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CD18-dependent and -independent mechanisms of neutrophil emigration in the pulmonary and systemic microcirculation of rabbits.

Neutrophil (PMN) migration in the systemic and pulmonary circulation of rabbits was compared by using different inflammatory stimuli to determine the role of the leukocyte adhesion complex, CD11/CD18, in each of these vascular beds. The adhesion complex was blocked by administering the anti-CD18 mAb 60.3. The data show that mAb 60.3 blocks PMN emigration into inflammatory foci in the abdominal wall produced by implanting sponges containing either hydrochloric acid, Streptococcus pneumoniae, Escherichia coli endotoxin, or PMA. mAb 60.3 also inhibited PMN emigration in response to peritoneal instillation of S. pneumoniae. The effect of mAb 60.3 on PMN emigration in the lungs varied depending upon the stimulus. PMN failed to migrate into the PMA-induced pneumonia; however, mAb 60.3 pretreatment only partially inhibited endotoxin-induced pneumonia and did not inhibit S. pneumoniae or hydrochloric acid-induced pneumonias. PMN lavaged from the alveolar spaces in the Streptococcal pneumonia had similar quantities of mAb 60.3 bound to their surfaces as the circulating PMN. We conclude that the CD11/CD18 complex mediates PMN adherence in the systemic circulation. However, PMN adherence in the pulmonary circulation may occur by either CD18-dependent or -independent mechanisms that are specific to the inciting stimulus.

Animals↗

The functions of polymorphonuclear leukocytes emigrating into the skin.

The functions of polymorphonuclear leukocytes (PMNs) emigrating into the skin and of others separated simultaneously from the circulation were determined and compared in healthy individuals. The PMNs emigrating into the skin were separated with a skin chamber technique. The C3 rosette forming capacities of the skin migrating and the circulating PMNs were similar. The chemotactic responsiveness was evaluated using three different chemoattractants: zymosan-activated serum, casein and lymphocyte-derived chemotactic factor. The skin PMNs gave practically no chemotactic response in the Boyden chamber, irrespective of the chemoattractant used. On the other hand, the skin PMNs exhibited higher plastic surface adherence, nitroblue tetrazolium reduction and Candida albicans killing activities. The data indicate that some functional activities of PMNs undergo alteration during in vivo emigration into the skin. The alterations, overall, may be of importance in the physiological protective function of the skin.

Adhesiveness↗

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 3rd communication: inhibitory effects on leucocyte emigration and proliferation of granulation.

The effects of 2-(10,11-dihydro-10-oxodibenzo [b,f]thiepin-2-yl)propionic acid (CN-100), which has a significant inhibitory effect on acute inflammatory reactions, on leucocyte emigration and proliferation of granulation were examined in this study. The compound obviously inhibited the protein exudation and polymorph emigration 6 h after application of carboxymethylcellulose pouch method. It also definitely inhibited the monocyte emigration occurring 24 h after carrageenin pleurisy, and the inhibitory activity of the compound was nearly equal to that of pranoprofen and weaker than that of indometacin. CN-100 inhibited the proliferation of granulation in the test by paper disk method, i.e., the compound inhibited wound healing. The antigranulation activity of CN-100 was also nearly equal to that of pranoprofen and weaker than that of indometacin. These results proved that CN-100 should definitely inhibit the reactions of the second and third inflammatory phases of the whole reactions from the exudative phase throughout proliferative phase, suggesting that the compound is a useful antiinflammatory drug.

Animals↗

Evidence of extensive lymphocyte death in sheep Peyer's patches. II. The number and fate of newly-formed lymphocytes that emigrate from Peyer's patches.

