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Abnormal antithrombin III with defective serine protease binding (antithrombin III "Denver").

A hereditary (three family members) deficiency of antithrombin III (AT-III) in which AT-III antigen (AT-III ag) is normal in spite of low heparin cofactor and antithrombin activity is described. Plasma levels were: AT-III ag, 0.92-0.96 U/ml; AT-III heparin cofactor activity, 0.54-0.62 U/ml; progressive antithrombin activity index, 0.13-0.18; anti-Xa activity, 0.50-0.56 U/ml. Plasma crossed immunoelectrophoresis (CIE) patterns performed with and without added heparin were normal, but serum CIE revealed a decreased complex peak. Purification of the patient's plasma AT-III by heparin-sepharose affinity chromatography showed a normal protein recovery and elution profile, but the purified AT-III fraction showed only 50% of the normal progressive thrombin neutralization and anti-Xa activity. When thrombin-antithrombin (TAT) complexes were formed by incubating with excess thrombin, SDS-polyacrylamide gel electrophoresis (PAGE) analysis revealed that half the patient AT-III formed TAT complexes while the remainder migrated as free AT-III. All the control AT-III formed TAT complexes. The patient's nonreacting AT-III (AT-III "Denver"), isolated by affinity chromatography, showed CIE and SDS-PAGE migration patterns characteristic of normal AT-III but failed to bind thrombin or Xa. Calculations from turnover studies in one patient and normal subjects with autologous 131I-AT-III suggested that AT-III "Denver" is removed from the plasma slightly more rapidly than normal. These studies indicate that the patients' variant AT-III molecule was characterized by normal heparin interaction but defective binding and inhibition of thrombin and Xa. These characteristics allow isolation of the nonreactive variant molecule by heparin-sepharose affinity chromatography.

Antithrombin III↗

Autocrine motility factor and the extracellular matrix. II. Degradation or remodeling of substratum components directs the motile response of tumor cells.

Autocrine motility factor is a tumor-secreted cytokine which regulates cellular growth and motility by a receptor-mediated pathway. In the accompanying report (Part I of II), it was demonstrated that high (K1735-M1) and low (K1735-C1.11) metastatic murine melanoma cells display distinct adhesion and spreading characteristics which correlate with their differential spontaneous and stimulated migrations on the extracellular matrix components fibronectin, laminin and collagen IV. These parameters were further related to discrete profiles of focal adhesion plaque integrity and reorganization. Here we describe unique migration patterns observed in these murine melanoma cells which reflect differences in degradation and/or remodeling of the cellular substratum. These profiles of matrix interaction were influenced distinctly by autocrine motility factor and dictated by both substrate composition and cellular phenotype. Since activation of the autocrine motility factor receptor stimulates invasion of a reconstituted basement membrane and enhances experimental metastasis by high- but not low-metastatic K1735 cells, differences in the invasive phenotypes of these cells may be due in part to their differential responses to external stimuli coupled with internal propensities toward either matrix degradation and migration (high-metastatic cells) or matrix remodeling and stasis (low-metastatic cells).

Animals↗

Habitat fragmentation causes bottlenecks and inbreeding in the European tree frog (Hyla arborea).

A genetic study of the European tree frog, Hyla arborea, in Denmark was undertaken to examine the population structure on mainland Jutland and the island of Lolland after a period of reduction in suitable habitat and population sizes. The two regions have experienced the same rate of habitat loss but fragmentation has been more severe on Lolland. Genetic variation based on 12 polymorphic DNA microsatellites was analysed in 494 tree frogs sampled from two ponds in Jutland and 10 ponds on Lolland. A significant overall deviation from Hardy-Weinberg expectations could be attributed to three ponds, all on Lolland. This was most probably caused by an inbreeding effect reducing fitness, which was supported by the observed significant negative correlation between larva survival and mean F(IS) value and mean individual inbreeding coefficient. A significant reduction in genetic variation (bottleneck) was detected in most of the ponds on Lolland. Population-structure analysis suggested the existence of at least 11 genetically different populations, corresponding to most of the sampled population units. The results indicated that the populations were unique genetic units and could be used to illustrate the migration pattern between newly established ponds arisen either by natural colonization of tree frogs or by artificial introduction. A high degree of pond fidelity in the tree frogs was suggested. A severe fragmentation process reducing population size and fitness within some of the populations probably caused the significant reduction in genetic variation of tree frog populations on Lolland.

