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B Schleiffenbaum

Publications and source records attributed to B Schleiffenbaum.

17 recordsLinked to original sources
PubMed1998

Inhibition of leukocyte emigration induced during the systemic inflammatory reaction in vivo is not due to IL-8.

In keeping with the multistep model of leukocyte-endothelial cell interaction, stimulation of endothelium by cytokines or endotoxin (LPS) in vitro leads to selectin/integrin-mediated neutrophil adhesion, followed by neutrophil endothelial transmigration. The i.p. injection of LPS in vivo induces a systemic inflammatory reaction in a mouse model with generalized activation of both endothelial cells (up-regulation of adhesion molecules ICAM-1, VCAM-1, E-selectin) and neutrophils (up-regulation of Mac-1). However, no intravascular endothelial adhesion or tissue emigration of neutrophils can be observed. Even more importantly, the in vivo emigration of polymorphonuclear cells at sites of a local inflammatory reaction (IL-8, TNF, LPS) is totally inhibited when the mice are pretreated systemically with LPS, although the neutrophils respond fully to a rechallenge with LPS ex vivo, and endothelial adhesion molecules are further up-regulated locally. The systemic application of TNF also caused a total inhibition of neutrophil emigration. However, while anti-TNF mAb abrogated the inhibitory activity induced by TNF, they had no effect on systemic LPS. The systemic application of IL-8 did not inhibit neutrophil emigration, nor did the pretreatment of mice with anti-IL-8 mAb before the systemic application of LPS abrogate the inhibitory activity induced by LPS. Therefore, the putative inhibitor of neutrophil emigration, which may be of great physiologic importance, as it prevents in vivo the generalized emigration of activated neutrophils, most likely is not IL-8.

Animals↗
PubMed1997

[Castleman's disease--a rare cause of a febrile state with lymphadenopathy].

HISTORY AND CLINICAL FINDINGS: A 26-year-old man had a prolonged fever, 10 kg weight loss and generalized lymphadenopathy, first diagnosed as a malignant lymphoma. On admission he was febrile and in a markedly reduced physical condition. Submandibular, angular, cubital and inguinal lymph nodes were slightly enlarged bilaterally. INVESTIGATIONS: Serology and blood cultures were negative. Sonography and computed tomography showed enlarged lymph nodes in the neck, mediastinum, axillae, retroperitoneum and mesentery. Biopsies of lymph nodes and bone marrow revealed changes characteristic of Castleman's disease. TREATMENT AND COURSE: Prednisone was administered, 20 mg daily for 20 days, the dose gradually reduced over 4 months. The fever ceased after 14 days and the patients's working capacity was fully restored after 7 weeks. CONCLUSION: In a case of prolonged fever of unknown cause Castleman's disease should be included in the differential diagnosis. It at first consists of polyclonal lymphatic proliferation. But transformation to malignant lymphoma and systemic Kaposi's sarcoma have been described in the disease's generalized form.

Adult↗
PubMed1996

[Emergency admission with suspected anemia-causing bleeding in the upper gastrointestinal tract].

The 33-year-old woman was violently beaten and suffered from concussion of the upper abdomen. Because of pain she took mefenamic acid for two days. Then she reported hematemesis, melena and vertigo. The value for hemoglobin was determined as 5.8 g/dl. Acute blood loss was suspected, but neither intraabdominal nor upper gastrointestinal hemorrhage could be detected. Further investigations revealed a Coombs-negative hemolytic anemia and thrombocytopenia, and microangiopathic hemolysis was suggested by the detection of fragmentocytes in a peripheral blood smear. The diagnosis of thrombotic thrombocytopenic purpura (TTP) was made, though the patient did not suffer from manifestations of impaired microcirculation like neurological symptoms or renal failure. The TTP was found to be associated with HIV infection. The hematological disease responded well to the treatment with fresh-frozen plasma.

Abdominal Injuries↗
PubMed1996

[Value of the blood picture and flow cytometry immunotyping in the early diagnosis of low-grade lymphoma].

