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Effect of arterial compliance on carotid sinus baroreceptor reflex control of the circulation.

Capacitive properties of the arterial and venous segments of the peripheral circulation are important in the regulation of cardiac output and arterial blood pressure. We examined whether an acute increase in arterial compliance C(a) would alter carotid sinus baroreflex control of the circulation. Eight mongrel dogs were anesthetized with pentobarbital sodium, and the carotid sinus regions were isolated and perfused with nonpulsatile pressures. Open-loop baroreflex response curves for systemic arterial pressure (SAP), heart rate (HR), aortic blood flow (ABF), peripheral vascular resistance (PVR), and left ventricular (LV) contractility were obtained when carotid sinus pressure (CSP) was changed in 25-mmHg steps between 50 and 200 mmHg under a control condition and when C(a) was increased by including two hydraulic compliant chambers to the arterial circulation (CS 1.72 ml/mmHg and CL 5.05 ml/mmHg). The compliant chambers significantly increased C(a) and altered the ratio of arterial to venous compliance C(a)/Cv). Changes in C(a)/Cv significantly decreased the maximal open-loop baroreflex gain (Gmax) for SAP (-2.3 +/- 0.5, -1.6 +/- 0.3, and -1.1 +/- 0.2 mmHg/mmHg, control vs. CS vs. CL, P < 0.05). Gmax for ABF was decreased by CS (-0.9 +/- 0.2 vs. -0.3 +/- 0.1 ml.kg-1.min-1, control vs. CS, P < 0.05), and CL reversed the reflex changes in ABF (Gmax: +0.6 +/- 0.3 ml.kg-1.min-1). Gmax for HR, PVR, and LV contractility was not altered when C(a) was increased (P > 0.05). These findings indicate that an increase in C(a) changes C(a)/Cv and alters carotid baroreflex control of SAP by modifying the ABF response. We conclude that a change in C(a)/Cv affects the reflex control of the circulation by altering the distribution of blood volume between the arterial and venous circulations.

Animals↗

LPS induces late cardiac functional protection against ischemia independent of cardiac and circulating TNF-alpha.

Lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-alpha independently induce cardioprotection against ischemia in the rat at 24 h after administration, suggesting that endogenously synthesized TNF-alpha may play a role in LPS-induced protection. The purposes of this study were 1) to delineate the time course of LPS-induced cardiac functional protection against ischemia and its relation with myocardial and circulating TNF-alpha profile, 2) to examine whether prior protein synthesis inhibition abrogates the protection, and 3) to assess the effects of TNF-alpha inhibition and neutralization on the protection. Rats were treated with LPS (0.5 mg/kg i.p.). Cardiac functional resistance to normothermic global ischemia-reperfusion was examined at sequential time points after LPS treatment in isolated hearts by the Langendorff technique. Myocardial and circulating TNF-alpha was determined by enzyme-linked immunosorbent assay at 1-24 h after LPS treatment. Protection was apparent at 24 h, 3 days, and 7 days but not at 2 or 12 h. Maximal protection at 3 days was abolished by cycloheximide pretreatment (0.5 mg/kg i.p. 3 h before LPS treatment). Increases in myocardial and circulating TNF-alpha preceded the acquisition of protection. Dexamethasone pretreatment (4.0 or 8.0 mg/kg i.p. 30 min before LPS treatment) abolished peak increase in myocardial TNF-alpha and substantially suppressed circulating TNF-alpha (54.3 and 85.9% inhibition, respectively) without an influence on the maximal protection. Similarly, maximal protection was not affected by TNF binding protein (40 or 80 microg/kg i.v. immediately after LPS treatment). The results suggest that LPS-induced cardiac functional protection against ischemia is a delayed and long-lasting protective response that may involve de novo protein synthesis. Although LPS-induced increase in myocardial and circulating TNF-alpha precedes the delayed protection, it may not be required for the delayed protection.

Animals↗

Control of glomerular filtration rate by circulating angiotensin II.

