Chronic and acute stress,gender, and serotonin transporter gene–environment interactions predicting depression symptoms in youth

Background: Many recent studies of serotonin transporter gene by environment effects predicting depression have used stress assessments with undefined or poor psychometric methods, possibly contributing to wide variation in findings. The present study attempted to distinguish between effects of acute and chronic stress to predict depressive symptoms at age 20 among 346 youth varying in polymorphisms of the 5HTT gene who had been assessed at ages 15 and 20. Methods: Interview measures assessed major acute life events between 15 and 19, and multiple interviews and questionnaires with youths and their parents at youth age 15 provided an index of chronic family stress. Lg alleles were reclassified as S. Results: Chronic family stress at age 15 predicted higher depression scores at 20 among those with one or two S alleles, and the effects of genetic moderation were significant only for females. Gene–environment interactions with acute stress were nonsignificant. Conclusions: Careful measurement and separation of the effects of chronic and acute stress, and gender, are encouraged in the study of mechanisms of the stress–depression association.     

The role of methylcellulose on colony growth of human myeloid leukemic progenitors (AML-CFU)

The use of a semisolid support like methylcellulose (MC) in a clonogenic assay prevents cell migration and nonspecific aggregation. However, the inhibitory effect of MC on myeloid cell lines has been reported. To assess the effect of MC on human leukemic progenitor cell growth (acute myeloblastic leukemia colony-forming units, AML-CFU), increasing concentrations of MC (0.36%, 0.72%, and 1.44%) were added in a double-feeder culture system. T-lymphocyte-depleted leukemic cells from 12 patients with AML were cultured in the presence of 2.5% phytohemagglutinin (PHA) in a liquid and a semisolid (MC) medium over a leukocyte feeder layer. The leukemic nature of the colonies was confirmed by cytogenetic studies. The median cloning efficiency in the optimal MC assay system was significantly higher (217 leukemic colony-forming units [CFU-L]/5 x 10(4) cells) than the one obtained in the liquid assay system (72.5 CFU-L/5 x 10(4) cells). However, three patterns of growth were observed: 1) colony formation was significantly better in MC than in the liquid assay system (seven of ten cases), 2) there was no difference in growth response (three of ten cases), and 3) colony formation was significantly better in the liquid assay system (one of ten cases). In the semisolid assay system, colony growth was dependent on MC concentration and varied among individual patients. A striking feature was the partial reduction of AML-CFU growth at 1.44% MC, with complete inhibition in 4/11 cases. This phenomenon was not observed for normal progenitors cultured under the same conditions. Cytological evaluation of AML-CFU showed an incomplete maturation to the myelocyte state, accompanied occasionally by macrophagic differentiation. In contrast, maturation of the granulocyte-macrophage colony-forming unit (CFU-GM) clones was harmonious, resulting in greater than 40% polynuclear cells, even from a 7-day culture. Despite a variable clonal response of leukemic progenitors from individual patients, we conclude that 0.72% MC is the optimal concentration of MC in our system, allowing clonal growth of AML-CFU.     

Lifetime Abstainers, Current Abstainers and Imbibers: A Methodological Note

Previous population studies of patterns of alcohol consumption have tended to assume that abstainers are a homogeneous group. As part of a Boston-area probability sample of 5,320 adults, those persons categorized as abstainers were examined on a variety of dimensions. The findings suggest that the abstaining population comprises three groups: lifetime abstainers (58 per cent), current abstainers who have not had a previous drinking problem. (34 per cent) and current abstainers who have had a previous drinking problem (9 per cent). This latter group appears, on a number of social and demographic characteristics, to be similar to persons who are frequent drinkers. The assumption of the homogeneity of the abstaining population is refuted and the results are discussed in terms of their theoretical and methodological implications.     

Reversible inhibitory effects and absence of toxicity of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in human long-term bone marrow culture.

