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Circulating BFU-E in sickle cell anemia: relationship to percent fetal hemoglobin and BPA-like activity.

Circulating 14-day erythroid progenitors (BFU-E) from sickle cell anemia (SS) patients were studied in culture to determine their frequency and their sensitivity to erythropoietin (Epo). Increased numbers of circulating BFU-E were found in half of the patients studied, whereas the remainder had a normal count. Patients with high circulating BFU-E counts had lower fetal hemoglobin (HbF) percentages (congruent to 4.5%) than patients with low circulating BFU-E counts (HbF congruent to 13%). This difference was highly significant (p less than 0.0001). In addition, SS circulating BFU-E expressed increased sensitivity to Epo due, at least partially, to an increased production of burst-promoting activity-like factor(s) generated by light-density mononuclear cells. These findings emphasize the possible role of the HbF level (and the extent of sickling) in BFU-E regulation under the continuous hemopoietic stress of SS disease.

Adult↗

In vivo effects of recombinant IL-2. I. Isolation of circulating Leu-19+ lymphokine-activated killer effector cells from cancer patients receiving recombinant IL-2.

This study was designed to isolate and phenotypically characterize lymphokine-activated killer (LAK) cells generated in vivo during administration of high dose rIL-2 to cancer patients. The development of circulating LAK effector cells in these patients was demonstrated by the ability of fresh PBL to exhibit lytic activity against the NK-resistant Daudi cell line and fresh tumor cells without prior in vitro culture with rIL-2. Kinetic studies demonstrated that circulating LAK effector cells are detectable 4 to 6 wk after the initiation of rIL-2 therapy. Cells isolated by FACS revealed that circulating LAK cells are Leu-19+, Leu-17+ but CD5-. We have previously reported that circulating Leu-19+ cells are heterogeneous with regard to the expression of CD16 and CD8. Since sorting of cells expressing Leu-19 and either low quantities of CD8 or CD16 resulted in cytolytic activity in both the positive and negative fractions, these latter two markers do not identify subpopulations of Leu-19+ cells with or without LAK cytolytic activity. Although all LAK cells generated in vivo were Leu-19+, we generated LAK cells from the Leu-19- subpopulation after in vitro culture with rIL-2, suggesting that at least some of in vitro generated LAK cells are derived from Leu-19- precursor cells. These LAK cells did not, however, express the Leu-19 surface marker. Based on the functional data reported in this paper, we conclude that circulating LAK effector cells are a phenotypically heterogeneous population that express surface Ag in association with NK cells and not T lymphocytes.

Antigens, Neoplasm↗

Failure of chronic theophylline therapy to alter circulating catecholamines.

An increase in circulating adrenaline and noradrenaline has been reported following acute dosing with theophyllines. This effect on catecholamines has been proposed as a possible mechanism of action of theophyllines. In a double-blind placebo controlled trial we have studied the effects of 5 days oral theophylline therapy on circulating catecholamines and adrenaline clearance. There were no significant changes in circulating catecholamines or adrenaline clearance following theophylline. We also examined the effects of theophylline on the hypokalaemic and haemodynamic actions of adrenaline. Theophylline increased the hypokalaemia, tachycardia and rise in systolic blood pressure which occurs in response to intravenous infusion of doses of L-adrenaline (0.02-0.06 microgram kg-1 min-1). Our results suggest that chronic theophylline therapy does not significantly increase circulating catecholamines. Increased circulating catecholamine concentrations are thus not an explanation for the chronic actions of theophylline. We have demonstrated significant, potentially hazardous metabolic and haemodynamic interactions between theophylline and adrenaline.

Adult↗

Activation, proliferation, and differentiation of circulating B cells in autoimmune thyroid disease.

