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PubMed1998

Impaired hyaloidal circulation function and uncoordinated ocular growth patterns in experimental retinopathy of prematurity.

PURPOSE: To test the hypotheses that, in the newborn rat model of retinopathy of prematurity (ROP), the hyaloidal circulation is functionally impaired and its development is not well coordinated with that of other ocular structures. METHODS: The functional response of the hyaloidal circulation to a carbogen inhalation challenge was noninvasively evaluated using magnetic resonance imaging (MRI) in day 12 rats raised under either variable oxygen conditions (experimental ROP, n = 8) or room air (control, n = 8). A similar MRI examination was performed in separate experiments using either day 18 newborn control rats (n = 3) or adult rats (n = 9). For each experiment, the hyaloidal circulation perfusion response to carbogen, the functional spatial extent of the hyaloidal circulation in vitreous, and the volumes of vitreous and lens were estimated from MRI enhancement maps. RESULTS: The hyaloidal perfusion response to carbogen breathing in the newborn rats decreased as follows: control day 12 > experimental day 12 > control day 18; no measurable hyaloidal function was found in the adult rat. Regression analysis indicated a relatively poorer superior-inferior correlation in the temporal response to carbogen inhalation for the experimental animals than in the control newborn rats. The vitreous volume decreased in control rats as expected (adult rat > day 18 > day 12). Good agreement was found between the MRI-determined adult rat vitreous volume (56 +/- 2 microliters) and that of previous reports. Functional hyaloidal volumes during carbogen breathing were not significantly different (P > 0.05) between day 18, day 12 control, and experimental newborn rats. The ratio of this functional hyaloidal circulation extent volume to vitreous volume was significantly different (P < 0.05) between these groups. Covariance analysis revealed a relatively less coordinated development between the functional hyaloidal volume and the vitreous volume in experimental animals than in age-matched control animals, whereas there was coordinated evolution of the hyaloidal circulation and the lens in all the animals. CONCLUSIONS: Carbogen-enhanced MRI appears to be a powerful new and noninvasive approach for assessing the functionality of the hyaloidal circulation (that is, its ability to respond to a carbogen challenge) and quantitatively comparing the functional hyaloidal extent to other ocular volumes in the same eye during development and during the disease process. Evidence is presented here for the first time that supports the authors' hypotheses that the function of the hyaloidal circulation in experimental ROP is impaired and that the growth of ocular components are less coordinated.

Animals↗
PubMed1989

Increased circulating endothelial cells in sickle cell crisis.

To determine whether increased numbers of circulating endothelial cells, a possible indicator of endothelial injury, are present in subjects with sickle cell disease, we measured circulating endothelial cells in 30 normal subjects and in 23 subjects with sickle cell anemia. Mean circulating endothelial cells were significantly higher (P less than 0.025) in the sickle cell subjects than in the normal subjects. Circulating endothelial cells were significantly higher than normal in 10 sickle cell subjects studied during painful crisis (P less than 0.01) but not in 13 sickle cell subjects studied while in the steady state. To control for the known stimulatory effect of cigarette smoking on circulating endothelial cells, we analyzed the results for smokers and nonsmokers separately. Mean circulating endothelial cells were not significantly higher in sickle cell subjects who smoked (n = 10) than in normal subjects who smoked (n = 8), but were significantly higher (P less than 0.05) in sickle cell nonsmokers (n = 13) than in normal nonsmokers (n = 22). Among nonsmoking sickle cell subjects, mean circulating endothelial cells were significantly higher than normal (P less than 0.01) during painful crisis (n = 7), but not in the steady state (n = 6). We conclude that circulating endothelial cells are significantly increased in sickle cell crisis, and may indicate the occurrence of acute endothelial injury during episodes of microvascular occlusion.

Acute Disease↗
PubMed2004

Dichotomous effects of complete versus partial class II major histocompatibility complex deficiency on circulating autoantibody levels in autoimmune-prone mice.

