Enhancement of DNA synthesis of mouse myelogenous cells by cyclic adenosine 3',5'-monophosphate (cAMP)

To observe the possible role of cAMP on the DNA synthesis during specialization-division of myelogenous precursor cells, the authors observed the DNA and RNA synthesis of the cells by in vitro autoradiography. And it is concluded that cAMP or its dibutyryl derivative added to the media penetrated into myelogenous precursor cells and metamyelocytes of mice and enhanced the DNA synthetic capacity of them. cAMP hardly enhanced RNA synthesis. Discussion is made on relation between enhancement of DNA synthesis of metamyelocytes and their possible rejuvenation.</p

Rice Annotation Database (RAD): a contig-oriented database for map-based rice genomics

A contig-oriented database for annotation of the rice genome has been constructed to facilitate map-based rice genomics. The Rice Annotation Database has the following functional features: (i) extensive effort of manual annotations of P1-derived artificial chromosome/bacterial artificial chromosome clones can be merged at chromosome and contig-level; (ii) concise visualization of the annotation information such as the predicted genes, results of various prediction programs (RiceHMM, Genscan, Genscan+, Fgenesh, GeneMark, etc.), homology to expressed sequence tag, full-length cDNA and protein; (iii) user-friendly clone / gene query system; (iv) download functions for nucleotide, amino acid and coding sequences; (v) analysis of various features of the genome (GC-content, average value, etc.); and (vi) genome-wide homology search (BLAST) of contig- and chromosome-level genome sequence to allow comparative analysis with the genome sequence of other organisms. As of October 2004, the database contains a total of 215 Mb sequence with relevant annotation results including 30 000 manually curated genes. The database can provide the latest information on manual annotation as well as a comprehensive structural analysis of various features of the rice genome. The database can be accessed at http://rad.dna.affrc.go.jp/

Pre-post changes in psychosocial functioning among relatives of patients with depressive disorders after Brief Multifamily Psychoeducation: A pilot study

<p>Abstract</p> <p>Background</p> <p>Depressive disorder is often chronic and recurrent, and results in a heavy psychosocial burden on the families of patients with this disorder. This study aims to examine the effectiveness of brief multifamily psychoeducation designed to alleviate their psychosocial burden.</p> <p>Methods</p> <p>Thirty-two relatives of patients with major depressive disorder participated in an open study testing the effectiveness of brief multifamily psychoeducation. The intervention consisted of four sessions over the course of 6 weeks. Outcome measures focused on emotional distress, care burden and Expressed Emotion (EE).</p> <p>Results</p> <p>The emotional distress, care burden and EE of the family all showed statistically significant improvements from baseline to after the family intervention. The proportion of relatives scoring 9 or more on K6, which indicates possible depressive or anxiety disorder, decreased from sixteen relatives (50.0%) at baseline, to only 3 relatives (9.3%) after the intervention.</p> <p>Conclusions</p> <p>This study suggests that brief multifamily psychoeducation is a useful intervention to reduce the psychosocial burden of the relatives of patients with depressive disorder. Further evaluation of family psychoeducation for relatives of patients with depressive disorder is warranted.</p

Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

<p>Abstract</p> <p>Background</p> <p>Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes.</p> <p>Methods</p> <p>Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets.</p> <p>Results</p> <p>Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors.</p> <p>Conclusion</p> <p>We established 6 xenograft canine HSA tumors in nude mice and found that the expressions of angiogenic growth factors and their receptors in xenograft HSAs were similar to those in spontaneous HSA. Furthermore, we detected the expression of angiogenic homeobox genes; therefore, xenograft models may be useful in analyzing malignant growth in HSA.</p

Collaborative Virtual Screening Identifies a 2-Aryl-4-aminoquinazoline Series with Efficacy in an In Vivo Model of Trypanosoma cruzi Infection

Probing multiple proprietary pharmaceutical libraries in parallel via virtual screening allowed rapid expansion of the structure-activity relationship (SAR) around hit compounds with moderate efficacy against Trypanosoma cruzi, the causative agent of Chagas Disease. A potency-improving scaffold hop, followed by elaboration of the SAR via design guided by the output of the phenotypic virtual screening efforts, identified two promising hit compounds 54 and 85, which were profiled further in pharmacokinetic studies and in an in vivo model of T. cruzi infection. Compound 85 demonstrated clear reduction of parasitemia in the in vivo setting, confirming the interest in this series of 2-(pyridin-2-yl)quinazolines as potential anti-trypanosome treatments

