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PubMed1995

Analysis of worm burden variation in human Schistosoma mansoni infections by determination of serum levels of circulating anodic antigen and circulating cathodic antigen.

Serum circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) concentrations, as a possible direct measure of worm burden, were compared with fecal egg counts in a heavily Schistosoma mansoni-infected population from Zaire to allow differentiation between worm loads and worm fecundity in relation to age and intensity of infection. Of the 517 subjects, 95% excreted eggs and 97% demonstrated circulating antigens. Fecal egg counts showed an age-related pattern characteristic for an area in which schistosomiasis is endemic with intense transmission levels. Regression analysis showed that antigen concentrations were strongly associated with egg counts. For CAA, but not for CCA, this relation was found to be nonlinear, which would be consistent with density-dependent fecundity or crowding. The trend was uniform for all age groups, which for this particular population indicated a genuine reduction of worm loads rather than reduced worm fecundity with age of the host.

Adolescent↗
PubMed1995

Levels of circulating intercellular adhesion molecule-1 and -3 but not circulating endothelial leucocyte adhesion molecule are increased in patients with rheumatoid vasculitis.

The aim of this study was to investigate whether levels of circulating adhesion molecules reflect vascular inflammation in rheumatoid vasculitis (RV). Levels of circulating intercellular adhesion molecule-1 (cICAM-1), c-ICAM-3 and circulating endothelial leucocyte adhesion molecule (cE-selectin) were determined in 14 patients with RV and compared to 47 patients with rheumatoid arthritis (RA) and 100 healthy donors (HD). Enzyme-linked immunosorbent assays were used to quantify cICAM-1, cICAM-3 and cE-selectin. We found that in RV significantly (P < 0.0001) elevated levels of cICAM-1 and cICAM3, but not cE-selectin, were found when compared with RA patients. Levels > 2 S.D. above the mean level of HD were present for cICAM-1, cICAM-3 and cE-selectin in 57, 71 and 21%, respectively of patients with RV and 2, 21 and 44%, respectively of the RA patients. Increased levels of both cICAM-1 and cICAM-3 were found in 43% of the RV patients and in none of the RA patients. Comparison of the serum levels of patients studied in an active and inactive phase of RV revealed significantly lower levels of cICAM-3 levels in the inactive phase. In conclusion we find that determination of cICAM-1 and cICAM-3 may be useful as a marker of vascular inflammation in patients with RV.

Aged↗
PubMed1996

Acute lung injury in endotoxemic rats is associated with sustained circulating IL-6 levels and intrapulmonary CINC activity and neutrophil recruitment--role of circulating TNF-alpha and IL-beta?

Endotoxemia initiates a cytokine response that is thought to mediate the syndromes of sepsis and multiple organ failure. This study measured cytokine levels in the blood and airways of rats at critical time points during the development of lung injury induced by chronic endotoxin (LPS) infusion in the rat. Tumor necrosis factor-alpha (TNF), interleukin-1-beta (IL-1), and interleukin-6 (IL-6) were measured in the blood and bronchoalveolar lavage fluid (BALF) of endotoxemic and control animals. BALF was also studied for the percentage of neutrophil (PMN) count and chemotactic activity. Lung histology was determined at 72 h following infusion of LPS. Chronic endotoxemia of > or = 48 h but not < or = 24 h resulted in severe acute lung injury (ALI). Circulating levels of TNF and IL-1 were only transiently elevated, whereas IL-6 remained elevated in the endotoxemic rats. TNF, IL-1, and IL-6 levels in BALF were only transiently elevated. Chemotactic activity, levels of cytokine-induced neutrophil chemoattractant (CINC), and the percentage of PMN counts in BALF all increased significantly by 36 h. Other potential chemoattractants; leukotriene B4 and transforming growth factor-beta were not elevated in BALF. In conclusion, severe ALI requires a minimum of 48 h LPS infusion in this model and is associated with high levels of circulating IL-6, increased CINC activity, and an increased percentage of PMN count in BALF. Local inflammatory events may be as important as the systemic cytokine milieu in mediating ALI. The signal for these local events does not appear to depend solely on the transient elevations of circulating TNF and IL-1 at the onset of endotoxemia, although sustained high levels of IL-6 may be important.

