Effects of S-phase-specific agents on granulocyte-macrophage and erythroid progenitor cells obtained from normal individuals and from patients with chronic myelogenous leukemia

The effects of three S-phase-specific agents, [3H]thymidine, hydroxyurea, and 1-beta-D-arabinofuranosylcytosine, on granulocyte-macrophage colony-forming units (CFU-C) and erythroid progenitor cells (erythroid burst-forming units) (BFU-E) from the bone marrow or peripheral blood obtained from 23 normal individuals and 12 patients with chronic myelogenous leukemia were investigated. CFU-C, regardless of their source, showed comparable degrees of sensitivity to each of the S-phase-specific agents, with perhaps a slightly greater level of sensitivity to [3H]thymidine. In contrast, the sensitivities of chronic myelogenous leukemia and normal marrow BFU-E to the 3 agents were quite different, with essentially all BFU-E being killed by [3H]thymidine, 50 to 70% being killed by 1-beta-D-arabinofuranosylcytosine, and only 15 to 20% being killed by hydroxyurea. BFU-E present in normal peripheral blood were insensitive to [3H]thymidine or hydroxyurea but were sensitive to 1-beta-D-arabinofuranosylcytosine. These studies demonstrated similarities between the CFU-C and BFU-E of CML patients and the CFU-C and BFU-E present in normal bone marrow. On the other hand, the sensitivities of normal peripheral blood progenitor cells to "S-phase-specific" agents differed from that of CML progenitor cells or the progenitor cells present in normal bone marrow. Additionally, these studies have demonstrated the limitations inherent in suicide techniques as methods for estimating the cell cycle characteristics of clonogenic cells.     

Untersuchung zur Kategorisierung des mandibulären Wachstumspotentials von Petrovic,Lavergne und Stutzmann

Zusammenassung In der vorliegenden Studie sollte untersucht werden, ob die vonPetrovic, Lavergne undStutzmann vorgeschlagene Kategorisierung des mandibulären Wachstumspotentials für die Behandlung mit dem Funktionsregler Geltung hat. Dazu wurden die Fernröntgenaufnahmen von 140 Patienten der Angle-Klasse II nach zirka zweijähriger Behandlung mit Funktionsreglern analysiert. Im Vergleich zu 133 unbehandelten Kindern mit Angle-Klasse II trat in fast allen Rotationsgruppen eine signifikant größere Zunahme der Unterkiefergesamtlänge ein. Zwischen der Kategorie 2 mit niedrigem Wachstumpotential und Kategorie 5 mit hohem Wachstumspotential wurden keine signifikant unterschiedlichen Zunahmen der Unterkieferlänge festgestellt.

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Summary The results of the study show whether the classification of mandibular growth potential, as proposed by Petrovic, Lavergne and Stutzmann has any influence on the treatment with a function regulator. X-rays of 140 class II patients were analysed after a treatment time of approximately 2 years. In comparison with 133 class II children without any treatment, a significant increase of the overall mandibular length was observed in almost all children treated. There was no significant difference in the increase of mandibular length between category 2 (low growth potential) and category 5 (high growth potential).

     

Inducible nitric oxide synthase expression elicited in the mouse brain by inflammatory mediators circulating in the cerebrospinal fluid

