Antigens shared by leukemic blast cell and lymphoblastoid cell lines detected by lymphocyte-dependent antibody.

Lymphocyte-dependent antibodies (LDA's) directed against antigenic determinants present on lymphoblastoid cell lines as well as human leukemia blast cells were demonstrated in heterologous antisera obtained by immunizing rabbits with a membrane fraction from RPMI-4265 (a lymphoblastoid cell line derived from a patient with chronic myelogenous leukemia). LDA was present at high titers against B-lymphoblastoid, myelomonocytic, and stem cell lines. The T-lymphoblastoid cell line MOLT-4, however, did not react. LDA was demonstrated against acute myelogenous as well as lymphoblastic leukemia cells. The reactivity was not directed against phytohemagglutinin-induced blastoid antigens, fetal antigens, or fetal calf serum. Absorptions with lymphoblastoid cell lines removed all LDA reactivity. Similar results were obtained by absorbing the rabbit antiserum with acute lymphoblastic and/or acute myelogeneous leukemia cells. These findings indicate the presence of cross-reactive antigens between lymphoblastoid cell lines and leukemia cells. Furthermore, cross-reactivity between acute lymphoblastic and acute myelogenous leukemia cells was demonstrated.

Angioscopic evaluation of atherosclerotic plaques: validation by histomorphologic analysis and association with stable and unstable coronary syndromes.

OBJECTIVES: We validated coronary angioscopic observations with histologic assessment of material removed by atherectomy. BACKGROUND: Up to now, angioscopic findings have been primarily descriptive, and the clinical significance still needs to be substantiated. The proposed Ermenoville classification is relevant but has not yet been validated by histomorphologic analysis. METHODS: We compared angioscopic findings in patients with different coronary syndromes and used atherosclerotic material retrieved by directional coronary atherectomy to validate the angioscopic observations. Coronary angioscopy was performed in 63 patients (56 men, 7 women) with stable (26 patients) and unstable angina (37 patients) before and after directional coronary atherectomy. The identity of atherectomized material was confirmed by ex vivo visualization with the angioscope and by postatherectomy angioscopy. Angioscopic and histologic findings could be compared in 44 of 63 patients. RESULTS: Angioscopic findings were grouped into gray-white and yellow lesions (gray-yellow, deep yellow, yellow-red or yellow-pink). We found that patients with unstable angina had predominantly yellow lesions (89%). In patients with stable angina, gray-white (43%) or yellow (57%) lesions were similarly distributed. Ruptured yellow plaques and red or pink thrombi were identified in 11% of patients with stable angina and 39% of patients with unstable or early postmyocardial infarction angina. Histologically, gray-white lesions represented fibrous plaque without degeneration in 64% and with degeneration in 36% of patients. Gray-yellow lesions were associated predominantly with degenerated plaque (64%) and, to a lesser extent, with fibrous plaque (14%) or atheroma (14%). Deep yellow and yellow-red lesions represented either atheroma (53%) or degenerated plaque (42%). CONCLUSIONS: Our study establishes a histomorphologic basis for classification and interpretation of angioscopic findings. Yellow plaque color is closely related to degenerated plaque or atheroma and is associated with unstable coronary syndromes.

The molecular weight of the endothelial cell IL-1 receptor is 78,000.

Human endothelial cells have been shown to be distinctive from other IL-1 responsive cells (e.g. murine thymocytes), in the equal units of murine and human IL-1 do not have the same endothelial cell stimulatory effect, as measured by increased lymphocyte adherence. In this paper, the cell surface IL-1 receptors of human endothelial cells, fibroblasts and T-lymphocytes have been compared, to investigate whether endothelial cells have a unique receptor for IL-1. IL-1 receptors were isolated by both immunoprecipitation and chemical cross-linking to the ligand. Both techniques demonstrated that human endothelial cells are similar to human T-lymphocytes and fibroblasts, in that they all have a 78,000 mol. wt IL-1 receptor.

The effects of histamine and serotonin on polymorphonuclear leukocyte accumulation in the rat.

Histamine and serotonin were evaluated for their effects on rat polymorphonuclear leukocyte (PMN) accumulation in vivo and PMN migration in vitro. Both of the mediators inhibited the accumulation of PMNs when injected into the pleural cavity in a saline vehicle, and reduced the PMN content of the peripheral blood. Histamine also reduced the cellular influx when administered in combination with an intrapleural injection of carrageenan. Peripheral blood leukocytes removed from rats injected intrapleurally with histamine and carrageenan had a lesser chemotactic responsiveness compared with those removed from rats injected only with carrageenan. The effects of histamine in reducing PMN accumulation was abolished by treatment with cimetidine, an H2 antagonist, but not by treatment with chlorpheniramine, an H1 antagonist. These results suggest that a local release of histamine may play a role in reducing cellular infiltration into an inflammatory site.