Low-grade malignant non-Hodgkin lymphoma [NHL] and chronic lymphocytic leukemia [CLL] as its special form are slowly progressing malignancies which may present with lymphadenopathy, splenomegaly or, more rarely, hepatomegaly. The diagnosis is made by bone marrow or lymph node histology, while laboratory tests are relatively unspecific and may only hint towards the diagnosis. In contrast to high-grade malignant lymphoma, low-grade malignant NHL is often associated with the appearance of malignant lymphoma cells in peripheral blood. These malignant lymphocytes may be differentiated microscopically from normal lymphocytes, so that the diagnosis of NHL may be suspected not only because of clinical symptoms or lymphocytosis, which may present late in the natural history of the disease, but also on morphological grounds. Three types of low-grade malignant NHL cells may be recognized in peripheral blood: A mature appearing lymphocytic type with only slight alterations of the nucleus, a lymphoplasmocytic type, and a lymphocytic type with prominent alterations of the nucleus. The appearance of smudge cells and a monotony in lymphocyte morphology may serve as further diagnostic aids. Once the diagnosis has been suspected on morphological grounds, it may be verified in the case of B-cell lymphomas by flow cytometry. The clonality of T-cell lymphoproliferative disorders in addition has to be proven by demonstrating a clonal rearrangement of the T-cell receptor in Southern blots. An early diagnosis of low-grade malignant NHL may not only provide new insights into the natural history of monoclonal cytopathies but may also be of importance in the clinical management of patients.

Blood Cells↗
PubMed1995

High grade malignant lymphoma with clinical characteristics and immunophenotype of natural killer cells.

The malignant proliferation of natural killer (NK) cells which are morphologically characterized as large granular lymphocytes (LGL) is a well known clinical entity which was named after its morphological appearance as LGL-leukemia/lymphoma. Similar to non-malignant NK-cells, these tumors can be divided into those which express the CD3-T-cell receptor complex and those which do not. The CD3-positive type of LGL-leukemia is immunophenotypologically characterized by the expression of CD16, and variably CD 56 and CD 57, and generally follows a more indolent course. In contrast, malignant proliferations of CD3-negative LGL express either CD16 or CD 56, and only occasionally CD 57 on their cell surface. Clinically, CD3-negative NK-lymphomas tend to progress rapidly. We report here the case of a high grade malignant lymphoma which was characterized by an immunophenotype typical for CD3-negative NK-cells (CD2+, CD3-, CD16+, CD56(+), CD57-). The disease proved to be rapidly fatal despite aggressive chemotherapy. Interestingly, the patient suffered from a high turn over pancytopenia, which also characterizes NK-cell leukemias/lymphomas of the LGL-type. However, our patient's lymphatic cells appeared highly immature, and cytoplasmic granules, characteristic for LGL-cells, could not be discerned either microscopically or electronmicroscopically. Furthermore, the malignant lymphatic population had the T-cell receptor beta-chain rearranged. We therefore concluded that our patient might have suffered from a malignant proliferation of a putative precursor cell intermediate between T-cells and NK-cells.

Adult↗
PubMed1995

Epinephrine test and plasma elastase as diagnostic tools in a patient with CD3+ large granular lymphocyte proliferation.

Large granular lymphocytes (LGL) proliferation is characterized by expansion of cytotoxic lymphocytes and associated with neutropenia. In a case of CD3+ LGL-proliferation the epinephrine stimulation test (EST) induced a striking elevation of CD3+, CD8+, CD57+ LGL in peripheral blood from 2.7 x 10(9)/l to 20 x 10(9)/l and might be an additional diagnostic tool in patients with normal or low absolute numbers of circulating LGL. After treatment with steroids, plasma elastase--a marker of neutrophil destruction--decreased from 162 to 40 micrograms/l (normal < 47 micrograms/l) which correlated well with a simultaneous increase in peripheral neutrophil counts from 0.14 to 1.0 x 10(9)/l. This finding supports the hypothesis that neutropenia in CD3+ LGL proliferation is due to neutrophil destruction, possibly mediated by LGL.

Aged↗
PubMed1994

Inhibition of leukocyte L-selectin function with a monoclonal antibody attenuates reperfusion injury to the rabbit ear.