Animals↗
PubMed1991

Multiparameter flow-cytometrical quantitation of circulating CD34(+)-cells: correlation to the quantitation of circulating haemopoietic progenitor cells by in vitro colony-assay.

A multiparameter flow-cytometrical method for the quantitation of CD34(+)-cells present in adult human peripheral blood cells (PBMC) has been developed. PBMC from 13 healthy adult subjects were analysed for CD34(+)-cells by flow-cytometry, with only the lymphoid population of cells negative for anti-CD3-moAb included in the analysis. At the same time mononuclear cells from the same individuals were depleted of CD3(+)- and CD14(+)-cells by immunomagnetic purging. These cells were cultured for haemopoietic colonies. A correlation coefficient of 0.92 was calculated by regression analysis of CD34(+)-cells number versus the numbers of colonies (CFU-GM, BFU-E). Purging with anti-CD34-moAb abrogated colony-growth. The flow-cytometrical method for the determination of circulating CD34(+)-cells was used for the determination of circulating haemopoietic progenitor cells in one patient, in order to time leukapheresis for subsequent autologous reinfusion following high-dose chemotherapy. Determination of CD34(+)-cells from human adult peripheral blood by multiparameter flow-cytometry promises to be a useful tool for monitoring circulating haemopoietic progenitor cells as identified by anti-CD34-moAb.

Adult↗
PubMed2004

Is the circulating urokinase plasminogen activator upregulated by the circulating p105 fraction of the HER-2/neu proto-oncogene in patients with cervical cancer?

It has been suggested that urokinase plasminogen activator (uPA) in cancer cells is upregulated by the p185 kD form of the HER-2/neu oncogene. This study was performed to see if the extracellular domain of HER-2/neu, the p105 fraction, which is found in the circulation, has any regulatory influence on uPA in patients with cervical cancer. Levels of uPA and p105 HER-2/neu were determined in blood from age-matched controls and patients with early and advanced cervical cancer. In the patients with cervical cancer, samples were obtained before treatment only. No significant increase in either uPA or HER-2/neu was seen in the patients before their treatment for cervical cancer. Additionally, correlation analysis of circulating uPA and HER-2/neu against each other in both the controls and cervical cancer indicated no relationship except in early stage disease. It appears that circulating uPA and HER-2/neu are not altered in patients with cervical cancer, either early or advanced stages. The upregulation of uPA by HER-2/neu seen in cancer cells in vitro appears to occur in vivo in early stage cervical cancer.

Adult↗
PubMed1991

Maturation of hypothalamic-pituitary-gonadal function in normal human fetuses: circulating levels of gonadotropins, their common alpha-subunit and free testosterone, and discrepancy between immunological and biological activities of circulating follicle-stimulating hormone.

The recent availability of both cordocentesis, a low risk and effective technique for fetal blood sampling, and ultrasensitive/highly specific two-site immunofluorometric assays (IFMA) for pituitary and chorionic glycoprotein hormone (I-LH, I-FSH, and I-CG) measurement prompted us to study the maturation of hypothalamic-pituitary-gonadal function in 114 normal human fetuses (49 females and 65 males) from 17-40 weeks gestation. The subjects were selected from 216 consecutive cordocenteses carried out for rapid karyotyping and diagnosis of fetal infection or hematological disorders. In addition, FSH bioactivity (B-FSH) was measured by rat Sertoli cell aromatase induction assay, glycoprotein hormone alpha-subunit (alpha-SU) by RIA, and circulating free testosterone (fT) by direct analog technique. No significant cross-reactions were recorded in the different measurement methods. In particular, alpha-SU did not interfere in any IFMA, and CG cross-reactivity in LH IFMA was 0.5%. Circulating I-LH, I-FSH, and B-FSH levels at 17-24 weeks gestation were significantly higher in female than in male fetuses (I-LH, 48 +/- 4 vs. 6.3 +/- 0.7 U/L; I-FSH, 35 +/- 2 vs. 0.7 +/- 0.1 U/L; B-FSH, 131 +/- 17 vs. 43.4 +/- 5.4 U/L). During the last weeks of gestation, a significant decrease in I-LH and I-FSH levels was seen in both female and male fetuses (I-LH, 0.24 +/- 0.05 and 1.0 +/- 0.3 U/L; I-FSH, 0.45 +/- 0.1 and 0.5 +/- 0.1 U/L), while serum B-FSH remained elevated, but the previously recorded difference between sexes disappeared (54.3 +/- 7.2 and 58.7 +/- 7.3 U/L). Circulating I-CG and alpha-SU levels at midgestation were elevated in both female and male fetuses (I-CG, 117 +/- 29 and 191 +/- 44 U/L; alpha-SU, 143 +/- 16 and 105 +/- 9 micrograms/L, respectively) and decreased thereafter (I-CG, 42 +/- 9 and 26 +/- 6 U/L; alpha-SU, 60 +/- 15 and 37 +/- 6 micrograms/L). Serum fT levels at midgestation were significantly lower in females than in males (4.3 +/- 0.9 vs. 10.0 +/- 0.8 pmol/L) and increased until term, when the difference between sexes disappeared (16.2 +/- 1.8 vs. 17.6 +/- 1.6 pmol/L).(ABSTRACT TRUNCATED AT 400 WORDS)

