Soluble interleukin-2 receptor is a thyroid hormone-dependent early-response marker in the treatment of thyrotoxicosis

Thyrotoxic patients exhibit increased levels of immune activation molecules (soluble interleukin-2 receptor [sIL-2R], intercellular adhesion molecule-1 [ICAM-1], and endothelial-leukocyte adhesion molecule-1 [ELAM-1]) in serum, although the clinical significance of these measurements remains unclear. In a randomized 4-week study, we have recently shown that in the treatment of hyperthyroidism, the combination of cholestyramine and methimazole (MMI) resulted in faster lowering of serum thyroid-hormone levels than did MMI alone. Stored serial serum samples from patients participating in this randomized treatment trial were analyzed for sIL-2R, soluble ICAM-1 (sICAM-1), and soluble ELAM-1 (sELAM-1). The levels of all three molecules were elevated in patients with hyperthyroidism. Although the levels of sICAM-1 and sELAM-1 remained elevated through the 4-week follow-up period in both groups of patients, the sIL-2R levels (normal levels, 1.0 to 4.2 ng/ml) decreased significantly in the 10 patients who received cholestyramine in addition to MMI (week 0, 14.2 +/- 1.5 ng/ml; week 2, 10.8 +/- 1.2 ng/ml; week 4, 8.9 +/- 1.5 ng/ml). In eight patients who received MMI alone, sIL-2R decreased less rapidly (week 0, 12.3 +/- 1.4 ng/ml; week 2, 12.3 +/- 1.3 ng/ml; week 4, 10.9 +/- 1.3 ng/ml). sICAM-1 and sELAM-1 were elevated at baseline but did not decrease during therapy. In the former group, free thyroxine and free triiodothyronine decreased faster. These data show that levels of sIL-2R in serum, but not those of sICAM-1 and sELAM-1, may be of clinical use in the early follow-up evaluation of medically treated patients.     

Neonatal catecholamine content of adrenal and extra-adrenal chromaffin tissue after prenatal exposure to dexamethasone

BACKGROUND: We hypothesize that serum levels of the soluble intercellular adhesion molecule-1 (s-ICAM-1) in patients with cervical cancer are significantly higher than that in healthy donors and this is examined in vivo, and in vitro. METHODS: We measured the serum levels of the s-ICAM-1 in patients with cervical cancer. Furthermore, in vitro, we examined the relationship between the expression of ICAM-1 on the cell surface of cultured cervical cancer cells and the s-ICAM-1 levels in the spent media. RESULTS: The mean+/-s.d. in the patients with cervical cancer 884.4+/-332.4 ng/ml were significantly (all, p<0.001) higher than those of normal controls (mean 364.6+/-134.8 ng/ml) and in patients with benign disease (536.3+/-204.8 ng/ml). Interferon-gamma (IFN-gamma) treated cells expressed more ICAM-1 on cell surfaces than did the non-treated cells, and s-ICAM-1 shed in the spent media from IFN-gamma treated cells were much higher than those of non-treated cells. CONCLUSIONS: These results indicate that the reason for increase of s-ICAM-1 in the patients with cervical cancer were both expression and shedding of ICAM-1 from cervical cancer cells especially influenced by cytokines, for example, IFN-gamma from surrounding lymphocytes.     

Increased serum levels of tumor necrosis factor-alpha are correlated to soluble intercellular adhesion molecule-1 concentrations in non-small cell lung cancer patients

Tumor necrosis factor (TNF)-alpha has been shown to induce shedding of ICAM-1. Experimental studies report that soluble intercellular adhesion molecule-1 (sICAM-1) may interfere with the host immunesurveillance system. Serum levels of TNF-alpha and sICAM-1 were determined by ELISA in 112 non-small cell lung cancer (NSCLC) patients. Serum concentration of TNF-alpha and sICAM-1 were related to tumor burden and progression; a significant correlation was observed between circulating levels of TNF-alpha and sICAM-1. Our study suggests that ICAM-1 could be a marker of TNF-alpha activity and that high levels of these molecules may have a prognostic value in lung cancer.     

