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We present a patient with emphysema and a right-sided pneumothorax in whom a chest tube was inadvertently positioned in the lower portion of the right major fissure. The tube migrated across the midsaggital plane, resulting in left shoulder pain with elevation of the left hemidiaphragm. Malfunctioning of the tube did not result, and following its removal the diaphragm returned to its original position.
UNLABELLED: In complex emergencies, especially those involving famine and/or widespread food insecurity, assessments of malnutrition are critical to understanding the population's health status and to assessing the effectiveness of relief interventions. Although the Democratic People's Republic of Korea (DPRK) has benefited from some of the largest, most sustained appeals in the history of the World Food Program (WFP), the government in Pyongyang has placed restrictions on international efforts to gather data on the health and nutritional status of the affected population. QUESTION: Lacking direct means to assess the nutritional status of the North Korean populace, what other methodologies could be employed to measure the public health impacts of chronic food shortage? The paper begins with a review of methods for assessing nutritional status, particularly in emergencies; a brief history of the North Korean food crisis (1995-2001), and a review of the available nutritional and health data on the DPRK. The main focus of the paper is on the results of a survey of 2,692 North Korean adult migrants in China. Recognizing certain biases and limitations, the study suggests that sample households have experienced an overall decline in food security, as evidenced by both the decline in government rations from an average of 120 grams per person per day to less than 60 grams per day, and by the increase in the percentage of households relying on foraging or bartering of assets as their principal source of food. It also is apparent that the period 1995-1998 has been marked by elevated household mortality, declining fertility, and steadily rising out-migration. Taken together, the signs point toward famine, whether that is defined as a discrete event--that is, as a regional failure in food production or distribution leading to elevated mortality from starvation and associated disease--or as a more complex social process whose sub-states include not only elevated mortality, but declining fertility, eating of alternative 'famine foods', transfer of assets, and the uprooting and separation of families.
Hyperprolactinemia has been reported in some patients with active systemic lupus erythematosus (SLE). To determine if there was an association between selected autoantibodies and hyperprolactinemia, we assayed prolactin concentrations in sera from women submitted to a reference antinuclear antibody laboratory. Autoantibody-positive samples were separated into groups that contained antibodies to double-stranded DNA (anti-DNA), antibodies to SSA/Ro (anti-SSA/Ro), or antibodies to both SSA/Ro and SSB/La (anti-SSA/Ro-SSB/La). Results were compared with autoantibody-negative sera from age-matched women, submitted to the same laboratory. We also compared the study groups with a separate cohort of 84 healthy women who were not referred for autoantibody testing. Elevated prolactin levels were clustered in 20% of sera from anti-DNA-positive women < or = 50 years of age. Twenty-one percent of anti-SSA/Ro-SSB/La-positive women < 50 years of age were hyperprolactinemic. Four of the 15 hyperprolactinemic women identified in this survey had no known cause of elevated prolactin. In the other 11 individuals secondary causes such as hypothyroidism, pregnancy, chronic renal failure, and medications may have accounted for high serum prolactin values. We also examined sera by Western blot, to determine if immunoblot patterns were associated with elevated serum prolactin concentrations. The hyperprolactinemic sera yielded novel bands migrating at 70 kd, 32 kd, and 16.5 kd. This study confirmed the reported associations of hyperprolactinemia with SLE and Sjögren's syndrome. Multiple factors appeared to contribute to elevated serum prolactin levels in women with connective tissue diseases, and the presence of hyperprolactinemia was related to unique findings on immunoblot analysis.