The leukocyte adhesion molecule L-selectin mediates neutrophil adhesive interactions with endothelial cells and is in part responsible for neutrophil rolling. We examined the role of L-selectin in ischemia-reperfusion injury of rabbit ears using a monoclonal antibody (MoAb) directed to a functional epitope of L-selectin. Arterial blood flow to the rabbit ear was occluded for six hours with ambient temperature at 23 degrees C to 24 degrees C. Rabbits were treated at reperfusion with saline (n = 8), the L-selectin function-blocking LAM1-3 MoAb (2 mg/kg), or the nonfunction-blocking LAM1-14 MoAb (2 mg/kg). Tissue injury was determined by measuring edema and necrosis. Edema in the LAM1-3 MoAb-treated group (peak = 25 +/- 4 mL) was significantly less (P < .05) than in saline-treated (peak = 40 +/- 8 mL) and LAM1-14 MoAb-treated (peak = 41 +/- 6 mL) groups. Tissue necrosis at 7 days was not observed in the LAM1-3 MoAb-treated group, whereas significant necrosis (P < .05) was seen in the saline- (8% +/- 3% necrosis) and LAM1-14 MoAb-treated (7% +/- 3% necrosis) group. We conclude that blocking L-selectin ameliorates necrosis and edema after ischemia and reperfusion in the rabbit ear, presumably by blocking neutrophil rolling.

Animals↗
PubMed1994

[Reduced oxygen transport capacity as a cause of dyspnea].

A reduction in the capacity of blood to carry oxygen leads to increased extraction of oxygen from the blood by peripheral tissues, and consequently to a decrease in the venous partial pressure of oxygen (pO2). At reduced venous pO2 pre-existing venous-arterial shunts gain in influence on arterial pO2 and arterial pO2 also decreases. In addition, physical exercise leads to lactate acidosis earlier and at lower levels of exercise than in healthy subjects. The low arterial pO2 and the low pH of acidosis are sensed by chemoreceptors of the carotid bodies and neural signals are transmitted to centers of the brain stem, where they are integrated and result in the sensation of shortness of breath (dyspnea). The capacity of the blood to carry oxygen is determined not only by the concentration of hemoglobin but also by the binding characteristics of hemoglobin for oxygen, which can be deduced from its molecular structure. In contrast to cases with acute anemia, dyspnea is often absent in patients in whom anemia develops gradually (down to hemoglobin levels of 7 g/dl). This tolerance is not mediated by pulmonary or cardiac compensatory mechanisms also at work in acute anemia, but is due to increases in the concentration of diphosphoglycerate. This allosteric effector molecule induces, by binding to hemoglobin, a decrease in the affinity of hemoglobin for oxygen, thereby leading to improved release of oxygen from hemoglobin in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗
PubMed1992

ELISA for quantitation of L-selectin shed from leukocytes in vivo.

L-selectin is a cell surface receptor on granulocytes, lymphocytes and monocytes that is responsible for the initial attachment of leukocytes to endothelium. The extracellular domain of L-selectin is proteolytically shed from leukocytes following cellular activation in vitro. The shed form of L-selectin (SL-selectin) is functionally active and at high concentrations can inhibit leukocyte attachment to endothelium. Therefore, an ELISA was developed to quantitate the levels of SL-selectin in biological fluids, biopsy specimens and during recombinant protein production. This simple, quantitative sandwich ELISA uses two monoclonal antibodies directed against the extracellular domain of SL-selectin. The assay has a detection range of 5-1300 ng/ml, is precise and sensitive. The ability of this assay to detect SL-selectin in serum, plasma, and culture supernatant fluid was demonstrated and it was used to quantitate circulating SL-selectin in normal and patient sera. Patients with sepsis and HIV infection showed markedly elevated SL-selectin levels in serum. Thus, the ELISA should prove useful both for laboratory purposes as well as in the diagnostic evaluation of patients with inflammatory diseases.

Animals↗
PubMed1992

Soluble L-selectin is present in human plasma at high levels and retains functional activity.

