Growth of mouse and human bone marrow in diffusion chambers in mice. Development of myeloid and erythroid colonies and proliferation of myeloid stem cells in cyclophosphamide- and erythropoietin-treated mice.

Both murine and human bone marrow cells were cultured in plasma clots which were formed inside diffusion chambers implanted into cyclophosphamide- and saline-treated mice. After an initial fall, the number of mouse bone marrow cells and numbers of mouse myeloid stem cells (CFU-C) and agar cluster-forming units rose faster in the cyclophosphamide-treated animals. These hosts also favored formation of myeloid (CFU-D-G) and erythroid (CFR-D-E) colonies and myeloid higher than those of CFU-C from the same marrow population. These observations suggest the existence of humoral factors stimulating granulocyte progenitor cell replication and differentiation. At its best the increment of CFU-D-E number was equivalent to that caused by a single 0.1 unit erythropoietin dose. Culture of normal human marrow cells resulted in colonies in the plasma clot containing only granulocytes and macrophages. Cyclophosphamide-treated host animals were essential for human CFU-D-G development. Plating efficiency for human marrow myeloid colonies was better in the conventional in vitro agar cultures than in diffusion chambers.     

A genome‐wide linkage map for the house sparrow (Passer domesticus) provides insights into the evolutionary history of the avian genome

The house sparrow is an important model species for studying physiological, ecological and evolutionary processes in wild populations. Here, we present a medium density, genome wide linkage map for house sparrow (Passer domesticus) that has aided the assembly of the house sparrow reference genome, and that will provide an important resource for ongoing mapping of genes controlling important traits in the ecology and evolution of this species. Using a custom house sparrow 10 K iSelect Illumina SNP chip we have assigned 6,498 SNPs to 29 autosomal linkage groups, based on a mean of 430 informative meioses per SNP. The map was constructed by combining the information from linkage with that of the physical position of SNPs within scaffold sequences in an iterative process. Averaged between the sexes; the linkage map had a total length of 2,004 cM, with a longer map for females (2,240 cM) than males (1,801 cM). Additionally, recombination rates also varied along the chromosomes. Comparison of the linkage map to the reference genomes of zebra finch, collared flycatcher and chicken, showed a chromosome fusion of the two avian chromosomes 8 and 4A in house sparrow. Lastly, information from the linkage map was utilized to conduct analysis of linkage disequilibrium (LD) in eight populations with different effective population sizes (N_e) in order to quantify the background level LD. Together, these results aid the design of future association studies, facilitate the development of new genomic tools and support the body of research that describes the evolution of the avian genome.     

Incident Hip Fractures among Community Dwelling Persons with Alzheimer’s Disease in a Finnish Nationwide Register-Based Cohort

Background

Previous cohort studies have shown that persons with Alzheimer’s disease (AD) have a higher risk of hip fractures but recent data from large representative cohorts is scarce.

Methods

We investigated the association between AD and prevalent and incident hip fractures in an exposure-matched cohort study conducted in Finland 2002–2009 (the Medication and Alzheimer’s disease in 2005 study; MEDALZ-2005). The study population included all community-dwelling persons with verified AD diagnosis in Finland on December 31, 2005 and one matched comparison person per AD case (N = 56,186, mean age 79.9 (SD 6.8) years, range 42–101 years). The diagnosis of AD was extracted from a special reimbursement register. Data on hip fractures during 2002–2009 was extracted from the Finnish National hospital discharge register. Analyses of incident hip fractures (n = 2,861) were restricted to years 2006–2009.

Results

Persons with AD were twice as likely to have previous hip fracture in 2005 (odds ratio, 95% confidence interval 2.00, 1.82–2.20) than matched aged population without AD. They were also more likely to experience incident hip fracture during the four-year follow-up (hazard ratio, 95% confidence interval 2.57, 2.32–2.84, adjusted for health status, psychotropic drug and bisphosphonate use). The AD-associated risk increase decreased linearly across age groups. Although people with AD had higher risk of hip fractures regardless of sex, the risk increase was larger in men than women.

Conclusion

Findings from our nationwide study are in line with previous studies showing that persons with AD, regardless of sex or age, have higher risk of hip fracture in comparison to general population. Although there was some suggestion of effect modification by age or sex, AD was consistently associated with doubling of the risk of incident hip fracture.     

Structural MRI in Frontotemporal Dementia: Comparisons between Hippocampal Volumetry,Tensor-Based Morphometry and Voxel-Based Morphometry

Background

MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods.

Objective

To compare FTD with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy.

Methods

Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups.

Results

We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55).

Conclusion

Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.     

<Emphasis Type="Italic">Cortinarius</Emphasis> sect. <Emphasis Type="Italic">Riederi</Emphasis>: taxonomy and phylogeny of the new section with European and North American distribution

Cortinarius is one of the most species-rich genera of mushroom-forming fungi. Based on phylogenetic and morphological evidence, Cortinarius, sect. Riederi, is introduced at sectional level (= subsect. Riederi sensu Brandrud & Melot). The taxonomy, phylogeny, ecology and distribution of not only mainly European but also including some North American taxa of this section are treated, which includes nine species and two varieties. Of these, three taxa are described as new (C. burlinghamiae, C. pallidoriederi and C. argenteolilacinus var. dovrensis). The sect. Riederi species possess morphological features similar to Phlegmacium group(s) and forms a phylogenetically isolated lineage, with no supported affinity to other phlegmacioid groups. Three taxa are known from both Europe and North America, two species are known only from North America and five only from Europe. Altogether, eight of the ten taxa are associated with conifers or northern (boreal-subalpine) deciduous trees (Betula spp.). Only two species occur in more temperate forests (Fagus forests), and no species have so far been found in thermophilous Quercus forests     

