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Biomedical subjects

J Fehr

Publications and source records attributed to J Fehr.

At least 91 records · Page 5Linked to original sources
PubMed1987

Diagnostic and prognostic value of monoclonal antibodies in immunophenotyping of T cell lymphomas.

6 cases of post-thymic T cell lymphoma (PTCL) and 4 cases of T lymphoblastic lymphoma were investigated with a panel of 21 monoclonal antibodies (MoAb). The PTCL group was composed of 2 by 2 cases of lymphoepithelioid cell lymphoma, T zone lymphoma and T immunoblastic lymphoma. In lymphoepithelioid cell lymphoma, the cell proliferating activity was low, and a malignant clone was not identifiable by the methods used. In the cases of T zone lymphoma and T immunoblastic lymphoma, malignant populations were detectable on the grounds of immunologic marker profile combined with cytologic particularities. The 4 cases of T lymphoblastic lymphoma were of a common cortical thymic phenotype (T4+, T8+, T6+) and presented with a mediastinal mass. In 3 of them, cell proliferation marker (Ki-67) was expressed by most tumor cells. Cell proliferating activity, however, did not inversely correlate with survival.

Adolescent↗
PubMed1986

[Microangiopathic hemolytic anemias. Clinical pattern, therapy and clinical course in 14 patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome].

Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) have in common a microangiopathic hemolytic anemia involving disseminated platelet aggregation and endothelial damage of the microvasculature mainly of the brain (TTP) and kidney (HUS). The underlying pathomechanism still remains unclear. The disease takes an acute, dramatic and frequently fatal course. Unfortunately a broadly approved therapeutic regimen is still lacking since the rarity of TTP and HUS makes study of a large group of patients impossible. We have observed and treated 14 patients with TTP and HUS during a period of 9 years. Most of the cases have been triggered by infectious diseases and pregnancy. Diagnostic cornerstones were hemolytic anemia, schistocytes on peripheral blood smears and consumption thrombocytopenia. Renal and cerebral symptoms were observed regularly, whereas lesions of the pancreas, liver and heart were much less frequent. The treatment included plasma transfusion (47%), plasma exchange (42%), high dose corticosteroids (74%), antiplatelet agents (53%), vitamin E (32%) and vincristin (11%). The outcome of 19 episodes of TTP or HUS was as follows: in 78% complete recovery, in 11% persistence of impaired renal function, and in 11% death. From analysis of our cases it is concluded that plasma transfusions and high dose corticosteroids improve the prognosis of TTP and HUS significantly.

Adolescent↗
PubMed1986

[Effectiveness and toxicity of high-dosage Ara-C. Clinical observations in 10 cases and review of the literature].

Ten patients with acute myeloid leukemia were treated with a high-dose ara-c regimen (3 g twice daily for 6 days). 5 patients (50%) achieved a complete remission lasting for a median duration of 5 months. These patients had all achieved a complete remission following standard treatment with ara-c. High-dose ara-c was ineffective in 2 patients resistant to standard ara-c protocols. The most important side effects of high-dose ara-c were conjunctivitis and cerebellar symptomatology. In one case a severe diffuse encephalopathy with cerebellar predominance set in at a remarkably late stage (45 days after starting treatment). Our results and those of other authors suggest that treatment with high-dose ara-c should be used with caution.

Adolescent↗
PubMed1986

Amodiaquine induced agranulocytosis and liver damage.

Seven cases of agranulocytosis and two of liver damage that were probably due to amodiaquine treatment were studied. In five cases agranulocytosis was combined with liver damage, and in one case of primary liver damage moderate neutropenia was present. Three patients died. High total doses or prolonged duration of treatment, or both, appear to favour the occurrence of these reactions. The clustering of five of the seven cases of agranulocytosis within six months in one medical centre indicates that the risk to benefit ratio of amodiaquine for malaria prophylaxis should be re-evaluated.