Embryonic and Fetal Development↗
PubMed1992

Passive immunization against circulating insulin-like growth factor-I (IGF-I) increases protein catabolism in lambs: evidence for a physiological role for circulating IGF-I.

Primed constant infusions of [14C]urea were used to determine the acute effect of passive immunization against circulating free and protein-bound insulin-like growth factor-I (IGF-I) on the rate of net protein catabolism (NPC) in castrated male lambs fasted for 48 h. Following an intravenous bolus of 50 ml IGF-I antiserum, the rate of NPC increased to a peak 30 min after injection of 1.69 +/- 0.16 g/kg per day from a baseline value of 1.45 +/- 0.22 g/kg per day (P < 0.05, n = 4). In three animals given 50 ml equivalents of the purified immunoglobulin fraction, NPC increased from 1.31 +/- 0.20 to 1.59 +/- 0.16 g/kg per day (P < 0.05). A similar trend was observed in animals given 25 ml antiserum (n = 4). The rate of NPC did not increase following a bolus of non-immune serum in control animals and the rate of NPC in the treated lambs returned to control levels within 60 min of antibody injection. Plasma insulin and glucose concentrations in both the treated and control groups were unchanged throughout the study. These data suggest that circulating IGF-I has a physiological role in regulating whole body protein turnover during starvation and possibly other catabolic states. The effect of immunoneutralization of circulating IGF-I is transient and this suggests that while IGF-I has an endocrine role in the regulation of protein turnover, other regulatory mechanisms are involved.

Animals↗
PubMed1985

Comparison of four schistosome excretory-secretory antigens: phenol sulfuric test active peak, cathodic circulating antigen, gut-associated proteoglycan, and circulating anodic antigen.

Several carbohydrate-containing antigens of schistosomes have been characterized and tests for these antigens or for the corresponding antibodies are increasingly being used for the diagnosis and clinical analysis of human schistosomiasis. Phenol sulfuric active peak (PSAP) and cathodic circulating antigen (CCA) are 2 soluble glycoproteins found in adult worms of Schistosoma mansoni. These antigens have some similar characteristics including solubility in trichloroacetic acid and non-binding or weak binding to DEAE cellulose which suggests these 2 compounds to be identical. PSAP and CCA were therefore compared using radioimmunoassays employing monoclonal antibodies to CCA and radiolabeled PSAP as well as inhibitory assays using the original glycoproteins as inhibitors. By these criteria PSAP and CCA were found to be different glycoproteins. Using similar techniques, 2 anodic schistosome compounds, gut-associated proteoglycan (GASP) and circulating anodic antigen (CAA) were found to be identical. We now propose to call this later material GASCAP (gut-associated circulating anodic proteoglycan).

Animals↗
PubMed1999

Effects of nilvadipine, a calcium antagonist, on rabbit ocular circulation and optic nerve head circulation in NTG subjects.

