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Type III hyperlipoproteinemia acquired by liver transplantation.

A case of type III hyperlipoproteinemia (HLP) (dysbetalipoproteinemia) acquired by liver transplantation is reported. The 50-year-old female patient was referred to the Frankfurt University Hospital for orthotopic liver transplantation. She had suffered from ethylic liver cirrhosis. The donor liver showed discrete signs of steatosis. The postoperative course of the patient was satisfactory. Enzyme levels and blood coagulation tests returned to normal within thirty days. However, both cholesterol and triglycerides gradually increased from approximately 2.00 g/L to values ranging from 2.50 to 3.50 g/L within 200 days after transplantation. Cutaneous xanthomas did not develop. The patient's lipoprotein pattern met the criteria of type III HLP: the cholesterol to triglyceride ratio in very low-density lipoproteins (VLDL) was 0.64. Intermediate-density lipoprotein(IDL) cholesterol was 0.48 g/L. Lipoprotein electrophoresis showed a broad beta-band, and beta-migrating particles were present in VLDL. Immunoblotting of apolipoprotein (apo) E from the patient's plasma revealed an E2/2 phenotype. However, restriction isotyping of an in vitro amplified apoE gene fragment showed the genotype of the patient to be epsilon 3/epsilon 4. These data suggest that the development of type III HLP in this patient was due to a change in the apoE phenotype from E3/4 to E2/2 after liver transplantation.

Apolipoproteins E↗

Quantitative time-course profiles of bronchoalveolar lavage cells following intratracheal instillation of lipopolysaccharide in mice.

This report shows the quantitative time-course profiles of transpulmonary migration of polymorphonuclear leukocytes (PMN) and the adhesive interaction of alveolar macrophages to the alveolar surface in response to intratracheally (i.t.) instilled endotoxin. Groups of mice received i.t. instillation of lipopolysaccharide (LPS), and free cells in the bronchoalveolar lavage (BAL) fluid were counted. PMN remaining in the lung tissue after the BAL procedure were also enumerated following enzymatic tissue digestion. Recovery of macrophages from the alveolar space by BAL was significantly decreased at 0.5 and 2 h post i.t. instillation and returned to the control value after 5 h, suggesting that alveolar macrophages became adhesive to the alveolar wall in response to LPS. Neither BAL nor lung tissue-associated PMN were increased until 0.5 h post i.t. instillation of LPS. The lung tissue-associated PMN peaked at 2 h, while the number of BAL PMN peaked at 5 h post instillation. Furthermore, although the number of BAL PMN remained at the maximum value even at 24 h post i.t. instillation of LPS, the lung tissue-associated PMN returned to the control level at this point. These results suggest that (1) the adhesive interaction of alveolar macrophages to the alveolar surface increased rapidly (< 0.5 h), (2) accumulation of PMN in the lung occurred later than the adhesion of alveolar macrophages (0.5 to 2 h) and (3) transpulmonary infiltration of PMN was completed within 24 h following i.t. instillation of LPS.

Algorithms↗

Regulation and functions of the protein C anticoagulant pathway.

The protein C pathway plays a critical role in the negative regulation of the blood clotting process. We recently identified an endothelial cell receptor for protein C/activated protein C (APC). The receptor is localized almost exclusively on endothelial cells of large vessels and is present at only trace levels or indeed absent from capillaries in most tissues. Patients with sepsis or lupus erythematosus exhibit elevated levels of plasma EPCR which migrates on gels as a single band and is fully capable of binding protein C/APC. There is no correlation with thrombomodulin levels, probably due to different vascular localizations and/or cellular release mechanisms. To understand the mechanisms by which EPCR plasma levels are elevated, we examined EPCR mRNA expression in a rat endotoxin shock model. The EPCR mRNA gene exhibited an early immediate gene response to endotoxin with the mRNA levels increasing nearly 4 fold in the first 3-6 hrs, before returning toward baseline. Plasma levels of EPCR also rose about 4 fold with little change in tissue EPCR levels. Both processes were markedly attenuated by hirudin suggesting that thrombin was responsible for increases in mRNA and plasma EPCR levels. At the level of mRNA, the induction is mediated by a thrombin response element in the 5' flanking region of the gene. Direct thrombin infusion and cell culture experiments support this contention. On endothelium, thrombin is capable of releasing cell surface EPCR and this process is blocked by the metalloproteinase inhibitor orthophenanthroline. Taken together these studies indicate that elevation in soluble plasma EPCR reflects endothelial cell activation in the larger vessels and is likely to be an indication of local thrombin generation near these vessel surfaces.

