Clinicopathological correlation of cell proliferation, apoptosis and p53 in cerebellar pilocytic astrocytomas

We have analysed 78 cerebellar pilocytic astrocytomas to assess whether histopathology, cell proliferation, apoptosis rate, p53 immunoreactivity, or flow cytometry could predict their long-term behaviour. Classic pilocytic/microcystic pattern was seen in 62 patients and 16 patients had mixed pattern with an additional non-pilocytic glial component. The overall 5-year survival was 93%, complete resection providing 100% survival. The four patients who died during the follow-up were more than 14 years of age, their primary operation had been incomplete and three of them were mixed variants. In 15 cases the tumour recurred giving a recurrence-free 5-year survival of 77%. The proliferation indices were low: Ki-67_MIB-1 (median 2.0%), PCNA (1.2%) and S-phase fraction (4.4%). The Ki-67_MIB-1-labelling index was significantly higher in young patients, but did not differ between the classic and mixed variants. Twenty-two per cent of the tumours were aneuploid with a significantly higher S-phase fraction than in diploid tumours. p53 seems to act as ardian of the genome' in pilocytic astrocytomas, because aberrant/increased expression of p53 and aneuploidy associated with enhanced apoptosis. Only patient age ( P =0.01), radicality of the primary operation ( P =0.0001) and histology (classic vs mixed, P =0.008) significantly correlated with survival. The poorer prognosis of the mixed variant suggests that this may represent a distinct entity. Although none of the novel parameters significantly predicted recurrence or survival, they indicate substantial biological variation among cerebellar pilocytic astrocytomas.     

Genetic aberrations in prostate cancer by microarray analysis

The aim of this study was to screen genetic as well as expression alterations in prostate cancer. Array comparative genomic hybridization (aCGH) to a 16K cDNA microarray was performed to analyze DNA sequence copy number alterations in 5 prostate cancer cell lines and 13 xenografts. The aCGH confirmed the previously implicated common gains and losses, such as gains at 1q, 7, 8q, 16p and 17q and losses at 2q, 4p/q, 6q, 8p, 13q, 16q, 17p and 18q, which have previously been identified by chromosomal CGH (cCGH). Because of the higher resolution of aCGH, the minimal commonly altered regions were significantly narrowed-down. For example, the gain of 8q was mapped to three independent regions, 8q13.3-q21.11, 8q22.2 and 8q24.13-q24.3. In addition, a novel recurrent gain at 9p13-q21 was identified. The concomitant expression analysis indicated that genome-wide DNA sequence copy number (gene dosage) was significantly associated with the expression level (p < 0.0001). The analyses indicated several individual genes whose expression was associated with the gene copy number. For example, gains of PTK2 and FZD6, were associated with the increased expression, whereas losses of TNFRSF10B (alias DR5) and ITGA4 with decreased expression. In conclusion, the aCGH mapping data will aid in the identification of genes altered in prostate cancer. The combined expression and copy number analysis suggested that even a low-level copy number change may have significant effect on gene expression, and thus on the development of prostate cancer.     

The Effect of Parenting Stress on Fathers' Availability and Engagement

The present study was designed to shed light on the relation between parenting stress, father's alcohol use, child characteristics and father's engagement and availability. The study cohort comprised 821 fathers of preschool children in Finland. Parenting stress and child's mood, acceptability and demandingness were related to father's engagement to the preschooler and to the extent of the father's availability. Parenting stress began a cycle of alcohol abuse and child-negative characteristics, and eventually led to a decrease in joint father-child activities, father's feeling of compulsory engagement, daily conflict situations, difficulty in including the child in everyday activities and a reduction in the amount of time spent directly or indirectly together.     

Multivariate genetic analysis of lifetime exercise and environmental factors

PURPOSE: We investigated whether the association between exercise and individual-specific factors that correlate with exercise may be explained by genetic or common environmental factors. METHODS: Lifetime exercise data were available from 147 MZ and 153 DZ adult male twin pairs with a mean age of 50 yr (SD = 8 yr). RESULTS: The best-fitting quantitative genetic model for adulthood exercise level consisted of additive genetic effects, genetic effects due to dominance and unique environment effects, with genetic effects explaining 51% (95% CI = 29-63%) of the variance. Factors associated with adulthood exercise level were adolescent exercise, participation in competitive sports, perceived health, smoking status, and percent body fat. In bivariate models, approximately half of the covariation between those factors and adulthood exercise level was accounted for by unique environmental effects (i.e., factors not shared by the co-twins). Additive genetic effects explained less (3-20%) than dominance genetic effects (23-53%) of the covariation between those factors and adulthood exercise. Shared environmental effects were present only in the bivariate model of adulthood and adolescent exercise, explaining 11% of the covariance. CONCLUSIONS:: The genetic component shared in common by exercise and factors associated with exercise suggests that there may be a complex pathway of genetic selection and predisposition for a physically active lifestyle.     