Measurement of serum p53 protein in patients with small cell lung cancer and results of its clinicopathological evaluation

Serum p53 protein levels were measured in 36 patients with small cell lung cancer (SCLC) and 35 patients with benign lung diseases in order to evaluate the relationship of these levels to clinicopathological features of SCLC. Serum levels of p53 protein were measured by an enzyme-linked immunosorbent assay, p53 protein level was 23.92 +/- 6.78 pg/ml in patients with SCLC, and similar to that (17.47 +/- 2.86 pg/ml) in patients with benign lung diseases. By the clinical stage of SCLC, the mean level of p53 protein was 16.68 +/- 4.62 pg/ml in 21 patients with limited disease, and lower than that in 15 patients with extensive disease (34.05 +/- 14.84 pg/ml) (P = 0.23). The levels of p53 protein were not correlated with age, smoking index, or presence of cancer history for patients with SCLC. However, immunohistochemical examination disclosed a mild correlation between the expression of p53 protein by SCLC tumor and p53 protein serum level (r = 0.45, P = 0.02). Two patients with SCLC had an elevated serum level of p53 protein (> 2 S.D. above the mean for benign lung diseases). However, measurement of p53 protein serum level was not found to be clinically useful for detection of SCLC.     

The EMG development of the longissimus and multifidus muscles after plugging the horizontal semicircular canals

The intercellular adhesion molecule-1 (ICAM-1) expressed by endothelial cells is crucial in promoting adhesion and transmigration of circulating leukocytes across the blood-brain barrier (BBB). Migrated immunocompetent cells, in turn, release mediators that stimulate glial and endothelial cells to express ICAM-1 and release cytokines, possibly sustaining cerebral damage. Following activation, proteolytic cleavage of membrane-anchored ICAM-1 results in measurable levels of a soluble form, sICAM-1. The aims of this study were to investigate the changes of sICAM-1 levels in ventricular CSF and serum and to elucidate the influence of structural brain damage as estimated by computerized tomography (CT) as well as the extent of BBB dysfunction as calculated by the CSF/serum albumin ratio (QA) in patients with severe traumatic brain injury (TBI). All investigated parameters revealed two subgroups. Patients belonging to group A had sICAM-1 levels in CSF above normal range, presented marked cerebral damage and a disturbance of the BBB (range 0.6-24.7 ng/ml, n = 8). In contrast, patients belonging to group B had no elevation of sICAM-1 values in CSF (range 0.3-3.9 ng/ml, n = 5; p < 0.017) and showed minor cerebral damage with an intact BBB in most cases. In addition, overall analysis showed that sICAM-1 in CSF correlated with the extent of BBB damage as indicated by the QA (r = 0.76; p < 0.001). These results suggest that increased sICAM-1 levels in CSF might depict ongoing immunologic activation and that sICAM-1 correlates with the extent of tissue and BBB damage. The origin of soluble ICAM-1 in CSF and its pathophysiologic role after TBI remains to be clarified.     

Inhibition of adhesion molecules by budesonide on a human epithelial cell line (lung carcinoma)

Inhaled corticosteroids in the treatment of asthma have been shown to produce marked reductions in the number of inflammatory cells (mainly mast cells and eosinophils) and their products at bronchial level (such as cytokines). Recently, it has been demonstrated that epithelial cells express ICAM-1/CD54 in allergic patients both during natural allergen exposure and after allergen challenge. We have previously demonstrated that deflazacort (a systemic steroid) reduces the expression of ICAM-1 on conjunctival epithelial cells. The present study aimed to evaluate the effects exerted by budesonide on adhesion molecule expression by a human epithelial cell line (lung carcinoma: DM) and on soluble ICAM-1. Budesonide was added at concentrations corresponding to 10(-8), 10(-7), and 10(-6) mol/l in cultured epithelial cells, either in the absence of any stimulus or in the presence of interferon-gamma (IFN-gamma) at 500 U/ml. After 24 h of incubation, cytofluorometric analysis was performed for ICAM-1 and CD29/VLA beta 1. The 24-h supernatants of the same cultures were collected and then evaluated for soluble ICAM-1 (sICAM-1). The results showed that budesonide inhibits ICAM-1 and CD29 basal expression on the cells studied (P < 0.05): budesonide was effective in a dose-dependent manner. In addition, budesonide reduced surface ICAM-1 upregulation induced by IFN-gamma at 500 U/ml (P < 0.05). Finally, cell cultures with budesonide showed decreased levels of soluble ICAM-1 in basal condition, but not after IFN-gamma stimulation.     