Animal Migration↗

Welfare payments and New Zealand migration: myth and reality.

"There has been much concern about the level of social welfare payments reputedly received by New Zealanders in Australia. Analysis of these payments shows that the recent renegotiation of the Australia and New Zealand Social Security Agreement will shift much of the financial burden to the New Zealand Government. Recent migration patterns show increasing shares of non-New Zealand-born persons and older persons amongst the New Zealand citizens arriving in Australia."

Age Factors↗

Analysis of aberrant neuronal migrations in the hereditary cerebellar vermis defect (CVD) rat using bromodeoxyuridine immunohistochemistry.

The hereditary cerebellar vermis defect rat (CVD) is a new neurological mutant characterized by cerebellar vermis defect and a dysplastic cerebellum, especially in the cerebello-pontine junctions. In this study, the cytokinetics of neuronal migrations in the CVD were analyzed using 5-bromo-2'-deoxyuridine (BrdU) as a labeling marker. From embryonic day 21, the CVD cerebellum was small in size with retarded foliation, but no significant differences were detected in the migration pattern of the BrdU-labeled cells between the unaffected controls and the CVD during the prenatal period. On postnatal day 0 (P0), heterotopic Purkinje cells, demonstrable by calbindin immunohistochemistry, were seen in the dorsal pons of the CVD. From P4, BrdU-positive external granule cells (EGCs), which were labeled by BrdU injection on P2, began to penetrate the pons. From P5, the EGCs aggregated around the blood vessels, leading to a disturbance of the cerebellar lamination both in the cerebello-pontine junctions and in the cerebellar hemispheres. Thereafter, the BrdU-labeled cells in the perivascularly aggregated EGCs migrated radially, and formed internal granular layers around the vessels, indicating an aberrant perivascular migration of the EGCs. These findings suggest that the EGC dislocation was preceded by an aberrant settlement of the Purkinje cells, and that the perivascularly aggregated EGCs resulted in cerebellar dysplasia in the CVD.

Aging↗

Maturing thymocytes in accelerated rejection of cardiac allografts in presensitized rats.

LBNF1 cardiac allografts are rejected within 36 hr in LEW rats sensitized with BN skin grafts 7 days earlier (acute rejection in unmodified hosts = 8 days). We have studied and compared the function and migration patterns of thymocytes one day after engraftment in sensitized recipients, unmodified hosts, and normal naive rats. Thymocytes from animals experiencing accelerated rejection were more mature and functionally active, as shown by a significant elevation in percentage of OX-44+ (CD37+) cells, increased alloreactivity to BN and WF antigens, and proliferative responses to Con A and exogenous IL-2. However, the cells could neither lyse BN targets in vitro nor trigger rejection of otherwise indefinitely functioning test cardiac allografts in immunologically unresponsive T cell-deficient (B) rats after adoptive transfer. The traffic of 111In-labeled thymocytes was then evaluated. The migration index increased significantly during accelerated graft rejection, with thymocytes preferentially circulating in the blood, penetrating peripheral lymph nodes--and, interestingly, migrating back to the thymus. Thus, immunoresponsive and functionally active thymocytes, which lack the ability to recognize primed specific antigen, appear during accelerated rejection of cardiac allografts in sensitized rats. These cells migrate to the periphery, and then return in large numbers to their site of origin, the thymus. Hence, this study describes a novel behavior of thymocytes in the state of host alloreactivity that is distinct from the physiological one in otherwise normal thymus.

Animals↗

Migration in an interregional macroeconometric model of the United States: will net outmigration from the Northeast continue?

"This paper reports on the specification, estimation and simulation of an interregional net migration model of the United States. The model makes use of time series data including, as explanatory variables, wage rates, unemployment rates, and population density. Simulation experiments are undertaken by joining the migration model with a multi-regional macroeconometric model to examine the effect [on] migration patterns of changes in national economic growth. In particular, the net outmigration trends in the Northeast are examined under alternative scenarios including faster national economic growth and a different energy pricing policy."

Americas↗

Migration along orthodromic sun compass routes by arctic birds.