Animals↗

Cell sorting within the prespore zone of Dictyostelium discoideum.

Dictyostelium discoideum forms elongate cell aggregates called "slugs" which migrate over the substrate before completing their conversion into fruiting bodies. Prespore cells are found in a zone which occupies the rear four-fifths of the slug. Both front- and rear-prespore cells, marked by a bacterial beta-galactosidase gene, sort out to their original positions in experiments in which slugs are reconstituted from disaggregated tissue. When cells from the rear of the prespore zone are transplanted to the middle or front, sorting is also observed: the transplanted cells return rapidly to the rear. Cells from the front of the prespore zone, however, were not observed to "home" to the front after transplantation to the rear. Since front-prespore cells sort out in disaggregation/reaggregation experiments, but fail to do so after transplantation to the rear, it is possible that the transplanted cells are converted to rear-prespore cells by extracellular signals present in the rear of the slug. In an experiment designed to test this hypothesis, front cells were transplanted to the rear and the host and transplant together then subjected to disaggregation/reaggregation. The results showed that front-prespore cells had not been converted to rear-prespore cells. Instead, there was an unanticipated effect: cells placed in the rear of the prespore zone underwent an anterior shift in positional preference, while cells placed in the front of the prespore zone showed a posterior shift. The specific sorting properties of front- and rear-prespore cells thus do not appear to result from the action of positional signals; positional signals destabilize rather than reinforce sorting preferences. Our observations are consistent with a model in which innate differences among cells bias them to differentiate as front-prespore or rear-prespore types, but the proportions of these types are also modulated by a negative-feedback mechanism.

Animals↗

Time-resolved spectroscopy of energy and electron transfer processes in the photosynthetic bacterium Heliobacillus mobilis.

The kinetics of excitation energy transfer and electron transfer processes within the membrane of Heliobacillus mobilis were investigated using femtosecond transient absorption difference spectroscopy at room temperature. The kinetics in the 725- to 865-nm region, upon excitation at 590 and 670 nm, were fit using global analysis. The fits returned three kinetic components with lifetimes of 1-2 ps and 27-30 ps, and a component that does not decay within several nanoseconds. The 1- to 2-ps component is attributed to excitation equilibration to form a thermally relaxed excited state. The 27- to 30-ps phase corresponds to the decay of the relaxed excited state to form a charge-separated state. The intrinsic energy and electron transfer rates were estimated using the experimental results and theoretical models for excitation migration and trapping dynamics. Taking into account the number of antenna pigments and their spectral distribution, an upper limit of 1.2 ps for the intrinsic time constant for charge separation in the reaction center is calculated. This upper limit corresponds with the trapping-limited case for excitation migration and trapping. Reduction of the primary electron acceptor A0 was observed in the 640 to 700 nm region using excitation at 780 nm. An instantaneous absorbance increase followed by a decay of about 30 ps was observed over a broad wavelength region due to the excited state absorption and decay of BChl g molecules in the antenna. In addition, a narrow bleaching band centered at 670 nm grows in with an apparent time constant of about 1.0 ps, superimposed on the 30-ps absorbance increase due to excited state absorption. Measurements on a longer time scale showed that besides the 670 nm pigment a BChl g molecule absorbing near 785 nm may be involved in the primary charge separation, and that this pigment may be in equilibrium with the 670 nm pigment. The bleaching bands at 670 nm and 785nm recovered with a time constant of about 600 ps, due to forward electron transport to a secondary electron acceptor. Energy and electron transfer properties of H. mobilis membranes are compared with Photosystem 1, to which the heliobacteria bear an evolutionary relationship.