OBJECTIVE: To assess the effects of altered class II major histocompatibility complex (MHCII) expression on circulating autoantibody levels in C57BL/6 (B6) mice congenic for the Sle1 (B6.Sle1 mice) or Nba2 (B6.Nba2 mice) regions. METHODS: H-2Ab(+/+) (MHCII-intact), H-2Ab(+/-) (MHCII-intermediate), and H-2Ab(-/-) (MHCII-deficient) littermate B6.Sle1 and B6.Nba2 mice were evaluated for spleen cell phenotype, numbers of splenic Ig-secreting cells, and serum levels of total IgM, total IgG, IgG antichromatin, IgG antihistone, and IgG anti-double-stranded DNA (anti-dsDNA). RESULTS: Compared with their MHCII-intact littermates, MHCII-deficient B6.Sle1 and B6.Nba2 mice developed markedly decreased circulating levels of IgG autoantibodies, along with decreased circulating levels of total IgG. In sharp contrast, MHCII-intermediate mice developed increased circulating levels of IgG autoantibodies. This was associated with increased numbers of splenic Ig-secreting cells and serum levels of total IgG in B6.Sle1 mice, but it occurred without concomitant increases in the numbers of splenic Ig-secreting cells or serum total IgG levels in B6.Nba2 mice. CONCLUSION: In 2 clinically healthy strains of mice with a genetic proclivity for developing autoantibodies, the effects of class II MHC expression on levels of circulating IgG autoantibodies were found to be complex. In the absence of MHCII expression, circulating IgG autoantibody levels were minimal. With full MHCII expression, circulating IgG autoantibody levels were considerable. With intermediate MHCII expression, circulating IgG autoantibody levels were even greater. These last findings may help explain why heterozygosity at the H-2 locus is associated with increased autoantibody titers and aggravated disease in certain lupus-prone mice.

Animals↗
PubMed2003

Circulating free insulin-like growth-factor-I (IGF-I) levels should also be measured to estimate the IGF-I bioactivity.

Free IGF-I by analogy with sex and adrenal steroids and thyroid hormones, may be the major biologically active hormonal form of IGF-I. Because of methodological difficulties in measuring the free IGF-I the measurement of total IGF-I in blood is often used to assess the activity of the endocrine GH-IGF-I axis in clinical studies. However, there is currently no reliable standard reference method for circulating total IGF-I against which individual samples can be calibrated. In addition, in many of the common methods used to measure circulating total IGF-I levels, remaining insulin-like growth factor, binding proteins (IGFBPs) or binding protein fragments after sample extraction, may still interfere and produce falsely increased or decreased circulating total IGF-I levels. This latter phenomenon occurs especially under pathologic conditions. In addition, it has also been suggested that altered post-sampling integrity of IGF-I in vitro might contribute to the reported inconsistencies in circulating total IGF-I levels in literature. Although at the moment there is also no "golden standard" for the measurement of circulating free IGF-I levels, we discuss some studies in this paper that in our opinion, have demonstrated conclusively that circulating free IGF-I levels in several conditions reflect the IGF-I bioactivity better than circulating total IGF-I levels. Therefore, when evaluating the IGF-I bioactivity in health and disease, we recommend measuring also circulating free IGF-I.

Blood↗
PubMed1979

Use of circulating immune complex levels in the serodifferentiation of endocarditic and nonendocarditic septicemias.

Distinguishing endocarditic from nonendocarditic septicemias is prognostically and therapeutically important. One hundred two patients with both valvular and nonvalvular sepsis were studied for the presence and quantitation of circulating immune complexes. Ninety per cent of the patients with infective endocarditis versus 50 per cent of septic patients without infective endocarditis had circulating immune complex levels (p less than 0.005). Mean circulating immune complex levels in patients with infective endocarditis were significantly higher than in those without infective endocarditis, 106 +/- 18.58 microgram/ml versus 31 +/- 7.4 microgram/ml (p less than 0.005). Only three of 52 patients without infective endocarditis had circulating immune complex levels greater than 100 microgram/ml, as opposed to 16 of 50 patients with infective endocarditis (p less than 0.005). Similarly, one of 52 patients without infective endocarditis has circulating immune complex levels greater than 200 microgram/ml, as opposed to eight of 50 patients with infective endocarditis (p less than 0.05). In 92 per cent of the patients without infective endocarditis and 76 per cent of those with infective endocarditis peak circulating immune complex levels developed within 14 days after their entry into the study, often on the initial sampling. In febrile, septicemic patients with clinical symdromes nonclassic for endocarditis, measurements of serial circulating immune complex levels may be of adjunctive diagnosis importance. If circulating immune complex levels are undetectable, endocarditis would appear less likely; alternatively, levels above 100 to 200 microgram/ml would suggest a valvular rather than nonvalvular septic focus.

