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At least 1,153 records · Page 64Linked to original sources
PubMed1993

In vivo monitoring of circulation in the intact anterior cruciate ligament using the laser Doppler flowmeter.

Laser Doppler flowmetry permits observation of circulation in the microcapillary regions of structures under in vivo conditions. We used a laser device manufactured by the Swedish company Perimed and a special probe to observe the capillary circulation in the anterior cruciate ligament during arthroscopic surgery. This produces measured values in millivolts; these values are relative in nature and cannot be used to determine an absolute value for capillary circulation by volume per unit time. Under standardized conditions, circulation measurements and simultaneous recordings with a two-channel recorder were made from 11 patients. In all cases, pulsations of the capillary circulation synchronous with the heart beat could be seen on three measuring points on the anterior cruciate ligament; these disappeared upon complete deprivation of blood supply. We found a large individual range of variation in the so-called blood cell flux values from 30 to 620 mV. The magnitude of the heart-synchronous pulsations ranged between 20 and 240 mV. Only vague linear relationships were found (a) between the individual measuring points and (b) between the flux values and the magnitude of pulsation; there was no relationship between the flux values and blood pressure and/or red blood count (erythrocyte count, hemoglobin, hematocrit).

Anterior Cruciate Ligament↗
PubMed1993

IL-2, IL-3, and IFN-gamma differently affect in vivo frequencies of circulating precursors of cytotoxic T lymphocytes (CTL-P).

Experimental animal and human in vivo studies have previously demonstrated the impact of exogenous administration of various cytokines on frequencies of circulating myeloid and LAK precursor cells. For the first time we investigated whether exogenous cytokines, in the absence of antigenic challenge, may also influence frequencies of circulating antigen-specific cytotoxic T-lymphocyte precursor cells. We further asked whether triggering of autoimmune pathways as has been reported for several cytokines can be confirmed on the cellular level by demonstration of induction of autoreactive CTL-p. Limiting dilution analysis was used to determine alloreactive CTL-p frequencies in 31 patients with nonhematologic diseases before and after short-term systemic treatment with either rIL-2 (4.8 x 10(6) IU/m2 bid), rIL-3 (2.5, 5.0 or 10.0 micrograms/kg qd), rGM-CSF (5 micrograms/kg qd), rIFN-gamma (200 or 400 micrograms qd), or IFN-alpha (3 or 5 x 10(6) IU qod). Simultaneously, autoreactive CTL-p frequencies were determined by split-well analysis in 25 of these patients. We found that rIL-2 significantly expands the circulating precursor pool of alloreactive CTL (p < 0.05). rIL-3 affected CTL-p frequencies in a dose-dependent fashion. Low and intermediate doses of rIL-3 did not exhibit significant effects, whereas 10 micrograms/kg rIL-3 led to expansion of alloreactive CTL-p in the same order of magnitude as did rIL-2. This effect was statistically significant when compared with rGM-CSF (p < 0.02), which apparently had no influence on alloreactive CTL-p frequencies. In contrast to rIL-2 and rIL-3, exogenous rIFN-gamma markedly reduced the circulating precursor pool of CTL. This again was statistically significant compared with rIFN-alpha (p < 0.03), which, like rGM-CSF, did not exhibit any effects on the level of alloreactive CTL-p. Frequencies of autoreactive CTL-p were invariably below the limit of detection in our system (< 1/300,000). In conclusion, these data demonstrate that (a) short-term systemic administration of rIL-2, rIL-3, and rIFN-gamma differently affects the clone size of circulating precursors of alloreactive CTL in man, while rGM-CSF and rIFN-alpha do not exhibit measurable effects, and (b) none of the cytokines administered is capable of uncovering detectable frequencies of autoreactive CTL-p.

Autoimmunity↗
PubMedDate not supplied

Beneficial effect of PGI2 on circulating endothelial cells.