Adolescent↗
PubMed1986

Binding of C-reactive protein to human polymorphonuclear leukocytes: evidence for association of binding sites with Fc receptors.

The functional similarities between C-reactive protein (CRP) and IgG raised the question as to whether human phagocytes are stimulated by CRP in the same way as by binding of antigen-complexed or aggregated IgG to their Fc receptors. Studies with the use of highly purified 125I-labeled CRP showed specific and saturable binding to human polymorphonuclear leukocytes (PMN) with a KD of 10.5 +/- 5.7 X 10(-8) M only when carried out in heat-inactivated plasma. The number of specific binding sites per cell was estimated at 1 to 3 X 10(6). Competitive inhibition of CRP binding by antigen-complexed or aggregated IgG suggests CRP binding sites to be associated with PMN Fc receptors. Only when assayed in heat-inactivated plasma did CRP binding induce adherence of cells to tissue culture dishes. However, no metabolic and potentially cytotoxic stimulation of PMN was detected during CRP plasma-dependent attachment to surfaces: induction of aggregation, release of secondary granule constituents, and activation of the hexose monophosphate pathway were not observed. These results imply that CRP-PMN interactions is dependent on an additional factor present in heat-inactivated plasma and is followed only by a complement-independent increase in PMN attachment to surfaces. Because CRP was found to be deposited at sites of tissue injury, the CRP-mediated adherence of PMN may be an important step in localizing an inflammatory focus.

Antigen-Antibody Complex↗
PubMed1985

[Hematologic complications in infectious mononucleosis].

In three patients with infectious mononucleosis the disease was severely complicated by, respectively, aplastic anemia, consumptive thrombocytopenia and hemolytic anemia with acute renal failure. In contrast to the regularly recurring basic signs and symptoms of the illness, serious complications occur in less than 1% of all patients. Changes in the immunologic system seem to play an important role in hematologic and other complications, as well as in the occasionally fatal Epstein-Barr virus infection. Pathophysiological, and particularly immunologic mechanisms, and possible therapy are discussed with reference to case reports of patients with similar clinical courses and the literature on infectious mononucleosis.

Acute Kidney Injury↗
PubMed1985

[Effect of interferon-alpha 2 (E. coli) in hairy cell leukemia].

Recombinant interferon-alpha 2 (E. coli) produced a clinically significant improvement in hemoglobin, granulocytes and platelets in 7 of 8 patients with hairy cell leukemia. Response to treatment was already noticeable in the fourth treatment week. In one case without improvement after 120 days, treatment was stopped. So far only one complete remission has been documented. Because of the remarkable improvement in the peripheral blood values, the induction of a complete remission may not be the ultimate goal of interferon treatment. The side effects of this subcutaneous low-dose treatment consisted mainly of mild flu-like symptoms of short duration. The results obtained with recombinant interferon-alpha 2 confirm the initial observation by Quesada et al. with partially purified leukocyte-interferon. In our experience, these results are superior to those obtained in similar conditions with chlorambucil.

Adult↗
PubMed1985

[Importance of prostaglandins for the in vitro adhesiveness and in vivo margination of neutrophilic granulocytes].

The (patho-)physiological role of prostaglandins and thromboxanes on granulocyte function remains controversial. In a combined in vitro and in vivo study, we analyzed the influence of these arachidonic acid metabolites on granulocyte adhesion and margination. A dichotomous dose-dependent effect on epinephrine-induced granulocyte demargination parallels the paradoxical effect of low (0.5 g)- and high (4 g)-dose aspirin on bleeding time. These observations suggest that prostacyclin acts as a modulator for low-affinity adhesion and margination of granulocytes. With respect to the induction of high-affinity adhesion, which is reflected in a state of hypermargination in vivo and accompanied by potentially cytotoxic cell activation, prostaglandins in general and prostacyclin in particular are without effect when such activation is induced, either by endotoxin, by formylated chemotactic peptide, or by activated complement.