Previous studies from our laboratory have provided evidence that the renin-angiotensin system plays an important role in controlling glomerular filtration rate (GFR) through an efferent arteriolar vasoconstrictor mechanism; however, the relative importance of circulating versus intrarenally formed angiotensin II (ANG II) in this control has not been determined. In the present study, the role of circulating ANG II in regulating GFR during reduced renal artery pressure (RAP) was examined in sodium-depleted dogs. After 90 min of infusion of the angiotensin-converting enzyme inhibitor SQ 14225, which presumably inhibited formation of both circulating and intrarenal ANG II, reduction of RAP to 81 +/- 2 mmHg resulted in marked decreases in GFR, filtration fraction (FF), and calculated efferent arteriolar resistance (RE), whereas renal blood flow (RBF) was maintained approximately 40% above initial control levels determined before SQ 14225 infusion. Replacement of circulating ANG II during SQ 14225 infusion, by intravenous infusion of ANG II at rates that decreased RBF to control levels, increased GFR, FF, and RE to levels not significantly different from control while RAP was maintained constant by aortic constriction. These observations suggest that circulating ANG II plays an important role in regulating RE and GFR during reductions in RAP. The importance of intrarenally formed ANG II in controlling GFR remains to be determined.

Angiotensin II↗

Cardiovascular changes after closure of uterine circulation during pregnancy.

To assess the effects of the presence of the uteroplacental circulation on the systemic arterial pressure, blood volume, and cardiac output during pregnancy, we measured those variables and plasma renin activity (PRA) during a 30-min period before and after occlusion of the uterine circulation. After uterine vascular occlusion, pregnant rabbits (n = 7) experienced a drop in mean arterial pressure of 8.7%, heart rate of 9.5%, cardiac output of 30.2%, and hematocrit of 18.2% (each with P less than 0.05). Stroke volume decreased an average of 29.7%; however, it did not reach significance. PRA and venous pressure did not change significantly from the control period (P greater than 0.1). Nonpregnant rabbits did not experience changes in arterial or venous pressures, hematocrit, heart rate, cardiac output, or PRA after closure of the uterine circulation. To exclude the possibility that the findings were secondary to the release of toxic products to the peritoneal cavity by the ischemic pregnant uterus, we also studied the effect of closure of the uterine circulation in five anesthetized pregnant guinea pigs. These animals' uteri were exteriorized and maintained in a sealed plastic container during the experiment. In these animals, arterial pressure decreased 15.6% by 10 min (P less than 0.05). The finding of a significant decrease in arterial pressure and heart rate is compatible with the idea that the uterine circulation produces a substance with a short half-life that has a significant direct effect on the heart and/or systemic vascular tone.

Animals↗

Temporary effects of circulating Amadori products on glomerular filtration properties in the normal mouse.

Previous studies have established a preferential glomerular filtration of glycated BSA (gBSA), as well as a facilitated filtration of BSA in the presence of gBSA. We intend to determine whether these modifications are permanent or transitory. gBSA was intravenously injected into anesthetized normal mice and maintained in circulation for 30 min, 1, 2, 24, and 48 h. Five minutes before death, FITC-BSA was injected. On immunocytochemical evaluations, increased glomerular filtration of FITC-BSA was found at all circulating time points. Changes at 24 and 48 h were less pronounced. Glomerular basement membrane (GBM)-to-lumen gBSA labeling ratios were similar at all time points suggesting no accumulation of gBSA in the GBM. Seventy percent of the gBSA was cleared from the circulation and the GBM after 24 h, and 95% after 48 h. This was confirmed in experiments with radiolabeled tracers. These results suggest that the alteration in GBM permeability to BSA in the normal mouse are due to the presence of gBSA and are gradually overcome along with its clearance from circulation. In early diabetes, increasing concentrations of circulating glycated proteins could be responsible for changes in glomerular permselectivity and probably for the alteration in glomerular filtration properties leading to diabetic nephropathy.