Association between Maternal Exposure to di(2-ethylhexyl) Phthalate and Reproductive Hormone Levels in Fetal Blood: The Hokkaido Study on Environment and Children's Health

Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23–35 weeks of gestation and the concentration of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), was measured. Concentrations of infant reproductive hormones including estradiol (E2), total testosterone (T), and progesterone (P4), inhibin B, insulin-like factor 3 (INSL3), steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone were measured from cord blood. Two hundred and two samples with both MEHP and hormones' data were included in statistical analysis. The participants completed a self-administered questionnaire regarding information on maternal characteristics. Gestational age, birth weight and infant sex were obtained from birth records. In an adjusted linear regression analysis fit to all study participants, maternal MEHP levels were found to be associated with reduced levels of T/E2, P4, and inhibin B. For the stratified analyses for sex, inverse associations between maternal MEHP levels T/E2, P4, inhibin B, and INSL3 were statistically significant for males only. In addition, the MEHP quartile model showed a significant p-value trend for P4, inhibin B, and INSL3 decrease in males. Since inhibin B and INSL3 are major secretory products of Sertoli and Leydig cell, respectively, the results of this study suggest that DEHP exposure in utero may have adverse effects on both Sertoli and Leydig cell development in males, which agrees with the results obtained from animal studies. Comprehensive studies investigating phthalates' exposure in humans, as well as their long-term effects on reproductive development are needed

Association of maternal whole blood fatty acid status during the prenatal period with term birth dimensions : a cross-sectional study

Objective: To investigate selected fatty acid (FA) profiles in maternal whole blood during normal pregnancy and to evaluate their associations with term birth dimensions. Methods: We characterized nine major maternal blood FAs representing four FA families during the second and third trimester of pregnancy, and explored their associations with birth weight, length, and chest or head circumferences by multivariate regression models, using data from 318 mother-newborn pairs of the Hokkaido Study. Results: The absolute and/or relative contents of maternal blood docosahexaenoic acid and arachidonic acid were lowest at 35–41 gestational weeks during pregnancy, as was the essential FA status index. Different from palmitic and stearic acids, palmitoleic and oleic acid contents were higher at 35–41 gestational weeks than those at 23–31 gestational weeks. Three FA components were identified through principal component analysis, and were used in association analysis. Component 3, which was positively and significantly loaded by eicosapentaenoic acid (EPA), was associated with chest circumference [β=0.281, 95% confidence interval (CI): 0.006, 0.556] at 35–41 gestational weeks (P=0.046). No significant associations were observed for Component 1 and 2 loaded by FAs except EPA. Conclusion: Maternal blood EPA content may have an important influence on infant chest circumference

Cytokine production by spleen cells from mice with ovalbumin-specific, IgE-selective unresponsiveness induced by ovalbumin-liposome conjugate

Ovalbumin coupled with liposomes (OVA–liposome) induced selective unresponsiveness of anti-OVA IgE antibody production in BALB/c mice, whereas OVA adsorbed with aluminum hydroxide (OVA–alum) induced a substantial amount of anti-OVA IgE antibody production. Ovalbumin–liposome and OVA–alum predominantly induced IgG2a and IgG1 anti-OVA production, respectively. These results suggest that OVA–liposome and OVA–alum induce type 1 and type 2 T helper (Th) immune responses, respectively. To further investigate this issue, we examined the cytokine production induced by these two distinct adjuvants. Spleen cells taken from mice immunized with either OVA–liposome or OVA–alum were cultured in vitro with OVA and the cytokine production from each culture was analyzed. It was demonstrated that spleen cells from mice immunized with OVA–liposome produced more interferon (IFN)-γ than those immunized with OVA–alum and, furthermore, interleukin (IL)-4 was produced only by spleen cells from mice immunized with OVA–alum. These results favor the notion that OVA–liposome and OVA–alum induce Th1 and Th2 cytokines, respectively. Interestingly, the production of IL-2, a Th1 cytokine, was higher in the OVA–alum-immunized group and the production of IL-10, a Th2 cytokine, remained at low levels in both groups after primary immunization; levels of IL-10 increased in the OVA–liposome-immunized group after secondary immunization. These results do not agree with the above notion and, thus, suggest that it may be important to consider the balance between IFN-γ-producing cells and IL-4-producing cells rather than that between Th1 and Th2 cells for the regulation of IgE antibody production