Flight directions of birds migrating at high geographic and magnetic latitudes can be used to test bird orientation by celestial or geomagnetic compass systems under polar conditions. Migration patterns of arctic shorebirds, revealed by tracking radar studies during an icebreaker expedition along the Northwest Passage in 1999, support predicted sun compass trajectories but cannot be reconciled with orientation along either geographic or magnetic loxodromes (rhumb lines). Sun compass routes are similar to orthodromes (great circle routes) at high latitudes, showing changing geographic courses as the birds traverse longitudes and their internal clock gets out of phase with local time. These routes bring the shorebirds from high arctic Canada to the east coast of North America, from which they make transoceanic flights to South America. The observations are also consistent with a migration link between Siberia and the Beaufort Sea region by way of sun compass routes across the Arctic Ocean.

Animals↗

Different in situ distribution patterns of dendritic cells having Langerhans (T6+) and interdigitating (RFD1+) cell immunophenotype in psoriasis, atopic dermatitis, and other inflammatory dermatoses.

Dendritic cells bearing Langerhans cell (OKT6+) or interdigitating cell (RFD1+) immunophenotype may be regularly detected within the dermis of chronic skin diseases characterized by a lymphohistiocytic (lymphoreticular) infiltrate. These 2 subsets of antigen-presenting cells within the dermis of lesions of exacerbating chronic plaque psoriasis, exacerbating nummular dermatitis (discoid eczema), atopic dermatitis, allergic contact dermatitis, pityriasis rosea, lichen ruber planus, and cutaneous lupus erythematosus were quantified using computer-assisted morphometry. The mean dendrite length per dermal dendritic cell was significantly higher for RFD1 than for OKT6 (74.4 +/- 0.98 microns vs 70.0 +/- 1.26 microns: p = 0.0023). The mean dendrite length per dermal dendritic cell was remarkably constant for each marker in the various diagnostic categories studied. Disease-specific patterns of total dendrite length and number (expressed per 100 infiltrating mononuclear cells) of these 2 dendritic cell types within the subepidermal infiltrates were obtained. Pityriasis rosea was characterized by its unique high percentage of OKT6+ Langerhans cells. Atopic dermatitis and psoriasis had relatively high percentages of both RFD1+ interdigitating cells and OKT6+ Langerhans cells. Nummular dermatitis had an intermediate number and total dendrite length for OKT6, but was relatively low in RFD1+ cells. Allergic contact dermatitis, lichen planus, and lupus erythematosus had low numbers and dendrite lengths for both dendritic cell subsets. It is suggested that pityriasis rosea is characterized by an abnormal migration pattern of Langerhans cells. Psoriasis and atopic dermatitis may be examples of diseases in which skin-localized antigen-presenting and T-cell-inducing events are continuously taking place. The other diseases may reflect inflammatory processes in which local antigen presentation is less relevant to the tissue reaction.

Antigen-Presenting Cells↗

Urban and rural dimensions of global population aging: an overview.

In keeping with the worldwide pattern of increased urbanization, the elderly population has become more concentrated in urban areas during the past 50 years. In developed countries as a whole, an estimated 73 percent of people aged 65 or over lived in urban areas in 1990, a figure that is projected to reach 80 percent by the year 2015. In developing nations, which are still predominantly rural, just over one-third of people aged 65 or over lived in urban areas in 1990, projected to exceed one-half by 2015. This article provides an overview of global data on urban elders, examines extant data on gender balances and migration patterns, and considers the importance of subnational urban/rural differences and whether rural elderly are disadvantaged relative to their urban counterparts.

Aged↗

Diminished expression of microtubule-associated protein (MAP-2) and beta-tubulin as a putative marker for ischemic injury in neocortical transplants.

The present study examined the immunoexpression of the neuronal cytoskeletal proteins, MAP-2 and beta-tubulin within a timed series of rat fetal neocortical transplants. beta-tubulin is a major component of microtubules and MAP-2 regulates the assembly and stability of neuronal microtubules and is a major site for the phosphorylation cAMP dependent protein kinase in neurons. Both proteins are strongly expressed in the soma and dendrites of normal neurons. MAP-2 has been shown to be a sensitive marker for ischemia in neurons and is downregulated in this form of injury. Immunoexpression of both MAP-2 and beta-tubulin in grafted cortical neurons was markedly reduced when compared to age-matched or even perinatal specimens at all post-operative times. Dendritic staining was confined to random, thin processes with no laminar patterns and staining within somata was very weak. In some specimens, somatic expression was increased and dendrites were more robustly stained when a portion of the graft was juxtaposed to a fiber tract even though in other regions of the same graft there was very weak immunostaining. The present results corroborate previous studies of cortical transplants indicating an immature structure and metabolism, and it is suggested here that the primary factor is a sublethal form of ischemic injury. Another possibility for the relative paucity of cytoskeletal protein expression could be that transplanted neurons undergo a new developmental scheme (neodevelopment) that is brought about by truncated migration patterns and abnormal synaptic connections.