Several studies of thyroid autoantibody production in vitro have been reported with the use of pokeweed mitogen, but the conclusions that have resulted regarding the immunoregulation of B cell function in thyroid disease are difficult to interpret due to the relatively nonphysiologic nature of pokeweed mitogen stimulation. We have therefore examined the responses of circulating B cells in Graves' disease and Hashimoto's thyroiditis by using a combination of lymphokines and other stimuli that act at various stages of the B cell cycle. In patients with autoimmune thyroid disease, nonspecific B cell proliferation and differentiation into IgG-secreting cells were both normal. However, a previously unsuspected heterogeneity among patients was found in their ability to produce autoantibodies in vitro. B cells of certain patients produced maximal autoantibody in response to pokeweed mitogen, some in response to Staphylococcus aureus Cowan strain I, and some in response to the lymphokines contained in the supernatants of stimulated T cell cultures. There was no correlation between serum autoantibody levels and those achieved in vitro. Attempts to stimulate antibody production by autoantigen (thyroglobulin) were unsuccessful, even when B cells were cultured with purified autologous OKT4+ T cells to avoid potential suppressor effects in the OKT8+ population. However, OKT4+ T cells enhanced pokeweed mitogen-driven autoantibody production. Our results show that several different functional stages of B cells exist in the circulation of patients with autoimmune thyroid disease, and that circulating B cells from such patients do not manifest a uniform response to B cell stimulators. This is presumably the result of differences in migration of circulating B cells and in their level of activation at the major sites of autoantibody production, such as the thyroid gland itself. In the light of these findings, caution is required in interpreting the results obtained from studies of circulating B cells as a means of elucidating the pathophysiology of autoimmune thyroid disease.

Autoantibodies↗

[Vertebral angiography of cerebellar astrocytoma-tumor stain, tumor circulation, CT and angiography in diagnosis (author's transl)].

Twelve cases of cerebellar astrocytoma experienced in the Department of Neurosurgery, Hokkaido University School of Medicine were examined primarily for tumor stain and pathological tumor circulation by angiography. In addition, comparison on neuroradiological findings between cerebellar astrocytoma and hemispheric supratentorial astrocytoma (low-grade) was carried out, and neuroradiological differential diagnosis of cerebellar astrocytoma and cerebellar hemangioblastoma was discussed on the basis of the present results and those which were already reported by other investigations and the authors. The results are as follows: 1) Tumor stain was observed in only one case. A tumor was demonstrated as an avascular mass in the remaining 12 cases. 2) Demonstration of cerebellar astrocytoma as hypovascular or avascular masses was related to their low-grade malignancy in histology and cystic nature in gross appearance, as already pointed out. Furthermore, the present study suggested that mural nodules of cystic lesions should have certain weight and sizes so that they could be demonstrated as tumor stain. 3) Abnormal findings concerning tumor circulation were mostly limited to the cases with tumor stain. Early filling veins were not found in any case. Neither feeding artery nor draining vein was clearly identified in some cases. In addition, the abnormal vessels lacked hypertrophic and tortuous changes. 4) In the supratentorial region, five of the 12 low-grade astrocytoma exhibited abnormal tumor stain and tumor circulation by cerebral angiogram and we think that supratentorial and posterior fossa astrocytoma must usually exhibit different pathological tumor circulation by cerebral angiogram, since each group has distinctive clinical and biological characteristics. 5) CT was performed in 7 of 13 cases. It appeared to be more useful than cerebral angiography in the morphological diagnosis Especially in cystic tumors, CT produced minute information concerning peritumoral edema, enhancement of margin of cystic astrocytoma after intravenous contrast medium, and marginal enhancement with layering in the dependent part of the cyst. 6) Neuroradiological different diagnosis of cerebellar astrocytoma and cerebellar hemangioblastoma by CT was difficult in our cases of cystic tumors. However, both tumors were differentiated from each other with ease by tumor stain and tumor circulation in cerebral angiography, since cerebellar astrocytoma was lacking in abnormal vessels, whereas cerebellar hemangioblastoma was marked by many abnormal vessels. Thus, we concluded that cerebral angiography is superior to CT in differential diagnosis between cerebellar astrocytoma and cerebellar hemangioblastoma.

Astrocytoma↗

Effect of treatment on retinal circulation, platelet aggregation and blood viscosity in insulin-dependent and noninsulin-dependent diabetics.

In order to investigate the influence of diabetic treatment, especially insulin treatment on diabetic retinopathy, disc-to-macula circulation time, platelet aggregation and blood viscosity were observed before and after treatment for 5 years in 42 diabetics (17 insulin-dependent diabetics [IDD] and 25 noninsulin-dependent diabetics [NIDD]). The disc-to-macula circulation time was significantly correlated with the mean blood glucose level. The platelet aggregation in IDD was enhanced significantly as compared with that in NIDD, however after treatment with insulin, the platelet aggregation revealed a significant decrease in IDD. The inter-period changes in the disc-to-macula circulation time before and after treatment in IDD were correlated with those of platelet aggregation, but not with those of blood viscosity. These results suggested that although the blood glucose level was considered to be one of the important factors influencing the retinal circulation, insulin had a direct effect on the platelet function in improving the retinal circulation in addition to lowering the blood glucose level.