CYFRA 21-1, a sensitive and specific new tumour marker for squamous cell lung cancer. Report of the first European multicentre evaluation. CYFRA 21-1 Multicentre Study Group

The present study was designed to determine whether CYFRA 21-1, measuring cytokeratin 19, could be a specific and sensitive tumour marker for non-small cell lung cancer (NSCLC). Serum measurements were made at diagnosis in 2250 patient samples by an immunoradiometric "sandwich type" assay, using two cytokeratin 19 specific monoclonal antibodies. Among healthy individuals (n = 711) and patients with benign lung disease (n = 546), 95 percentiles were 1.2 and 2.95 ng/ml, respectively. Cumulative distribution analysis curves were established. From these data, 3.3 ng/ml gave 96% specificity. Using this cutoff, the sensitivity for small cell lung cancer was 16% (n = 74) compared to 41% for NSCLC (n = 547). In histological sub-groups, sensitivity was 57% for squamous cell lung cancer, 34% for undifferentiated large cell carcinoma and 27% for adenocarcinoma, the level of CYFRA 21-1 was correlated with tumour size and UICC stage. In squamous cell lung cancer, the sensitivity of the squamous cell carcinoma marker was 30%, 25% for carcinoembryonic antigen and 46% for tissue polypeptide antigen, using the same series of samples and cutoffs defined at 96% specificity. In conclusion, CYFRA 21-1 is a sensitive tumour marker for NSCLC, especially squamous cell lung cancer.     

Serum levels of interleukin 6 in patients with lung cancer

Serum interleukin 6 (IL-6) levels were measured in 75 patients with lung cancer and in 20 patients with benign lung diseases. IL-6 was detectable in 29 patients with lung cancer (39%), but was not detectable in any of the patients with benign lung diseases. Serum C-reactive protein levels and plasma fibrinogen levels were significantly higher and serum albumin concentration was significantly lower in lung cancer patients with detectable serum IL-6 levels than in those without detectable serum IL-6 levels and in patients with benign lung diseases. On the other hand, no significant difference was observed in blood platelet counts in these three groups. Moreover, serum IL-6 levels were not significantly different in lung cancer patients with or without clinically demonstrated distant metastasis. These results suggest that IL-6 may be a mediator of various reactions including an inflammatory response in lung cancer patients.     

The circulating adhesion molecules sICAM-1 and sP-selectin in patients with sepsis