Endothelial damage is an early event in atherogenesis. Recent data present evidence that the counting of circulating endothelial cells in human peripheral blood may provide reliable information about endothelial integrity. We therefore assessed the influence of PGI2 on the number of circulating endothelial cells in patients suffering from peripheral vascular disease. As cigarette smokers and patients with hyperlipoproteinemia show an increased number of circulating endothelial cells, they were excluded from this investigation. PGI2 causes a certain drop in circulating endothelial cells. In parallel, a prolongation in platelet half-life can be noted. This is most pronounced at a daily duration of infusion between 4 an 12 h. A shorter duration of PGI2 therapy is less effective in reducing circulating endothelial cells. All of the three different doses used, however, were equally effective. Placebo controls were ineffective. These findings indicate that PGI2 might exert a rather long-lasting beneficial action on endothelial integrity and the hemostatic balance.

Adult↗
PubMed1996

Circulating intercellular adhesion molecule-1 (ICAM-1) in patients with hepatolithiasis.

We evaluated the role of circulating intercellular adhesion molecule-1 in the pathogenesis of hepatolithiasis. From December 1994 to May 1995, 40 patients with hepatolithiasis were included. All the patients met the following criteria: (1) presence of hepatolithiasis, (2) no obvious clinical evidence of an associated intrahepatic cholangiocarcinoma, (3) no clinical manifestation of cholangitis for at least 72 hr, (4) no immunomodulatory agents in the last three weeks, and (5) no blood transfusion in the last three weeks. Venous blood samples were collected both before surgery and at least three months after complete clearance of the stones, and the serum concentrations of circulating intercellular adhesion molecule-1 were measured with a sandwich enzyme immunoassay method. Fifteen healthy subjects were used as a control group. Bile specimens routinely obtained during surgery were cultured for aerobes and anaerobes. The x-ray films of cholangiography were all reviewed in detail. The mean value (834 +/- 128 ng/ml) of circulating intercellular adhesion molecule-1 (ICAM-1) in the patient group before surgery was significantly higher than that (346 +/- 68 ng/ml) of the control group (P < 0.01). The mean value (677 +/- 139 ng/ml) of circulating ICAM-1 in the patient group at least three months after complete clearance of the stones was significantly lower than that (834 +/- 128 ng/ml) of the patients before surgery (P < 0.01), but this mean value (677 +/- 139 ng/ml) was still significantly higher than that (346 +/- 68 ng/ml) of the control group (P < 0.01). Bacteria was present in the bile of all patients. The total number of bacterial species was 135, and there were an average of 3.4 bacterial species cultured per patient. Intrahepatic stricture was demonstrated in cholangiography in 33 patients (82.5%). In addition to the high incidence of intrahepatic bile duct strictures and bile infection, a significant elevation in circulating intercellular adhesion molecule-1 (sICAM-1) was shown in patients with hepatolithiasis. Our preliminary results seem to be promising and the real role of sICAM-1 deserves further investigation and elucidation.

Adult↗
PubMed2001

Influences of female reproductive hormones on sympathetic control of the circulation in humans.

The significant increase in cardiovascular disease risk with the loss of estrogen and progesterone at menopause has lead to increasing interest in the cardiovascular influences of female reproductive hormones. In addition to direct influences of estrogen to promote endothelium-dependent vasodilation, recent evidence demonstrates important influences of both estrogen and progesterone on the neural control of the peripheral circulation. These influences have been studied in two general contexts. First, the effects of these hormones on the sympathetic control of the cutaneous circulation have received substantial attention. The control of neurogenic vasodilation in the skin in response to hyperthermia is shifted to higher and lower internal temperatures by progesterone and estrogen, respectively. Reflex vasoconstrictor control of skin blood flow is shifted to higher internal temperatures when the hormones are elevated. Second, reproductive hormones have recently been shown to significantly alter sympathetic neural control of the skeletal muscle circulation. Sympathetic neural control of the skeletal muscle circulation (measured directly as muscle sympathetic nerve activity [MSNA]) is altered by hormone status such that resting MSNA is decreased by estrogen, as is the MSNA response to exercise. Furthermore, the baroreflex control of MSNA is significantly modified by estrogen and progesterone. Therefore, female reproductive hormones have widespread influences on the sympathetic control of the circulation in humans. The individual influences of estrogen and progesterone often antagonize one another, and when both hormone concentrations are increased, the net effect probably depends on their relative concentrations and bioactivity. The mechanisms responsible for these influences and their health-related implications deserve further attention.