L-selectin expressed by granulocytes, lymphocytes, and monocytes is responsible for initial leukocyte attachment to inflamed endothelium and high endothelial venules of peripheral lymph nodes. After leukocyte activation in vitro, L-selectin is rapidly shed from the cell surface. In this study, shed L-selectin (sL-selectin) from both lymphocytes and neutrophils was demonstrated to be present in high levels in human plasma by Western blot analysis and using a quantitative ELISA. In serum from normal human blood donors, a mean sL-selectin level of 1.6 +/- 0.8 micrograms/ml (n = 63) was found by ELISA. In addition, semipurified sL-selectin from plasma inhibited L-selectin-specific attachment of lymphocytes to cytokine-activated endothelium in a dose-dependent manner. L-selectin-dependent leukocyte attachment was completely inhibited at sL-selectin concentrations of 8-15 micrograms/ml, while physiological concentrations of sL-selectin caused a small but consistent inhibition of lymphocyte attachment. sL-selectin in plasma also inhibited anti-L-selectin mAb (2-5 micrograms/ml) binding to the surface of leukocytes. Interestingly, one epitope present within the EGF-like domain of L-selectin was lost in sL-selectin, suggesting a conformational change in the structure of the receptor after shedding. The presence of serum sL-selectin with functional activity indicates a potential role for sL-selectin in the regulation of leukocyte attachment to endothelium.

Blotting, Western↗
PubMed1992

TNF-specific deactivation of granulocytes in vivo: a possible mechanism of self-protection.

Granulocytes (PMN) have recently been shown to be specifically deactivated towards tumor necrosis factor (TNF) by preexposure to TNF itself and to other stimuli such as endotoxin and complement C5a in vitro. When TNF (200 micrograms/m2) was infused to a male volunteer, we found ex vivo an almost complete TNF-specific deactivation of PMN adhesion (57 +/- 3* vs 6 +/- 2%**), of exocytosis of secondary granules (37 +/- 1* vs 7 +/- 1%**) and of the respiratory burst as measured by hexose monophosphate shunt activation (74 +/- 1* vs 12 +/- 3** nM/10(7) PMN/45 min). Furthermore, up- and down-regulation, respectively, of the PMN surface adhesion molecules Mac-1 and LAM-1 became TNF-resistant. Similar to the results obtained in vitro, deactivation correlated with a decrease in the number of cellular TNF receptors. In PMN of 4 patients exposed to activated complement during hemodialysis, a state of TNF-specific cross-deactivation could also be demonstrated.

Adult↗
PubMed1990

The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factor-induced neutrophil responses by receptor down-regulation.

Despite numerous reports, the role of tumor necrosis factor (TNF) in polymorphonuclear leukocyte (PMN) function remains controversial. We found TNF to be a potent, pertussis toxin-independent stimulator of PMN adhesion (ED50 2.6 pM). TNF-stimulated PMN under adherent conditions released up to 65% of their transcobalamine content (ED50 3.9 pM) and increased their burst activity 10-fold (ED50 3.2 pM) as measured by the hexose monophosphate shunt, whereas PMN held in suspension hardly degranulated at all and only little burst activity was demonstrable. However, preincubation of PMN with TNF in suspension led to a decrease in cellular adhesiveness, degranulation, and burst activity in response to a secondary stimulus of TNF under adherent conditions, although cells remained fully responsive toward phorbol myristate acetate. A concomitant dose-dependent decline of TNF receptor numbers that correlated well with the inhibition of PMN function (r = 0.91) suggests receptor down-regulation as the mechanism of functional PMN deactivation. Remarkably, preincubation with other PMN stimuli such as N-formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, leukotriene B4, complement component fragment 5a (C5a)/C5a (desarginated), and endotoxin also led to a reduction of TNF-specific PMN responses (cross-deactivation) from 35% (LTB4) to 90% (endotoxin), corresponding with the down-regulation of TNF receptors. Deactivation and receptor down-regulation are independent of pertussis toxin-sensitive G proteins and protein kinase C but seemed to depend on changes in calcium metabolism. Granulocyte hyporesponsiveness towards TNF in sepsis (with elevated blood levels of endotoxin and TNF) might be a mechanism of self-protection or, to the contrary, might impair a possibly central mode of host defense.