PURPOSE: To study the effects of nilvadipine, a Ca2+ antagonist, on tissue circulation in the optic nerve head (ONH), choroid, and retina in rabbits and on the ONH circulation in normal tension glaucoma (NTG) patients. METHODS: Nilvadipine (3.2 microg/kg) or vehicle solution was injected intravenously into urethane-anesthetized rabbits, and the normalized blur value (NB), a quantitative index of in vivo tissue blood velocity, was measured in the choroid and in an area of the ONH and retina free of visible surface vessels before and for 90 minutes after injection, using the laser speckle method. The effects of nilvadipine on the ONH circulation was also studied using the H2 gas clearance method in separate groups of rabbits. Oral nilvadipine (4 mg/d) or placebo was administered to NTG patients in a double-masked manner, and NB in an area of the ONH rim free of visible surface vessels was measured by the same method before and 2, 4, 8, and 12 weeks after administration. RESULTS: The NB obtained from the ONH, choroid, or retina during the experimental period was increased by approximately 10% to 25% in the nilvadipine group compared with the NB in the control group (P < 0.0001, ANOVA), although systemic condition parameters and intraocular pressure (IOP) showed no significant intergroup difference except for a transient decrease in blood pressure in the nilvadipine groups. Blood flow rate in the ONH determined by the H2 gas clearance method also showed an approximately 25% increase in the nilvadipine group. The NB in the ONH of the oral nilvadipine-treated patients was significantly increased, by approximately 20% compared with the placebo-treated patients throughout the follow-up period. No significant intergroup difference was seen in blood pressure, pulse rate, or IOP. CONCLUSIONS: Nilvadipine increased blood velocity and, probably, blood flow in the ONH, choroid, and retina of rabbits. It also increased blood velocity in the ONH of NTG patients.

Adult↗
PubMedDate not supplied

The circulating urokinase plasminogen activator (uPA) and its soluble receptor (suPAR) are not up-regulated by the circulating P105 fraction of the HER-2/neu proto-oncogene: in vivo evidence from patients with advanced non-small cell lung cancer (NSCLC).

It has been suggested that uPA in cancer cells is up regulated by the p 185 kD form of the HER-2/neu oncogene. We elected to see if the extra cellular domain of HER-2/neu, the p 105 fraction, which is found in the circulation, has any regulatory influence on uPA or uPAR in those patients with NSCLC Levels of uPA, uPAR and p 105 HER-2/neu were determined in blood from age-matched controls and patients with advanced NSCLC. In the patients with NSCLC, samples were obtained before and following treatment. A large increase in both uPA and uPAR compared to controls was seen in the patients prior to treatment. The uPAR level post-treatment decreased from pre-treatment values, which is favorable. There was a significant increase in uPA and a decrease in HER-2/neu in the post-treatment time frame. Additionally, correlation analysis of circulating uPAR, uPA and HER-2/neu against each other in both the controls and treatment groups indicated no relationship. It appears that circulating uPA and uPAR are elevated in NSCLC patients. The up-regulation of uPA by HER-2/neu seen in lung cancer cells in vitro is apparently lost in the blood in vivo as is evidenced by the lack of correlation between them which is also true for the receptor as well.

Carcinoma, Non-Small-Cell Lung↗
PubMed1991

[Pathology of the placenta. VI. Circulation disorders of the placenta. Maternal circulation (intervillous space)].

Disorders of intervillous circulation are covered in this sixth part of the account of Pathology of the Placenta. Proposed in this paper are a new setup and modified nomenclature in which the term of "infarction" is definitely abandoned, as there can be neither genuinely anaemic nor haemorrhagic infarction in the placenta. Alterations which we consider as a formally pathogenetic chain are discussed by the order of focus of villous collapse, reticular intervillous fibrin deposition, and chronic disorder of intervillous circulation. These should be distinguished from subchorionic fibrin deposition, a special case of chronic circulatory disorder. Reference is finally made to intervillous haemorrhage and retroplacental haemorrhage (premature detachment of the placenta). An attempt is made, in conclusion, to give an account of the causative genesis of impairment to intervillous circulation together with various pathologic-anatomic findings recordable from myometrial and decidual arteries.

Arteries↗
PubMed1986

Detection and quantification of circulating antigen in schistosomiasis by monoclonal antibody. II. The quantification of circulating antigens in human schistosomiasis mansoni and haematobium: relationship to intensity of infection and disease status.