Antigen-Antibody Complex↗
PubMed1988

Role of lipoprotein lipase activity on lipoprotein metabolism and the fate of circulating triglycerides in pregnancy.

The mechanism that induces maternal hypertriglyceridemia in late normal pregnancy, and its physiologic significance are reviewed as a model of the effects of sex steroids on lipoprotein metabolism. In the pregnant rat, maternal carcass fat content progressively increases up to day 19 of gestation, then declines at day 21. The decline may be explained by the augmented lipolytic activity in adipose tissue that is seen in late pregnancy in the rat. This change causes maternal circulating free fatty acids and glycerol levels to rise. Although the liver is the main receptor organ for these metabolites, liver triglyceride content is reduced. Circulating triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels are highly augmented in the pregnant rat, indicating that liver-synthesized triglycerides are rapidly released into the circulation. Similar increments in circulating VLDL-triglycerides are seen in pregnant women during the third trimester of gestation. This increase is coincident with a decrease in plasma postheparin lipoprotein lipase activity, indicating a reduced removal of circulating triglycerides by maternal tissues or a redistribution in their use among the different tissues. During late gestation in the rat, tissue lipoprotein lipase activity varies in different directions; it decreases in adipose tissue, the liver, and to a smaller extent the heart, but increases in placental and mammary gland tissue. These changes play an important role in the fate of circulating triglycerides, which are diverted from uptake by adipose tissue to uptake by the mammary gland for milk synthesis, and probably by the placenta for hydrolysis and transfer of released nonesterified fatty acids to the fetus. After 24 hours of starvation, lipoprotein lipase activity in the liver greatly increases in the rat in late pregnancy; this change is not seen in virgin animals. This alteration is similar to that seen in liver triglyceride content and plasma ketone body concentration in the fasted pregnant rat. In the fasting condition during late gestation, heightened lipoprotein lipase activity is the proposed mechanism through which the liver becomes an acceptor of circulating triglycerides, allowing their use as ketogenic substrates, so that both maternal and fetal tissues may indirectly benefit from maternal hypertriglyceridemia. Changes in the magnitude and direction of lipoprotein lipase activity in different tissues during gestation actively contribute both to the development of hypertriglyceridemia and to the metabolic fate of circulating triglycerides.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1997

Enhancement of the in vivo circulation lifetime of L-alpha-distearoylphosphatidylcholine liposomes: importance of liposomal aggregation versus complement opsonization.

Incorporation of N-(omega-carboxy)acylamido-phosphatidylethanolamines (-PEs) into large unilamellar vesicles (LUVs) of L-alpha-distearoylphosphatidylcholine (DSPC) was found to dramatically increase the in vivo liposomal circulation lifetime in rats, reaching a maximal effect at 10 mol.% of the total phospholipid. Neither pure DSPC liposomes nor those with the longest circulating derivative, N-glutaryl-dipalmitoylphosphatidylethanolamine (-DPPE), were found to significantly bind complement from serum. Therefore, the relatively short circulation time of pure DSPC liposomes did not appear to be related to greater complement opsonization leading to uptake by the reticuloendothelial system. However, N-(omega-carboxy)acylamido-PEs were particularly efficient inhibitors of a limited aggregation detected for pure DSPC liposomes. The aggregation tendency of DSPC liposomes incorporating various structural analogs of N-glutaryl-DPPE correlated inversely with the circulation lifetimes. Therefore, it is concluded that such PE derivatives enhance the circulation time by preventing liposomal aggregation and avoiding a poorly understood mechanism of clearance that is dependent on size but is independent of complement opsonization. At high concentrations of N-glutaryl-DPPE (above 10 mol.%), the liposomes exhibited strong complement opsonization and were cleared from circulation rapidly, as were other highly negatively charged liposomes. These data demonstrate that both the lack of opsonization and the lack of a tendency to aggregate are required for long circulation. Liposomal disaggregation via N-(omega-carboxy)acylamido-PEs yields a new class of large unilamellar DSPC liposomes with circulation lifetimes that are comparable to those of sterically stabilized liposomes.

Amino Acids↗
PubMed1998

Fetal plasma levels of circulating endothelial cell adhesion molecules in normal and preeclamptic pregnancies.