AIM: The aim of this study was to investigate whether the plasma levels of the circulating adhesion molecules sICAM-1 and sE-selectin could serve as early predictors of developing sepsis and its severity. METHODS: Twenty-four patients admitted to an intensive care unit with a high risk of developing septic complications were enrolled in this study. Patients were divided into three groups: group I, with infection without systemic sepsis, n = 8; group II, surviving patients with severe sepsis and multi-organ failure (MOF), n = 8; and group III, nonsurviving patients with severe sepsis and MOF, n = 8. Classification of patients was performed according to the clinical criteria defined by the Sepsis Consensus Conference in 1992. Blood samples were taken at 7 a.m. starting from the day of admission until the 7th day after diagnosis of sepsis. Plasma levels of sICAM-1 and sE-selectin were determined in all samples taken between the 3rd pre-septic day and the 7th day after the diagnosis of sepsis was made. RESULTS: In group I, both sICAM-1 (354.21 +/- 128.60 ng/ml, 86 samples) and sE-selectin (30.41 +/- 7.20 ng/ml, 86 samples) levels remained within the reference range over the whole period of observation. The sICAM-1 levels of group II (between 550.82 +/- 275.67 ng/ml and 445.08 +/- 243.63 ng/ml) tended to show values above the reference range without being significant. Mean sICAM-1 levels in group II did not differ from those of group I. From the 2nd pre-septic day onwards the sICAM-1 levels of group III increased, but not significantly. Significant differences in sICAM-1 levels between group I and group III were observed, with peaks at the samples of the 2nd preseptic day and after the 3rd day of sepsis, respectively (P < 0.05). The sE-selectin levels in group II were elevated from the 3rd preseptic day onwards, with a peak value on the 2nd day of sepsis (P < 0.05). Afterwards, levels decreased to initial values despite ongoing sepsis. Mean values of sE-selectin levels of group I and II were significantly different with the onset of sepsis (P < 0.05). Plasma levels of sE-selectin in group III were significantly elevated (66.30 +/- 9.00 ng/ml on the 3rd pre-septic day), reaching their maximal values of 106.67 +/- 21.66 ng/ml at the end of the observation period. Significant differences between sE-selectin levels of groups I and III existed from the 3rd pre-septic day onwards, and between group II and III on the 7th and 8th day of sepsis. CONCLUSION: Our results show that sICAM-1 is a relatively non-specific indicator for sepsis. In contrast, sE-selectin seems to be a good and early predictor of the beginning of severe sepsis with MOF. Furthermore, sE-selectin levels seem to have a prognostic value for the severity, possible course, and outcome of developing sepsis.     

Elevated serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) closely reflect tumour burden in chronic B-lymphocytic leukaemia

The present study is the first to report elevated serum levels of soluble (s)VCAM-1 in B-cell chronic lymphocytic leukaemia (B-CLL). A large cohort of 106 untreated patients was studied. sVCAM-1 was compared to known prognostic serum markers (soluble (s)ICAM-1; lactate dehydrogenase, LDH; sCD23; thymidine kinase, TK; beta2microglobulin, beta2m). The serum levels of sVCAM-1 reflected tumour burden as expressed by Binet/Rai stages more closely than any other marker. sVCAM-1 also reflected the kinetics of the disease as revealed by lymphocyte doubling time. sVCAM-1 was the only one of the studied markers which showed elevated levels in smouldering disease compared to controls. sVCAM-1, sICAM-1 and sCD23 (but not LDH, TK, beta2m) separated smouldering from non-smouldering B-CLL. Only sICAM-1, sCD23 and TK added independent prognostic information for survival to that of stage and lymphocyte doubling time. The expression of both adhesion molecules was examined in lymph node and splenic specimens. VCAM-1 and ICAM-1 were overexpressed by vascular endothelium and stroma, but the intensity of expression correlated poorly with serum levels of the soluble molecules. In conclusion, serum levels of sVCAM-1 correlated with tumour burden and other prognostic markers in B-CLL. VCAM-1 was overexpressed in tumour tissue as was ICAM-1. sVCAM-1 could prove a valuable marker in younger early-stage patients eligible for therapeutic trials.     

Characterization of soluble E-cadherin as a disease marker in gastric cancer patients

The soluble fragment of E-cadherin protein (S-ECD) is reported to be increased in the peripheral blood of cancer patients. In this study, we investigated the clinical significance of serum S-ECD in 81 patients with gastric cancer. The amount of serum S-ECD was significantly higher in the gastric cancer patients (4735 +/- 2310 ng ml(-1)) than in healthy volunteers (2515 +/- 744 ng ml(-1)). With the normal range cut-off at average +2 s.d., 67% patients showed abnormally high serum S-ECD levels. This frequency was significantly higher than that of other tumour markers, such as CEA (4.4%) or CA19-9 (13.3%). However, there was no significant correlation between the amount of S-ECD and clinicopathological factors. Serum S-ECD might be derived from cancer tissue, as removal of cancers by surgical treatment results in quick decline of the serum S-ECD and S-ECD can be detected by immunoblot in cancer tissues but not in normal epithelium. The serum S-ECD amount was compared with the E-cadherin expression in cancer tissues, which were classified into those showing preserved (+), partially reduced (+/-) or lost (-) expression. Interestingly, E-cadherin (+/-) tumours showed higher serum S-ECD levels than the other types, and a higher amount of S-ECD in the immunoblot analysis. Thus, the serum level of S-ECD may serve as an excellent tumour marker with high sensitivity. Furthermore, analysis of S-ECD in serum and cancer tissue can offer clues for elucidating the mechanism of reduction of E-cadherin expression in cancer cells.     