Animals↗

Molecular characterization of three rabbit rotavirus strains.

We report biochemical (RNA and protein patterns and gene-coding assignments) and serologic (serotype and subgroup) properties of three strains of rabbit rotaviruses--Ala C11 and R2. The RNA electropherotypes were a standard "short" pattern for R2, an unusual "short" pattern for Ala, and an unusual "long" pattern for C11. Serologic studies indicated that these viruses were all group A serotype 3 rotaviruses. In addition, the Ala and C11 viruses were found to possess subgroup I specificity, whereas the R2 virus possessed subgroup II specificity. In contrast to their distinctive RNA patterns, the polypeptide patterns of the rabbit viruses were similar to those of SA11. To identify cognate genes and determine gene-coding assignments for the rabbit rotaviruses, cDNA probes of individual SA11 genes were hybridized to rabbit rotaviral genomic RNA segments that had been separated by polyacrylamide gel electrophoresis and transferred to filters (Northern blots). The order of genome segments 7-11 for each of the rabbit rotaviruses was unique and differed from that of SA11 genes. These differences were possibly due to rearrangements of the RNA sequences within these individual genome segments. Sequence analysis of the individual RNA segments will confirm whether genome rearrangements are the molecular basis for these novel migration patterns.

Animals↗

Socio-demographic structure of Sydney's perimetropolitan region.

"The paper conceptualizes processes driving change in perimetropolitan regions then, using Sydney [Australia] as a case study, analyses population growth rates and internal migration patterns between 1981 and 1991. Next, a set of social and demographic variables derived from the 1986 Census is analysed to derive four key dimensions of socio-spatial structure, namely: disadvantage, rurality, socio-economic status and retirement."

Australia↗

Specific lymphocyte-endothelial cell interactions regulate migration into lymph nodes, Peyer's patches, and skin.

Lymphocyte migration is a critical component of a functional immune system. It increases the efficiency of the regional immune responses and disseminates locally induced effector cells to distant inflammatory sites. Central to the migratory process is the ability of lymphocytes to extravasate from the blood by selectively binding to segments of venules lined by high endothelium in lymph nodes and mucosal-associated lymphoid tissues. Recent studies have demonstrated that the specific recognition and adhesion of lymphocytes to high endothelial venules (HEV) is mediated by receptor/ligand systems that are different between lymph nodes (LN) and Peyer's patches (PP). The differential expression of lymphocyte surface receptors accounts for the preferential migration patterns of distinct lymphocyte subsets. More recently, the existence of specialized dermal endothelial cells in cutaneous tumors and inflamed skin that are capable of supporting lymphocyte adherence has been documented. This lymphocyte-endothelial cell interaction is an energy- and calcium-dependent process that involves surface glycoprotein and carbohydrates, requirements that are analogous to lymphocyte binding to HEV in LN and PP. Interestingly, antibodies directed against surface molecules mediating adhesion to HEV of LN and HEV of PP have no effect on lymphocyte binding to the dermal endothelium, suggesting that an additional receptor/ligand system promotes lymphocyte traffic into this site. Moreover, similar but additional receptor/ligand interactions may exist and may mediate lymphocyte migration into other sites. The identification and isolation of these receptor/ligand systems will provide important insights into both regional specialization of the normal immune response and pathophysiology of inflammatory diseases in diverse organs and tissues.

Animals↗

Kinetics of liver trapping of infective larvae in murine toxocariasis.

Mice sensitized by prior infection with Toxocara canis eggs trap many larvae of a challenge infection within the liver. In this study the distribution of challenge larvae in sensitized mice was examined to determine the earliest onset of liver trapping and to establish if the previously described phenomenon truly represented larval trapping. In all experiments, C57BL/6J mice were infected with a sensitization dose of 125 infective T. canis eggs on day 0 postinfection (PI) and challenged with 500 infective eggs on day 28 PI. In the initial experiments, larval numbers were determined within the intestinal contents, intestinal wall, mesenteric tissues, liver, lungs, skeletal muscle, and brain of each mouse on days 0.5, 1, 2, 3, 5, and 6 postchallenge (PC). Migration patterns were similar among the test and control groups except the peak of larval numbers in the liver, seen at 1 day PC in control mice, was delayed until 3 days PC in the test group. Larval trapping occurred within the liver of test mice at least by day 5 PC. In subsequent experiments, larval numbers were determined within the liver, skeletal muscle, brain of each mouse, and within the eyes of each mouse group at 4, 8, 12, and 16 wk PC. Larval numbers within the liver of test mice were similar both at 5 days PC and 16 wk PC, implying that larvae were trapped in this organ rather than delayed in their migration to other body sites. Liver trapping did not protect the eyes or brain of sensitized mice from larval migration, nor did it result in larval killing.