In vivo and in vitro effects of dexamethasone on leukocyte migration in the rat adjuvant arthritis model.

When polymorphonuclear leukocytes (PMNs) and mononuclear cells were isolated from the blood of dexamethasone-treated normal rats, in vitro mononuclear cell migration was inhibited and PMN migration was stimulated in comparison to controls. Inflammogen-induced PMNs showed inhibited cell migration due to dexamethasone treatment. Gamma camera imaging was then used to detect cells in vivo after labeling with indium-111. When the dexamethasone-treated blood cells were injected into adjuvant arthritis diseased rats, mononuclear cells showed depressed migration into the inflamed paws, while PMNs showed stimulated migration into the inflamed paws in comparison to controls. When the recipient adjuvant arthritic animals were treated with dexamethasone, both normal mononuclear cell and normal PMN migration to the inflamed paws were inhibited.

[Catheter-induced thromboses--duplex ultrasound studies of incidence and extent]. / Katheterinduzierte Thrombosen--duplexonographische Untersuchungen zu Häufigkeit und Ausmass.

The aim of the study was to detect the frequency and the extension of thrombosis caused by central venous catheters by means of Doppler-duplex ultrasound. 36 patients were examined. The visualization rate of catheters in jugular (91%) and femoral (62%) veins was excellent. In contrast, catheters in the subclavian vein could be detected only in 33 per cent of all cases. As a result the overall patency rate of catheters was only 37 per cent after a period between 8 hours and 60 days (12.2 +/- 11.3 days) following the introduction. There was no significant relation between the type of catheter, the management with central venous catheters and the rate of thrombosis.

Biochemical studies on a cell surface determinant involved in T-cell proliferation.

Previous studies have shown that a monoclonal antibody (TH5.2) recognizes a cell-surface determinant which is involved in the proliferative capability of T cells. The work reported here demonstrates that the T-cell-surface antigen recognized by TH5.2 is a glycoprotein of 55,000 to 60,000 molecular weight. The molecule shows a single molecular weight species upon reduction and denaturation, and it contains only a few percent of tunicamycin-sensitive carbohydrate structures. As shown in sequential immunoprecipitation studies, the TH5.2 antigen is on a molecule distinct from the interleukin-2 (Tac) receptor and the T4 molecule. Cell-surface antigenic modulation experiments indicate that the TH5.2 antigen does not comodulate with, and therefore is distinct from, the T3, T4, T8, and Leu-5 T-cell antigens.

Gangliosides induce selective modulation of CD4 from helper T lymphocytes.

The cluster designation (CD)4 molecule is one of several nonpolymorphic T lymphocyte surface proteins that have been implicated in T cell-target cell interactions, and is thought to play an important role in regulating T helper cell function. Previously, we found that gangliosides inhibited the function of rat T helper cell lines, and simultaneously inhibited the expression of the rat CD4 molecule identified by the W3/25 antibody. We have now evaluated the generality and mechanism(s) of ganglioside-induced modulation of CD4 expressed by mouse, rat, and human T helper lymphocytes. Ganglioside pretreatment induced rapid and selective disappearance of the CD4 molecule from T helper cells of all three species. The ganglioside effect was temperature- and dose-dependent, reversible within 24 hr of ganglioside removal, azide-insensitive, and was neutralized completely by 10% serum. CD4 modulation appeared to be a general property of gangliosides since the effect could be induced similarly by highly purified individual gangliosides with varying amounts of sialic acid, or by mixed gangliosides. The activity of gangliosides appeared to require both the lipid and sialated oligosaccharide moieties. Gangliosides did not inactivate antibody function, but prevented binding at the cell surface by 12 different monoclonal antibodies specific for a variety of different CD4 epitopes. Preclearance of CD4 by antibody-mediated capping reduced binding of 3H-GM1 to T helper cells. Labeled GM1 bound to several detergent-extracted and transblotted lymphocyte-associated proteins, but apparently did not bind directly to the CD4 molecule under these conditions. These results indicate that gangliosides induce a profound change in the molecular orientation of CD4 within the T helper cell membrane which renders epitopes on the CD4 molecule inaccessible to antibody. This ganglioside effect represents a novel pathway which may contribute to the understanding of the role of CD4 as a regulatory molecule and as a specific receptor for the acquired immune deficiency syndrome virus.