Bacteria↗

THE ROLE OF LYMPHOCYTES IN THE SENSITIZATION OF RATS TO RENAL HOMOGRAFTS.

In order to study the role of blood-borne small lymphocytes in the sensitization of rats to renal homografts 2 techniques for the perfusion of isolated rat kidneys were employed: (a) the in vitro perfusion of kidneys with thoracic duct cells suspended in either an artificial medium or in blood; the perfusates were then injected into rats syngeneic with the lymphocyte donors; (b) the in vivo perfusion of kidneys with blood issuing from the femoral artery and returning to the femoral vein of living rats. The degree of sensitization conferred on the recipients by the perfusates was assessed by applying a skin homograft from the kidney donor and scoring the epithelial necrosis at 6 days. The in vitro experiments indicated that parental strain thoracic duct cells, which had passed through an F(1) hybrid kidney could confer upon a parental rat sensitivity to an F(1) skin graft. Several perfusions with radioactively labelled lymphocytes showed that the injected cells migrated to the lymph nodes and spleen of the recipients Labelled large pyroninophilic cells were occasionally seen in the spleen and lymph nodes of recipients, and it was suggested that these had arisen from the injected cells. Although the in vitro perfusions with blood indicated that renal homografts might sensitize their hosts within 1 hour, the in vivo perfusions suggested that about 5 to 12 hours were required. The more rapid sensitization in vitro was possibly due to the more frequent opportunity for contact between lymphocytes and kidney vascular endothelium which was afforded by the conditions in vitro.

Allografts↗

A study of tuberculosis among foreign-born Hispanic persons in the U.S. States bordering Mexico.

In 1996, 10% of the 20,973 U.S. tuberculosis (TB) cases were among foreign-born (FB) Hispanic persons, with the four states bordering Mexico accounting for 83% of FBH cases. Limited information is available on this population's health care seeking and migration practices and on differences between FB Hispanic patients in border and nonborder areas. Therefore, we conducted interviews and record reviews for all consenting FB Hispanic TB patients from eight counties bordering Mexico (BC; n = 167) and seven urban nonborder counties (NBC; n = 158) in these States during 1995-1997. BC patients had resided in the U.S. longer than NBC patients (17.4 versus 10.8 yr; p < 0.01), had immigrated more often from Mexican border communities (62.4% versus 25.4%; p < 0.01), and had returned to Mexico more often in the past 12 mo (71.5% versus 47.3%; p < 0. 01). TB symptoms were present for >/= 6 mo in 37% of BC and 34% of NBC patients. Binational collaboration is essential for improving TB control in both countries and should extend beyond border areas of Mexico.

Adult↗

In vivo initiation of unstimulated in vitro interleukin-1 release by alveolar macrophages.

Alveolar macrophages (AM) can be stimulated in vitro with material such as lipopolysaccharide, and this activation releases cytokines, collectively called interleukin-1, that can stimulate local cells such as fibroblasts, systemic cells such as lymphocytes, and/or distant parenchymal cells such as hepatocytes. During murine infection with the nematode Nippostrongylus brasiliensis, AM are activated as the parasite larvae migrate through the lung. We examined AM for unstimulated release of lymphocyte-activating factor (LAF) and hepatocyte-stimulating factor (HSF) as evidence of in vivo activation. Two days after infection, marked unstimulated release of LAF was demonstrated along with a smaller increase in unstimulated release of HSF activity. Release of both activities could be further augmented by in vitro stimulation with lipopolysaccharide. Eight days after infection unstimulated HSF activity was even higher than on Day 2, whereas unstimulated LAF release returned to normal. These findings suggest that a natural infective process causes activation of the resident AM population, resulting in release of potent immune and inflammatory-modulating cytokines in situ and that AM play a crucial role in the initiation of host defense and repair responses to infection.

Animals↗

Characteristics of human sperm chromatin structure following an episode of influenza and high fever: a case study.