Adult↗

[Circulating immune complexes in patients with lymphoproliferative and myeloproliferative diseases].

Circulating immune complexes have been studied with a competitive immune-enzymatic method on 9 controls, on 34 patients with lymphoproliferative disease (41.6 +/- 26.8) and in those with myeloproliferative disease (62.1 +/- 30) have been found significantly higher than in controls (20.3 +/- 14.1). The percentage of incidence of circulating immune complexes with values greater than 35 (normal value greater than 35) is found to be 58.8% in lymphoproliferative disease and 77.7% in myeloproliferative disease. Higher values of circulating immune complexes have been observed in patients with a depressed count of circulating monocytes, of lymphocytes with a dot-like alpha-naphthyl-acetate-esterase reaction and of nitroblue tetrazolium positive granulocytes, suggesting that circulating immune complexes can modulate cellular immune response as blocking factors.

Adolescent↗

Cell surface carbohydrate recognition and the viability of erythrocytes in circulation.

The presence of sialic acid on the cell surface is crucial for the survival of mammalian erythrocytes in circulation. In contrast, sialidase-treated chicken erythrocytes retain their viability in circulation. Galactose oxidase treatment of chicken red blood cells has no effect on their viability. However, after sialidase treatment, galactose oxidase treatment results in the rapid elimination of the chicken erythrocytes from circulation. This is compatible with the interpretation that consecutive treatment with the 2 enzymes abolishes the ability of the chicken erythrocytes to regenerate the sialic acid on the cell surface. Mammalian asialo-erythrocytes are sequestered in the liver and spleen. We have shown that at the cellular level there is a preferential recognition of sialidase-treated as compared to normal erythrocytes by mononuclear spleen cells and Kupffer cells of the liver. This recognition manifests itself in both autologous and homologous systems by rosette-like adhesions. These adhesions may represent the normal physiological mechanism for the removal of senescent erythrocytes from circulation by liver and spleen since it has been previously reported that older erythrocytes contain decreased amounts of sialic acid. The mechanisms in mammals for the elimination from circulation of asialo-erythrocytes and asialo-glycoproteins, while analogous in many respects, are definitely not identical.

Animals↗

Circulating immune complex levels in patients with molar pregnancy.

Circulating immune complex levels were measured in patients with molar pregnancy to investigate the relationship between circulating immune complex and trophoblastic tumor burden. When 27 (87%) of 31 patients with molar pregnancy were first seen, circulating immune complex values were in the normal range. Three of the 4 patients with elevated levels had concurrent medical illness. Eighteen patients were followed with serial measurements until gonadotropin remission was achieved and all 18 patients developed increased levels as they entered remission (P less than .001). Circulating immune complex values remained elevated during gonadotropin remission from 6 to 16 weeks and then declined to initial levels. Further investigation should be undertaken to evaluate possible interactions between circulating immune complex and host immune defenses.

Antibody Formation↗

[Circulating anticoagulant, recurrent abortions and venous thrombosis: a new entity or a pre-lupus syndrome? 2 cases].

The authors report the presence of a circulating anticoagulant in two patients who had suffered multiple abortions. The circulating anticoagulant was discovered during evaluation of repeated phlebothromboses in the first case and of a chronic inflammatory syndrome in the second. While the apparently paradoxical relationship between the circulating anticoagulant and venous thrombosis is relatively well-known, that between the circulating anticoagulant and repetitive abortions is more difficult to establish. The rarely reported association of these three events leads us to a discussion of the nosologic place of this pathology and of the common ground it shares with S. L. E., as the circulating anticoagulant is of the antiprothrombinase variety, the antibody commonly called the lupus anticoagulant.

Abortion, Habitual↗

Effect of protein synthesis inhibition by cycloheximide on lymphocyte circulation.