Relationship between adherence, chemotaxis and the accumulation of rat polymorphonuclear leukocytes at an inflammatory site.

The effects of a nonsteroidal anti-inflammatory agent, indomethacin, a steroidal anti-inflammatory drug, dexamethasone and an antirheumatic agent, levamisole, on rat polymorphonuclear leukocyte (PMN) adherence and migration were examined. Adherence was evaluated using nylon fiber columns and migration was studied in vitro using Boyden chambers In addition, the effects of these drugs on PMN accumulation in he carrageenan-injected pleural cavity was evaluated. PMNs removed from animals treated with indomethacin, 1 mg/kg p.o., had a significantly reduced adherence, and fewer cells accumulated at an inflammatory site. Cellular migration measured in vitro was unaffected. PMNs removed from animals treated with dexamethasone, 0.1 and 1.0 mg/kg p.o., had a significantly reduced adherence and fewer cells accumulated at an inflammatory site. Cell migration was not consistently affected. After treatment with levamisole, 5 and 25 mg/kg p.o., adherence and chemotaxis were reduced, whereas PMN accumulation was unaffected. These results demonstrate that no simple relationship exists between PMN adherence, chemotaxis and their accumulation at an inflammatory site. Neither a reduction in adherence nor migration, as measured in vitro with a Boyden chamber, was predictive of a change in inflammatory cell migration.

Determination of measles, mumps, and rubella immunization status using oral fluid samples.

OBJECTIVE: To determine if oral fluid samples can be used to reliably assess protective blood levels of antibodies to measles, mumps, and rubella. DESIGN: A comparison of matched serum and oral fluid samples from asymptomatic subjects in enzyme-linked immunosorbent assays for measles, mumps, and rubella antibodies. A longitudinal study compared matched serum and oral fluid samples from 11 subjects after measles-mumps-rubella vaccination. SETTING: Five US clinical sites with samples tested at the reporting laboratory. PARTICIPANTS: A total of 157 asymptomatic subjects including 55 subjects younger than 18 years. MAIN OUTCOME MEASURES AND RESULTS: The presence of antibodies in oral fluid specimens correlated with that in serum with the following levels of sensitivity and specificity: measles, 97% and 100%, respectively; mumps, 94% and 94%, respectively; rubella, 98% and 98%, respectively. Longitudinal studies of subjects after vaccination showed similar seroconversion profiles in oral fluid and serum samples. CONCLUSION: Protective blood levels of antibodies to measles, mumps, and rubella can be assessed by means of an oral fluid sample with good reliability.

Clinical evaluation of oral fluid samples for diagnosis of viral hepatitis.

Oral fluid samples were compared with serum samples as a specimen source for hepatitis A, B, and C virus markers. Oral fluid was obtained with a treated absorbent pad and tested by using existing commercial enzyme immunoassays with only minor modifications. Compared with serum sampling the sensitivity and specificity of oral sampling were 100% (51 of 51 samples) and 98% (46 of 47 samples) for hepatitis A virus immunoglobulin M, 100% (29 of 29 samples) and 100% (29 of 29 samples) for hepatitis B virus surface antigen, and 100% (13 of 13 samples) and 100% (13 of 13 samples) for hepatitis C virus antibody, respectively. The decline of hepatitis A virus immunoglobulin M in oral samples was parallel to, though somewhat more rapid than, that of hepatitis A virus immunoglobulin M in serum samples. It is proposed that oral sampling represents a safer and more convenient procedure for reliable hepatitis virus testing than blood sampling and that it has wide application in patient and outbreak management.

Invasive strategies to discriminate stable and unstable coronary plaques.

Unstable coronary plaques with surface erosion and plaque rupture lead to acute coronary thrombosis, unstable angina pectoris and myocardial infarction. The in-vivo detection of plaque instability by angiography, intravascular ultrasound or angioscopy or by newly developed techniques, such as optical coherence tomography or by the observation of local temperature increases, offers the opportunity for deeper understanding of the mechanisms underlying plaque rupture and erosion. Pharmacological and transcatheter therapy might be directed more exclusively to unstable plaques, once more detailed knowledge about pathophysiological mechanisms as well as direct information about the individual plaque being treated is available.

[Stent implantation in severe tracheal and bronchial compression caused by aortic aneurysm]. / Stentimplantation bei hochgradiger Trachea- und Bronchuskompression durch ein Aortenaneurysma.