The emigration of newly produced lymphocytes from Peyer's patches (PP) of lambs was studied. Mesenteric lymph nodes (MLN) were excised from most animals a few weeks after birth, and then at 8 to 10 wk of age, the dividing cells in 3 to 4 m of the small intestine were labeled in situ with [3H]thymidine. An extracorporeal perfusion system was used to restrict the 15-min period of labeling to the perfused lengths of intestine, which included either the large continuous ileal PP or a number of smaller jejunal PP. One or 3 days later, the number of labeled cells in the perfused tissue and in other lymphoid organs was studied by autoradiography. In the perfused tissues, labeled lymphocytes accounted for 63.7% of ileal PP cells by 1 day and for 86.7% by 3 days compared with only 9.6% of lymphocytes in the perfused MLN. Labeled lymphoid cells in the perfused PP were nearly all in the follicles. Labeled lymphocytes that must have been produced in the segments of ileum or jejunum at the time of the perfusion, subsequently emigrated via the lymphatics, and were identified in the spleen, MLN, other lymph nodes, blood, jejunal PP, and at a lower frequency in the thymus, nonperfused ileal PP, and bone marrow. In lymph nodes, spleen, and nonperfused PP, more than 80% of the immigrant newly formed PP-derived cells were small- and medium-sized lymphocytes, and about 15% were large lymphocytes. The nature of the labeled cells in the lamina propria of the nonperfused small intestine was quite different in that approximately 50% were plasma cells as early as 24 hr after the cells were born in the perfused gut. It is proposed that terminal B cell differentiation was most likely initiated within the PP in response to the entry of antigen. It was estimated that at both 1 and 3 days after perfusion there were about 100 times more labeled cells in the perfused ileal PP than could be accounted for by emigration to other organs. It was concluded that these results provide additional support for the view that PP in lambs produce a tremendous number of lymphocytes, but relatively few leave their site of production; most apparently die in situ.

Animals↗

Human skin proteases: effect of separated proteases on vascular permeability and leukocyte emigration in skin.

The effect of human skin proteases on vascular permeability and leukocyte emigration in rabbit skin was investigated. The alkaline protease of human skin capable of hydrolysing trypsin substrate effectively increased vascular permeability. This effect was not inhibited by antihistamine, but almost totally so by Trasylol. The reaction was protracted. Leukocyte emigration in skin, primarily of PMN-cells at 12 hrs, and later a migration of mononuclear cells, also resulted. Swelling of the dermal fibres was noted. The alkaline protease of human skin capable of hydrolysing chymotrypsin substrate also increased vascular permeability, but this phenomenon was effectively inhibited by antihistamine and the reaction was of brief duration. The leukocyte emigration caused by this enzyme was remarkable. The acid proteases of human skin resembling cathepsin B1 and D also caused brief increased vascular permeability, which was effectively inhibited by antihistamine. The cellular reactions to these acid proteases were mild. The role of protease inhibitors in skin in the enzyme reactions is discussed.

Animals↗

Intravenous interleukin-8 inhibits granulocyte emigration from rabbit mesenteric venules without altering L-selectin expression or leukocyte rolling.

Injection (i.v.) of the granulocyte chemoattractant/activator IL-8 has been shown to reduce neutrophil recruitment into dermal inflammatory sites in vivo. To further investigate the mechanism of this phenomenon, we examined the effect of i.v. [Ser-IL-8]72 (12-20 micrograms/kg) on leukocyte rolling and chemoattractant-induced emigration in mesenteric venules of New Zealand White rabbits and on expression of L-selectin (mAb LAM1-3) and CD18 (mAb 60.3) on circulating rabbit granulocytes. Within 1 min of IL-8 i.v., granulocytes virtually disappeared from carotid blood samples for approximately 5 min. Concomitantly, the flux of rolling leukocytes in mesenteric venules fell from 83 +/- 21 to 2 +/- 1 leukocytes/min. Both rolling leukocyte flux and systemic granulocyte count returned to or exceeded control values within less than 30 min. The chemoattractant/activator FMLP (0.15 microgram/kg i.v.) produced similar results. A second i.v. injection of IL-8 or FMLP, 90 min after the first challenge, had equipotent effects. Local extravascular application of IL-8 via micropipette close to a venule induced adhesion and emigration of 63 +/- 21 leukocytes per site before, but only 26 +/- 9 leukocytes per site 50 to 75 min after i.v. IL-8, when systemic granulocyte count and rolling leukocyte flux had reached or exceeded control values. This was not due to agonist-specific desensitization, because a similar reduction of leukocyte emigration was seen after FMLP i.v. Rabbit granulocytes circulating in vivo uniformly expressed near-control levels of L-selectin at all times between 3 and 360 min after IL-8 i.v. CD18 expression transiently increased after IL-8 i.v. and returned to base line by 90 min. These findings show that IL-8 i.v. reduces granulocyte recruitment to inflammatory sites by inhibiting function(s) necessary for transmigration that are independent of L-selectin and subsequent to rolling.