Adult↗
PubMed1985

The hypersplenic spleen. A contractile reservoir of granulocytes and platelets.

Epinephrine-induced mobilization of noncirculating granulocytes and thrombocytes was evaluated in 13 subjects with marked variation in spleen size and correlated with the sonographically recorded contraction of the spleen. The effects of epinephrine on blood granulocyte and thrombocyte counts correlated highly with splenic contraction but not with spleen size. The findings provide further insight into mechanisms of hypersplenism, suggest that the big spleen of hypersplenism mimics the contractile reservoir function of the spleen of certain animals, and point out that the "marginal" granulocyte pool mobilized by epinephrine is not randomly distributed throughout the body.

Adult↗
PubMed1985

Transcobalamin II: a marker for macrophage/histiocyte proliferation.

Increased blood levels of (apo-)transcobalamin II have been observed in several clinical conditions, but persistent inability to find a common denominator for this plasma protein aberration has hampered its introduction as a clinically useful laboratory parameter. Because several observations suggested a relationship between reticuloendothelial cell activity and transcobalamin II, the finding of an extreme transcobalamin II elevation in a patient with malignant histiocytosis was taken seriously. Of 14 consecutive patients with proliferative histiocytosis (8 malignant, 6 reactive), all revealed marked to extreme elevations of transcobalamin II. Macrophage/histiocyte origin of this protein is supported by a close parallelism to increased serum angiotensin-converting enzyme activity. Comparative pre- and postoperative measurements of transcobalamin II and angiotensin-converting enzyme in four patients with histiocytic proliferation who underwent splenectomy, an intervention that led to immediate reduction of the macrophage/histiocyte cell pool, revealed a parallel and impressive drop of both parameters, further corroborating the histiocytic origin of transcobalamin II. It is suggested that transcobalamin II determination provides useful information on activity and size of the macrophage/histiocyte system, and supplements measurements of the traditional acute phase reactants (e.g., C-reactive protein, red blood cell sedimentation rate).

Adult↗
PubMed1985

Antiadhesive properties of biological surfaces are protective against stimulated granulocytes.

Despite the fact that a series of endogenous and exogenous inflammatory mediators are potent activators of circulating granulocytes, damage of vascular endothelium, a primary target tissue, is a rather unusual event in systemic inflammatory states. Since mediator-induced neutrophil hyperadhesiveness on plastic tissue culture dishes is invariably accompanied by intense release of lysosomal granule constituents and respiratory burst activation, thus representing a powerful model to investigate neutrophil cytotoxic states, comparative studies with neutrophils suspended in autologous plasma in the presence or absence of N-formyl-Met-Leu-Phe (2.5 microM), the most potent adhesion inducer, were performed on different biologic surfaces. On optimally adherent closed monolayers of cultured endothelial cells or fibroblasts we observed poor stimulation of adhesion as well as minimal granule release and hexose monophosphate pathway activation. Functional behavior of neutrophils on single molecular components of basal laminas such as fibronectin and collagen (type IV) coats was intermediate, with positive adhesion promotion but markedly reduced metabolic activation. When tested on endothelial cell-derived extracellular matrices, neutrophils again showed functional nonresponsiveness to N-formyl-Met-Leu-Phe. Scanning electron microscopy revealed an impressive congruency between the degree of cellular spreading and metabolic activation in the presence of N-formyl-Met-Leu-Phe, with maximally flattened neutrophils on plastic vs. nonspread, polarized cells on monolayers. Identical results were obtained by using other adhesion inducers such as complement-activated plasma or endotoxin. Lack of cell injury by N-formyl-Met-Leu-Phe-exposed neutrophils was corroborated by the absence of tracer release from [111In]tropolonate-labeled endothelium. These results indicate that biologic surfaces possess antiadhesive properties that protect them from cytotoxic damage by stimulated angry phagocytes.