Expression of inducible nitric oxide synthase (iNOS) protein was studied in the brain after intracerebroventricular injections of interferon (IFN)-gamma, and IFN-gamma combined with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha, compared to ovalbumin as control. Wild-type mice and mice with targeted deletion of the IFN-gamma receptor gene were used. Findings based on iNOS immunoreactivity were evaluated at 1, 2, 4 and 7 days post-injection, using also quantitative image analysis and double labeling with glial cell markers. IFN-gamma administration induced iNOS immmunostaining in activated microglia and macrophages in the parenchyma surrounding the ventricular system, several cortical fields and fiber tracts. IFN-gamma-elicited iNOS immunoreactivity was down-regulated after 1 day. The number of iNOS-immunopositive cells was significantly enhanced by co-administration of LPS or TNF-alpha; IFN-gamma+TNF-alpha injections also resulted in longer persistence of iNOS immunoreactivity. No immunopositive cells were seen in the brain of IFN-gamma receptor knockout mice after IFN-gamma administration; very few immunostained macrophages were detected in these cases, mostly around the injection needle track, after co-administration of LPS or TNF-alpha. Western blot analysis confirmed a marked iNOS induction in the brain of wild-type mice 24 h after IFN-gamma+LPS injections. The findings show that inflammatory mediators circulating in the cerebrospinal fluid induce in vivo iNOS in the brain with topographical selectivity and temporal regulation. The data also demonstrate that the signaling cascade activated by IFN-gamma binding to its receptor is critical for iNOS induction, and the synergistic action of LPS and TNF-alpha as iNOS inducers in brain cells is largely mediated by the receptor-regulated action of IFN-gamma.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

Identifying normosmics: a comparison of two populations

An olfactory function test developed by the Connecticut Chemosensory Clinical Research Center (CCCRC) was administered to 65 normal subjects to determine its ability to identify normosmic subjects. The CCCRC test categorizes individuals into five distinct levels of olfactory functioning according to composite score ranges derived from odor identification and butanol threshold subtests. These categories are: normosmic (normal); mildly, moderately, and severely hyposmic (impaired functioning); and anosmic (no sensation). Comparing score distributions from CCCRC with ours revealed that a greater percentage of our subjects were categorized as hyposmic because of higher butanol thresholds. The butanol threshold subtest was studied further to determine test-retest reliability and normal day-to-day variability in scores. Norms are the basis for interpreting test scores and are important in diagnosing and treating smell disorders.     

Ueber das Auftreten kernhaltiger rother Blutkörperchen im circulirenden Blute

Ohne Zusammenfassung     

The Influence of Early Life Nutrition on Epigenetic Regulatory Mechanisms of the Immune System

The immune system is exquisitely sensitive to environmental changes. Diet constitutes one of the major environmental factors that exerts a profound effect on immune system development and function. Epigenetics is the study of mitotically heritable, yet potentially reversible, molecular modifications to DNA and chromatin without alteration to the underlying DNA sequence. Nutriepigenomics is an emerging discipline examining the role of dietary influences on gene expression. There is increasing evidence that the epigenetic mechanisms that regulate gene expression during immune differentiation are directly affected by dietary factors or indirectly through modifications in gut microbiota induced by different dietary habits. Short-chain fatty acids, in particular butyrate, produced by selected bacteria stains within gut microbiota, are crucial players in this network.     

Executive functions in intellectual disabilities: A comparison between Williams syndrome and Down syndrome

Executive functions are a set of high cognitive abilities that control and regulate other functions and behaviors and are crucial for successful adaptation. Deficits in executive functions are frequently described in developmental disorders, which are characterized by disadaptive behavior. However, executive functions are not widely examined in individuals with intellectual disability. The present study is aimed at evaluating the etiological specificity hypotheses pertaining to executive functions by comparing individuals with intellectual disability of different etiology, as Williams syndrome and Down syndrome, on different aspects of executive functions. To this aim a battery evaluating attention, short-term and working memory, planning, categorization, shifting and inhibition, was administered to 15 children, adolescents and adults with Williams syndrome, to 15 children, adolescents and adults with Down syndrome and to 16 mental-age-matched typically developing children. The two groups with intellectual disability showed impairment in a set of executive functions, as auditory sustained attention, visual selective attention, visual categorization and working memory, and preserved visual sustained attention, auditory selective attention and visual inhibition. However, a distinctive profile has been found between the two syndromic groups on other executive functions. While participants with Down syndrome were poor in shifting and verbal aspects of memory and inhibition, those with Williams syndrome were poor in planning. The specific weakness and straights on executive functions may support the etiological specificity hypothesis accounting for distinctive cognitive development syndrome-specific.