding than the other variants. CONCLUSIONS: The most prevalent variant, Der p 2. 0101, was the most active for T cell stimulation and although its IgE binding was slightly less than other variants that was highly correlated. The variant Der p 2. 0104 which contains the known common polymorphic changes had a response which was similar to Der p 2. 0101 and thus these two variants were the most stimulatory representations of Der p 2. The T cell responses to the less common variants 0107 and 0108 however, showed consistent differences demonstrating that changes in the sequence could change the cytokine response.

Adult↗

Increased CD4+ T-lymphocyte senescence fraction in advanced human immunodeficiency virus type 1 infection.

Human immunodeficiency virus type 1 (HIV-1) infection is accompanied by peripheral CD4+ T-cell losses. CD4+ T-cell numbers often increase during antiviral treatment of acquired immune deficiency syndrome (AIDS), however, alterations in the CD4+ T-cell repertoire have not been completely corrected for these patients. Such individuals remain at increased risk of infection. Although senescence of the CD4+ T cells has not been adequately evaluated for advanced HIV-1 infection, hypothetically, replicative senescence could complicate therapeutic reconstitution of the CD4+ T cells in AIDS. In this study, correlates of replicative senescence, terminal restriction fragment (TRF) length and percentage short (< 5.0 kb) telomeric DNA (senescence fraction), were measured for the CD4+ T cells of HIV-1-infected patients with peripheral CD4+ T-cell counts of < 200/mm3. The results show that for advanced HIV-1 infection the TRF length of the CD4+ T cells is decreased (P < 0.01), and the senescence fraction increased (P < 0.05), when compared with uninfected controls. These findings suggest that cellular senescence may contribute to disruption of CD4+ T-cell diversity observed following the therapeutic, immunologic reconstitution of AIDS.

Adult↗

Effects of G-CSF on telomere lengths in PBMCs from human immunodeficiency virus-infected patients: results from a randomized, placebo-controlled trial.

Telomeres are unique terminal chromosomal structures, the length of which has been shown to decrease with cell division in vitro and with increased age in vivo for human somatic cells. In human immunodeficiency virus (HIV)-1 infection, decrease of telomere length is primarily found in CD8+ T cells, and not in CD4+ T cells. In this double-blind placebo-controlled study, we investigated the effect of granulocyte colony stimulating factor (G-CSF) treatment combined with highly active antiretroviral therapy (HAART) on mean telomere length in peripheral blood mononuclear cells (PBMC). The terminal restriction fragment (TRF) length showed no changes during G-CSF treatment although the number of lymphocytes increased significantly. The mean TRF length correlated positively (R = 0.552, P = 0.009) and negatively (R = -0.503, P = 0.02) to the proportion of CD4+ memory and naïve cells, respectively. Our data suggest that during G-CSF treatment lymphocytes are recruited by a combination of central and peripheral proliferation.

Adult↗

Population-based genetic screening for the estimation of Type 1 diabetes mellitus risk in Finland: selective genotyping of markers in the HLA-DQB1, HLA-DQA1 and HLA-DRB1 loci.

AIMS: To improve sensitivity and specificity of the diabetes risk assessment of the population-based genetic screening used in the Finnish Diabetes Prediction and Prevention (DIPP) trial. METHODS: One thousand consecutive newborns enrolled in the DIPP were compared with 316 samples from children with Type 1 diabetes mellitus. A modification of the previously described technique based on hybridization of relevant PCR products with five lanthanide-labelled probes detected by time-resolved fluorometry (TRF) was used. A new probe was designed and allowed discrimination between DQB1*0602 and 0603 alleles, in addition to DQB1*02, *0301 or *0302, each of which required specific probes. A new, added screening strategy was developed for individuals carrying low-risk genotypes through specific typing of DQA1 *05 and *0201 alleles in DQB1*02 positive, and DRB1 typing for DR4 subtypes in DQB1*0302 positive subjects, with a new specifically designed high-resolution TRF-based DR4 subtyping technique. RESULTS: This two-step screening approach enhanced the sensitivity of the detection of genetic risk for Type 1 diabetes mellitus in this cohort up to 85.4%. In the general population cohort, 24.4% were identified for prospective follow-up, 2.6% of these are expected to develop Type 1 diabetes mellitus before the age of 15 years. Exclusive typing for HLA-DQB1 locus as an alternative screening strategy had sensitivities of 26.3-77.2% with general population cohorts of 2.3-23.1% identified for follow-up. CONCLUSIONS: The described strategy for genetic prediction of Type 1 diabetes mellitus relies on the convenient genotyping procedure and could be applied in large scale screening projects such as DIPP.