OBJECTIVE: Circulating levels of endothelial cell adhesion molecules are elevated in women with preeclampsia. The aim of the present study was to determine levels of these molecules in the fetal circulation of normal pregnancies and pregnancies complicated by preeclampsia. STUDY DESIGN: Fetal plasma samples from the umbilical vein and peripheral maternal plasma and serum sample were collected at delivery from women with preeclampsia and women with normal pregnancy. Women with non-proteinuric pregnancy-induced hypertension (PIH) were excluded from the study. A sandwich ELISA technique was employed to quantitate concentrations of soluble ICAM-1 (CD54), VCAM-1 (CD106), and E-selectin (CD62E). RESULTS: The normal values of soluble endothelial cell adhesion molecules in the fetal circulation were determined as 162+/-45 ng/ml for ICAM-1, 1612+/-582 ng/ml for VCAM-1, and 154+/-58 ng/ml for E-selectin. They were found to markedly differ from the corresponding normal values in the maternal circulation (sICAM-1: 247+/-65 ng/ml; sVCAM-1: 715+/-170 ng/ml; sE-selectin: 34+/-14 ng/ml). The concentrations of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in women with preeclampsia compared to healthy control pregnant women. In contrast, there was no difference in the circulating fetal concentrations of these molecules between normal pregnancies and pregnancies complicated by preeclampsia. CONCLUSIONS: Normal values of sICAM-1, sVCAM-1, and sE-selectin in fetal circulation are markedly different from the values obtained for healthy adults. Plasma concentrations of these molecules are elevated in women with preeclampsia but not in the fetal circulation of preeclamptic pregnancies suggesting that based on the analysis of soluble adhesion molecules the fetal circulation may not be affected by the factor(s) that lead to disturbed endothelial cell function in women with preeclampsia.

Adult↗
PubMed1997

The effect of cardiopulmonary bypass on circulating megakaryocytes.

Megakaryocytes (Mks) are found in the lungs and the blood stream as well as in the bone marrow. We modified a whole blood filtration method for Mks by immunostaining for CD61 using biotin streptavidin, and used this technique to study Mks and their morphology in the central venous and arterial circulations before, during and after cardiopulmonary bypass (CPB) in haematologically normal patients undergoing routine cardiac surgery. Blood samples were taken immediately after the insertion of central venous (V) and arterial (A) catheters and after thoracotomy, immediately before bypass. Further samples were taken after 60-90 min on-CPB and 180-240 min post-bypass. In comparison with the steady state before bypass, circulating Mk levels in blood on bypass increased dramatically, from (V) 10.93 +/- 3.94/ml (mean +/- SD) to 36.48 +/- 11.52/ml and from (A) 8.37 +/- 4.39/ml to 38.65 +/- 20.68/ml. This effect was still present, to a lesser extent, 180-240 min post-bypass. Circulating levels of Mks were consistently lower in the arterial circulation than in the venous circulation off bypass, but levels in the two circulations were comparable during CPB, confirming previous suggestions that the lungs are net removers of Mks from the circulation. Type 4 Mks, the largest and most normal morphologically, were rarely seen in arterial blood, but increased significantly during CPB, indicating that the lungs selectively remove large Mks. The lungs appear to play an active role in the regulation of Mk levels. This is lost during CPB and despite the extracorporeal 40 microm arterial line filter, large Mks enter the systemic circulation. More effective extracorporeal filtration of large Mks might reduce the neurological impairment seen in some patients who have undergone CPB.

Adult↗
PubMed1996

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in patients with sarcoidosis.

sICAM-1 has been elevated in sera of specific inflammatory diseases, and circulating sICAM-1 concentrations reflect disease activity in these diseases. We measured circulating sICAM-1 concentrations and serum angiotensin-converting enzyme (SACE) activity in patients with sarcoidosis. Patients with sarcoidosis had significantly increased circulating sICAM-1 concentrations (62.8 +/- 33.5 U/ml) and SACE activity (23.7 +/- 7.4 U/l) compared with controls (circulating sICAM-1 50.9 +/- 12.1 U/ml, and SACE 13.5 +/- 3.8 U/l). Successive measurements showed that circulating sICAM-1 values changed in parallel with disease activity in sarcoidosis. In the progressive disease group (progressed or without change for 2 years or more), circulating sICAM-1 values (102.2 +/- 35.3 U/ml) at the time of diagnosis were significantly increased compared with those in the regressive disease group (disappeared or regressed within 2 years) 46.4 +/- 12.6 U/ml). However, there was no significant difference in SACE activity of the regressive and progressive disease groups. Fifteen patients with a high value of circulating sICAM-1 (> 75 U/ml, mean of controls + 2 s.d.) all had progressive disease, while only 15 of 44 patients with a high value of SACE had progressive disease. Circulating sICAM-1 will be a useful blood marker to predict outcome and to monitor disease activity in sarcoidosis.