BACKGROUND: Lymphocyte recirculation is directed by glycoprotein adhesion molecules on lymphocytes and endothelial cells of lymphoid tissues. Lymphocyte circulation in different lymphoid tissues is dependent on the type of glycoprotein adhesion molecules present. In the present study, the effects of inhibiting new protein synthesis on the ability of lymphocytes to circulate and home to different lymphoid tissues was investigated. EXPERIMENTAL DESIGN: New Zealand White rabbits and Lewis white rats were treated with cycloheximide or buffer. Total circulating lymphocyte counts and lymphocyte subsets were measured. Rabbits were given autologous, 111indium-labeled lymphocytes to determine if there were changes in the organ distribution of lymphocytes after cycloheximide treatment. RESULTS: After cycloheximide treatment, the number of circulating lymphocytes but not neutrophils increased significantly by 2 hours in both rabbits and rats. T cells, B cells, and L-selectin-positive lymphocytes showed similar increases. Measurements of the distribution of the radiolabeled, autologous lymphocytes in cycloheximide-treated animals showed significantly greater numbers circulating in the peripheral blood and decreased numbers in Peyer's patches, mesenteric lymph nodes, and spleens compared with controls. In contrast, the number of radiolabeled lymphocytes in the lung was not decreased after cycloheximide administration. CONCLUSIONS: These results indicate that protein synthesis inhibition causes lymphocytosis due to decreased lymphocyte homing to mesenteric nodes, Peyer's patches, and spleen, but not lung. This effect was not specific for distinct lymphocyte subsets, including T cells, B cells, or lymphocytes expressing L-selectin. These data show that molecules modulating lymphocyte homing in some organs have rapid turnover rates and suggest that changes in homing during the inflammatory process can be rapidly regulated by changes in protein translation.

Animals↗

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils.

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1-antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.

Adult↗

In vivo biotinylation demonstrates that reticulated platelets are the youngest platelets in circulation.

In both mice and humans, a subset of platelets can be identified that shows increased labeling with nucleic acid-specific fluorescent dyes, such as thiazole orange. Termed "reticulated platelets," they have been postulated to be platelets that have recently entered the circulation. Their numbers appear to reflect the rate of new platelet production in a number of clinical and experimental situations. To determine whether reticulated platelets really are the youngest platelets in circulation and to estimate the length of time that they are identifiable after entering the circulation, we have employed a technique of "in vivo biotinylation" in mice that labels the entire cohort of circulating cells with covalently bound biotin. Blood samples can then be double-labeled with fluorescent avidin derivatives and thiazole orange, permitting correlated measurement of both surface biotin content and nucleic acid content. The biotinylation occurs rapidly, is complete within 30 minutes, is stable for several days, and does not appear to alter platelet function. The results show that within 24 hours after in vivo biotinylation, platelets appear in the circulation with decreased levels of biotinylation and that these are the reticulated platelets. The estimated lifespan of reticulated platelets is 1.8 days, and the lifespan of all platelets by this method is 4.5 days, which is in agreement with estimates made by other methods.

Animals↗

Anti-idiotype antibodies and circulating immune complexes after immunisation with tetanus-toxoid.

OBJECTIVES: To determine if anti-idiotype antibodies and circulating immune complexes in individuals before and after immunisation with tetanus toxoid play a role in the immune response. DESIGN: A study of individuals who were administered a single dose of tetanus toxoid (TT) and who were unimmunized. SETTING: Out patient departments of a large public hospital in Bombay, India. SUBJECTS: Thirty eight individuals pre-immunisation and forty five individuals post-immunisation with tetanus toxoid, tested at 1, 3, 6, and 12 months. MAIN OUTCOME MEASURE: Development of anti-tetanus anti-idiotype antibodies and circulating immune complexes. RESULTS: Pre-immunisation cases did show presence of anti-tetanus antibodies but in lower titres than post-immunisation up to six months, after which there was a reduction. Specific anti-idiotype antibodies were detected in 19 cases. One and three months after immunisation more cases had high titre antibodies and circulating immune complexes, though after six months, there was a fall in anti-tetanus antibody titres. Circulating immune complexes were seen in those samples having anti-idiotype antibodies. CONCLUSIONS: Though a significant rise in anti-tetanus antibody anti-idiotype antibodies, protective levels in mice and circulating immune complexes are seen after immunisation with TT it lasts for six months. When followed up for a period of one year it is observed that in cases having auto anti-idiotype antibodies, the anti-tetanus antibodies are maintained for a longer period.