HEMOPOIETIC STEM CELL PROLIFERATION AND MIGRATION FOLLOWING BORDETELLA PERTUSSIS VACCINE

The ability of a single injection of killed, intact bacteria to effect an increase in the proliferative rate of hemopoietic stem cells was studied. The total numbers of colony forming units in bone marrow, spleen and peripheral blood as well as the proportion of CFU in cycle was assessed. Splenic CFU were observed to rise exponentially due initially to in situ proliferation and later to proliferation in bone marrow with migration via the blood to the spleen. The results are discussed in the light of current concepts of stem cell regulation.     

Haematological cell proliferation and differentiation responses to perturbations of polyamine biosynthesis

Combined administration of methylglyoxal-bis-guanylhydrazone (MGBG) (25 mg/kg) with difluoromethylornithine (DFMO), or MGBG alone at a higher dose (50 mg/kg), to mice resulted in a decreased white cell count (WBC) in the peripheral blood while DFMO or MGBG alone at a lower dose (25 mg/kg) had no effect. As expected, DFMO alone increased the number of colony forming units spleen (CFU-s), colony forming units diffusion chamber granulocyte (CFU-dg) and colony forming units culture (CFU-c) in the bone marrow. MGBG treatment led to an increase in CFU-dg alone. Combined treatment seemingly had no effect on marrow stem cells. Total tibial and differential counts were not affected by any of the treatments. Cell proliferation in diffusion chamber cultures, as judged by CFU-dg colony formation, was impaired by MGBG alone or in combination with DFMO, at dose levels which had no effect or increased the precursor cell number in the bone marrow. This effect was partially reversed with either putrescine or spermidine. Determination of intracellular polyamine concentrations, demonstrated decreased putrescine and spermidine levels after DFMO administration. As expected, MGBG treatment resulted in decreased spermidine and spermine levels, concomitant with an increase in putrescine. In mice which received both agents, rather than only MGBG, after 3 days higher intracellular polyamine concentrations were observed. After 11 days, however, there was no significant difference between the two groups.     

Gender influence on vasoactive hormones at rest and during a 70 degrees head-up tilt in healthy humans.

To evaluate the influence of age and gender on the neuroendocrine control of blood pressure in normal subjects, a 13-min 70 degrees head-up tilt (HUT) was applied after 3 h of recumbency to 109 healthy men and women aged 23-50 yr (age group I) and 51-77 yr (age group II). We found that age and gender had a significant influence on plasma norepinephrine (PNE) concentration at baseline and in the upright position. PNE was significantly higher in older men compared with the younger men and women of both age groups, suggesting a divergent age-related activation of the sympathetic nervous system between genders at baseline as well as during a sustained orthostatic challenge. There was no significant influence of age or gender on plasma epinephrine at baseline or during HUT. Plasma renin activity was significantly higher at baseline as well as in the upright position during HUT in elderly men than in women. Age or gender had no influence on plasma vasopressin (PAVP), and, regardless of age, nonhypotensive HUT induced an extremely modest increase in PAVP. The syncopal subjects displayed a hormonal pattern associating increased PNE and a surge in plasma epinephrine and PAVP minutes before syncope during HUT. The orthostatic intolerance appears not to be a feature of healthy aging per se. In healthy subjects, both age and gender modulate markedly the cardiovascular and neuroendocrine responses to an orthostatic challenge and must be taken into consideration, particularly when catecholamine responses are studied.     

Blood glutathione homeostasis as a determinant of resting and exercise-induced oxidative stress in young men

Although the importance of glutathione in protection against oxidative stress is well recognized, the role of physiological levels of glutathione and other endogenous antioxidants in protecting against exercise-induced oxidative stress is less clear. We evaluated the role of glutathione and selected antioxidant enzymes as determinants of lipid peroxidation at rest and in response to exercise in men (n = 13-14) aged 20-30 years, who cycled for 40 min at 60% of their maximal oxygen consumption (VO2max). Levels of plasma thiobarbituric acid reactive substances (plasma TBARS) and blood oxidised glutathione (GSSG) increased by about 50% in response to exercise. Mean blood reduced glutathione (GSH) decreased by 13% with exercise. Of the measured red blood cell (RBC) antioxidant enzyme activities, only selenium-dependent glutathione peroxidase (Se-GPX) activity rose following exercise. In univariate regression analysis, plasma TBARS levels at rest predicted postexercise plasma TBARS and the exercise-induced change in total glutathione (TGSH). Blood GSSG levels at rest were strongly determinant of postexercise levels. Multiple regression analysis showed blood GSH to be a determinant of plasma TBARS at rest. The relative changes in TGSH were determinant of postexercise plasma TBARS. In summary, higher blood GSH and lower plasma TBARS at rest were associated with lower resting, and exercise-induced, lipid peroxidation. Subjects with a favourable blood glutathione redox status at rest maintained a more favourable redox status in response to exercise-induced oxidative stress. Changes in blood GSH and TGSH in response to exercise were closely associated with both resting and exercise-induced plasma lipid peroxidation. These results underscore the critical role of glutathione homeostasis in modulating exercise-induced oxidative stress and, conversely, the effect of oxidative stress at rest on exercise-induced changes in glutathione redox status.