Female↗
PubMed1977

Substrate metabolism in the perfused lung: response to changes in circulating glucose and palmitate levels.

The effects of circulating levels of glucose and palmitate in the isolated perfused rat lung were investigated. Rat lungs were perfused for 1.5 hr with washed bovine erythrocytes (15% hematocrit) in Krebs-Henseleit bicarbonate buffer containing 5 g% bovine serum albumin. Glucose uptake in the perfused lung varied directly with circulating glucose concentration. Lactate production was affected proportionately more by high glucose levels than by low concentrations. Pyruvate production was decreased by both low glucose and palmitate concentration in the circulating medium. Oxidation of glucose to CO2 was depressed by low glucose and by high palmitate concentrations. Glucose incorporation into lung lipids was more strongly influenced by glucose concentration than by circulating palmitate levels. These data indicate acute changes in circulating levels of glucose and palmitate alone can act to either inhibit or stimulate glycolysis, glucose oxidation, and lipid synthesis in the perfused lung.

Animals↗
PubMed1996

[Determination of blood circulation time for optimizing contrast medium administration in CT angiography].

INTENTION: CT angiography of intracranial vascular lesions requires a constant and high intra-arterial concentration of the contrast medium over the period of data acquisition. The volume of the injected contrast medium can be minimized by exact timing of the bolus injection. Non-predictable interindividual variance of veno-arterial circulation time, e.g., in patients with impaired cerebral hemodynamics after subarachnoidal hemorrhage, requires determination of the appropriate prescan delay. METHODS: We used the CT scanner (Philips SR 7000) with a low-dose scan parameter to determine the veno-arterial circulation time with a bolus injection of 20 ml contrast medium IV and compared these values with the results of an algorithm (t = n x 60 x f-1) based on the duration of n = 12 heart actions. On CT seven scans (1-s scan time) without table feed were applied at the level of the circle of Willis 4 s after the beginning of contrast medium bolus injection (5 ml/s). An interscan delay of 4 s was used. A region of interest was placed exactly on the most evident part of one of the cerebral base arteries contralateral to pathology. RESULTS: In 35 patients we measured circulation times between 10 and 25 s, all of which were confirmed by CT angiography, which followed. There was no correlation with systolic or diastolic blood pressure, heart rate or body length, body weight or body surface. Differences of up to 18 s were seen between the measured and calculated circulation times. CONCLUSION: Transit time to peak concentration in cerebral vessels following antecubital bolus injection of contrast medium cannot be calculated on the basis of hemodynamic parameters or body measurement, even in patients without cardiopulmonary or occlusive vessel disease. The quick method presented for measurement of the veno-arterial circulation time with a test bolus of contrast medium using the CT scanner and scan parameters with low-radiation exposure provided an exact time setting and saved on the amount of contrast medium needed in CT angiography.

Adult↗
PubMed2005

Melanoma-specific tumor-infiltrating lymphocytes but not circulating melanoma-specific T cells may predict survival in resected advanced-stage melanoma patients.