The effects of acetyl-N-Ser-Asp-Lys-Pro (Ac-SDKP) in human long-term bone marrow cultures (LTBMCs) were assessed by measuring the number of progenitors and the development of stromal cells over a 6-week course. In a first set of experiments, AcSDKP was added weekly at each medium change. Under these conditions, no significant effect of the peptide was observed. In contrast, by adding AcSDKP daily at 10(-10) M, the growth of the progenitors of the non-adherent (NA) compartment was inhibited by about 35%. This inhibition was entirely reversible; after stopping the addition of the peptide at the fourth week, the number of progenitors returned to control level within 2 weeks. Conversely, AcSDKP did not significantly change the number of the progenitors present in the adherent layer. In addition, AcSDKP did not affect the formation of the stromal layer nor induce the secretion of cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), granulocyte colony-stimulating factor (G-CSF), interleukin 3 (IL-3), or interleukin 6 (IL-6). Our results indicate that AcSDKP has inhibitory but reversible effects on NA progenitors and does not induce long-term modifications of the microenvironment, both of particular interest for its clinical application.     

Long-term effects of recombinant human erythropoietin on bone marrow progenitor cells

Eleven uraemic patients were treated with recombinant humanerythropoietin (rHuEpo). Seven haemodialysis patients and fourperitoneal dialysis patients received a starting dose of 80IU/kg i.v. and 40 IU/kg s.c. respectively, thrice weekly. Thenumber of burst-forming-unit erythroid (BFU-E), colony-forming-uniterythroid (CFU-E), granulocyte-monocyte (CFU-GM) and megakaryocyte(CFU-Mk) were assayed 2 weeks before (DO), and 1 (M1) and 6months (M6) after the initiation of rHuEpo treatment by meansof a commonly applied in-vitro clonal assay. All the patientsshowed the same haematopoietic response. A significant increaseof CFU-E and CFU-Mk could be observed within 1 month of treatment.At this time, no significant modification was observed in BFU-Eand CFU-GM number. At the 6th month the increase of CFU-E wasmaintained, whereas a significant fall of BFU-E, CFU-GM andCFU-Mk was observed. These results suggest that in-vivo effects of rHuEpo are notrestricted to the erythroid lineage but that erythropoietinmight also act as a co-factor of megakar-yopoiesis. In the longterm erythropoietin might induce erythroid differentiation inmultipotent progenitor cells at the expense of the non-erythroidprogenitors.     

Religious values, practices and pregnancy outcomes: a comparison of the impact of sect and mainstream Christian affiliation

In this report 6566 women enrolled in the Mater-University of Queensland Study of Pregnancy (MUSP) were separated into three groups; members of religious sects, Christians who attend church frequently and Christians who are infrequent attenders. These three groups, respectively labelled Christian sects, Christian attenders and lukewarm Christians were compared on a number of social background, lifestyle and pregnancy outcome variables. The sect members appeared to have the most favourable health, lifestyles and healthy babies at delivery, though this latter finding appears attributable to specific characteristics of the mother and her lifestyle. On most measures the children of lukewarm Christians appear to manifest the worst health while Christian attenders form a group whose children's health is between that of sect members and lukewarm Christians.     

A new combination of two intercalating agents (mitoxantrone + daunomycin) in adult refractory acute leukemia: the DON protocol

Summary A combination of two interacalating agents, mitoxantrone and daunorubicin with vincristine (the DON regimen) was studied in 16 patients with refractory acute leukemia, including three patients with myeloblastic transformation of refractory anemia with excess of myeloblasts after the failure of first-line chemotherapy and one additional patient with AML relapsing while off therapy. All patients had been heavily pretreated prior to receiving the DON regimen, and all but two had previously received high-dose anthracyclines. Of the 17 patients, nine (53%) who achieved complete remissions (CR) had myeloblastic leukemia. The three patients with acute lymphocytic leukemia did not achieve CR. Cardiac toxicity occurred in two patients and contributed to death in one. These results in very poor risk leukemia suggest a possible synergism in the action of the two intercalating agents and absence of increased cardiotoxicity.Presented in part at the 4th International Symposium on Therapy of Acute Leukaemias. Rome, February 7–12/1987     

Vindesine-prednisone in the treatment of blast crisis of chronic myeloid leukemia

Eight patients with chronic myeloid leukemia in blast crisis were treated with a combination of vindesine and prednisone. Complete remission was achieved in three patients; partial remission was achieved in three. All six responders received maintenance treatment with hydroxyurea and 6-mercaptopurine. The median duration of survival was 9 months. Two patients had long-term survival: one survived 32 months and the other is alive after 30 months. These data suggest that vindesine-prednisone polychemotherapy might improve the prognosis of blast crisis in chronic myeloid leukemia.