Animals↗

Histamine release and circulating cells after antigen inhalation in allergic dogs.

Histamine can be recovered from the blood of ragweed-sensitized dogs after aerosol antigen challenge, although its source is unknown. Neutrophils and eosinophils have been recovered from bronchoalveolar lavage fluid (BALF) obtained under identical conditions. We investigated the time course of changes in histamine levels in plasma and BALF taken from ragweed-sensitized dogs after aerosol challenge. Changes in the numbers of circulating neutrophils, eosinophils, lymphocytes, monocytes, and platelets were also studied. After 3 min, total pulmonary resistance (RL) was maximally increased and systolic blood pressure was maximally decreased. Histamine levels in plasma and BALF were increased and circulating eosinophils and neutrophils were decreased. After 15 min, platelet numbers were reduced. By 90 min, changes in RL, blood pressure, plasma and BALF histamine concentrations, and circulating neutrophils and eosinophils had returned to base-line values, but platelet numbers remained significantly decreased. Sham challenge caused no significant changes in any of these variables. Intravenous administration of histamine in doses large enough to attain plasma levels comparable with those achieved after aerosol antigen challenge resulted in no concomitant rise in BALF histamine levels. We conclude that antigen challenge in sensitized dogs causes increases in BALF and plasma histamine levels and is associated with a reduction in circulating neutrophils, eosinophils, and platelets. It is likely that antigen causes airway mast cells to release mediators that move down a concentration gradient from the airways to the pulmonary circulation.

Administration, Inhalation↗

Vascular remodeling in the circulations of the lung.

The lung is unique in its double sources of perfusion from the pulmonary and systemic circulations. One striking difference between the two circulations is the capacity for angiogenesis. The bronchial circulation has a capacity that seems quite similar to all systemic arteries, whereas the pulmonary circulation seems relatively inert in this regard. Extra-alveolar pulmonary arteries can grow somewhat in length, and septal capillaries seem to have the capability of reforming, but these processes do not seem to occur with nearly the same intensity associated with the bronchial arteries. In this review, we emphasize these differences between the two circulations of the lung, anticipating that future research will allow more focused probing into the molecular signaling that regulates the novel mechanistic and pathological pathways of each.

Animals↗

Expression of pro- and antiapoptotic proteins in circulating CD8+ T cells of patients with squamous cell carcinoma of the head and neck.

OBJECTIVE: Apoptosis of T lymphocytes in the circulation of patients with squamous cell carcinoma of the head and neck (SCCHN) was shown to target effector CD8+ rather than CD4+ T cells. This study evaluates the contribution of pro- and antiapoptotic components of the mitochondria-dependent pathway to apoptosis of circulating CD8+ T cells in these patients. EXPERIMENTAL DESIGN: Blood samples were obtained from 77 patients with SCCHN and 51 normal control(s) (NC). Percentages of CD8+Annexin V+ (ANX+) and CD8+CD95+ cells, changes in mitochondrial membrane potential and levels of expression of Bcl-2, Bcl-XL, and Bax in CD8+ T lymphocytes were measured by quantitative flow cytometry. RESULTS: Elevated percentages (P < 0.001) of early apo-ptotic (CD8+ANX+ CD95+) T cells in the circulation distinguish SCCHN patients from NCs but not patients with no evidence of disease (NED) from those with active disease (AD). Circulating CD8+ but not CD4+ T cells in patients were found to contain higher levels of proapoptotic Bax and antiapoptotic Bcl-XL (P < 0.01) than NC cells. The Bax/Bcl-2 ratio was elevated in CD8+ T cells of patients relative to NCs (P < 0.01), and it correlated with the percentage of ANX+CD8+ T cells (P = 0.007). The Bax/Bcl-XL ratio discriminated AD from NED patients. CONCLUSION: Apoptosis of circulating CD8+T cells is found in SCCHN patients with AD or NED. Up-regulated Bax and Bcl-XL expression, the elevated Bax/Bcl-2 ratio and its association with ANX binding implicate the mitochondrial pathway in death of CD8+ T cells of patients with SCCHN. Understanding of molecular mechanisms of T-cell death and survival is essential for the development of more effective biotherapies for SCCHN.