PURPOSE: To study the effect of autologous tumor cell vaccinations on the presence and numbers of circulating CD8+ T cells specific for tumor-associated antigens (TAA) in metastatic melanoma patients. To investigate the correlation between the presence of tumor-infiltrating lymphocytes (TIL) and circulating TAA-specific CD8+ T cells before and after autologous tumor cell vaccination with overall survival. EXPERIMENTAL DESIGN: Twenty-five stage III and resected stage IV metastatic melanoma patients were adjuvantly treated with a series of intracutaneously injected autologous tumor cell vaccinations, of which the first two contained BCG as an immunostimulatory adjuvant. Tumor samples and blood samples obtained before and after vaccination of these patients were studied for the presence of TAA-specific T cells using HLA-tetramers and results were correlated with survival. RESULTS: In 5 of 17 (29%) melanoma patients, circulating TAA-specific T cells were detectable prior to immunizations. No significant changes in the frequency and specificity were found during the treatment period in all patients. Presence of circulating TAA-specific T cells was not correlated with survival (log rank, P=0.215). Inside melanoma tissue, TAA-specific TIL could be detected in 75% of 16 available tumor samples. In case of detectable TAA-specific TIL, median survival was 22.5 months compared to median survival of 4.5 months in case of absence of TAA-specific T cells (log rank, P=0.0094). In none of the patients, TAA-specific T cells were found both in tumor tissue and blood at the same time. CONCLUSIONS: These data suggest that the presence of TAA-specific TILs forms a prognostic factor, predicting improved survival in advanced-stage melanoma patients. The absence of TAA-specific T cells in the circulation suggests that homing of the tumor-specific T cell population to the tumor site contributes to the effectiveness of antitumor immunity.

Adjuvants, Immunologic↗
PubMed2005

The effect of circulating nitric oxide level on axial bone mineral density in postmenopausal Turkish women with rheumatoid arthritis: A preliminary report.

The aim is to investigate the differences in the circulating nitric oxide (NO) levels of rheumatoid arthritis (RA) patients, healthy controls and osteoporotic (OP) patients. We also examined whether the circulating NO levels may be correlated with bone mineral density (BMD) in RA patients. Forty-five patients with RA, 30 healthy women and 30 osteoporotic patients were recruited from the outpatient clinic. All the subjects were female and postmenopausal. Serum NO levels were measured (Nitrite/Nitrate, calorimetric method 1746081, Roche diagnostics, Mannheim, Germany) and BMD was measured at the spine and hip using dual energy X-Ray absorbtiometry (DEXA, Norland XR-46). Height and weight were measured and body mass index was calculated. Circulating NO levels were significantly higher in RA patients than other groups. Moreover, the RA group showed significantly higher BMD at lumbar spine and femoral neck regions compared to osteoporotic patients. However, the RA group showed significantly lower BMD at all sites than the controls. There was no correlation between circulating NO levels and BMD in all groups. We suggest that, unlike postmenopausal osteoporosis, inflammation induced osteoporosis is associated with RA is characterised by relatively preserved bone mass at the axial bone regions, and circulating NO levels as a parameter or determinant of inflammation are not correlated with axial BMD in RA patients.

Arthritis, Rheumatoid↗
PubMed2001

Effect of local blood circulation and absolute torque on muscle endurance at two different knee-joint angles in humans.

The effects of the local blood circulation and absolute torque on muscle endurance at different knee-joint angles were determined. The rate of muscle deoxygenation (using near-infrared spectroscopy), and the rate of muscle fatigue (using the slope of integrated electromyography, iEMG) were evaluated concurrently. Nine healthy subjects performed submaximal (50% maximal voluntary contraction. MVC) static knee extension at 50 degrees (extended position, EXT) and 90 degrees (flexed position, FLEX) joint angles until the target torque could no longer be maintained: that time was measured as the endurance time. They exercised with the circulation occluded (OCCL), and without (FREE) to study the possible effects of the local circulation. Although MVC torque was independent of joint angle [mean (SD) FLEX 250.6 (51.7) Nm and EXT 246.5 (46.6) N x m], significantly shorter (P<0.01) endurance time in FLEX [FREE 71.1 (10) s and OCCL 63.1 (8.8) s] than at EXT [FREE 115.3 (30) s and OCCL 106.7 (29.1) s] were obtained in both circulatory conditions. The iEMG-time slope was significantly greater in FLEX at the proximal and distal portion (P<0.05) in both circulatory conditions. Muscle deoxygenation rate in OCCL was significantly greater (P<0.05) at FLEX [20.8 (8.0)%] than EXT [10.9 (4.0)%]. The results would suggest that different knee-joint angle affects muscle endurance even if the local circulation is controlled. Circulatory disturbance would further reduce muscle endurance in EXT, but not in FLEX. Because of the greater muscle internal force in FLEX, local blood flow might be already limited even with a free circulation. The greater muscle deoxygenation and muscle fatigability would be related to the shorter muscle endurance in FLEX.