Antibodies, Anti-Idiotypic↗

Aplastic anemia with circulating erythroblasts.

Since the presence of erythroblasts (Ebl) in the peripheral blood of patients suspected to have aplastic anemia (AA) has been thought to suggest an error in diagnosis, such patients may not receive appropriate therapy promptly, with potentially fatal results. However, we recently experienced patients who had the typical features of AA except for circulating Ebl, and responded well to therapy for AA. In this study, we examined 55 untreated AA patients for the presence of circulating Ebl. Seven patients (12.7%) had circulating Ebl (at least one Ebl per 200 leukocytes counted). These seven patients showed the typical features of AA. There were no significant differences in age or hematologic parameters, including the morphology of bone marrow Ebl, between the AA patients having circulating Ebl (Ebl(+) AA) and the AA patients without Ebl. All but one of the Ebl(+) AA patients responded well to the therapy for AA. During 12.0-110.4 months of follow-up, transformation to other diseases did not occur, and all seven patients were alive. We conclude that circulating Ebl are not rare in patients who have otherwise typical features of AA, and that if such Ebl(+) AA patients are severely cytopenic, they should receive treatment for AA without delay.

Adolescent↗

[A surveillance system for the study of the circulation of influenza in Madrid during the 1986-1991 quinquennium. The Influenza Surveillance Group of Madrid].

BACKGROUND: The creation of a surveillance system allowing the study of the evolution of the tendency of influenza and act as an alert system for undertaking control measures is necessary due to the great variability characteristic of the circulation of influenza virus. The Madrid Influenza Surveillance Group was therefore designed. The activity carried out during its first five years of existence is evaluated. METHODS: The field work of the Group is based on the clinical study of patients with influenza, among which some are selected for virologic study with the aim to isolate and characterize the circulating virus. The data obtained by the work group itself are used as the dates of the System of Obligatory Disease Declaration and the System of Microbiologic Information as epidemiologic support to define the outbreaks observed. RESULTS: All the virus isolated were similar to those recommended by the World Health Organization for their inclusion in anti-influenza vaccination, with their circulation being largely reproduced throughout Europe. In three of the five seasons studied the type A virus prevailed leading to earlier outbreaks and a greater number of cases than in the two seasons with type B prevalence. CONCLUSIONS: The circulation of the influenza virus in Madrid coincides with that of the rest of Spain at both the maximum peak and relative incidence as well as the type of prevailing virus. The minor circulation detected by the Madrid Group is in concordance with the data provided by the other autonomic communities.

Disease Outbreaks↗

[A method for measurement of circulating blood volume with fluorescein isothiocyanate labeled red blood cells].

We developed a new method to measure the total circulating blood volume using fluorescein isothiocyanate (FITC) labeled autologous red blood cell as an indicator. Red blood cells were labeled by incubation with 0.1 mg.ml-1 FITC in PBS (pH 7.2) for 30 min at 37 degrees C. Eighteen dogs were given an intravenous injection of FITC labeled red blood cells, which were approximately 0.1% of the total circulating red blood cells estimated from the body weight. The ratio of labeled cells to the normal circulating red blood cells was determined by a flow cytometry. The total blood volume was calculated from its dilution rate. The average circulating blood volume determined by this method was 76.8 +/- 9.2 ml.kg-1 (mean +/- SD). This result coincides well with the values reported previously. This method using non radioactive tracers enables a reproducible measurement of circulating blood volume and its change with time.

Animals↗

[New findings about placental circulation using ultrasound].

Introduction of transvaginal color Doppler has enabled precise analysis of placental circulation in early pregnancy. The purpose of this paper is to summarize the current understanding of the anatomy and physiology of the early placental circulation. Study of uteroplacental circulation has demonstrated a progressive decrease of peripheral resistance from large toward small branches during first and early second trimester of pregnancy. Doppler study of umbilical circulation has also shown a significant fall of resistance from umbilical artery to its branches. Analysis of uteroplacental circulation in abnormal early pregnancy has shown differences in comparison with normal values. Using of transvaginal color Doppler in early pregnancy is not successful in prediction of abnormal late pregnancy. Color Doppler is useful in diagnosis of placental and umbilical cord pathology. The duration of pulsed Doppler examination in early pregnancy should be reduced to minimum if we want to avoid excessive heating of embryonic tissue.

Female↗