Adult↗

Circulating aminopeptidase N/CD13 is an independent prognostic factor in patients with non-small cell lung cancer.

PURPOSE: Aminopeptidase N, also known as CD13, has important roles in tumor metastasis and angiogenesis. Its expression in tumor tissue has been reported to be associated with poor prognosis. However, the clinical significance of circulating aminopeptidase N/CD13 in patients with solid tumors is unknown. We previously developed an aminopeptidase N/CD13-specific monoclonal antibody (mAb) MH8-11, which inhibits cell motility and angiogenesis in vitro. The aim of this study was to evaluate the clinical significance of circulating aminopeptidase N/CD13 protein detected by mAb MH8-11 in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We used electrochemiluminescence immunoassay with mAb MH8-11 to determine circulating aminopeptidase N/CD13 levels in 90 healthy volunteers and 90 patients with NSCLC. Circulating aminopeptidase N/CD13 levels were measured in sera taken before treatment and evaluated for a relationship with clinical outcomes. RESULTS: A significant correlation was found between tumor progression and serum aminopeptidase N/CD13 concentrations (r=0.23, P=0.029). High serum aminopeptidase N/CD13 levels (n=17) were associated with advanced stage (P=0.004) or poor performance status (P=0.001). The overall survival rate for patients with high serum aminopeptidase N/CD13 levels (n=17) was significantly less than that of patients with low serum aminopeptidase N/CD13 levels (n=73, P<0.0001). In a multivariate survival analysis in patients with NSCLC, serum aminopeptidase N/CD13 levels had an independent influence on survival (relative risk, 4.1; 95% confidence interval, 1.9-8.8). CONCLUSIONS: Our data suggest that a high level of circulating aminopeptidase N/CD13 at diagnosis is an independent prognostic factor in patients with NSCLC.

Antibodies, Monoclonal↗

Maternal circulating nitrite levels are decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.

OBJECTIVE: To evaluate whether maternal nitric oxide synthesis in pregnancies with preeclampsia is different from that in normal normotensive pregnancies. MATERIALS: Maternal circulating combined nitrate and nitrite levels or nitrite level were compared between 10 normotensive nonpregnant women, 30 normotensive pregnant women (10 first-trimester, 10 second-trimester, and 10 third-trimester pregnancies), 20 normotensive postpartum women (10 at 1 week after delivery, and 10 at 4 weeks after delivery), and 13 preeclamptic women (32 to 40 weeks' gestation). End-products of nitric oxide synthesis were measured from maternal venous blood samples using a fluorometric assay. RESULTS: Maternal circulating nitrite levels in nonpregnant women (1.13 +/- 0.22 microM) were significantly higher than those in the first-trimester pregnant women (0.68 +/- 0.13 microM), second-trimester pregnant women (0.65 +/- 0.13 microM), third-trimester pregnant women (0.48 +/- 0.17 microM), first puerperal week women (0.36 +/- 0.16 microM), and fourth puerperal week women (0.67 +/- 0.17 microM), respectively (p < 0.05). Maternal circulating nitrite level was decreased with advancing gestation, still remained low just after delivery, and was increased 4 weeks later. There was no significant difference in maternal circulating nitrite level between preeclamptic women (0.40 +/- 0.17 microM) and third-trimester pregnant women (0.48 +/- 0.17 microM). However, there were no significant differences in maternal circulating combined nitrate and nitrite levels among the groups. CONCLUSION: These results suggest that the maternal nitric oxide synthesis is not changed in normal normotensive pregnancies and pregnancies with preeclampsia. However, plasma nitrite level, which has stronger spasmolytic activity than the activity of the nitrate, was decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.