Cell Adhesion↗
PubMed1985

Hairy cell leukemia: an interferon deficient disease?

rIFN-alpha 2 is an effective substance in the treatment of HCL. Although the complete eradication of hairy cells from the bone marrow is rarely possible, a dramatic improvement of profound cytopenias can be obtained in most patients, 12 out of 13 in this study. The response can be seen after a median treatment duration of about 2 months and appears to be independent of the presence of the spleen. Once a stable improvement of the peripheral blood values is achieved, one dose of rIFN-alpha 2 every other week may be sufficient to maintain the cell counts. The mechanism(s) by which IFN acts remain unclear. We speculate, that HCL is an IFN deficient syndrome because monocytes which are the major source of IFN-alpha are severely depressed in this lymphoproliferative disorder. Following this hypothesis, the IFN therapy would be comparable to the substitution of insulin in diabetic patients.

Adult↗
PubMed1984

Complement-induced granulocyte adhesion and aggregation are mediated by different factors: evidence for non-equivalence of the two cell functions.

Cell-cell aggregation and cell-substratum adherence, two functional manifestations of granulocytes of potential clinical relevance, are widely considered to result from identical cell membrane alterations. Our study casts doubt on this assumption and defines the complement-derived adhesion-inducing (pectic)/enzyme releasing activity as an entity that is clearly separable from the chemotactic/aggregating activity (C5adesArg). Using selective activators of the alternative and the classical pathway of the complement system, unexpected dissimilarities were observed. Adhesion inducing potency that went in parallel with secondary granule content liberation, and respiratory burst activation (hexose monophosphate shunt activation), was confined to alternate pathway activators, was heat-labile (50 degrees) and could be inhibited by the protease inhibitor di-isopropylfluorophosphate. In contrast, plasma activated with aggregated gamma-globulin or cobra venom factor had no pectic/burst activating capacity but was equally potent in inducing heat- and DFP-resistant chemotactic-aggregating activity. It was further shown that, even in the presence of cytochalasin B, C5adesArg (evoked in whole plasma) does not liberate secondary granule constituents. These findings were corroborated by using highly purified C5adesArg. Our data suggest that the complement system plays a dual role in PMN accumulation at the inflammatory focus: whereas C5adesArg orientates cellular movement toward the site of bacterial invasion, the complement-dependent pexin(s) is mainly involved in confining infections localized by the adhesion-induced trapping of highly reactive cells.

Cell Adhesion↗
PubMed1983

[Acute osteomyelofibrosis. An overview and 2 personal cases].

Two cases of acute myelofibrosis are described which exemplify diagnostic and therapeutic possibilities in this clinical and morphologic entity. Delimiting criteria against other diseases with bone marrow fibrosis are also presented. This malignant myeloproliferative disorder is characterized by acute onset, minimal or absent splenomegaly, blood cytopenias with a highly variable percentage of blast cells in circulating blood, often unimpressive tear-drop poikilocytosis, intense marrow fibrosis, and a rapid clinical course. In one case, typical proliferation of all three hematopoietic cell lines was lacking and proliferating blast cells could be classified as myeloblasts/promyelocytes histochemically. In the other case, a single course of intensive combination chemotherapy resulted in marked dissolution of the marrow fibrosis and prolonged survival in partial remission.

Adult↗
PubMed1983

In vivo complement activation by polyanion--polycation complexes: evidence that C5a is generated intravascularly during heparin--protamine interaction.

In vitro studies have established the complement-activating potency of polyanion-polycation interaction. By transferring the heparin-protamine model to an animal (rabbit) system that picks up ongoing intravascular complement activation by documenting acute granulocytopenia due to margination, evidence that intravascular polyanion-polycation complexing leads to instantaneous activation of the C system in vivo that goes beyond C1, C4, and C2, and results in generation of biologically highly reactive products, such as C5a, is provided. Dependence of the phenomenon on an activable complement system is documented by its complete abolishment when animals were complement depleted by cobra venom factor administration. Therefore, activation of the complement system may play a causative role for untoward effects following heparin neutralization by protamine under clinical conditions. Furthermore, these studies suggest an in vivo role of nonimmune generation of inflammatory mediators by interaction of naturally occurring polyions.