Semen samples from a fertile patient presenting with influenza and a 1-day fever of 39.9 degrees C were obtained and analyzed at 18-66 days postfever (dpf) for sperm nuclear proteins, DNA stainability, free thiols (-SH), and susceptibility to DNA denaturation in situ. At 18 dpf, 36% of sperm demonstrated denatured DNA as measured by the sperm chromatin structure assay (SCSA), and decreased to 23% by 39 dpf. Samples at 33 and 39 dpf contained 49% and 30%, respectively, of cells with increased DNA stainability (HIGRN). A unique sperm nuclear protein band migrating between histones and protamines on acid-urea gels appeared at 33 and 39 dpf and nearly disappeared by 52 dpf. Amino acid sequencing of the first 8 N-terminal residues identified this protein as the precursor to protamine 2. The protamine P1 and P2 ratio remained normal, whereas the histone to protamine ratio increased slightly at 33 to 39 dpf. Flow cytometric measurements of nuclear -SH groups revealed the greatest reduction in free nuclear thiols at 33 dpf, and returned to normal by 45 dpf. The time of appearance of the unprocessed protamine 2 precursor and the relative increase in histone suggest a fever-related disruption of the synthesis of mRNA that codes for a P2 processing enzyme or enzymes. Increased DNA staining is likely due to the increased histone/protamine ratio. This case study demonstrates that fever/influenza can have latent effects on sperm chromatin structure and may result in transient release of abnormal sperm.

Cell Nucleus↗

[Clinical and paraclinical changes in cattle with traumatic pericarditis before and after pericardial puncture].

A puncture of the pericardium has been performed on cows with a traumatic pericarditis. The clinical status has been taken and paraclinical investigations prior to and after the puncture have been carried out. Following a puncture of the pericardium, up to the 12th hour, the movements of the rumen decrease or entirely disappear, and are restored again later, while respiratory movements and the heart activity become ever more frequent. A leucocytosis occurs without a trend towards a return to the initial level as well as neutrophilia with a nuclear left-shifting to metamyelocytes. The clinical and paraclinical changes in cattle with a traumatic pericarditis, after a puncture of the pericardium, point to a deterioration in the condition and a possible exitus.

Animals↗

Changes in small bowel myoelectrical activity following laparotomy.

Recordings of the myoelectrical activity have been obtained from the small intestine of 4 dogs by means of serosally implanted electrodes. The occurrence of the activity front (phase III) of the migrating myoelectrical cycle (MMC) in the recordings obtained each day after abdominal surgery have been compared. No activity fronts were seen on postoperative days 1 and 2. From days 3 to 6 there was a slightly reduced incidence, but from day 7 onwards an activity front was observed in each recording. It is concluded that the normal pattern of cyclic myoelectrical activity in the small intestine is disrupted for at least 2 days following a laparotomy, and the view that small bowel motility returns to normal soon after routine abdominal surgery may be inaccurate.

Animals↗

Expression and RNA binding properties of the chloroplast ribosomal protein S1 from Chlamydomonas reinhardtii.

The gene encoding the chloroplast ribosomal protein S1 from Chlamydomonas reinhardtii, CreS1, was cloned and the RNA binding properties and the expression patterns were studied. Gel-shift analysis revealed that CreS1 binds AU-rich 5'-untranslated regions (5'-UTR) of chloroplast mRNAs with higher affinity than the corresponding sequence of a GC-rich nuclear transcript. The binding affinity of CreS1 for a mutant form of the psbD 5'-UTR with a deletion of a U-rich stretch that is required for translation decreases 4-fold as compared to the wild-type 5'-UTR. Our results suggest that CreS1 protein interacts with U-rich sequences. Most of CreS1 is bound to high-molecular-weight complexes which co-migrate with the 30S small ribosomal subunit, and only a small fraction of CreS1 exists in its free form. CreS1 is localized mainly to the chloroplast stroma albeit a significant fraction is associated with chloroplast membranes. The results suggest that most of CreS1 is associated with the 30S ribosomal subunit throughout the translation process. Upon a shift of cells from the dark to the light, the mRNA levels of CreS1 and Psrp-7, both components of the 30S ribosomal subunit, increase transiently and return to the dark levels after 8 h. However, during this dark-to-light transition the levels of CreS1 and of other components of the 30S subunit remain the same suggesting that either protein synthesis or degradation is regulated. The possible implications of these findings are discussed.