Accruing evidence indicates that the levels of extracellular Mg2+ and Ca2+ can have a distinct impact on the adhesive and migratory activities of many cell types. The physiological relevance of these observations, however, has remained largely unexplored. In the present study, wound fluids collected throughout the early stages of cutaneous wound repair were examined for possible Mg2+ and Ca2+ fluctuations. Early in the process, when cell migration into the wound site is initiated, Mg2+ is elevated and Ca2+ is reduced (Mg2+:Ca2+ = 1). As wound healing progresses, wound fluid concentrations of Mg2+ and Ca2+ begin to return to normal plasma levels (Mg2+:Ca2+ = 0.4). When macrophages, keratinocytes, fibroblasts, and endothelial cells were exposed to dialyzed wound fluid, the migration stimulated by undialyzed wound fluid was lost. Addition back to dialyzed wound fluid of 24 h, postinjury concentrations of Mg2+ and Ca2+ restored all migratory stimulus. This observed migration is approximately twofold greater than when normal plasma Mg2+ and Ca2+ concentrations are present. Changes in the levels of Mg2+ and Ca2+ in wound fluid occur during the same period that inflammatory cells, keratinocytes, fibroblasts, and neovasculature have been shown to migrate during wound healing in vivo. Together, these data suggest that the impact of these changes on integrins and E-cadherin may play a direct role in the activation and maintenance of the migratory phenotypes of the cells involved in the wound healing process.
To investigate intracellular cAMP inhibitory mechanisms related to migration of guinea-pig peritoneal macrophages, we examined the effects of cAMP-elevating drugs on the Ca2+ efflux and actin polymerization in macrophages stimulated with fMet-Leu-Phe, a chemotactic peptide. The stimulation with 1 X 10(-8) M fMet-Leu-Phe enhanced the Ca2+ efflux, and induced actin polymerization. Dibutyryl cAMP, theophylline and papaverine, which continuously increased the levels of intracellular cAMP, inhibited the enhancement of Ca2+ efflux and induction of actin polymerization by fMet-Leu-Phe. On the other hand, isoproterenol, which transiently increased the cAMP level, inhibited only the early phase of Ca2+ efflux and not the actin polymerization. As additions of both cAMP and cAMP-dependent protein kinase did not modify the Ca2+ uptake of phagocytic vesicles, the inhibition of Ca2+ efflux by these drugs may be due to the inhibition of the Ca2+ release from the intracellular store site(s). The cAMP-elevating drugs increased the monomeric actin content without change in the total actin content, indicating an induction of the depolymerization of filamentous actin. From these findings, we conclude that the inhibition of macrophage migration induced by cAMP may be due to the inhibition of both the increase of intracellular Ca2+ concentration and actin polymerization. Furthermore, the intracellular levels of cAMP probably play a role in regulating actin states in the macrophages.
The specific aim of this study was to extend the analysis of retirement migration patterns to older Blacks. The 1980 Census public use sample A provided the data for this analysis. Because of their strong initial southern settlement and their labor force out-migration patterns in this century, many older Black migrants are "provincial return migrants" to the South, a migrant type that may decline among Blacks in the future. There is also a regional counterstream migration pattern among older Black migrants. Out-migrants in this stream from the South have elevated indicators of dependency. Suggestions are made for other related studies of Black retirement migration.
Cell migration is a dynamic process involving formation of a leading edge in the direction of migration and adhesion points from which tension is generated to move the cell body forward. At the same time, disassembly of adhesion points occurs at the back of the cell, a region known as the trailing edge. Syndecan-4 (S4) is a transmembrane proteoglycan thought to be involved in the formation of focal adhesions. Recent studies have shown that its cytoplasmic domain can engage in signal transduction, making S4 a bona fide receptor. Here, we show that ligand clustering of cell surface S4 on endothelial cells initiates a signaling cascade that results in activation of Rac1, induction of cell polarization, and stimulation of cell migration that depends on S4 interaction with its PDZ-binding partner. Expression of an S4 mutant lacking its PDZ-binding region (S4-PDZ(-)) leads to decreased cell motility and a failure to form a trailing edge. On clustering S4, but not S4-PDZ(-), targets activated Rac1 to the leading edge of live cells. Cells lacking synectin, a PDZ domain containing protein that interacts with S4, fail to migrate in response to S4 clustering. Both S4-PDZ(-)-expressing and synectin(-/-) endothelial cells exhibit elevated basal levels of Rac1. Thus, our data suggest that S4 promotes endothelial cell migration in response to ligand binding by activating Rac1 and localizing it to the leading edge, and that these processes are dependent on its PDZ-binding domain interaction with synectin.