Animals↗

Retroviral transfer of antisense integrin alpha6 or alpha8 sequences results in laminar redistribution or clonal cell death in developing brain.

To assess the roles of two integrin alpha subunits (alpha6 and alpha8) in the developing chicken optic tectum, progenitors were infected with retroviral vectors that contained the marker gene lacZ plus antisense sequences from either the alpha6 or alpha8 integrin subunit cDNAs. On embryonic day 3 (E3), the vector was injected into tectal ventricles of chicken embryos. On E6, E7.5, E9, or later, chicken embryos were killed, and optic tecta were dissected and processed for histochemical detection of lacZ-positive cells. The antisense-bearing cell clones (descendants of a single infected progenitor) were analyzed for proliferation and migration patterns and were compared with lacZ-only vector-infected control clones. At E6, both alpha6 and alpha8 integrin antisense-containing cell clones were similar to controls. At E7.5, integrin alpha8 antisense-containing clones exhibited a cell number reduction in upper laminae (intermediate zone and tectal plate), and at E9, they exhibited a reduction in the ventricular zone as well. Integrin alpha6 antisense-containing cell clones exhibited no difference in total cell number at E9 but had a net laminar redistribution of more cells in the ventricular zone and less cells in the tectal plate. Our data show that different integrins play different roles during brain development: alpha6 integrin is essential for migration of tectal cells into specific laminae, and alpha8 integrin is essential for the survival of optic tectum cells. Also alpha8 integrin-substrate interactions may suppress early programmed cell death in premigratory and migratory neuroblasts.

Animals↗

Ectoderm cell--ECM interaction is essential for sea urchin embryo skeletogenesis.

Paracentrotus lividus sea urchin nectin (Pl-nectin) is an extracellular matrix (ECM) protein of the sea urchin embryo on the apical surface of the ectoderm and has been shown to be an adhesive substrate for embryonic cells. A monoclonal antibody (McAb) to Pl-nectin was generated that inhibits the adhesion of blastula cells to Pl-nectin-coated substrates in an in vitro functional assay. To examine for possible in vivo functions of Pl-nectin, Fab fragments (Fabs) of Pl-nectin McAb were added to early blastulae. Ingression of primary mesenchyme cells was not affected by Fabs. As control embryos reached the pluteus stage, treated embryos showed a severe inhibition of skeletal elongation and patterning. When the Fabs were injected directly into the blastocoel, even at higher concentration than was applied externally, skeletogenesis was normal. Therefore, the effect of the antibody on spiculogenesis was indirect. The treatment was partially reversible as embryos eventually seemed to recover and elongate spicules, although with an incorrect patterning. Migration of pigment cells was also affected by the Fabs, since they did not disperse throughout the ectoderm but remained clustered in ectopic areas. In contrast, the development of endoderm structures was not affected. Our results indicate that in the sea urchin embryo the appropriate contact of ectodermal cells with outer ECM components is essential for the correct morphogenesis of inner mesodermal structures.

Animals↗

European economic restructuring: demographic responses and feedbacks.

The relationship between economic restructuring in Europe and various aspects of demographic change, such as demographic aging and fertility decline, is examined. The focus is on changes in the labor market. "Changing employment conditions--the growth of the secondary labour market, the flexibilization of labour demand and increasingly also of supply, growing female labour force participation rates, generally high ethnic minority unemployment--reflect different aspects of the transition from the Fordist to the postFordist regime as well as changing demographic and life-style influences. Together they have deeply transformed the European landscape of employment and unemployment. The specific role of international migration is also analysed and it is seen to have fundamentally altered between the Fordist and postFordist eras. Less clear to interpret are changing internal migration patterns: has counterurbanization stopped in response to restructuring and integration and is a new postFordist population map unfolding? The paper concludes by evaluating the nature of the relationship between economic restructuring and population trends and identifying pointers for future research."

Birth Rate↗