Clinical usefulness of serum cytokeratin 19 fragment as a tumor marker for lung cancer

Serum soluble cytokeratin 19 fragment (CYFRA) levels were measured in 251 patients with lung cancer and 139 patients with benign lung diseases to determine the clinical usefulness of CYFRA level determination in the diagnosis and monitoring of lung cancer. Serum levels of CYFRA were measured by a 2-step sandwich ELISA method. When the cut-off value was defined as 3.5 ng/ml, which was associated with a specificity of 95% for benign lung diseases, CYFRA had a high sensitivity (53%) in all patients with lung cancer. Both the serum level of CYFRA and its sensitivity increased significantly with the increase in clinical stage. A comparison of areas under receiver operating characteristic curves showed that CYFRA had the most power of discrimination in the diagnosis of lung cancer among markers including carcinoembryonic antigen, squamous cell carcinoma antigen, carbohydrate antigen 19-9, and neuron-specific enolase. A good correlation was found between serial changes in serum CYFRA levels during therapy and clinical responses for 18 patients who underwent chemotherapy and/or radiotherapy. Our findings suggest that CYFRA may be a marker of choice for screening and monitoring of lung cancer, particularly squamous cell carcinoma.     

Smoking-associated mitochondrial DNA mutations and lipid peroxidation in human lung tissues

BACKGROUND/AIMS: The objective of the present study was to analyze the expression and regulation of intercellular adhesion molecule-1 (ICAM-1) in organotypic cultures of rat liver slices, which preserve the normal microenvironment of liver cells. METHODS: Rat liver slices were maintained in culture for 15 min to 24 h and examined for ICAM-1 expression by immunohistochemistry and Western blotting in basal conditions and after stimulation with 1000 IU/ml interferon-gamma (IFNgamma), 1000 IU/ml tumor necrosis factor-alpha (TNF alpha) and 50 microg/ml endotoxin. Immunohistochemical results were evaluated using a semiquantitative scoring system. RESULTS: In uncultured slices, ICAM-1 was not detected on hepatocytes. In unstimulated liver slices maintained in organotypic culture, ICAM-1 was induced at the surface of scattered hepatocytes (score at 15 min, 0.33+/-0.47 and at 24 h, 1.17+/-0.69). After 4 h of stimulation, a significant increase in ICAM-1 expression by hepatocytes and adjacent sinusoidal cells, but not by intra-hepatic biliary epithelial cells, was observed for IFNgamma (score: 2.35+/-0.47) and endotoxin (score: 2.67+/-0.47), but not with TNF alpha (score: 0.66+/-0.47). After 24 h of stimulation, a further increase in the extent of ICAM-1 expression by hepatocytes was observed for IFNgamma (score: 3.67+/-0.47) and endotoxin (score: 4.0+/-0.0), and a significant overexpression of ICAM-1 by hepatocytes was detectable after treatment with TNF alpha (score: 3.67+/-0.47). CONCLUSIONS: In rat liver organotypic cultures, TNF alpha, IFNgamma and endotoxin induce the expression of ICAM-1 in hepatocytes and adjacent sinusoidal endothelial cells, but not in portal tracts.     

Circulating levels of intercellular adhesion molecule-1 (ICAM-1) and soluble interleukin 2 receptors (IL-2R) in patients with B cell chronic lymphocytic leukaemia