We used a two-compartment coculture model comprising human endothelial cells (EC) and non-small cell lung carcinoma (CA) cells to study capillary formation. Elevated NO concentrations, contributed in part by CA cells, lead to inhibited capillary formation (Phillips PG, Birnby LM, Narendran A, and Milonovich WL. Am J Physiol Lung Cell Mol Physiol 281: L278-L290, 2001). Here we demonstrate using gelatin substrate zymography that high NO concentrations, whether produced endogenously or by NO donor spermine-NONOate or peroxynitrite-generating compound SIN-1, significantly inhibit MMP-9 expression and activation. Furthermore, high NO concentrations decrease Cav-1 abundance and alter its cellular distribution in EC. Cav-1 is essential for capillary formation in this model because Cav-1 antisense treatments targeted to EC significantly inhibit capillary formation. Laser confocal microscopy demonstrated extensive colocalization of MMP-9 with Cav-1 in sprouting EC, primarily at the basolateral surfaces of EC in focal structures associated with directed migration. This codistribution was NO concentration dependent, and elevated NO concentrations lead to marked dissociation of these two proteins. We propose that compartmentalization of MMP-9 within caveolar structures does occur, and that this could facilitate directed proteolysis essential for early migratory and invasive processes. Our data suggest elevated NO concentrations could impact on capillary formation via a combination of direct effects on MMP activation and by altering the distribution or abundance of Cav-1. Consequences of Cav-1 alterations may include impaired activation of proteolytic enzymes that utilize caveolar structure for stabilization and/or compartmentalization of MMP-9 as well as other putative members of an ECM proteolytic cascade.
The prevalence of asthma symptoms varies markedly throughout the world. However, the asthma mechanisms involved are not defined. Studying the effects of migration can help identify the reasons for this geographic variation. The aims of this study were to examine the prevalence of asthma symptoms, airway hyperresponsiveness (AHR), and induced sputum eosinophils in adolescents who migrate to Australia. The study was conducted in Sydney, Australia, where adolescent students completed a video symptom questionnaire, hypertonic saline challenge, sputum induction, and allergy skin testing. The 211 students had widely different cultural backgrounds, including Asian, South Pacific, Middle Eastern, European, and African countries. Among adolescents who were migrants to Australia, the prevalence of asthma symptoms was higher than that reported using a similar methodology in their country of origin. Asthma symptom prevalence was related to residence time in Australia. The prevalence of wheeze was 17.2% in recent arrivals, 20.5% in adolescents living in Australia for >2 years, and 36.3% in those living all their lifetime in Australia (P = 0.013). For every year of residence in Australia, there was an 11% increase in prevalence of current wheeze (odds ratio, 1.11; P = 0.02). This effect was not related to atopy, AHR, or eosinophilic airway inflammation. Sputum neutrophils were elevated in recent arrivals. In conclusion, adolescents who migrate to Australia report increased asthma symptoms, compared to their country of origin, and asthma symptoms are further increased for every additional year of residence in Australia. The development of wheeze after migration to Australia was independent of eosinophilic inflammation and consistent with noneosinophilic asthma mechanisms.
Nonimmune mice infected with Listeria monocytogenes exhibited elevated expression of macrophage colony-stimulating factor (M-CSF) mRNA and the enhanced migration of Mac-1 antigen-positive bone marrow-derived mononuclear phagocytes (BMMP) to their livers. Treatment with monoclonal anti-M-CSF antibody diminished the traffic of BMMP and promoted the replication of listeriae. Immune animals infected with listeriae expressed significantly lower levels of M-CSF mRNA than did nonimmune animals. Moreover, listerial infections did not elicit the migration of BMMP to the livers of immune mice, nor did anti-M-CSF affect the capacity of immune animals to respond to infection. Adoptive immunization experiments suggest that T lymphocytes can mediate protective immunity to listeriae in the absence of M-CSF and migrating BMMP. These findings indicate that M-CSF and the enhanced migration of BMMP are critical factors in primary but not secondary host defenses to listerial infections.