Circulating cathodic and circulating anodic antigens were quantified in sera of patients infected with S. mansoni, S. haematobium or both parasites. A monoclonal antibody and a polyclonal antiserum were applied in precipitation and solid phase immunosorbent techniques using radio- and enzyme-labelled antibody as a tracer to detect the cathodic and anodic antigen respectively. The results show that circulating cathodic antigen can frequently be detected in an immunoprecipitation or an immunoradiometric assay in serum of infected patients. The serum concentration of this antigen was found to be significantly correlated to the number of S. mansoni worms and to be higher in patients with the hepatosplenic form of the disease than in those without such complications. Examining paired serum samples before and after specific treatment the determination of this antigen by monoclonal antibody reliably indicated efficacy of chemotherapy in patients having received different forms of treatment.

Adolescent↗
PubMed1978

Circulation and migration of small blood lymphocytes in the rat. I. Kinetics of lymphocyte circulation in the lymphoid organs.

Seventy male Wistar rats were the recipients of labeled small lymphocytes (1.5 X 10(7) each) collected from the peripheral blood of syngeneic donors. The migrating labeled lymphocytes were traced in the various organs 1 to 60 minutes following their transfusion. Lymphoid organs and liver were processed for extraction of labeled nucleotides and for radioactivity assay. The purpose of this work was to study the dynamics of the circulation of the small lymphocytes between blood and lymphoid system. This study was done before equilibrium between these two compartments was reached. The result of this work showed that the small blood lymphocytes recirculate continuously between peripheral blood and the lymph node with duration less than 3 minutes per cycle. In a lymph node, this circulation is 80 times more efficient than the circulation via the thoracic duct lymph.

Animals↗
PubMed1997

Homing potentials of circulating lymphocytes in humans depend on the site of activation: oral, but not parenteral, typhoid vaccination induces circulating antibody-secreting cells that all bear homing receptors directing them to the gut.

Specific Ab-secreting cells (ASC) appear in the human blood as a response to oral and parenteral vaccination. The actual contribution of these cells to the defense of the body depends on their final effector site. The homing potentials of mucosally and parenterally induced ASC were compared by examining the homing receptor (HR) expression of circulating specific ASC in the blood of volunteers vaccinated orally or parenterally with the same Ag, Salmonella typhi Ty21a. Circulating lymphocytes were separated into receptor-positive and -negative populations, and the numbers of specific ASC were assayed. The alpha4 beta7 integrin, which acts as a gut HR, was expressed on all (99%) of the mucosally activated ASC, but on only 58% of the parenterally induced ASC or 58% of all Ig-secreting cells of the unvaccinated controls. L-selectin, the peripheral lymph node HR, showed an inverse distribution; it was found on 42% of mucosally activated ASC and on 86% of parenterally induced ASC. These results reveal that all of the circulating ASC after oral vaccination are committed to migrate to the mucosal compartment of the immune system, strongly arguing for a recirculation of activated mucosal cells in humans. By contrast, ASC induced by parenteral vaccination with the same Ag are mostly directed to the systemic compartment, yet a part of them has mucosal homing attitudes as well. These differences indicate that the site of Ag encounter determines the homing potential of the cell.

Administration, Oral↗
PubMed1990

Pulmonary circulation and systemic circulation: similar problems, different solutions.

Both the systemic and the pulmonary circulations respond to local hypoxia in the appropriate manner, the former by vasodilating, thereby providing more oxygen, and the latter by constricting and rerouting blood flow to areas where more O2 is available. In either case, changes in local conductance affect total conductance, and through that variable, the perfusing pressure; as a result, the effects of local vasomotion should be reduced. In the systemic circulation, arterial pressure can be prevented from falling by two important mechanisms: vasoconstriction of other vascular beds, and an increase in cardiac output. There are no similar means for protecting pulmonary arterial pressure against a rise when vessels in hypoxic areas contract; the only defense is provided by passive expansion of the vascular bed. Thus, in the lung regional circulatory readjustments conflict with the need to maintain a reasonably low pulmonary arterial pressure and local regulation (and maintenance of arterial oxygenation) may be subordinate to prevention of pulmonary hypertension.

Animals↗
PubMed1992

Complete correction of the tetralogy of Fallot in adults using separated extracorporeal circulation to block intrathoracic collateral circulation and improve perfusion of the renal vasculature.