Adult↗

Circulating interleukin-1-beta levels after acute and prolonged exposure to low temperatures: human and rat studies.

In this study we have investigated whether IL-1 acts as a mediator of stress responses elicited by exposure to low temperatures. We also sought whether IL-1 is released from the adrenal gland under basal conditions or after exposure to low temperatures. Normal and adrenalectomized (ADX) rats were used for acute studies, whereas the effects of a prolonged exposure were investigated in a group of human subjects during a 45-day stay in Antarctica. Circulating levels of interleukin-1beta (IL-1beta) were taken as a marker of systemic IL-1 production both in humans and rats. In the latter, serum corticosterone (Cort) was also estimated. In intact rats, exposure to low temperatures (-25 or -35 degrees C) for 30 or 90 min did not modify circulating IL-1beta levels with respect to controls taken at +20 degrees C. Adrenalectomy was associated with an increase in cytokine levels only in the group exposed to -35 degrees C for 90 min; such increase is statistically significant compared to all groups of normal rats, whatever the experimental condition, as well as to ADX rats exposed to +20 degrees C and -25 degrees C for 30 and 90 min. In normal rats, the increase in circulating Cort levels was already maximal after exposure to -25 degrees C for 30 min. In humans, circulating IL-1beta levels after 45 days in Antarctica were significantly lower than those measured on arrival in the same subjects. Thus, no change in circulating IL-1beta was associated with acute low-temperature stress in rats, whereas a marked decrease in serum cytokine was observed in humans after prolonged exposure to a cold environment. Experiments with ADX rats indicated that the contribution of the adrenal glands to total-body IL-1beta production is negligible or absent.

Adrenalectomy↗

Circulating cytokeratin 8:anti-cytokeratin 8 antibody immune complexes in sera of patients with pulmonary fibrosis.

BACKGROUND: It has been suggested that the humoral immune system plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). Although circulating immune complexes in patients' sera have been suggested, none of the antigens have been characterized. OBJECTIVES: The purpose of this study is to characterize the antigen of the immune complexes in patients' sera of pulmonary fibrosis. METHODS: As we previously established that one of the antibodies against A549 cells (lung alveolar type II cells) was anti-cytokeratin 8 (CK8), we confirmed the existence of anti-CK8 antibody in patients' sera by Western immunoblot. In addition, we tried to demonstrate circulating CK8:anti-CK8 immune complexes in patients' sera by Western immunoblot. Furthermore, we established an enzyme-linked immunosorbent assay to quantitate CK8:anti-CK8 immune complexes. RESULTS: In patients with pulmonary fibrosis, anti-CK8 antibodies were clearly demonstrated in sera by Western immunoblot. In addition, circulating CK8:anti-CK8 immune complexes were also clearly demonstrated by Western immunoblot. It was possible to establish ELISA to quantitate CK8:anti-CK8 immune complexes. If the cutoff value, which was determined based on the highest value of normal volunteers, was introduced, high CK8:anti-CK8 antibody complexes were demonstrated in 9 of 31 patients (29.0%) with IPF and PF-CVD. CONCLUSIONS: This is the first study to clarify the antigen of the circulating immune complex in sera of patients with IPF. These results suggest that circulating CK8:anti-CK8 immune complexes may have played a role in the process of lung injury in pulmonary fibrosis.

Aged↗

Effect of carotid artery stenting on ocular circulation and chronic ocular ischemic syndrome.