A major problem for neuroscience has been to find a means to achieve reliable regeneration of synaptic connections following injury to the adult CNS. This problem has been solved by the leech, where identified neurons reconnect precisely with their usual targets following axotomy, re-establishing in the adult the connections formed during embryonic development. It cannot be assumed that once axons regenerate specific synapses, function will be restored. Recent work on the leech has shown following regeneration of the synapse between S-interneurons, which are required for sensitization of reflexive shortening, a form of non-associative learning, the capacity for sensitization is delayed. The steps in repair of synaptic connections in the leech are reviewed, with the aim of understanding general mechanisms that promote successful repair. New results are presented regarding the signals that regulate microglial migration to lesions, a first step in the repair process. In particular, microglia up to 900 microm from the lesion respond within minutes by moving rapidly toward the injury, controlled in part by nitric oxide (NO), which is generated immediately at the lesion and acts via a soluble guanylate cyclase (sGC). The cGMP produced remains elevated for hours after injury. The relationship of microglial migration to axon outgrowth is discussed.
Angiogenesis involves multiple steps including proliferation and migration of endothelial cells. In the present study, we determined the effect of inostamycin (an inhibitor of phosphatidylinositol synthesis) on vascular endothelial growth factor (VEGF)-induced proliferation and migration of human umbilical vein endothelial cells (HUVECs). Inostamycin significantly attenuated both VEGF-induced proliferation and migration of HUVECs. Inostamycin inhibited activation of mitogen-activated kinases (ERK and p38) and elevation of cyclin D1 induced by VEGF. These data suggest that inostamycin reduced both proliferation and migration of HUVECs by targeting ERK-cyclin D1 and p38, respectively.
Changes in ovarian maturation-inducing steroid (MIS; 17,20 beta, 21-trihydroxy-4-pregnen-3-one [20 beta-S]) membrane receptor concentrations during the reproductive cycle were investigated in spotted seatrout (Cynoscion nebulosus) captured at their spawning grounds. Ovarian receptor concentrations increased gradually during ovarian recrudescence and subsequently increased rapidly during oocyte maturation, reaching 3.5-fold the prematuration values by the beginning of ovulation. The significant elevation of receptor concentrations by the germinal vesicle migration stage of oocyte maturation was accompanied by increases in circulating levels of gonadotropin (LH, GTH II) and MIS (20 beta-S). The regulation and physiological significance of the increase in ovarian MIS membrane receptor concentrations were investigated in a double in vitro incubation system. Incubation of fully grown, follicle-enclosed oocytes with hCG (10 IU/ml) for 6 h caused a two- to fourfold increase in oocyte and ovarian MIS receptor concentrations and the development of oocyte maturational competence (OMC; ability to complete oocyte maturation in vitro in response to exogenous 20 beta-S in a second incubation). Both upregulation of the MIS receptor and development of OMC in response to gonadotropin were blocked by coincubation with actinomycin D or cycloheximide, which are inhibitors of mRNA and protein synthesis, respectively, but not by cyanoketone, which is an inhibitor of 3 beta-hydroxysteroid dehydrogenase-dependent steroid synthesis. Incubation with a variety of steroids, including 20 beta-S, failed to increase receptor concentrations or to induce OMC, further supporting a steroid-independent mechanism of gonadotropin action. In contrast, insulin-like growth factor I (IGF-I) mimicked the actions of gonadotropin, which suggests IGF-I may be a component of the hormone signaling pathway. A close correlation was found between the relative increase in MIS receptor concentrations and the percentage of oocytes that became maturationally competent after treatment with different concentrations of gonadotropins and drugs that elevate cAMP levels. The finding that upregulation of the MIS receptor in response to gonadotropin and other treatments is invariably associated with the development of OMC indicates that these two processes are intimately related, and it suggests that the increase in MIS receptor concentrations is a critical regulatory step in the hormonal control of oocyte maturation.