Adult↗
PubMed2001

Direct evidence for genome segment reassortment between concurrently-circulating human rotavirus strains.

Extensive heterogeneity in electropherotypes observed among group A human rotaviruses has been considered as a result of two major mechanisms; i.e., the accumulation of point mutations and genetic reassortment between concurrently-circulating strains. However, no evidence was reported thus far indicating that any one of field isolates of rotavirus was formed by direct reassortment of concurrently circulating two parental strains. Comparison of the genome of human rotavirus specimens collected over a six year period by electropherotyping and by the sequencing of selected gene segments identified two reassortants that were generated in nature between strains circulating co-dominantly in the same epidemic season. This is the first report directly showing that at least some part of electrophoretic diversity observed among rotavirus strains was explained by genetic reassortment between strains concurrently circulating in the human population. This supports the hypothesis that genetic reassortment among co-circulating strains operates as a key mechanism for the genetic variability of rotaviruses in nature.

Base Sequence↗
PubMed2004

Decreased frequency and function of circulating plasmocytoid dendritic cells (pDC) in hepatitis B virus infected humans.

The Type 2 precursor plasmacytoid dendritic cells (pDC) represent the most important cell type in antiviral innate immunity. To understand the function of pDC during hepatitis B virus infection, the frequency and function of circulating pDC were analyzed by flow cytometric analysis, and IFN-alpha secretion of total PBMCs was determined by ELISA assay in 25 healthy subjects and 116 patients at various stages of chronic hepatitis B virus infection (CHB). The number of circulating pDC was found to be significantly lower in patients with CHB and associated liver cirrhosis (LC). The ability of PBMCs to secrete IFN-alpha also decreased significantly. There was a corresponding decrease of circulating NK cells and CD8+ T cells. We observed that lamuvidine antiviral therapy restored the number of circulating pDC and there was a reversal of pDC frequency with the control of HBV replication in chronic HBV patients, indicating these subjects are unlikely to be totally immunocompromised. The decrease of pDC was found to be related to nosocomial infections in LC patients. Our results suggest that CHB patients probably have a quantitative and qualitative impairment of circulating pDC or NK cells, which may be associated with HBV persistent infection as well as the nosocomial infections that arise in LC patients.

Adult↗
PubMed2000

Circulating IL-2 and IL-10 in chronic active hepatitis C with respect to the response to IFN treatment.

BACKGROUND: The importance of circulating immunoregulatory cytokines in response to IFN treatment and the change of in vivo production of these cytokines during interferon (IFN) treatment are not well known. We aimed to determine whether pretreatment serum levels of IL-2 and IL-10 are predictive of the response to IFN treatment and to investigate if treatment response or nonresponse has any effect on the circulating levels of these cytokines. PATIENTS AND METHODS: 37 patients (18 responders and 19 non-responders) with chronic hepatitis C virus (HCV) infection who received IFN-alpha2b for 6 months were studied. Responders were defined by complete alanine aminotransferase (ALT) normalization and loss of HCV RNA as detected by bDNA assay while patients who had elevated ALT levels and positive HCV RNA after 6 months were considered as nonresponders. RESULTS: Genotype distribution, ALT and HCV RNA levels were similar in responders and nonresponders. A significant number of patients with chronic hepatitis C (20/37 = 54%) had elevated IL-2 levels while IL-10 levels were not different from controls. No difference in baseline cytokine levels was observed between responders and non-responders. In the posttreatment serum samples some patients lost their detectable IL-2 or IL-10; some patients developed detectable cytokine levels after treatment irrespective of the treatment response. CONCLUSION: These results suggest that active liver injury in chronic hepatitis C is associated with increased circulating Th1 cytokine IL-2 but not with Th2 cytokine IL-10 and that circulating levels of these cytokines do not predict the response to IFN treatment. There is no constant and regular change in circulating levels of these cytokines under IFN treatment with respect to treatment response.