Animals↗

CD18-dependent and L-selectin-dependent neutrophil emigration is diminished in neonatal rabbits.

Human neonatal neutrophils manifest decreases in mobility, adherence, and emigration compared with adult neutrophils that may contribute to the increased susceptibility of neonates to infection. In a developmental rabbit model, we show a reduced ability of neutrophils from 1-day-old rabbit pups to emigrate to inflamed peritoneium (3.7 +/- 0.35 x 10(6) neutrophils/mL peritoneal exudate) compared with 14-day-old (8.5 +/- 0.7 x 10(6)/mL) and adult rabbits (9.4 +/- 1.4 x 10(6) mL, P < .05) despite significantly increased blood neutrophil counts. Because the reductions in functional Mac-1 (CD11b/CD18) as well as the amount of surface L-selectin are hypothesized to be primarily responsible for the differences in human neonatal neutrophil mobility, we examined CD11b/CD18 and L-selectin in our model. Using flow cytometric analysis we found that similar to human neonates, neutrophils from 1-day-old rabbit pups had 57% of adult rabbit levels of L-selectin and, in contrast with adults, failed to show significant decreases in L-selectin after chemotactic stimulation. In addition, neutrophils from 1-day-old pups compared with adults showed a significantly diminished capacity to upregulate CD11b/CD18 after chemotactic stimulation in vitro, or after emigration to the inflamed peritoneum. Systemic administration of anti-L-selectin monoclonal antibody (MoAb) resulted in significant reduction in peritoneal neutrophils in adult (47%, P < .05) and 14-day-old rabbits (47%, P < .05), but was without effect in 1-day-old rabbits. Administration of anti-CD18 MoAb resulted in significant reduction in peritoneal neutrophil accumulation in all age groups though less in 1 day and 14 day (58% and 65%, respectively) than in adults (91%, P < .05). Only in the 14-day-old rabbits was there an additive effect of anti-L-selectin and anti-CD18 MoAbs compared with anti-CD18 alone (84% v 65%, P < .05). The findings in this in vivo rabbit model support the hypothesis that the previously described in vitro defects in human neonatal L-selectin and CD11b/CD18 may be major contributors to human neonatal inflammatory deficits.

Age Factors↗

Effects of immune-mediated enteroluminal neltrophil emigration on intestinal function in pigs.

Intestinal function was assessed in cannulated loops of porcine proximal jejunum during immune-mediated emigration of neutrophils into the intestine. Net water, net sodium, net chloride, undirectional sodium and unidirectional chloride fluxes were measured before and after intestinal exposure to an antigen in both sensitized and nonsensitized pigs. Neutrophil emigration was assessed histologically. The results indicate that fluid and electrolyte movements in the intestine are not significantly altered during immune-mediated enteroluminal neutrophil emigration suggesting that the neutrophil response does not interfere with intestinal function.

Animals↗

Emigration of neural crest cells from macaque optic vesicles is correlated with discontinuities in its basement membrane.