Through depositing waste products, animals influence the spatial distribution of elements across landscapes. Yet the relationship between animal movement and element distribution remains poorly characterized. We developed a spatially explicit agent-based model to test how migratory versus resident red deer (Cervus elaphus) influence nitrogen redistribution across an alpine landscape in the Central-Eastern Italian Alps. Specifically, we asked how both local-scale and landscape-scale movement alter the spatial extent and magnitude of nitrogen deposition. We parameterized our model with GPS telemetry from 2021 to 2024 and remotely sensed vegetation data. We simulated four different scenarios which allowed us to disentangle the relative effects of large-scale (migration persisting) and fine-scale (resident behaviour) movement: (i) mixed migratory-resident (300 deer), (ii) fully resident (300 deer), (iii) reduced resident (150 deer) and (iv) reduced migratory (150 deer). The potential for nitrogen intake, assimilation, and excretion occurred hourly across a seasonally dynamic landscape. Across all scenarios, tree cover density and slope consistently emerged as positive predictors of nitrogen transport. Thus, regardless of resident or migratory status, red deer act as mediators of local element transport. Similarly, proximity to roads/trails reduced nitrogen inputs and created closed systems, indicating that barriers constrain both local and landscape-scale element transport. Migration substantially expanded the spatial extent of nitrogen redistribution and enabled the upward movement of elements, both locally upslope and into higher elevation habitats, effectively transporting elements against gravitational forces. Consequently, the loss of migration is likely to weaken these large-scale element linkages and reduce associated ecosystem functions. Our results demonstrate that different animal movement patterns play distinct and complementary roles in connecting element pools across landscapes. While both resident and migrant foraging redistribute elements locally, migratory movements link lowland and alpine habitats, expanding the spatial reach of element redistribution. Thus, loss of migration not only reduces the spatial extent of element distribution but also alters the topographic pathways through which elements are cycled. These findings highlight the broader ecosystem consequences of declining animal movement extent, and migration in particular, and underscore the importance of conserving behavioural diversity to maintain element heterogeneity and ecosystem functioning in mountain systems.
OBJECTIVE: During atherogenesis, macrophages migrate into the subendothelial space where they ingest deposited lipoproteins, accumulate lipids, and transform into foam cells. It is unclear why these macrophages do not remove their lipid loads from the region. This study was aimed at testing the hypothesis that macrophage behavior is altered when membrane cholesterol levels are elevated, as might be the case for cells in contact with lipoproteins within atherosclerotic lesions. METHODS AND RESULTS: We examined the effects of elevating membrane cholesterol on macrophage behavior. J774 macrophages were treated with either acetylated low-density lipoprotein (ac-LDL) and ACAT inhibitor or cholesterol-chelated methyl-beta-cyclodextrin (chol-MbetaCD) to increase membrane cholesterol levels. Our results show that elevating the membrane cholesterol of J774 macrophages induced dramatic ruffling, stimulated cell spreading, and affected F-actin organization. Cellular adhesion was required for these effects, and Rac-mediated signaling pathways were involved. Additionally, 3-dimensional transwell chemotaxis assays showed that migration of J774 macrophages was significantly inhibited when membrane cholesterol levels were raised. CONCLUSIONS: These findings indicate that increased membrane cholesterol causes dramatic effects on macrophage cellular functions related to the actin cytoskeleton. They should provide new insights into the early steps of atherogenesis.