Adult↗
PubMed1977

Effect of plasma exchange on circulating immune complexes and antibody formation in patients treated with cyclophosphamide and prednisone.

A patient with systemic lupus erythematosus (SLE) and a patient with an immune complex disease resembling Goodpasture's syndrome were treated with cyclophosphamide, prednisone and repeated plasma exchanges. Circulating immune complexes decreased, and symptoms of central nervous system disease remitted for up to 15 to 20 days after plasma exchange in the patient with SLE. In vitro lymphocyte blastogenic responses to antigens were also transiently increased on two occasions following treatment. In the second patient, decreases in circulating immune complexes and clinical improvement were ascribed chiefly to immunosuppressive drug treatment. Serum antibody to keyhole limpet hemocyanin was relatively unaffected by plasma exchange in both patients. These results suggest that plasma exchange may help to deplete circulating immune complexes or alter the equilibrium between soluble antigen and antibody which causes complexes to form and circulate. It may be less effective in reducing circulating antibody levels in patients who continue to produce new antibody.

Adult↗
PubMed1990

Inhibition of stress-induced gastric mucosal injury by a long acting superoxide dismutase that circulates bound to albumin.

To determine whether oxygen-derived free radicals play an important role in the pathogenesis of stress-induced tissue injury, the effect of a superoxide dismutase derivative, which binds to albumin and circulates with a half-life of 6 h in intact rats, on acute gastric mucosal lesion was observed in rats which were given water-immersion-restraint. This enzyme derivative also circulated bound to albumin with a half-life of 8 h in rats which were challenged with water-immersion-restraint. This treatment significantly perturbed systemic circulation of animals by decreasing the effective volume of circulating blood, increased vascular permeability of the gastric mucosa, and induced acute gastric mucosal lesion. Intravenous administration of this enzyme derivative normalized both systemic circulation and vascular permeability of the gastric mucosa and prevented the occurrence of stress-induced gastric injury. These findings suggest that the superoxide radical and/or its metabolite(s) plays an important role in the pathogenesis of stress-induced acute gastric mucosal lesion.

Animals↗
PubMed1991

Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target.

Dioleoyl-N-(monomethoxy polyethyleneglycol succinyl)-phosphatidylethanolamine (PEG-PE) (mol. wt. of PEG = 5000), an amphipathic polymer, can be incorporated into the liposome membrane and significantly prolong the blood circulation time of the liposome. As little as 3.7 mol% of PEG-PE in liposome resulted in maximal enhancement of liposome circulation time. However, this activity of PEG-PE was only seen with relatively small liposomes (d less than or equal to 200 nm); larger liposomes containing PEG-PE showed an unusually high level (approx. 35% injected dose) of accumulation in the spleen. We have tested whether the small, PEG-PE containing liposomes are suitable for immuno targeting by incorporating a lung-specific monoclonal antibody on the liposome surface. While another amphiphile, ganglioside GM1, which is well known for its activity to prolong the liposome circulation time, significantly enhanced the lung binding of the immunoliposomes, PEG-PE incorporation of immunoliposomes resulted in a low level of target binding. To test if the reduced target binding is due to a steric barrier effect of the surface PEG polymer, we have incorporated a small amount of N-biotinaminocaproylphosphatidylethanolamine into the PEG-PE containing liposomes and examined the liposome agglutination induced by the addition of streptavidin. As little as 0.72 mol% PEG-PE in these liposomes completely abolished agglutination. In contrast, incorporation of GM1 in liposomes only reduced the rate, but not the extent, of liposome agglutination. These results strongly support the hypothesis that PEG-PE prolongs liposome circulation time by providing a strong steric barrier which prevents close contact with another liposome or cell. Since GM1 provides only a weak steric barrier effect, its activity to prolong the liposome circulation time must involve another yet unknown mechanism.