Calcium↗
PubMed1989

The cell surface glycoprotein Mac-1 (CD11b/CD18) mediates neutrophil adhesion and modulates degranulation independently of its quantitative cell surface expression.

It has previously been shown that during degranulation Mac-1 (CD11b/CD18)--a glycoprotein that plays a central role in neutrophil adhesion-is up-regulated on PMN surfaces. It has been assumed that this quantitative change in adhesion Ag expression on the cell surface would in turn lead to increased cellular adhesiveness. In contrast, we found that at an incubation temperature of 16 degrees C, stimulated neutrophil adhesion to plastic tissue culture dishes in the presence of FMLP (2.5 x 10(-6) M), TNF (10 ng/ml), or PAF (1 x 10(-4) M) occurred without cellular degranulation or Mac-1 surface up-regulation as measured cytofluorometrically. As shown by functional inhibition studies employing monoclonal antibodies 60.3 (anti-CD18) and 60.1 (anti-CD11b), adhesion at 16 degrees C, where no CD11b/CD18 up-regulation was seen, is mediated by CD11b/CD18 just as it is at 37 degrees C, where degranulation and CD11b/CD18 up-regulation could be demonstrated. The physiologic importance of these findings was underscored by experiments done on endothelial monolayers, which showed that PMN association with endothelial cells is absolutely independent from the quantitative up-regulation of Mac-1 on PMN surfaces. When neutrophils were stimulated at 37 degrees C by endotoxin, an agent that does not induce aggregation (a form of intercellular adhesion), Mac-1 surface expression increased only after cells had become adherent, whereas cells held in suspension to prevent cell-substrate adhesion neither degranulated nor up-regulated their Mac-1 surface expression. Thus, not only is adherence independent of degranulation and Mac-1 cell surface up-regulation, but both degranulation and Mac-1 surface up-regulation appear to depend on the process of adhesion. Correspondingly, incubation of neutrophils with antibodies 60.1 and 60.3 inhibited not only adhesion of cells stimulated with FMLP at 37 degrees C but degranulation as well. These results indicate that Mac-1 influences degranulation as well as it controls adhesion not by its mere quantity on the cell surface, but rather by an yet undefined molecular modulation.

Antibodies, Monoclonal↗
PubMed1989

Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage.

In an attempt to understand the regulatory mechanisms governing passage of neutrophils from the vascular bed to the interstitial tissue, we analyzed the effect of the pleiotropic monokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) on transendothelial neutrophil traffic. Short-time preincubation of human umbilical vein endothelial cell (HUVE) monolayers with IL-1 and TNF led to an impressive time- and dose-dependent increase of endothelial cell-associated neutrophils when working in a full plasma system on petri dishes. Electron microscopic analysis revealed junctional penetration of monolayers by neutrophils. More quantitatively, when using a monolayer-on-filter-system, priming led to a severalfold increase in complete layer passage occurring in the absence of an external chemotactic gradient. Direct comparison with an upside-down modification of the system together with data demonstrating the vectorial behavior of such migration revealed that IL-1-stimulated transendothelial neutrophil traffic is polarized. The described enhancement of neutrophil transendothelial passage was found to be a unique feature of IL-1/TNF-activated HUVE since HUVE-dependent transmigration potentiation was not observed as a consequence of mere neutrophil attachment to endothelial cells (e.g., induced by Fc-mediated adherence of PMN to HUVE). IL-1 acts selectively on endothelial cells as demonstrated by total inhibition of its effect by actinomycin D. Moreover, IL-1 does not induce HUVE monolayers to secrete a chemotaxin, and the neutrophil passage guiding principle is removable from the HUVE surface by short trypsin exposure. Congruent results were obtained with human adult arterial as well as saphenous vein endothelial cells. As shown by blockade of neutrophil migration with pertussis toxin, IL-1- and TNF-inducible transendothelial migration can be dissected into an initial anchoring step, which is succeeded by active neutrophil migration, possibly along a putative endothelial membrane-bound gradient.

Cell Adhesion↗