Biomarkers↗

Antiproliferative and apoptotic effects of tocopherols and tocotrienols on preneoplastic and neoplastic mouse mammary epithelial cells.

Studies were conducted to determine the comparative effects of tocopherols and tocotrienols on preneoplastic (CL-S1), neoplastic (-SA), and highly malignant (+SA) mouse mammary epithelial cell growth and viability in vitro. Over a 5-day culture period, treatment with 0-120 microM alpha- and gamma-tocopherol had no effect on cell proliferation, whereas growth was inhibited 50% (IC50) as compared with controls by treatment with the following: 13, 7, and 6 microM tocotrienol-rich-fraction of palm oil (TRF); 55, 47, and 23 microM delta-tocopherol; 12, 7, and 5 microM alpha-tocotrienol; 8, 5, and 4 microM gamma-tocotrienol; or 7, 4, and 3 microM delta-tocotrienol in CL-S1, -SA and +SA cells, respectively. Acute 24-hr exposure to 0-250 microM alpha- or gamma-tocopherol (CL-S1, -SA, and +SA) or 0-250 microM delta-tocopherol (CL-S1) had no effect on cell viability, whereas cell viability was reduced 50% (LD50) as compared with controls by treatment with 166 or 125 microM delta-tocopherol in -SA and +SA cells, respectively. Additional LD50 doses were determined as the following: 50, 43, and 38 microM TRF; 27, 28, and 23 microM alpha-tocotrienol; 19, 17, and 14 microM gamma-tocotrienol; or 16, 15, or 12 microM delta-tocotrienol in CL-S1, -SA, and +SA cells, respectively. Treatment-induced cell death resulted from activation of apoptosis, as indicated by DNA fragmentation. Results also showed that CL-S1, -SA, and +SA cells preferentially accumulate tocotrienols as compared with tocopherols, and this may partially explain why tocotrienols display greater biopotency than tocopherols. These data also showed that highly malignant +SA cells were the most sensitive, whereas the preneoplastic CL-S1 cells were the least sensitive to the antiproliferative and apoptotic effects of tocotrienols, and suggest that tocotrienols may have potential health benefits in preventing and/or reducing the risk of breast cancer in women.

Animals↗

Teacher assessment of behaviour in children with new-onset seizures.

RATIONALE: Recent data suggest that children with new-onset seizures may be at increased risk for behaviour problems. Teachers are an excellent source of data about such problems. They do not have the potential bias that a parent worried about a new onset of seizures might have and, furthermore, they are accustomed to comparing performance of children and work in an environment in which the behavioural problems associated with epilepsy may be quite evident. We obtained teachers' reports of behaviour problems in children in the 2 months prior to their first recognized seizure. We also obtained similar data on children with new-onset, moderate severity asthma. In addition to comparing behavioural scores between children with seizures and children with asthma, we compared teachers' assessments of behaviour in children with no prior seizures to those of children with previously unrecognized seizures. METHODS: We evaluated 192 children with new-onset seizures, including 129 children with no prior episodes and 63 children with recognized prior seizure-like episodes. The comparison group consisted of 78 children with new-onset, moderate severity asthma. Behaviour was assessed by the teacher's report form (TRF) of the child behaviour checklist (CBCL) or the caregiver-teacher report form for ages 2-5 (C-TRF). Mean scores were compared by two-sample t -tests and analysis of variance (ANOVA). RESULTS: The children with new-onset seizures had more thought problems than children with asthma. In comparison to children with no prior seizures, the children with prior unrecognized seizures had higher scores in total behaviour problems, internalizing problems, somatic complaints, anxious/depressed, thought problems, and attention problems. CONCLUSIONS: In this sample, children with prior unrecognized seizures were already at increased risk of teacher-rated behaviour problems before starting medication and before any possible stigma effects related to seizures. This sequence suggests underlying neurological problems causing both behavioural problems and seizures.

Adolescent↗

Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation.

High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) (n = 17), or 4 x FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT (n = 16). Haemoglobin, MCV, leukocyte-and platelet numbers were assessed prior to (t(0)), 5 months after (t(1)) and 9 months after chemotherapy (t(2)); these parameters were decreased at t(1)and t(2)compared to t(0)(high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t(1). Paired individual leukocyte samples of t(0)and t(1)showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from +0.8 to -2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t(0)and t(1). Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment.

Antineoplastic Combined Chemotherapy Protocols↗