Agranulocytosis↗
PubMed1983

Role of cell surface contact in the kinetics of superoxide production by granulocytes.

The complement-derived anaphylatoxin C5a and a putative analogue of bacterial chemotactic factor (N-formyl-methionyl-leucyl-phenylalanyl [fMLP]), as well as bacterial lipid A, all stimulate human granulocyte (PMN) adhesiveness and superoxide (O-2) production in a concentration-dependent manner. Since attachment of particulate matter to the PMN membrane is an early event in the triggering of respiratory burst of these cells, we further examined how adherence might modulate the release of O-2 induced by soluble mediators of inflammation. We found that both the quantity and kinetics of O-2 production depend on prior attachment of the cells to a surface. In stirred suspensions of PMN, fMLP induces only a short burst (2.5 min) of O-2 release associated with reversible PMN aggregation. The magnitude, but not the time course, of both these responses depend on the fMLP concentration. Unlike the short respiratory response of cells in suspension, PMN allowed to settle onto stationary petri dishes, then overlaid with fMLP, rapidly spread and attach to the surface where they remain and release O-2 throughout the 60-min test period. Prolonged O-2 release also follows fMLP stimulation in suspensions of PMN pretreated with cytochalasin B, in which case aggregation becomes irreversible during the 20-min burst. If fMLP is slowly infused into a suspension of cells at 37 degrees C or if PMN are challenged at 0 degrees C, and then warmed to 37 degrees C, O-2 release greatly decreases or becomes undetectable. Suspended PMN do not respond to a second challenge by the same stimulus regardless of the rate or temperature at which the first stimulus was added, a phenomenon formerly described as desensitization. However, if PMN challenged with fMLP in suspension undergo the short respiratory response and then are later placed in petri dishes, they adhere and resume production of O-2 without further stimulation. Chemotactic factor-induced adherence and O-2 release of PMN on a surface is entirely independent of either the mode of activation or prior O-2 release during preincubation in suspension. Human C5a also promotes PMN adherence and prolonged O-2 release in petri dishes. Furthermore, lipid A increases O-2 release and adherence of settled PMN, but fails to elicit either response from suspended PMN. These results indicate that cell surface contact plays an essential role in triggering the respiratory burst of PMN activated by soluble stimuli. This long-lasting O-2 release by chemotactic factor-stimulated PMN may play a significant role in inflammatory reactions when PMN become adherent in vivo.

Adult↗
PubMed1983

Granulocyte activation by endotoxin. II. Role of granulocyte adherence, aggregation, and effect of cytochalasin B, and comparison with formylated chemotactic peptide-induced stimulation.

PMN stimulation by endotoxin is heavily dependent on incubation conditions: although marked increase of PMN adhesiveness, enzyme release, and hexose monophosphate shunt activity, as well as superoxide production, occur when endotoxin-challenged cells are incubated in stationary petri dishes, absolutely no such response is observed with cells kept in suspension. Preincubation with cytochalasin B does not alter this reaction pattern. Hyperadhesiveness of endotoxin-challenged PMN is retained after thorough washing, eliminating the possibility that adhesion is due to absorption of endotoxin to petri dishes. In contrast to formylated chemotactic peptides that stimulate PMN adherence as well as aggregation, endotoxin elicits absolutely no aggregatory response (+/- cytochalasin B). Preexposure to endotoxin does not block the aggregatory response to subsequent addition of chemotactic peptides, whereas effects of endotoxin and formylated peptides on PMN in the stationary system are additive. These findings indicate that contact to surfaces is an essential primary event in PMN stimulation.

Cell Adhesion↗