The serum concentrations of circulating ICAM-1 (cICAM-1) and soluble receptors for interleukin-2 (sIL-2R) were evaluated on 48 patients with B-cell chronic lymphocytic leukaemia (B-CLL) and on 15 healthy control subjects. The mean +/- SD concentration of cICAM-1 was significantly higher (p < 0.002) in B-CLL patients (407.7 +/- 164.3 ng/ml) than in healthy controls (245.4 +/- 76.7 ng/ml). Patients with progressive disease had higher cICAM-1 levels than patients with "indolent" disease (440.38 +/- 32.3 ng/ml versus 321.36 +/- 14.45 ng/ml; p < 0.0001). Serum levels of cICAM-1 were also significantly higher (p < 0.0002) in patients with advanced stage (III-IV) than in those with early stage (I-II). The increase of cICAM-1 levels was positively correlated to increases of soluble receptors for interleukin-2 (r = 0.9; p < 0.0001). These results seem to show that the measurement of serum levels of cICAM-1 may be an useful tool for monitoring disease activity and tumoral mass in patients with B-CLL. However, further studies are needed to define the functional role of high cICAM-1 levels in the immunological dysregulation of patients with malignancy.     

High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression

BACKGROUND & AIMS: Contribution of transforming growth factor beta 1 (TGF-beta 1) to tumor progression has been suggested. However, little is known about the role of TGF-beta 1 in colorectal cancer. Plasma TGF-beta 1 levels and its expression were analyzed in patients with colorectal cancer. METHODS: Plasma TGF-beta 1 levels were measured in 22 patients with colorectal cancer using a TGF-beta 1 enzyme-linked immunosorbent assay. Expression of TGF-beta 1 messenger RNA and immunohistochemical distribution of the protein in colorectal cancer tissues were examined. RESULTS: Plasma TGF-beta 1 levels in patients with colorectal cancer (14.8 +/- 8.4 ng/mL) were significantly higher than in normal controls (1.9 +/- 1.4; n = 22) (P < 0.001). After curative surgical resection, plasma TGF-beta 1 levels decreased in examined patients from 11.9 +/- 6.7 to 3.8 +/- 1.2 ng/mL (P < 0.01). TGF-beta 1 messenger RNA was about 2 1/2 times more abundant in colorectal cancer tissues than in control (P < 0.01). TGF-beta 1 was detected in the cytoplasm of colorectal cancer cells immunohistochemically. Both TGF-beta 1 messenger RNA expression in colorectal adenocarcinoma tissues and its plasma levels were associated with tumor stage of Dukes' classification (P < 0.05). CONCLUSIONS: These results suggest that plasma TGF-beta 1 levels may reflect overexpression of the gene in colon cancer tissues and are associated with disease progression.     

Arteriovenous fistula of the jugular vein: detection and follow-up with color-coded duplex ultrasound]

Increased levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been reported in various diseases, including lung cancer. The role of the soluble form of the IL-6 receptor (sIL-6R) remains to be explored. We therefore measured IL-6, IL-8 and sIL-6R in effusion fluid and blood serum of 10 lung cancer patients with carcinomatous pleurisy (5 men, 5 women, age 64.3 +/- 4.4 years) by enzyme-linked immunosorbent assays. Serum levels of healthy individuals served as control. Concentrations of sIL-6R were much higher in serum compared to pleural effusion fluids of tumor patients (25,698 +/- 1,993 vs. 9,438 +/- 1,407 pg/ml: p < 0.0001). In contrast, IL-6 and IL-8 were found at high concentrations in carcinomatous pleural effusions in comparison to serum (IL-6: 964 +/- 176 vs. 10.2 +/- 1.3 pg/ml, p < 0.0001; IL-8: 319 +/- 85 vs. 9.6 +/- 9.6 pg/ml, p < 0.0001). The serum concentrations of IL-6 were not significantly increased in lung cancer patients (10.2 +/- 1.3 pg/ml) in comparison to controls (7.3 +/- 1.0 pg/ml). IL-8 was detected in the serum of only 1 patient and in low levels in the serum of controls (8.0 +/- 1.5 pg/ml; all values are mean +/- SEM). We conclude from this study that decreased levels of sIL-6R, but increased levels of IL-6 and IL-8, are found in pleural effusion fluid of patients with lung cancer and carcinomatous pleurisy. The low sIL-6R levels in the presence of high IL-6 levels in pleural effusions and the high sIL-6R levels in the presence of low IL-6 levels in serum may suggest a downregulation of sIL-6R expression of sIL-6R shedding in the presence of excessive amounts of IL-6.     

Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis

An enzyme-linked immunosorbent assay using monoclonal antibodies to human lung surfactant protein A (SP-A) was applied to sera from patients with lung diseases. We examined whether SP-A appears in the sera of patients with diseases that are known to cause alterations in surfactant composition in bronchoalveolar lavage fluids, and we characterized the SP-A that was found. The level of SP-A in sera from 57 healthy volunteers was 45 +/- 3 ng/ml (mean +/- SEM). The levels in patients with idiopathic pulmonary fibrosis (IPF) (205 +/- 23 ng/ml, n = 32) and pulmonary alveolar proteinosis (PAP) (285 +/- 23 ng/ml, n = 6) were significantly higher than those in healthy control subjects (p < 0.01), whereas those of sarcoidosis (n = 16), pneumonia (n = 14), and tuberculosis (n = 14) were 52 +/- 27 ng/ml, 65 +/- 11 ng/ml, and 49 +/- 23 ng/ml, respectively. Electrophoresis and immunoblotting analysis demonstrated that the fraction isolated from serum of a patient with PAP or IPF by anti-SP-A immunoaffinity column chromatography consisted chiefly of human IgG and IgM, and that it also contained SP-A. Furthermore, IgG was found in preparation of purified human SP-A. SP-A was demonstrated to bind to nonimmune IgG coated onto microtiter wells. Gel filtration analysis revealed that serum SP-A was eluted at fractions of larger molecular size than was the purified SP-A. These findings suggest that SP-A appears in the bloodstream as a complex with immunoglobulin in IPF and in PAP.     

CYFRA 21-1 enzyme-linked immunosorbent assay. Evaluation as a tumor marker in non-small cell lung cancer

BACKGROUND: The CYFRA 21-1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21-1 is a sensitive and specific tumor marker for non-small cell lung cancer. METHODS: CYFRA 21-1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer. RESULTS: The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21-1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivity. The median level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p<0.001). The serum level and sensitivity of CYFRA 21-1 were well correlated with staging and tumor size in squamous cell carcinoma. The CYFRA 21-1 values were measured for monitoring progression of disease in 20 patients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients with progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was observed in patients with stabilized disease (p>0.1). CONCLUSION: For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.     

MR arthrography of the shoulder: rethinking traditional imaging procedures to meet the technical requirements of MR imaging guidance

Increased serum levels of mucin-associated antigen have been previously demonstrated in patients with cystic fibrosis (CF) and interstitial pneumonia, and in lung-transplant recipients. The present study assessed the serum airway mucin levels in patients with acute respiratory distress syndrome (ARDS). An enzyme-linked immunosorbent assay (ELISA) method with a human-airway-mucin-specific monoclonal antibody (17Q2) was used to measure serum mucin levels in normal subjects, chronic smokers, patients with chronic bronchitis and other pulmonary diseases, patients with acute cardiogenic lung edema, and patients with ARDS. The serum mucin levels measured 9.9 +/- 0.8 ng/ml (mean +/- SEM, n = 59) in normal subjects, 12.7 +/- 1.6 ng/ml (n = 29) in chronic smokers, 21.8 +/- 1.9 ng/ml (n = 28) in patients with chronic bronchitis and other pulmonary diseases, 9.0 +/- 3.1 ng/ml (n = 5) in patients with acute cardiogenic lung edema. The serum mucin level was 53.8 +/- 6.6 ng/ml (n = 13) in patients with ARDS (p < 0.05, as compared with the four other groups). Serial measurements of serum mucin levels were obtained in patients with ARDS. Statistical analysis showed an inverse correlation of serial measurements of serum mucin with static respiratory-system compliance (p = 0.021), an inverse correlation of sequential serum mucin levels and log(Pa(O2)/Fl(O2)) (p = 0.016), and a positive correlation of sequential serum mucin levels and lung injury score (LIS) (p = 0.019). Gel-filtration analysis showed that mucin-associated antigens in ARDS sera were polydispersed and smaller than the antigens in normal sera. This study indicates that an increasing amount of degraded mucin occurs in patients with ARDS.