It is established that cranial neural crest cells play critical roles in normal development, but the production of neural crest cells from the prosencephalon has received little attention, especially in primates. We therefore investigated the emigration into adjacent mesenchyme of neuroepithelial cells from macaque optic vesicles. Paraffin sections prepared from 13 embryos (Macaca fascicularis) representing developmental stages 10-14 were examined following standard immunoperoxidase staining for laminin and type IV collagen. At stage 10 the optic vesicle basement membrane was closely applied to that of the surface ectoderm except at its posterior border, where it contacted mesenchyme. The basement membrane was continuous and showed no evidence of cell migration. By stage 11 the optic vesicle basement membrane exhibited numerous gaps along its posterior border. These defects were frequently occupied by cells emigrating from the optic vesicle epithelium, as judged by the deflection of basement membrane fragments. Gaps were also seen along the lateral border, where migrating neuroepithelial cells were positioned between the surface ectoderm and optic vesicle. This cell migration appeared to increase during stage 12, with deterioration of all areas of the optic vesicle basement membrane. Basement membranes of the surface ectoderm, adjacent mesencephalon, and telencephalon anlage remained intact. By stage 13 the basement membranes of the optic vesicles were repaired and nearly continuous, with migrating cells rarely seen. Development of the optic cups at stage 14 indicated a near absence of basement membrane defects and emigrating cells.

Animals↗

Expansion of mature thymocyte subsets before emigration to the periphery.

A small population of DNA-synthesizing mature thymocytes could be defined by analyzing cell surface markers and 5-bromo-2'-deoxyuridine (BrdUrd) labeling by four-color cytofluorometry. These cells have a completely mature phenotype (CD4- CD8+ or CD4+ CD8- TCR(high), HSA-, Qa-2(high)) and expand only weakly after BrdUrd incorporation. They recovered immediately in total number and in DNA synthesis rate after treatment with the antimitotic drug demecolcin, thus much faster than immature CD4+ CD8+ thymocytes. These data demonstrate the existence of a late intrathymic expansion phase, independent of that of developing CD4+ CD8+ immature cells, and involving phenotypically mature cells renewed each day. In mixed chimeras prepared by transfer of bone marrow and lymph node cells into RAG-2(-/-) mice, all cycling mature thymocytes were bone marrow derived. They are thus produced in situ and do not correspond to peripheral T cells reentering the thymus. Double FITC/BrdUrd detection showed that a high proportion (10-20%) of recent thymic emigrants were BrdUrd+ just postcycling cells and that around 50% of cycling mature thymocytes are just ready to emigrate to the periphery in the few hours after DNA synthesis. The late intrathymic expansion phase demonstrated here increases the daily thymic cell export by at least 30%. It could play a role in the adjustment of the T cell repertoire before emigration and in the regulation of the thymic cell output into the peripheral T cell pool.

Animals↗

High frequency apoptosis of recent thymic emigrants in the liver of lymphopenic diabetes-prone BioBreeding rats.

Diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous autoimmune diabetes. DP-BB thymocyte export is reduced, and most thymic emigrants disappear rapidly from peripheral lymphoid tissues. DP-BB rats are consequently lymphopenic and circulate severely reduced numbers of T cells. Peripheral T cells present are phenotypically immature (Thy1+) and appear activated. We hypothesized that DP-BB recent thymic emigrants have a shortened life span and disappear by apoptosis. The percentage of T cells with an alphabetaTCR(low) B220+ CD4- CD8- phenotype was increased in DP peripheral lymphoid tissues when compared with normal, nonlymphopenic diabetes-resistant (DR) BB rat tissues. There was no evidence of DNA fragmentation in freshly isolated DP- or DR-BB rat cells, but, after 24 h of culture, a higher proportion of DP- than DR-BB splenic T cells underwent apoptosis. We then tested the hypothesis that BB rat T cells with the alphabetaTCR(low) B220+ CD4- CD8- phenotype accumulate and undergo apoptosis in the liver. Such cells were observed undergoing apoptosis in both DP- and DR-BB rats, but comprised approximately 80% of intrahepatic T cells in DP vs approximately 20% in DR-BB rats. Most alphabetaTCR(low) B220+ CD4- CD8- cells in the liver were also Thy1+. The data suggest that T cell apoptosis in the DP-BB rat is underway in peripheral lymphoid tissues and is completed in the liver. Increased intrahepatic apoptosis of recent thymic emigrants appears in part responsible for lymphopenia in DP-BB rats and the concomitant predisposition of these animals to autoimmunity.