Src kinase plays a central role in growth factor signalling, regulating a diverse array of cellular functions including proliferation, migration and invasion. Recent studies have demonstrated that Src activity is frequently elevated in human tumours and correlates with disease stage. We have previously demonstrated that, upon acquisition of tamoxifen resistance, MCF7 cells display increased epidermal growth factor receptor (EGFR) activation and a more aggressive phenotype in vitro. Since tumours exhibiting elevated EGFR signalling may possess elevated levels of Src activity, we wished to investigate the role of Src in our MCF7 model of endocrine resistance. Src kinase activity was significantly elevated in tamoxifen-resistant (TamR) cells in comparison to wild type MCF7 cells. This increase was not due to elevated Src protein or gene expression. Treatment of TamR cells with the novel Src inhibitor, AZD0530, significantly reduced the amount of activated Src detectable in both cell types whilst having no effect on total Src levels. AZD0530 significantly suppressed the motile and invasive nature of TamR cells in vitro, reduced basal levels of activated focal adhesion kinase (FAK) and paxillin and promoted elongation of focal adhesions. Furthermore, the use of this compound in conjunction with the EGFR inhibitor, gefitinib, was markedly additive towards inhibition of TamR cell motility and invasion. These observations suggest that Src plays a pivotal role in mediating the motile and invasive phenotype observed in endocrine-resistant breast cancer cells. The use of Src inhibitors in conjunction with EGFR inhibitors such as gefitinib may provide an effective method with which to prevent cancer progression and metastasis.
Donor myoblast migration is a major limiting factor in the success of myoblast transfer therapy, a potential treatment for Duchenne muscular dystrophy. A possible strategy to promote the migration of donor myoblasts into host muscle is to enhance their proliferation and delay their fusion, two properties that are major characteristics of myoblasts in regenerating skeletal muscle in MyoD null (-/-) mice. Here we investigate whether the migration of MyoD (-/-) donor myoblasts into host muscle is enhanced in vivo. Sliced muscle grafts from male MyoD (-/-) or normal control (Balb/c) mice were transplanted into the muscles of female normal (Balb/c) host mice. Muscles were sampled at 1, 3, and 12 weeks after grafting, and the fate of male donor myoblasts within female host muscles determined by in situ hybridization with the mouse Y-chromosome-specific Y-1 probe. MyoD (-/-) donor myoblasts migrated into host muscle continuously over 1, 3, and 12 weeks after grafting, in contrast with Balb/c donor myoblasts, whose overall numbers and migratory distances did not increase significantly after 1 week. These results strongly support a role for elevated donor myoblast proliferation and/or their delayed fusion in enhancing migration into host muscle in vivo, and endorse the use of either genetically engineered donor myoblasts, or the administration of exogenous myoblast mitogens to improve donor myoblast migration in myoblast transfer therapy.
Atrioventricular (AV) septal defects resulting from aberrant endocardial cushion (EC) formation are observed at increased rates in infants of diabetic mothers. EC formation occurs via an epithelial-mesenchymal transformation (EMT), involving transformation of endocardial cells into mesenchymal cells, migration, and invasion into extracellular matrix. Here, we report that elevated glucose inhibits EMT by reducing myocardial vascular endothelial growth factor A (VEGF-A). This effect is reversed with exogenous recombinant mouse VEGF-A165, whereas addition of soluble VEGF receptor-1 blocks EMT. We show that disruption of EMT is associated with persistence of platelet endothelial cell adhesion molecule-1 (PECAM-1) and decreased matrix metalloproteinase-2 (MMP-2) expression. These findings correlate with retention of a nontransformed endocardial sheet and lack of invasion. The MMP inhibitor GM6001 blocks invasion, whereas explants from PECAM-1 deficient mice exhibit MMP-2 induction and normal EMT in high glucose. PECAM-1-negative endothelial cells are highly motile and express more MMP-2 than do PECAM-1-positive endothelial cells. During EMT, loss of PECAM-1 similarly promotes single cell motility and MMP-2 expression. Our findings suggest that high glucose-induced inhibition of AV cushion morphogenesis results from decreased myocardial VEGF-A expression and is, in part, mediated by persistent endocardial cell PECAM-1 expression and failure to up-regulate MMP-2 expression.