Search PubMed⌕ Search

Biomedical subjects

J Fehr

Publications and source records attributed to J Fehr.

At least 109 records · Page 6Linked to original sources
PubMed1983

Granulocyte activation by endotoxin. I. Correlation between adherence and other granulocyte functions, and role of endotoxin structure on biologic activity.

Reminiscent of high concentrations of formylated chemotactic peptides, another group of bacteria-derived products, the lipopolysaccharides and lipid A, stimulate PMN adherence to petri dishes. Attachment and spreading of PMN is accompanied by intense release of secondary granule constituents and marked stimulation of the hexose monophosphate shunt activity. Dose-response studies with endotoxin preparations of diverse activity show that induction of PMN adherence, enzyme release, and respiratory burst activation are highly correlated, suggesting that this functional triad is mediated by a common mechanism. Hyperadhesiveness inducing concentrations of the chemotactically inert endotoxin lead to marked inhibition of PMN migration without affecting the direction-finding mechanism of the cell toward formylated peptides and C-derived chemotaxin(s). Endotoxin preparations at a lower grade of aggregation are more active, and the polysaccharide chains of the molecule are not essential with respect to PMN stimulation. Under our experimental conditions, endotoxin-induced stimulation of PMN is not inhibited by indomethacin, suggesting independence of cyclooxygenase-derived products. This type of PMN activation may play an important role in endotoxin-mediated tissue damage in vivo. Furthermore, hyperadhesion-induced inhibition of PMN migration to inflammatory sites during endotoxemia might hamper host resistance.

Arachidonic Acids↗
PubMed1983

Cyclic neutropenia: amplification of granulocyte oscillations by lithium and long-term suppression of cycling by plasmapheresis.

A patient with well documented cyclic neutropenia (CN) was given chronic lithium therapy as well as a short course of plasmapheresis with therapeutic intention. While on lithium therapy, an increase in the amplitude of the granulocyte oscillations was observed, but recurrent agranulocytotic periods persisted. A 2-wk course of plasmapheresis (total exchange 17 liters) resulted in a gradual decrease of granulocyte oscillations, with the granulocyte count remaining above 500/cu mm at all times, and the patient became asymptomatic. The improvements in the clinical state of the patient have now persisted for more than 9 mo. Quantitative analysis of the oscillation period and the phase lags between peak counts of the hematologic cell lines revealed a 20-day cycle for granulocytes, monocytes, reticulocytes, and platelets, but not for lymphocytes. The observed phase lags, together with the literature values for the intramarrow maturation times of the hematologic cell lines, suggest that the feedback regulation abnormality, believed to be at the basis of CN, primarily affects the stem cell that is still capable of differentiating into granulocytes and monocytes, but that the oscillations of reticulocytes and platelets are the result of a stem cell competition for uncommitted precursor cells by the primarily oscillating granulocyte and monocyte production.

Aged↗
PubMed1982

Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gamma globulin.

Since recent observations indicate that treatment with high-dose intravenous polyvalent intact immunoglobulin leads to a rapid reversal of thrombocytopenia in the idiopathic thrombocytopenic purpura (ITP) of childhood, we decided to apply this treatment to adults with ITP and to test the possibility that the effect of the immunoglobulin might be attributable to transient blockade of the reticuloendothelial system. Using sequential clearance studies of autologous 99mTc-labeled and anti-Rh(D)-sensitized erythrocytes in four adults with ITP who were treated with total doses of 1 to 1.5 g of immunoglobulin per kilogram of body weight, we found that a transient rise in platelet counts to normal levels within four to five days was accompanied by a marked temporary prolongation of the immune-particle clearance time. These data suggest that commercial intravenous immunoglobulin preparations may interfere with phagocyte Fc-receptor-mediated immune clearance. Since platelets in ITP treated with immunoglobulin were fully hemostatic, this type of therapy may allow surgical procedures to be performed safely in patients with this disease.

Adolescent↗
PubMed1982

[Idiopathic splenomegaly: the preliminary stage of a malignant lymphoma? Report on 2 cases].

Two patients with splenomegaly and a mild degree of hypersplenism are presented. Both underwent diagnostic splenectomy and in both the histologic examination of the spleen disclosed follicular lymphoid hyperplasia. The clinical picture and histologic findings were compatible with the diagnosis of idiopathic splenomegaly. 33 months after splenectomy a non-Hodgkin lymphoma was diagnosed in one patient. The literature on idiopathic splenomegaly is reviewed and the high incidence of non-Hodgkin lymphoma in the follow-up of such patients is pointed out.

Adult↗
PubMed1982

Acute myelogenous leukemia: successful treatment of relapse with cytosine arabinoside, VP 16-213, vincristine and vinblastine (A-triple-V).

Between March 1980 and January 1982, 15 patients with acute myelogenous leukemia (AML) in relapse were treated with one or more cycles of a combination chemotherapy consisting of cytosine arabinoside (Ara-C), VP 16-213, vincristine and vinblastine (A-triple-V). Of a total of 20 treatment cycles given, one partial and 15 complete remissions were achieved, there was no change in the bone marrow in two cases, one patient died due to Pseudomonas septicemia during an apparently normal bone marrow regeneration and one patient died of Candida infection while in aplasia. With 15 out of 20 (75%) successful relapse treatment courses, A-triple-V should be tested in first-line protocols.