Adolescent↗
PubMed1996

Circulating red cells usually remain of host origin after bone marrow transplantation for severe combined immunodeficiency.

BACKGROUND: Patients with severe combined immunodeficiency (SCID) treated with allogeneic bone marrow transplantation often receive a milder conditioning regimen than patients who undergo transplantation for hematologic malignancy, and they regularly retain circulating white cells of host origin. The origin of circulating red cells following successful bone marrow transplantation to treat SCID is not known. STUDY DESIGN AND METHODS: Review of the medical records identified all patients with SCID who underwent ABO-mismatched bone marrow transplantation at the University of California, San Francisco, between 1982 and 1994. The ABO and Rh phenotype at >6 months after transplantation was determined for all successful transplants by review of the medical record or the taking of a fresh blood sample for analysis. Patient-conditioning and donor bone marrow-preparative regimens were reviewed to assess their possible influence on the red cell phenotype after successful bone marrow transplantation. RESULTS: Nine of 35 SCID patients who underwent successful transplantation received marrow from ABO-mismatched donors. Eight of the nine patients had only host red cells circulating at 6 to 84 months after transplantation, while one patient had only donor red cells circulating at 48 months after transplantation. None of the patients had circulating red cells of both host and donor origin. Conditioning regimens included cyclophosphamide and antithymocyte globulin for all nine patients; only three patients also received total body irradiation. Seven of the nine patients received related-donor, HLA-mismatched bone marrow, and two patients received HLA-identical bone marrow; eight patients received T-cell-depleted bone marrow. The one patient whose red cell phenotype converted to that of the donor received T-cell-depleted, haploidentical marrow, and the preparative regimen included chemotherapy and total body irradiation. CONCLUSION: SCID patients successfully treated with allogeneic bone marrow transplantation typically fail to show circulating red cells of donor phenotype; this finding is in contrast to the universal presence of circulating donor red cells following successful bone marrow transplantation to treat hematologic malignancies and other diseases. The milder conditioning regimens typically given to patients with SCID, along with T-cell depletion and HLA mismatching, may play a role in this different outcome. It is not known whether the inability to find circulating red cells of donor origin is due to a failure to engraft donor pluripotent stem cells or a failure of engrafted donor stem cells to differentiate along the erythroid lineage.

Blood Grouping and Crossmatching↗
PubMed1993

High levels of circulating RNA in patients with symptomatic HIV-1 infection.

OBJECTIVE: To evaluate the concentration of circulating RNA (viraemia) in patients with symptomatic primary HIV infection and relate it to sero-immunological parameters. METHODS: Semiquantitation of circulating HIV RNA and proviral HIV DNA was performed using the polymerase chain reaction. Circulating HIV RNA concentrations were expressed as virus equivalent (RNA copies/2) per ml serum. RESULTS: The mean CD4+ lymphocyte count for 19 patients with symptomatic primary HIV infection was 583 x 10(6)/l. Fifteen (79%) patients had detectable levels of p24 antigen (median 462 pg/ml). Circulating HIV RNA (median 2.3 x 10(7) virus equivalent/ml serum) and proviral HIV DNA (median 3630 copies/ml blood) were detected in all samples tested. Follow-up data for five patients (200-1600 days) showed a 1-3 log reduction in circulating RNA within 2 months. Later, circulating RNA concentrations were consistently greater than 10(3) virus equivalent/ml serum. Within 10 days no p24 antigen was detectable. Levels of CD4+ cells varied markedly from patient to patient during the follow-up and, in this small group, no evident correlation was observed between circulating RNA levels and CD4+ lymphocyte counts. CONCLUSIONS: High concentrations of circulating RNA (viraemia) were present in 19 patients with symptomatic primary HIV infection. Although a decrease in viraemia was observed during the following 2 months, viraemia persisted in all patients with long-term follow-up. This suggests that active viral replication is a continuous process in HIV-infected patients.

Adult↗
PubMed1999

Circulating intercellular adhesion molecule-1 as an early predictor of hepatic failure in patients with septic shock.