During the last 10 years, complete correction of the tetralogy of Fallot (TOF) has been performed on 28 adult patients using the "separated extracorporeal circulation" (separated ECC) technique developed by us. In addition to the usual ascending aortic and dual right arterial cannulations for ECC, the separated ECC also involved femoral arterial cannulation and the insertion of a catheter with two balloons via the other femoral artery. Flow via the ascending aorta and femoral artery were maintained separately during ECC. The urine output during separated ECC was significantly better than that during ordinary ECC (P < 0.01) and the operative field for intracardiac correction was clearer as a result of blocking the collateral circulation. Thus we believe separated ECC to be a superior method for total correction of TOF in adults, which may enhance the operative outcome.

Adult↗
PubMed1986

The first open-heart repairs of ventricular septal defect, atrioventricular communis, and tetralogy of Fallot using extracorporeal circulation by cross-circulation: a 30-year follow-up.

From March 26, 1954, to July 19, 1955, 45 patients with major cardiac malformations not previously correctable underwent open repair utilizing cross-circulation between patient and donor without donor deaths. All operations were carried out at normothermia with lowered flow rates based on azygos flow studies. Twenty-seven patients, more than half of them infants, had ventricular septal defects closed. There were 8 hospital deaths, and there have been only 2 late deaths in 30 years. Fourteen (87.5%) of 16 who underwent recatheterization have closed defects. The 17 30-year-survivors are all in New York Heart Association Functional Class I. Five patients 4 months to 10 years old were operated on for atrioventricular canal (complete form). All had intractable failure, and 4 had pulmonary hypertension. Two of the 3 hospital deaths were due to heart block. The long-term survivor, a 15-month-old infant at the time of operation (severe pulmonary hypertension, 90/50 mm Hg), underwent repair 31 years ago and is now married with 3 children. Recatheterization disclosed normal pulmonary pressure (20/4 mm Hg), no shunts, and mild mitral regurgitation. Ten cyanotic tetrads 13 months to 14 years old were operated on with 5 hospital deaths. Of the 3 late deaths, 1 was accidental at 17 years, 1 occurred suddenly at home 13 years after operation in infancy for atresia, and the third occurred at reoperation 10 years later. The 2 remaining patients (1 the first patient operated on) are in excellent health. The surgical methods used and the physiological advantages of cross-circulation (temporary placenta) that made these results possible at a time when surgical knowledge was primitive are described.

Cardiac Catheterization↗
PubMed1999

Extracorporeal circulation does not induce intra-alveolar release of Endothelin 1, but only a modest overproduction in pulmonary circulation.

OBJECTIVE: To investigate whether ECC may produce regional liberation of inflammatory mediators capable of inducing vascular effects and organ damage. EXPERIMENTAL DESIGN: Comparative study [corrected]. SETTING: Cardiac surgery department in a University hospital. PATIENTS: Fifteen patients undergoing coronary artery bypass grafting (CABG, group A) and ten patients operated for infrarenal abdominal aortic aneurysm (controls, group B) have been studied. MEASURES: Levels of Interleukin 1beta (IL1), Tumor Necrosis Factor alpha (TNF), Interleukin 6 (IL6), and Endothelin 1 (ET1) were measured in pulmonary capillary, arterial, and venous blood and in bronchoalveolar lavages (BAL) before, during and after extracorporeal circulation (ECC) or surgical intervention. RESULTS: TNF-alpha (never >35 pg/ml) and IL1beta (range 20-300 pg/ml) values did not change over time for both groups. IL6 concentrations in all samples of group A increased between five and twenty fold, during and after ECC (from 3-5 pg/ml up to 240 pg/ml, p<0.001). This trend was similar in controls after surgical stress. Endothelin 1 was always undetectable in the BAL fluid, with a modest, but significant increase in pulmonary capillary blood of group A, after ECC, (from 11+/-4 pg/ml to 18+/-5 pg/ml, p<0.001). This increment correlated well with the PVR increase, but was transient and after 24 hours, ET1 values returned to baseline levels. Mean values of ET1 increased also in controls, but not significantly. CONCLUSIONS: ECC may induce ET1 liberation in pulmonary circulation with transient pulmonary vasoconstriction, but wihout intra-alveolar release, or lung damage. Augmented concentrations of IL6 probably express a response to surgical procedure rather than an effect exclusively related to ECC.

Adult↗