A space-occupying growth in the left upper area of the lung was confirmed in a female patient of 75 years of age suffering from progressive cough and intermittent dyspnoea. Fibre bronchoscopy revealed distal stenosis of the trachea, the total findings being interpreted as pointing to the existence of a mediastinal tumour. A few hours after bronchoscopy the patient suffered from respiratory insufficiency, and the patient was referred to us with continuously increasing positive airway pressure breathing, for further clarification. We performed as an emergency measure bilaterally an endobronchial stent implantation. After airway pressure breathing had returned to normal, and subsequent extubation, compression of a stent occurred followed by renewed compulsory breathing. Ventilation could be optimised by an additional implantation of a stent. Cause of the compression was later identified as a monstrous aneurysm of the thoracic and abdominal aorta. During further conservative treatment there was a progressive bronchopneumonia and renal insufficiency requiring dialysis. The patient died on the 8th day after stent implantation. Autopsy showed that the stents were properly in position.

Characterization of a T-cell determinant defined by a monoclonal antibody (TH5.2) which is involved in the interleukin-2-producing and proliferative capabilities of T cells.

Utilizing an OKT-4-positive human T-cell lymphoma cell line as immunogen, we have produced a monoclonal antibody (MAb), designated TH5.2, which is capable of augmenting the interleukin-2 (IL-2) production and proliferation of antigen-activated T cells. TH5.2 MAb by itself is not mitogenic for T cells; the enhanced IL-2 production and proliferation requires costimulation with either antigen or mitogen. TH.2 MAb recognizes all peripheral blood T cells at varying intensities, but does not react with monocytes. Using dual-color fluorescence analysis, it was determined that TH5.2 MAb reacts at a higher intensity on Leu-3a-positive T cells compared to Leu-2a-positive cells. Sorting T cells on the basis of fluorescent intensity with TH5.2 MAb demonstrated that the T cells reacting at high TH5.2 intensity were able to respond to mitogen at a higher rate (5-10X), as well as produce higher concentrations of IL-2 in response to mitogen as compared to the low IL-2 intensity cells. Cytotoxically treating peripheral blood mononuclear cells (PBMC) with TH5.2 MAb plus complement, which resulted in an approximate 8% decrease in the total population, significantly reduced the ability of the cells to proliferate to both mitogen and antigen. Addition of recombinant IL-2 to the cultures was able to restore the proliferative capability of the cells. In further analyzing the ability of TH5.2 MAb to augment the proliferative capability of PBMC to antigen and mitogen stimulation in vitro, it was determined that TH5.2 MAb was capable of acting synergistically with antigen or mitogen in increasing the Il-2-producing capability of T cells. Taken together the data suggest that the TH5.2 determinants is involved in the proliferative capability of T cells and is functioning at the level of IL-2 synthesis and/or secretion.

Recombinant murine and human IL 1 alpha bind to human endothelial cells with an equal affinity, but have an unequal ability to induce endothelial cell adherence of lymphocytes.

Consistent with the reports of others, we have demonstrated that human peripheral blood lymphocytes adhere to cultured human umbilical vein-derived endothelial cells (EC) in vitro. In our studies adherence was increased twofold to threefold by a 6-hr preincubation of the EC with IL 1. Recombinant human IL 1 alpha induced a maximal adherence response at less than 1 U per 2 X 10(4) EC. In contrast, recombinant murine IL 1 alpha was found to be 250- to 1250-fold less active in the adherence assay, based on units of IL 1 activity defined by the murine thymocyte proliferation assay. Moreover, when EC were preincubated with excess murine IL 1, no inhibition of the adherence-inducing effect of human IL 1 was noted. To characterize further this dichotomy of biological potency of murine and human IL 1 on the adherence assay, IL 1 binding studies were initiated. Recombinant human and murine IL 1 alpha were equally effective in inhibiting the binding of 125I-labeled human and murine IL 1, based on both micrograms of protein and units of IL 1 activity. The results of this study demonstrate that although human and murine IL 1 bind with equal affinity to receptors on human EC, human IL 1 is significantly more potent at inducing the increased EC adhesiveness for lymphocytes. The implications of these results for endothelial cell IL 1 receptor function are discussed.

[Implantation of vena cava filters in acute pulmonary embolism]. / Zur Implantation von Vena-cava-Filtern bei akuten Lungenembolien.

The long-term results of 222 patients (pts) with transvenously implanted vena cava filters are critically reviewed. A total of 98 pts were given a Mobin-Uddin filter, 102 pts a Günther filter, and 16 pts a LGM filter. Among the serious complications observed during long-term follow-up were vena cava occlusions and increasing symptoms ranging from congestion of the deep leg veins, perforations into ureters, fractures and embolizations of the filters in up to 40% of the patients, if Günther filters were implanted.