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PubMed2003

Regulation of multiple tumor microenvironment markers by overexpression of single or paired combinations of ErbB receptors.

The progression of primary tumors to an invasive phenotype requires dynamic changes in multiple cellular and local tumor microenvironment markers. In this study, we report a genomic approach to assess gene transcriptional changes upon overexpression of ErbB receptors, in vitro and in vivo, focusing on markers involved in the regulation of the tumor microenvironment. ErbB receptors (ErbB-1/epidermal growth factor receptor, ErbB-2, ErbB-3, and ErbB-4) were stably overexpressed in a polyclonal cell population as single or paired combinations using murine and human breast cell models. The overall numbers of known genes that are up- or down-regulated was significantly higher in cells and tumors overexpressing paired combinations of receptors compared with cells and tumors overexpressing single ErbB receptors. Genes encoding components of cell-cell structures, extracellular matrix, coagulation factors, and angiogenesis were predominantly affected by the most active ErbB receptor combinations and were predictive of the aggressive in vivo tumorigenicity, a feature that was not always seen in vitro. Among ErbB-regulated tumor microenvironment markers detected by the genomic analysis, thrombospondin 1, an endogenous inhibitor of angiogenesis, was additionally validated in relation to tumor growth phenotype. Thrombospondin 1 mRNA and protein were down-regulated by specific ErbB receptors, in vitro and in both rodent and human ErbB-induced tumors, consistent with the extent of tumor growth and tumor vascularization associated with specific ErbB receptors. In summary, our genomic results highlight the broad diversity of ErbB-regulated cancer-associated genes and revealed several novel targets that may have potential therapeutic applications for targeting tumor progression involving aberrations of ErbB receptors.

3T3 Cells↗
PubMed2003

Segregation and coactivation of developing neocortical layer 1 neurons.

Layer 1 in the developing cerebral cortex is populated by two basic neuronal cell types, Cajal-Retzius (CR) cells and non-CR cells. We generated transgenic mice in which green fluorescent protein (GFP) was driven by the promoter of metabotropic glutamate receptor subtype 2 and expressed specifically in CR cells during cortical development. On the basis of the precise identification of CR cells with GFP fluorescence, we pursued developmental changes and synaptic mechanisms of both CR and non-CR cells during the postnatal period. Immunostaining in combination with GFP fluorescence imaging showed that GFP and reelin, a protein involved in corticogenesis, completely overlap in CR cells at postnatal day 0. At the subsequent postnatal stage, reelin-positive neurons are segregated and categorized into GFP-positive/GABA-negative CR cells and GFP-negative/GABA-positive non-CR cells. Individual and simultaneous whole-cell recordings of CR and non-CR cells in developing cerebral slices revealed that spontaneous and electrically evoked postsynaptic currents (sPSCs and ePSCs) measured in CR and non-CR cells are differentially mediated by GABA(A) receptors versus GABA(A), AMPA, and NMDA receptors, respectively. Furthermore, CR and non-CR cells show synchronized repetitive barrages of sPSCs that reflect a network-driven activity in the developing cerebral cortex. These findings imply that the layer 1 neurons dynamically change and play a distinct and integral role in the postnatal developing neocortex.

Animals↗
PubMed2004

[Maximum likelihood analysis for mapping dynamic trait QTL in outbred population. I . Methodology].

The quantitative traits whose phenotypic values change with time in life or other quantitative factors, were defined as dynamic traits. Based on the idea about random regression test-day model for estimating breeding values in animal evaluation, a mathematic model was constructed for mapping dynamic trait loci by using Legendre polynomials to model dynamic changes of each genetic effect. The Maximum likelihood analysis implemented via EM algorithm was used to estimate the parameters, including QTL position, fixed genetic regression effects for dynamic trait QTL mapping in outbred population. Compared with the existing method for dynamic trait mapping QTL, the new method presented here not only allowed to sample dynamic trait in disequillibrium way, but also can achieve to map dynamic traits QTL in any resource population by just one step. The further study on dynamic trait mapping QTL was theoretically discussed by incorporating genetic analysis of dynamic trait into general mapping QTL.