OBJECTIVE: To investigate whether endotoxin, interleukin-6, and circulating adhesion molecules, measured sequentially in blood, can predict mortality and organ dysfunction in sepsis. DESIGN: Inception cohort study with follow-up for 28 days. SETTING: Surgical intensive care unit at a university hospital. PATIENTS: A total of 14 consecutive patients were enrolled in the study within the first 24 hrs after onset of septic shock. Seven healthy subjects were studied as controls. INTERVENTIONS: Patients were analyzed for mortality and development of organ dysfunction. MEASUREMENTS AND MAIN RESULTS: At the end of the 28-day follow-up period, seven of the patients were still alive (survivors) but the other seven (nonsurvivors) had died. At the time of enrollment in the study (day 0), the Acute Physiology and Chronic Health Evaluation II score was 28.4 in survivors (n = 7) and 28.7 in nonsurvivors (n = 7). In contrast, circulating intercellular adhesion molecule-1 (ICAM-1) was significantly higher in nonsurvivors than in survivors. Circulating ICAM-1 predicted mortality in patients with septic shock with a sensitivity and a specificity of 71.4% each. Endotoxin, interleukin-6, circulating L-selectin, P-selectin, E-selectin, and platelet endothelial cell adhesion molecule-1, however, did not distinguish between survivors and nonsurvivors. In addition, circulating ICAM-1 at day 0 showed a significant correlation with the highest serum bilirubin observed during the entire study period (r2 = 0.963). CONCLUSIONS: Because only circulating ICAM-1 was higher in nonsurvivors than in survivors at day 0, circulating ICAM-1 may serve as an early prognostic marker for outcome in septic shock. In addition, measurement of circulating ICAM-1 facilitates identification of those patients with the highest risk of developing liver dysfunction.

APACHE↗
PubMedDate not supplied

Endotoxemia after burn injury: effect of early excision on circulating endotoxin levels.

Serial circulating endotoxin measurements (quantitative chromogenic limulus assay) were performed in sera from 19 burned patients to determine the profile of circulating serial circulating endotoxin after burn and the effect of early wound excision on serial circulating endotoxin level. Results indicate an early endotoxemia with the peak serial circulating endotoxin levels 7 to 12 hours and 4 days after burn. More importantly, the level of circulating serial circulating endotoxin can be diminished by early excision; late wound excision was associated with a transient increase of serial circulating endotoxin level. Early excision, therefore, may play a critical role in limiting endotoxemia after burn injury.

Adult↗
PubMed2005

Circulating CD10-/CD16low neutrophils provide a quantitative index of active bone marrow neutrophil release.

Circulating neutrophil phenotype and function are altered during neutrophilia associated with acute inflammatory states, however, the contribution of bone marrow neutrophil release to these changes has been difficult to quantify in humans. Accelerated release of neutrophils, with potentially distinct attributes, from the bone marrow and their dilution within the circulating pool may produce these apparent changes. Unfortunately selective analysis of these newly emergent neutrophils is difficult given their morphologic similarity to those already in the circulation and the coincident effect of soluble inflammatory mediators on circulating neutrophil phenotype and function. Using whole blood flow cytometry and cardiac surgery as an inflammatory stimulus, we demonstrate the emergence of a unique subpopulation of circulating neutrophils characterised as CD10(-)/CD16(low), indicative of active bone marrow neutrophil release peri-operatively. CD10(-)/CD16(low) neutrophils emerge at the same operative stages as band forms and a left shift, yet represent over 40% of circulating neutrophils postoperatively, and generate a greater stimulus-induced [Ca(2+)](i) flux than their CD10(+) counterparts. We conclude that CD10(-)/CD16(low) neutrophils represent a significant proportion of the circulating pool after cardiac surgery and that bone marrow release, a major contributor to neutrophilia, influences the phenotype and functional activity of circulating neutrophils following this acute inflammatory stimulus.

Adult↗
PubMed1980

Inflammatory bowel disease associated circulating immune complexes.