Animals↗

The production of diaspora: Algerian emigration from colonialism to neo-colonialism (1840-1970).

"This paper is part of a larger project investigating the production and regulation of North African immigrants in the greater Paris automobile industry. Its aims are twofold. First, to reverse the emphasis placed on immigrants in the receiving countries and to (re-)explore the historical production of Algerian emigration into metropolitan industry, more specifically within the automobile industry....Second, in adopting an ¿articulation of modes of production' (AMOP) narrative as an alternative to other Eurocentric approaches, the first part of this paper emphasizes the contradictory layering of various modes which have produced an Algerian colonial diaspora. The latter half of the paper argues that the history of post-independence Algeria confirms that emigration was reinforced through a complex neocolonial relationship during a period of rapid acceleration of Algerian migration to France."

Africa↗

Portuguese emigration 1958-1985: some empirical evidence.

"Supplying work in the home country or abroad must be seen as the result of the same decisional process. If that is true, the same set of variables should be used to explain the participation in the labor market and the emigration rates. Based upon empirical results [for Portuguese emigrants], we discuss some of the traditional conclusions of the economic literature. Our empirical results, for example, show that: (1) there is...strong support for considering home wages and the wages in the country of destination asymmetrically, (2) imperfections in the capital markets seem to play an important role when workers must pay for their moving expenses and (3) there is a differential in coefficients between the period before 1974 and after that date, as 1974 is the year most of the Central European countries changed their immigration policies."

Demography↗

Depressive episodes in Sardinian emigrants to Argentina: why are females at risk?

BACKGROUND/OBJECTIVE: To compare the frequency of ICD-10 depressive episodes in a community sample of Sardinian immigrants in Argentina and a community sample of Sardinian residents in Sardinia, Italy. METHOD: A search of telephone directories provided all subscribers with Sardinian surnames in the Argentinean area involved. A 75.8% of all subjects thus identified took part in the study (n = 210). The characteristics of randomisation methods used to identify the community sample in Sardinia (n = 1040) have already been published elsewhere. All subjects were interviewed using the Composite International Diagnostic Interview Simplified. RESULTS: A higher frequency of depressive disorders was observed among the Sardinian immigrants in Argentina (26.7 vs. 13.5%, P < 0.0001). Females in particular showed a higher risk with respect to the Sardinian sample resident in Sardinia. DISCUSSION: On comparison of the present findings with the lifetime rate of depressive episodes in Sardinian immigrants in Paris (France), reported in a previous research study, a lower prevalence was observed among the latter group than in Sardinian immigrants in Argentina but the young male immigrants in Paris were at risk. CONCLUSION: The results obtained seem to suggest that emigration to a country where economic conditions have since dramatically changed may predispose subjects to depressive disorders, particularly when compared to the percentage of affected subjects in their native population and among subjects who had emigrated to more economically stable countries. Further epidemiological studies are warranted in order to confirm the present results and to clarify the determinants of the major risk for females in such a condition.

Adolescent↗

Emigration of New Zealand and Australian physicians to the United States and the international flow of medical personnel.

One in five physicians practising in the US received their initial medical qualifications in another country. Contrary to expectations, a large cadre come from developed nations such as New Zealand and Australia. In particular, these two countries provide a unique prism with which to view the international flow of medical talent. While they differ from developing nations that primarily export physicians without attracting others in return, they are distinguished from importing nations such as the US which rarely export. Our analysis is based on a unique dataset collected from three cross-sectional sources. We found that, compared to post-resident physicians remaining at home, New Zealand medical graduates (NZMGs) and Australian medical graduates (AMGs) in the US are typically older, more likely to be male, more likely to have received their initial medical qualifications from certain schools, less likely to be employed in a public hospital setting, more likely to work in a medical school and more likely to practice in a specialty than primary care. Additional findings show that NZMGs and AMGs in the US are more likely than other US physicians to have established themselves in areas with 50,000 or more people and are therefore more likely to serve a population with sociodemographic characteristics typical of the nation's urban centers. It appears then, that NZMGs and AMGs may be emigrating to the US for educational and professional opportunities that may be unavailable at home. In short, the emigration of NZMGs and AMGs may be an instance of what has come to be called the 'international equity problem' or 'brain drain'. However, losses resulting from the disproportionate migration of New Zealand and Australian physicians to the US may be compensated for by the importation of foreign trained physicians from other nations. Future analysis must be extended to take this facet of the international flow phenomena into account.