Likelihood Functions↗
PubMed1992

Role of the health professional in ending the tobacco pandemic: clinic, classroom, and community.

Physicians and other health professionals have become complacent about the tobacco pandemic, because there is a mistaken belief that the war on smoking has been won. In reality, the survival from lung cancer is little better than it was 30 years ago, and cigarettes have become the most advertised and promoted product in society. The prevalence of overall smoking in the United States has declined by only 0.5%/y during the past decade. Among certain US minority populations, the decline has been far less or nonexistent. Traditional efforts to control the tobacco pandemic have been reactive and static, whereby government agencies, schools, and health professionals provide the public with generic information about the adverse health effects of smoking. As a result of these efforts, it is assumed that individuals will act to change their behavior. In contrast, the tobacco industry is proactive and dynamic, changing its brand-name strategies through advertising and promotion. To more effectively combat tobacco use, health officials need to move beyond patient education and adopt a more active model that includes clinic-based, school-based, and community-based tobacco-control strategies. Use of humorous, satirical images as part of paid counteradvertising campaigns and proactive health education curricula should be part of a concerted effort to end the tobacco pandemic and limit the promotional influence of tobacco companies.

Consumer Advocacy↗
PubMed2005

Dynamic changes in environment condition and microbial community structure in trench and flat seabed sediments of Tokyo Bay, Japan.

Dynamic changes in the chemical environment in the bottom of overlying water and microbial community structure in trench and flat seabed sediments were evaluated during summer and autumn in Tokyo Bay, Japan, to elucidate the response of microbial community changes as a consequence of dredging activity. Quinone profile analysis was performed to evaluate the changes in microbial community structure in the sediments. Bottom shape and location of each station affected the chemical environment of the overlying water. The trench bottom shape had longer anoxic conditions than the flat bottom shape. Nitrogen and phosphorus concentrations affected the microbial density in the sediment. During anoxic conditions, the ubiquinone/menaquinone ratio (UQ/MK) was less than unity and increased with rising dissolved oxygen (DO) concentrations. The dominant quinone species in the trench and flat seabed sediments were MK with 6 and 7 isoprene units (MK-6 and MK-7) and UQ with 8 and 9 isoprene units (UQ-8 and UQ-9). MK-6 and UQ-8 containing bacteria might have a great influence on the sulfur cycle of the aquatic ecosystem. While, MK-7 and UQ-9 containing bacteria correlated with the deposition of phototropic bacteria cells onto the seabed sediment. The trench bottom shape contained higher concentrations of MK-6, MK-7, UQ-8 and UQ-9, especially during summer.

Bacteria↗
PubMed1991

[Various results of the study of medico-biological aspects of alcoholism in Siberia and Far East].

To study the dynamic changes in alcohol abuse, a new methodological approach has been developed which implies staged realization. Stage one was aimed at the search for integral clinical-dynamic characteristics as well as social and psychological properties to make identification of the clinical phenotype reliable. Stage II--at introduction of integral constitution-morphology indicators representative of the disease predisposition-stability. The analysis of medicosocial characteristics for the last 8 years has been performed at Stage III. Calcium homeostasis and related hormones and enzymes were evaluated at Stage IV. The data obtained permitted identification of a complex of structural manifestations underlying alcohol embryopathy of the brain.

Alcoholism↗
PubMed2006

[Land use and land cover changes and driving forces in the upper reach of Minjiang River].

The upper reach of Minjiang River is the representative of mountainous area in Southwest China in the aspects of natural environment, ecosystem structure, economic development, and social culture. The characteristics of the dynamic changes of its land use and land cover stood for the common questions occurred in the land resources and usage of this area. Woodland and grassland are the main types of land use and land cover, and many changes in land use/cover types happened from 1974 to 2000. Among forestland, shrub land, economic forestland, grassland, cropland and resident land,changes mainly happened between woodland and grassland, and all occurred bilaterally. The area of forestland changed mostly and kept decreasing from 1974 to 2000, while that of other land types increased. The changes of land use and land cover happened between 1974 and 1986 were larger than those happened between 1986 and 2000. Population and economy were the main driving factors for the changes of land use and land cover in the upper reach of Minjiang River. Since the programs of Natural Forest Protection and Withdrawing Cropland to Woodland and Grassland carried into execution, the land use and land cover have changed rationally.