Amino Acid Sequence↗

[Retroperitoneoscopic pyeloplasty for primary hydronephrosis: preliminary results of the first 30 procedures].

OBJECTIVE: To evaluate the preliminary results of retroperitoneoscopic pyeloplasty (RP) for the treatment of primary ureteropelvic junction syndrome (PUPJS) in terms of operating time, operative and postoperative complications, clinical functional and radiographic results, length of hospital stay and resumption of physical activity. MATERIAL AND METHODS: From November 1997 to June 2000, from a consecutive series of 59 patients treated for an anomaly of the ureteropelvic junction (UPJ), the 29 patients (18 females and 11 males, mean age: 35.6 years [range: 17-68]) operated by RP for PUPJS (bilateral in one case) were reviewed. Twelve patients presented a lower pole vascular pedicle and 24 patients had an extrasinusal renal pelvis. The RP technique was identical for all patients (4 ports) and the UPJ repair was performed according to the technique described by Anderson-Hynes and Küss (28 cases) or Y-V plasty (2 cases). RESULTS: The mean operating time was 150 minutes (range: 120-240) and the mean hospital stay was 4.2 days (range: 3-10). There were no intraoperative complications, but one conversion (3.3%) was necessary because of major adhesions. postoperative complications (23.3%) consisted of: four urinary tract infections with one case of acute pyelonephritis, perirenal haematoma, urine leak in the Redon drain due to obstructed double J stent, migration of the double J stent underneath the anastomosis leading to unstentable cicatricial stricture (treated by open pyeloplasty 3 weeks later). With a mean follow-up of 19.7 months (range: 7-40), 28 patients were asymptomatic and one patient presented persistent lumbar pain at 9 months with no signs of recurrence. The 3-month IVU, performed in 27 patients, showed reduction of hydronephrosis in 85.7% of cases and a patent ureteropelvic junction in 96.3% of cases. Complete resumption of physical activity and return to work were possible an average of 1 month postoperatively (a fortnight for the population under the age of 40 years). CONCLUSION: PUPJS can be treated by RP according to the same principles as conventional surgery. RP pyeloplasty can be performed with an acceptable operating time and morbidity. The functional and radiological results in terms of patency of the UPJ need to be assessed in the longer term.

Adolescent↗

[Migration and proliferation of smooth muscle cells in the vessel wall].

1. Intimal migration and proliferation causing artery stenoses in the course of atherogenesis can be inhibited by various drugs. 2. Secondary stenoses after ballooning of arteries are caused mainly by proliferation of smooth muscle cells. 3. Ballooning of arteries or repeated transmural electrical stimulations of artery walls with weak electrical current is followed by an increased mitotic activity of smooth muscle cells in the ballooned resp. stimulated area which reaches a maximal value about one week following the onset of the experiment. The mitotic activity returns then slowly to initial levels. 4. Adaptations to proliferation-inducing stimuli are possible. The experiments demonstrate that the proliferative phases in atherogenesis can be explained as a sequence of adaptations and deadaptations (= change of disposition) to the proliferation-inducing stimuli. 5. To select qualified drugs for an inhibition of the development of intimal proliferates in the course of atherogenesis makes it necessary to combine in vivo tests in animal experiments with tests on cell cultures of human cells from artery walls.

Arteriosclerosis↗

Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues.

The origins of immunoglobulin-containing cells in intestinal, respiratory, mammary, and genital tissues were studied in CBA/J female mice by using an adoptive lymphocyte transfer method. Within 24 hr after transfer, [3H]thymidine-labeled donor mesenteric lymph node (MLN) cells were observed in recipient gut, cervix and vagina, uterus, mammary glands, and MLN, where approximately 60% contained IgA and 25% IgG. In peripheral lymph nodes (PLN), 44% of the labeled cells after MLN transfer contained IgG, whereas only 8% were of the IgA isotype. The preference of the MLN to populate mucosal sites was clear from the results. Labeled PLN cells were transferred and the majority of these returned to their sites of origin and contained IgG. Of the small number of labeled PLN cells found in mucosal tissues, approximately equal percentages (30%) of IgA- anti IgG-containing cells were seen. Dividing cells prepared from mediastinal (bronchial) lymph nodes (BLN) showed a propensity to localize in the lungs rather than the intestine. However, the predominant immunoglobulin content of these donor cells in gut, lungs, and MLN was IgA. In recipient PLN, most labeled BLN cells contained IgG. These data support the concept of a common mucosal immunologic system.