Agglutination↗
PubMed1990

Low density lipoprotein-containing circulating immune complexes and coronary atherosclerosis.

Blood serum of most patients with coronary heart disease (CHD) caused a 2- to 5-fold increase in the lipid content of smooth muscle cells cultured from unaffected human aortic intima, i.e., possessed an atherogenic potential manifested in culture. Treatment of the CHD patients' serum with 2.5% polyethylene glycol 6000 removed the circulating immune complexes. The serum subjected to this treatment lost its atherogenic properties, i.e., failed to increase the content of lipids in cultured cells. Incubation of smooth muscle cells derived from human aortic intima with circulating immune complexes isolated from an atherogenic patient's serum caused a 1.5- to 3-fold rise in the intracellular cholesterol. Circulating immune complexes contained apolipoprotein B (apo B), but not apolipoproteins A1 and E. The apo B content strongly correlated with the total cholesterol content. The cholesterol/apo B ratio of the complexes was characteristic of low density lipoproteins (LDL), but not of very low density lipoproteins or intermediate density lipoproteins. The composition of the main lipid classes in these complexes was similar to that in LDL. Blood sera of most (90%) CHD patients was characterized by a high cholesterol and apolipoprotein B content in circulating immune complexes. The ability of these sera to induce lipid accumulation in cultured cells directly correlated with the cholesterol and apolipoprotein B level of circulating immune complexes (r = 0.91). These findings suggest that the atherogenic potential of CHD patients' blood serum is due to LDL-containing immune complexes.

Adult↗
PubMed1996

Characteristics of low density lipoprotein isolated from circulating immune complexes.

Circulating immune complexes (CIC) containing low density lipoprotein (LDL) were recently found in the blood of patients with coronary atherosclerosis. In the present study, we investigated the chemical composition and physical characteristics of the lipoprotein constituents of these CIC. CIC were isolated from the blood of atherosclerotic patients by affinity chromatography using anti-human immunoglobulin G-agarose. Low density lipoprotein of these complexes (CIC-LDL) was obtained by ultracentrifugation. CIC-LDL was compared with free circulating LDL isolated from the blood plasma of the same patients. Plasma LDL was fractionated by lectin-chromatography on RCA120-agarose to obtain desialylated LDL (atherogenic) and sialylated LDL (nonatherogenic). Both CIC-LDL and desialylated LDL, but not native (sialylated) lipoprotein, induced a 1.8- to 3-fold increase in the intracellular contents of free and esterified cholesterol of cells cultured from grossly normal areas of human aorta. The sialic acid level in CIC-LDL was 1.3- and 2.1-fold lower than in desialylated or native LDL, respectively. The neutral lipid and phospholipid contents of CIC-LDL and desialylated LDL were reduced as compared to native LDL. The levels of lipid-oxidation products, thiobarbituric acid-reactive substances and hydroperoxides, were similar in all lipoprotein preparations. However, desialylated LDL and CIC-LDL had an elevated oxysterol content. Gradient ultracentrifugation revealed that CIC-LDL particles had a higher density than native LDL. The mean diameters of native, desialylated and CIC-LDL accounted for 24.0, 21.3 and 19.5 nm, respectively. Like desialylated LDL, CIC-LDL displayed a higher electrophoretic mobility compared with that of native LDL. Thus, LDL obtained from circulating immune complexes appears to be a multiple-modified lipoprotein possessing many similarities to desialylated LDL. It was also found that the LDL content of circulating immune complexes correlates well with the desialylated LDL level in human plasma but not with the total LDL concentration. We believe that desialylated LDL predominately interacts with antibodies forming immune complexes. Taken together, our findings suggest that multiple-modified desialylated LDL is the circulating autoantigen for anti-LDL autoantibodies.

Adult↗