China↗
PubMed1990

[Myosin ATPase activity in somatic muscle fibers in different degree of pH of the pre-incubation medium].

The problem on presence of muscle fibers (MF) types is an actual one, since it is a prerequisite to forecasting certain changes in MF under different conditions. The aim of the investigation has been to find out whether independent groups of MF exist or whether they react as a whole population to gradual changes in pH of the preincubational medium, when dynamic changes in m-ATPhase activity are studied. In serial transversal cryostate slices 10 mcm thick m-ATPhase activity has been defined in MF at preincubation of the slices in media having various pH. The experiment has had three series. In the I--the ventral denticulate muscle with universal biomechanical properties has been investigated; preincubation has been carried out in media having pH from 3.0 up to 11.0 with the intervals 0.5 pH. In the II--besides the muscle mentioned the fast brachial muscle and the force triceps muscle have been studied; preincubation has been performed only at pH 9.5, since in the I series two dissociated groups of MF have been distinguished. In the III series, at studying the same three muscles m-ATPhase activity has been detailed with their preincubation at pH from 3.8 up to 4.5 with the interval 0.1. The m-ATPase activity begins to manifest in various MF at pH of the preincubational medium within the limits of 3.8-4.2. A gradual increase in amount of MF that are revealing, as pH is gradually increasing, evidences most likely against independence of separate groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. III. Morphometric assessment of the dynamic changes in post-capillary venules as regulatory elements of lymphocyte recirculation in tumor-draining lymph nodes.

To evaluate the dynamics of lymphocyte recirculation in tumor-bearing mice, the post-capillary venules (PCV) were subjected to quantitative measurements in the regional (RLN) and nonregional (NRLN) lymph nodes during the progression of P815X2 mastocytoma in syngeneic DBA/2 mice. Mice were sacrificed at two-day intervals, and RLNs and NRLNs were analysed for their content of B- and T-lymphocytes and their subsets, demonstrated by immunoperoxidase technique using monoclonal antibodies; Anti-Thy 1.2 (T cells), Anti-Lyt 1 (T-helper cells), Anti-Lyt 2 (T-suppressor cells), and Anti-I-Ad (B cell) antigens, separately in the B- and T-cell compartments. In the PCVs, migration index (MI) and endothelial height (Hend) were measured. There was a biphasic elevation of MI in the RLNs, as compared with only a late rise in the NRLNs, reaching the peak (1.54) on day 14. In RLNs, there was a sharp reduction in Hend starting from the values (6.37 microns) on day 2, down to 4.79 microns on day 8. This is followed by rapid elevation close to the second-day values, e.g. 6.07 on day 10. The changes in MI paralleled the early influx of B cells, as evidenced by the decrease of Thy 1.2+/I-Ad+ cell ratio and a late recruitment of T cells as indicated by the elevation of that ratio as well as the Hend values in both the RLNs and NRLNs. The present experiment shows that morphology of PCVs in the RLNs and in NRLNs of P815X2-bearing mice is subjected to alterations reflecting the dynamics of lymphocyte recruitment into these organs. When combined with lymphocyte subset enumeration using monoclonal antibodies, the quantitative analysis of the PCVs permits predictions to be made on the recirculatory activity of these cell populations during the tumor progression.

Animals↗
PubMed1996

Persistence of dominant T cell clones in synovial tissues during rheumatoid arthritis.