BACKGROUND: The authors evaluated the effect of carotid artery stenting (CAS) on ocular circulation and chronic ocular ischemic syndrome. METHODS: We examined 38 patients with carotid artery stenosis (>80%) at its origin treated with CAS. Ocular circulation and symptoms were examined before, within 24 h, and 1 week, 1 month, and 3 months after CAS based on ophthalmic artery color Doppler flow imaging and ophthalmological examinations. RESULTS: Ocular circulation: Before CAS, 13 patients showed reversed ophthalmic artery flow, and 25 antegrade flow. Average peak systolic flow velocity was -0.038 m/s. Within 24 h after CAS, all patients showed antegrade ophthalmic artery flow; reversed flow before CAS was thus resolved. Average peak systolic flow velocity rose significantly to 0.36 m/s (p < 0.05). One week, 1 month and 3 months after CAS, there were no significant changes compared to the findings at 1 week after CAS. Ocular symptoms: Before CAS, 8 patients showed chronic ocular ischemic syndrome. During the follow-up period (mean: 2.8 years), the visual acuity improved in 7 cases. Average retinal artery pressure and arm-to-retina circulation time improved significantly to the normal level (p < 0.05). The other 30 patients complained of recurrent and worsened visual symptoms during the follow-up period. CONCLUSION: CAS was effective in improving ocular circulation, and also improved the chronic ocular ischemic syndrome caused by the severe carotid artery stenosis.

Aged↗

Circulating ICAM-1 and VCAM-1 levels in patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS)-induced hypoxic stress modulates circulating inflammatory mediators causing accelerated atherogenesis. OBJECTIVES: We hypothesized that OSAS-induced hypoxia might result in cardiovascular disease due to increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial surface. METHODS: Thirty-nine subjects with moderate-to-severe OSAS and 34 non-apneic controls matched for age, gender, body mass index (BMI), smoking history, and cardiovascular disease were included in this prospective study. Overnight polysomnography was performed. Circulating ICAM-1 and VCAM-1 levels in the serum were measured by enzyme-linked immunosorbent assay. RESULTS: Circulating levels of both ICAM-1 (480.1 +/- 216.7 vs. 303.4 +/- 98.6 ng/ml, p < 0.0001) and VCAM-1 (1,156.6 +/- 79.8 vs. 878.8 +/- 71.1 ng/ml, p = 0.002) were significantly increased in the OSAS group compared to the control group. For an ICAM-1 cutoff level of 375 ng/ml, predictive sensitivity and specificity for OSAS were 69.2% (95% confidence interval, CI: 52.4-83.0%) and 82.4% (95% CI: 65.5-93.2%), respectively. For a VCAM-1 cutoff level of 859 ng/ml, predictive sensitivity and specificity for OSAS were 74.4% (95% CI: 57.9-86.9%) and 64.7% (95% CI: 46.5-80.2%), respectively. There was a significant positive correlation between circulating levels of ICAM-1 and ln of AHI (r = 0.276, p = 0.018). Multiple logistic regression analyses showed that OSAS was associated with high ICAM-1 and high VCAM-1 levels independent of age, gender, BMI, smoking status and cardiovascular disease. CONCLUSION: We conclude that OSAS can independently increase circulating levels of adhesion molecules

Adult↗

Normal growth spurt and final height despite low levels of all forms of circulating insulin-like growth factor-I in a patient with acid-labile subunit deficiency.

BACKGROUND: In a recently described patient with acid-labile subunit (ALS) deficiency, the inability to form ternary complexes resulted in a marked reduction in circulating total insulin-like growth factor (IGF)-I, whereas skeletal growth was only marginally affected. To further study the role of circulating versus locally produced IGF-I in skeletal growth in this patient, we now describe in detail growth changes and their relationship with several components of the circulating IGF system. DESIGN AND METHODS: We followed growth and development up to the final height in a patient with complete ALS deficiency and determined both spontaneous and growth hormone (GH)-stimulated changes in the IGF system, including measurements of total, free and bioactive IGF-I, total IGF-II and insulin-like growth factor binding protein (IGFBP)-1, IGFBP-2 and IGFBP-3. RESULTS: The patient had a delayed growth and pubertal onset. Six months of GH treatment had no effect on growth. At the age of 19.3 years, he spontaneously completed puberty and had a normal growth spurt for a late adolescent (peak height velocity of 8.4 cm/year). A normal final height was attained at 21.3 years (167.5 cm; -0.78 SDS). During as well as after puberty, basal levels of total, free and bioactive IGF-I were low, as were total IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3. GH treatment for 6 months normalized free IGF-I and increased bioactive IGF-I, but had no effect on growth velocity. CONCLUSIONS: This case story shows that in the presence of complete ALS deficiency, a height within normal limits can be obtained despite low levels of all forms of circulating IGF-I. Furthermore, the patient presented a delayed but normal growth spurt without any marked increment of circulating IGF-I.