Animals↗

Experimental schistosomiasis mansoni: characterization of connective tissue cells in hepatic periovular granulomas.

Connective tissue cells present in periovular granulomas, induced in mice livers by schistosomal infection, were studied in situ and in an in vitro culture after cell migration from explanted granulomas. They were compared to cells of the adjacent hepatic tissue. Connective tissue cells in granulomas and granuloma-derived primary cell lines were characterized as myofibroblasts. The presence of lipid droplets in cells of early granulomas, and comparison with adjacent perisinusoidal cells, indicated their origin through activation and mobilization of lipocytes from the adjacent hepatic tissue. This origin was confirmed in long-standing cultures of granuloma-derived cells, in the stationary phase of growth, in which myofibroblasts could return spontaneously into the fat-storing phenotype.

Animals↗

Dynamic exercise leads to an increase in circulating ICAM-1: further evidence for adrenergic modulation of cell adhesion.

Acute mental and physical stress lead to a marked lymphocytosis, with circulating natural killer cell numbers showing the most prominent increase. Many studies have linked these acute stress effects on lymphocytes with an increase in catecholamine levels. However, the molecular mechanisms which mediate this redistribution of lymphocytes from lymphocyte reservoirs into the circulation remain unknown. We hypothesized that this form of lymphocytosis was in part due to shedding of cell adhesion molecules from the cell surface and a subsequent detachment of lymphocytes adhering to the vascular endothelium in lymphocyte reservoirs. In this study, healthy human volunteers (n = 12) were exercised on a treadmill until exhaustion. The circulating levels of the soluble cell adhesion molecules ICAM-1 and E-Selectin were determined by ELISA. The subjects were then randomly assigned to treatment with either propranolol or metoprolol and repeated the exercise protocol after 1 week of treatment. Prior to drug treatment, soluble ICAM-1 levels rose from 258 +/- 19 to 321 +/- 28 ng/ml following exercise and returned to approximate baseline levels of 263 +/- 22 ng/ml after 1 h of rest. This highly significant effect of exercise on circulating ICAM-1 levels (p < .005) was mitigated after treatment with the beta-adrenergic antagonists. Soluble E-Selectin levels were not significantly affected by exercise. These results suggest that dynamic exercise leads to shedding of the cell adhesion molecule ICAM-1 via adrenergic mechanisms. We believe that these findings will contribute to the understanding of how physical and mental stress modulate lymphocyte migration and adhesion.

Adrenergic beta-Antagonists↗

Cyclic motility in canine colon: responses to feeding and perfusion.

To further characterize colonic motility in the dog and to examine the effects of intraluminal contents, motor activity in conscious animals was recorded by perfused intraluminal catheters. Animals were studied first with the bowel intact and, later, the colon was fashioned into an isolated loop. In the fasting state, cycles of motility recurred approximately each 30 min. These consisted of sequences of phasic contractions (bursts) that migrated variable distances in either direction; stationary bursts were also recorded. The fasting patterns recorded from intact bowel and isolated loops were not different. Feeding increased colonic motility, and the mean periodicity of cyclic bursts was reduced significantly to approximately 20 min. Moreover, differences were observed between intact bowel and isolated loops in the postprandial period. Diversion of chyme from the colon significantly reduced the motor response to food, but only in the late (2-4 hr) postprandial period, when the less frequent, fasting cycle returned to the loops. Perfusion of isolated loops with chyme or saline reestablished the postprandial pattern seen in intact bowel. The results suggest that the volume, but not the composition, of luminal contents modify postprandial motility in the canine colon. Additional experiments confirmed that, in particular, volatile fatty acids were probably not important determinants of colonic motility in the dog.

Animals↗