In a previous study, we showed that the T cell repertoire is biased in the synovial membrane (SM) compared with peripheral blood during rheumatoid arthritis (RA). The same bias was observed in different joints from the same patient and seems to be the same over time. To discover whether this bias was due to expansion of a clonal subset resulting from activation by conventional Ag(s) or to polygonal stimulation by superantigen(s), we sequenced more than 650 TCRBV-D-J junctional regions from freshly isolated SM and peripheral blood of two DR4-RA patients. From each patient, two SM were obtained on the same day, and a third was obtained later. Several dominant clones were found in SM but not in peripheral blood. Some of them were found only at the first time point in anatomically different SM, the majority persisted over time, and others were detected only at the second time point. Analysis of the complementarity-determining region 3 (CDR3) showed a bias in TCRBD and amino acid usage. Valine, encoded by randomly inserted N nucleotides, was used by 45% of dominant clones compared with 18% in the control population (p less than 0.001). In addition, GXXG and TSG motifs were frequently observed in the CDR3 of these dominant clones. These data indicate a dynamic TCR selection process during the perpetuation phase of RA. The dynamic changes of dominant clones also suggest a determinant spreading mechanism during RA.

Amino Acid Sequence↗
PubMed1996

Seasonal population dynamics of Halipegus occidualis and Halipegus eccentricus (Digenea:Hemiuridae) in their amphibian host, Rana clamitans.

The seasonal population dynamics of Halipegus occidualis and Halipegus eccentricus (Hemiuridae) in their amphibian host, the green frog (Rana clamitans), were examined for 3 yr (weekly, April through October). Frogs were caught, marked, and examined for H. occidualis and H. eccentricus, both of which occur as immatures and adults in the buccal cavity. Frogs were then released and allowed to continue natural recruitment and loss of the parasites. It was thus possible to monitor individual infrapopulations over successive time periods. One-hundred and forty-nine frogs were caught and released, with a total of 328 observations. Overall, the levels of both parasites among male and female frogs were similar, as were levels of infection among adult and juvenile hosts. There was, however, no correlation between the total number of H. occidualis and the body size (snout-vent length) of R. clamitans. In contrast, there was a significant correlation between the total number of H. eccentricus and frog size. Recruitment of both species began in May, peaked in June/July, and ended in July (H. eccentricus) or August (H. occidualis). In general, both the prevalence and relative density of H. occidualis was greater than that of H. eccentricus and may be related to space constraints in the buccal cavity of R. clamitans. Adults of both species were observed from April through October. Following increases in parasite recruitment, infrapopulation sizes declined in September 1992 and in August of 1993 and 1994. Examination of variance to mean ratios indicated that both species were overdispersed in the frogs. Large declines in the variance to mean ratios for H. occidualis after periods of greatest recruitment are most likely associated with the loss of larger infrapopulations, suggesting that there may be density-dependent regulation of infrapopulation size. By monitoring individual hosts using the mark-release-recapture protocol, dynamic changes in parasite infrapopulations were observed, e.g., there were losses of immature worms and rapid changes in infrapopulation sizes, observations that would not be made with typical host-parasite systems.

Animals↗
PubMed1997

Stimulation-dependent redistribution of charge movement between unavailable and available states.

A previous study (Stroffekova and Heiny 1997) demonstrated that changes in resting, intracellular free Ca2+ can modulate the amount of charge which is available to move upon depolarization and do excitation-contraction-coupling (E-C coupling). Charge movement reflects voltage-driven conformational changes of the dihydropyridine receptor which couple membrane excitation to Ca2+ release from the sarcoplasmic reticulum (SR) and contractile activation (c.f. review: Melzer et al. 1995). The present study demonstrates that dynamic changes in free Ca2+ that occur in the triadic gap during SR Ca2+ release can likewise produce a stimulation-dependent increase in the amount of available charge. Thus this modulation occurs in the physiological range of Ca2+ changes that occur in the triad during normal muscle activity. The modulation of charge movement by intracellular Ca2+ was rapid and maintained; it occurred within 2-3 suprathreshold depolarizations and remained for 5-10 minutes. It could be prevented by intracellular BAPTA and by depleting the SR of Ca2+, but not by EGTA or agents known to alter ion channel phosphorylation. These results are explained by a model in which a Ca2+ binding site on or near the voltage-sensor is normally populated by Ca2+ ions released into the triadic junction during activity and modulates the distribution of voltage sensors between available and unavailable states.

Animals↗