Adult↗

Insulin-like growth factor binding proteins in the human circulation: a review.

The actions and bioavailability of the insulin-like growth factors (IGFs) are regulated by a family of six IGF binding proteins. IGFBP-3, the major circulating IGFBP, is unique in combining with a glycoprotein, the acid-labile subunit (ALS), to form a ternary complex with IGF-I or IGF-II. Each component of this trimer is growth hormone-dependent, and the hypoglycemic potential of circulating IGFs appears neutralized in this form. IGFs in the complex have a greatly extended circulating half-life, their stability being conferred by the presence of ALS, which is itself very stable in the circulation. IGFBP-1 does not appear to be a carrier of IGFs, but to act as an acute modulator of their metabolic activities. In this role it can be viewed as an insulin counter-regulator, blocking 'free' insulin-like activity during fasting or hypoglycemia. IGF-I administration causes complex changes in circulating IGFBPs, so that a detailed knowledge of their regulation is essential if the therapeutic potential of IGF-I is to be optimised.

Adult↗

Circulating gamma delta-T-cell-receptor-positive lymphocytes in sarcoidosis.

We investigated phenotypic surface markers of peripheral blood lymphocytes including expression of gamma delta T cell receptor (TCR gamma delta) in 185 patients with sarcoidosis and 42 normal subjects. The proportion of TCR gamma delta+ lymphocytes in peripheral blood of patients with sarcoidosis (5.5 +/- 5.4%) was significantly higher than in normal subjects (3.6 +/- 2.2%; p < 0.05). A number of patients with sarcoidosis had prominently increased levels of circulating TCR gamma delta+ lymphocytes. Successive measurements of circulating TCR gamma delta+ lymphocytes demonstrated the persistence of increased levels of circulating TCR gamma delta+ lymphocytes. We divided the patients with sarcoidosis into two groups, one with high, the other with low TCR gamma delta+ expression. Compared with the low-value group, the high-value group had significantly decreased levels of circulating CD4+ lymphocytes, decreased incidence of a positive tuberculin reaction, and higher levels of serum angiotensin-converting enzyme and lysozyme, suggesting that these two groups may differ in their immunological response and disease activity of sarcoidosis. Measurement of TCR gamma delta+ expression in the circulation seems to be useful for estimating the disease activity of sarcoidosis.

Adolescent↗

Lack of circulating immune complexes in inflammatory bowel disease.

Multi-organ involvement and especially extraintestinal manifestations have suggested an immune complex-mediated pathogenesis of ulcerative colitis and Crohn's disease. Using various techniques controversial data have been reported on the incidence and levels of circulating immune complexes and their correlation to clinical presentation. Sera of 131 patients with inflammatory bowel disease (78 Crohn's disease, 53 ulcerative colitis) representing a wide spectrum of disease activity, treatment and presence or absence of extraintestinal manifestations were tested for circulating immune complexes using Raji cell indirect immunofluorescence assay, Raji cell radioimmunoassay, C1q solid phase assay and polyethylene glycol precipitation coupled with measurements of optical density and subsequent immunoelectrophoresis or radial immunodiffusion. Circulating immune complexes in low concentrations were observed in a small number of patients with inflammatory bowel disease, the frequency and concentrations being slightly higher in patients with Crohn's disease than in those with ulcerative colitis. No association of concentrations of circulating immune complexes with disease activity or presence of extraintestinal manifestations could be demonstrated. These data do not support the claim for a major role of circulating immune complexes in the pathogenesis of inflammatory bowel disease.

Adolescent↗