Primary cutaneous T-cell lymphomas show a deletion or translocation affecting NAV3, the human UNC-53 homologue

Multicolor fluorescent in situ hybridization (FISH) was used to identify acquired chromosomal aberrations in 12 patients with mycosis fungoides or Sézary syndrome, the most common forms of primary cutaneous T-cell lymphoma (CTCL). The most frequently affected chromosome was 12, which showed clonal deletions or translocations with a break point in 12q21 or 12q22 in five of seven consecutive Sézary syndrome patients and a clonal monosomy in the sixth patient. The break point of a balanced translocation t(12;18)(q21;q21.2), mapped in the minimal common region of two deletions, fine mapped to 12q2. By locus-specific FISH, the translocation disrupted one gene, NAV3 (POMFIL1), a human homologue of unc-53 in Caenorhabditis elegans. A missense mutation in the remaining NAV3 allele was found in one of six cases with a deletion or translocation. With locus-specific FISH, NAV3 deletions were found in the skin lesions of four of eight (50%) patients with early mycosis fungoides (stages IA-IIA) and in the skin or lymph node of 11 of 13 (85%) patients with advanced mycosis fungoides or Sézary syndrome. Preliminary functional studies with lentiviral small interfering RNA-based NAV3 silencing in Jurkat cells and in primary lymphocytes showed enhanced interleukin 2 expression (but not CD25 expression). Thus, NAV3 may contribute to the growth, differentiation, and apoptosis of CTCL cells as well as to the skewing from Th1-type to Th2-type phenotype during disease progression. NAV3, a novel putative haploinsufficient tumor suppressor gene, is disrupted in most cases of the commonest types of CTCL and may thus provide a new diagnostic tool.     

Maternal human polyomavirus infection and risk of neuroblastoma in the child

To investigate if polyomavirus infection during pregnancy is linked to development of neuroblastoma in the child, serum samples of 115 index mothers from the pregnancy where the child eventually developed neuroblastoma were identified and matched with serum samples from 8 control mothers per index mother. The samples were tested for specific IgG and IgM antibodies to BK and JC virus using enzyme immunoassays based on purified yeast-expressed virus-like particles (VLPs). The serum samples as well as 10 neuroblastoma cell lines were also analyzed using Real Time (TaqMan) PCR for detection and quantification of BK virus DNA. The BK virus IgG seroprevalence was similar among index mothers (80%) and control mothers (83%) [OR 0.8; 95% confidence interval (95% CI): 0.5-1.3]. BK virus IgM was also not associated with neuroblastoma risk (OR was OR = 0.6; 95% with CI, 0.2-1.9). Also JC virus had no association, neither for IgG (OR = 0.9; 95% CI, 0.6-1.4) nor for IgM (OR = 0.9; 95% CI, 0.4-1.9). All serum samples and all neuroblastoma cell lines were negative for BKV DNA. In summary, a comprehensive cohort using both serology and polyomavirus DNA detection found no evidence for association between BKV or JCV polyomaviruses and neuroblastoma.     

Incidence,treatment and outcome of peripartum sepsis

BACKGROUND AND METHODS: Clinical and microbiological features of maternal sepsis in the peripartum period (7 days before to 7 days after delivery) were analyzed to determine possible risk factors, optimal treatment and outcome. In 43 483 deliveries during 1990-98, laboratory-confirmed bacteremia was found in 41 (5.1%) out of 798 clinically suspected septic infections. RESULTS: Preterm deliveries were associated with a crude 2.7-fold risk for peripartum sepsis as compared to term deliveries. Antepartum sepsis was associated with a crude 2.6-fold risk for cesarean section, while postpartum sepsis was 3.2 times more likely to occur after cesarean section than after vaginal delivery. A combination of cefuroxime and metronidazole was used in 80% (33/41) of all treatments. All mothers recovered well, and only one suffered from septic shock. In total, 42 bacterial strains, representing 18 different bacterial species, were isolated from the blood cultures; 37 strains (88%, 37/42) were aerobic and five (12%, 5/42) were anaerobic. The most common species were betahemolytic streptococci, Escherichia coli and Staphylococcus aureus. Most microbes (81%, 34/42) were found to be susceptible to first- or second-generation cephalosporins. CONCLUSION: Our analysis shows that peripartum sepsis is associated with preterm pregnancies and cesarean sections. Treatment of peripartum sepsis with second-generation cephalosporin is usually effective, and the outcome is good.