Age Factors↗

The psychological effects of forced emigration on Muslim Albanian children and adolescents.

OBJECTIVES: The object of this study was to investigate the psychological effects of forced emigration on Muslim Albanian children and adolescents who were forced to emigrate due to the war in Kosova. METHOD: The sample of the study consisted of 150 children between the ages 9-12 and 100 adolescents between the ages 15-19 living in the Gaziosmanpaşa Refugee Shelter in Turkey, and as a control group, 66 children and 52 adolescents; making a total of 368 subjects were included in the study. We applied State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Children's Depression Inventory (CDI) as well as a semi-structured open-ended questionnaire investigating the socio-demographic characteristics and psychiatric symptoms of the study and control groups. RESULTS: Trait anxiety (TAI) levels of the children in the study group are higher than these in the control group. The analysis of the average Depressive Symptom scores of study group children (M = 15.70) and control group children (M = 7.37) was conducted with the application of t-test. The highly significant values of t = 7.73 p < 0.0001 indicate depressive symptoms among study group. Trait anxiety (TAI) scores of study group adolescents were higher than these in the control group (M = 43.56) and (M = 35.59), respectively and the values of t = 5.95, p < 0.0001 show that this is a highly significant difference. The comparison of the average depressive (BDI) symptom scores of study group and control group adolescents (M = 17.57 and M = 4.59 respectively) revealed the very significant values of t = 7.88, p < 0.0001. The evaluation of the semi-structured questionnaires also revealed that depressive symptoms, somatic symptoms and other psychiatric symptoms were also higher in the study group. CONCLUSION: Our findings support the common opinion that war and terror incidents severely hurt children.

Adolescent↗

[Emigration of German psychiatrists to England. 1: England as a refuge for psychiatrists].

During Nazi time some 100 German psychiatrists emigrated to the U.K. and worked there for the rest of their lives or a number of years. An approximately equal number of them came into close contact with (a) the developing modern British psychiatry and (b) with psychoanalysis, which had already been established for a long time. With the exception of the Maudsley Hospital and the British Psychoanalytic Society, no groups have been established, so that there are many individual life histories of the former German psychiatrists in the U.K. in a series of papers we intend to review the movement and its consequences. Long before the emigration movement began there were already convergent evolutions in the British and German psychiatry. The current paper studies the historical conditions encountered by the psychiatric clinicians and classical-psychiatric immigrants on their arrival in Britain.

Emigration and Immigration↗

Emigrant physicians evaluate the health care system of the former Soviet Union.

This study is a retrospective evaluation of the Soviet health care system by 1,100 Jewish physicians who immigrated to Israel in 1990, but were professionally active in the former Soviet Union before and during the Gorbachev era. Medical education and the process of specialization; gender differences within the medical profession; sources of work satisfaction and dissatisfaction; self-evaluations of professional behavior; and assessments of patient behavior are included in this empirical study. Although high levels of dissatisfaction were found regarding instrumental aspects of work, the physicians reported high levels of satisfaction with their relationships with colleagues and patients. The recent emigrants assessed their own role behavior and that of their patients more critically than did physicians who left the Soviet Union in 1972, and who answered identical questions in 1975. Among the recent emigrants, men, older physicians, and those with higher status within the profession tended to be more satisfied with their work and less critical about their own and their patients' behavior than their female, younger and lower status colleagues. The subjective perceptions of former "insiders," which complement the reports that have appeared in recent years in the medical literature, are discussed in terms of the impact of glasnost and perestroika on reporting behavior and on the real deterioration that occurred in the health care system of the former Soviet Union.

Aged↗