Circulating immune complexes have been detected in patients with inflammatory bowel disease (IBD). To determine if these complexes are related specificially to IBD or more generally to loss of intestinal mucosal integrity, we compared circulating immune complex levels in the sera of 86 IBD patients, nine pseudomembranous and nine bacterial colitis patients, and 42 healthy controls. Immune complexes were measured by a Raji cell radioimmunoassay. Raji detectable circulating immune complex levels were significantly higher in the IBD group than in the healthy controls (P<0.001). Circulating immune complex levels in the pseudomembranous-bacterial colitis group and the healthy controls were essentially identical. While nearly 20% of the IBD patients (16 of 86) had abnormally high levels, none of the patients with the other forms of intestinal inflammation (0 of 18) had abnormal levels. These data suggest that the circulating immune complexes present in inflammatory bowel disease patients are related to the IBD process rather than to non-specific mucosal cell (barrier) damage. Patients with intestinal inflammation and normal peripheral immune complex levels also had normal mesenteric vein levels. These data suggest that lack of formation, rather than more efficient hepatic reticuloendothelial clearance, was primarily responsible for the absence of detectable complexes in Raji negative individuals. Circulating immune complex levels did not correlate with type, location, severity, or extraintestinal manifestations of inflammatory bowel disease. The absence of Raji detectable circulating immune complexes in the majority of patients, even in those with extraintestinal manifestations, raises serious doubts about the pathogenic significance of such complexes. Nevertheless, as the circulating immune complexes appear to be disease related, they may be used to isolate and identify disease specific antigen(s) of possible aetiological importance.

Antigen-Antibody Complex↗
PubMed1997

Polymorphonuclear leukocytes L-selectin expression decreases as they age in circulation.

We recently reported that L-selectin expression increases on circulating polymorphonuclear leukocytes (PMN) during active bone marrow release, which suggests that older cells in the circulation have lower levels of L-selectin than those recently released from the bone marrow. The present study was designed to test the hypothesis that L-selectin expression reduces on PMN as they age in the circulation. In vitro studies using flow cytometry showed that PMN L-selectin decreased to 14.6 +/- 2.3% of baseline during a 24-h incubation at 37 degrees C. To test this hypothesis in vivo, rabbit PMN, labeled in vivo with 5'-bromo-2-deoxyuridine (PMN-brdU) in donor animals, were infused into recipient rabbits as whole blood (n = 5) and followed over 24 h in the circulation with a double immunolabeling technique. These results showed that the fraction of the L-selectin-negative PMN-BrdU in the circulation increased with time (P < 0.001), and nearly all of the PMNBrdU in the circulation were L-selectin negative after 24 h. Removal of L-selectin from the surface of PMN-BrdU with chymotrypsin before infusion did not change their rate of removal from the circulation (half-life or t 1/2 262 vs. 296 min, P = NS). We conclude that there is a continuous loss of L-selectin from PMN during their life span in the circulation, which supports the hypothesis that L-selectin expression decreases on PMN as they age.

Animals↗
PubMed2004

Detection and characterization of circulating microsatellite-DNA in blood of patients with breast cancer.

Increased levels of circulating DNA have been reported in the blood of cancer patients but not healthy individuals. Tumor-specific genomic aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), can be detected in this free extracellular DNA. Identification of these genetic aberrations may play an important role in cancer diagnosis and prediction of disease progression. Moreover, the genomic regions involved might harbor potential targets for therapies. To evaluate the incidence of microsatellite alterations in circulating DNA, we assessed the blood serum of 34 patients with primary (n = 8) and metastatic (n = 24) breast cancer. Samples were also analyzed for the presence of circulating tumor cells using an immunocytological cytokeratin assay, and the concentration of the tumor marker CA 15-3 was determined. Genomic DNA extracted from serum and normal blood leukocytes, as a control, was amplified by the polymerase chain reaction using markers at 4 microsatellite loci of chromosomes 10q22-23, 16q22-23, 17q11-12, and 17q21. In 17 of 34 cancer patients, tumor-specific alterations were detected in serum samples. In 16 patients, LOH at various loci was observed, whereas MSI was only detected in the serum of one patient. The pattern of LOH was very heterogeneous, and LOH was detected at chromosomal loci 10q22-23, 16q22-23, and 17q11-12 but not 17q21. No correlation was found between the detection of circulating tumor DNA and the presence of circulating tumor cells in the blood or serum concentration of CA 15-3. In conclusion, genomic aberrations on chromosomes 10, 16, and 17 are frequent in the circulating DNA of breast cancer patients. However, circulating tumor DNA does not reflect the presence of tumor cells in blood or the level of tumor-associated protein markers such as CA 15-3. Thus, screening for circulating tumor DNA may provide additional diagnostic information.

Biomarkers, Tumor↗