Adult↗
PubMed1982

Pyridoxine-responsive primary acquired sideroblastic anaemia. In vitro and in vivo effects of vitamin B6 on decreased 5-aminolaevulinate synthase activity.

The activity of 5-aminolaevulinate (ALA) synthase, the first and rate-limiting of haem synthesis, was markedly reduced (13% of controls) in erythroblasts of a patient with acquired, primary sideroblastic anaemia (PASA). The reduced activity of ALA synthase could not be restored in vitro with 1 mmol/l pyridoxal-5-phosphate (PLP). Treatment of the patient with pyridoxine for several months increased the ALA synthase activity from 13% to 50% of controls in the absence and to 100% in the presence of PLP in the incubation medium. These studies suggest that both increased degradation of apo-ALA synthase and decreased affinity of ALA synthase for PLP may be involved in pyridoxine-responsive PASA.

5-Aminolevulinate Synthetase↗
PubMed1981

[Acquired, vitamin B6-responsive, primary sideroblastic anemia, an enzyme deficiency in heme synthesis].

The activity of delta-aminolevulinic acid synthetase (ALAS), the rate-limiting enzyme in heme synthesis, has been found to be markedly reduced (13% of controls) in erythroblasts of a patient with acquired, primary sideroblastic anemia. Administration of vitamin B6 (pyridoxin, 200-600 mg/d) resulted in complete reconstitution of erythroblastic ALAS-activity with concomitant disappearance of all hematologic abnormalities. The findings show that the therapeutic efficacy of pyridoxin in primary sideroblastic anemia is due to its effect on defective ALAS. More generally, the data support the view that almost all features of primary sideroblastic anemia can be ascribed to a disturbance of heme synthesis in erythroblasts.

5-Aminolevulinate Synthetase↗
PubMed1981

Granulocyte demargination by epinephrine in evaluation of hypersplenic states.

The usefulness of the epinephrine stimulation test in detecting granulocytic hypersplenism is evaluated. In 8 hypersplenic patients, an increment of the granulocyte count of 170% over baseline values was found, compared to 38% (P less than 0.001) in normal subjects and 44% )P less than 0.002) in patients neutropenic from other causes. No overlap of individual test results was found among the hypersplenic and the control groups. Epinephrine test discriminates between neutropenia from hypersplenism and neutropenia from other causes. Furthermore, this test is found to be a valuable adjunct to the hydrocortisone stimulation test in kinetic evaluation of neutropenia from any cause.

Adult↗
PubMed1980

[Acute leukemia after kidney allotransplantation (author's transl)].

Four cases of acute myelogenous leukemia and six cases of chronic myelogenous leukemia after treatment with azathioprine and prednisone for renal allotransplantation have been described in the literature. We report another two cases of acute leukemia 10 and 5 years after successful renal allotransplantation. Patient 1, a 29-year-old farmer, exhibited the signs of acute lymphatic leukemia resistent to treatment with cytostatic agens. Death was due to pneumonia. Patient 2, a 47-year-old salesman, developed pancytopenia together with splenomegaly. After splenectomy an atypical subacute myeloid leukemia became apparent which was not treated due to withdrawal of the patient. He died 2 months after diagnosis. Both patients received long-term immunosuppressive therapy with azathiopine and prednisone until the leukemia was diagnosed. A relationship between long-term immunosuppression and the occurrence of leukemia is postulated.

Adult↗
PubMed1980

Receptor-directed inhibition of chemotactic factor-induced neutrophil hyperactivity by pyrazolon derivatives. Definition of a chemotactic peptide antagonist.

The two pyrazolon derivatives, phenylbutazone and sulfinpyrazone, selectively inhibit chemotactic peptide-induced effects on neutrophils. As they antagonize the induction of acute neutropenia in vivo and of cellular hyperadhesiveness, lysosomal enzyme release, hexose monophosphate shunt activity, and superoxide production in vitro, these effects occur with a specificity not shared with other prostaglandin biosynthesis inhibition by these drugs resembles the competitive type of antagonism and occurs at concentrations attainable in vivo under clinical conditions. The locomotory machinery, the direction-finding mechanisms, and the basic metabolic machinery of the cell are unaffected. These drugs interfere with specific binding of the formylpeptide to its receptor on neutrophils.

Agranulocytosis↗
PubMed1979

Total sialic acid content of glycophorins during senescence of human red blood cells.

Glycophorins extracted from membranes of young and old human red blood cells have within an error of +/- 1.5% the same sialic acid content when referred to a relative measure of the number of glycophorins. The degree of surface iodination in glycophorins, which was shown to be the same in young and old cells, served as this relative measure. This finding implies that senescent human red blood cells hardly reveal desialylated surface proteins (less than or equal to 3%). However, the sialic acid content per cell was repeatedly reported to be 10 to 15% lower in old than in young cells. Therefore, we conclude 1) that human red blood cells lose intact glycophorin together with membrane during red blood cell senescence, and 2) that removal of desialylated and senescent red blood cells from the circulation proceeds by different routes.

Borates↗
PubMed1979

[Pharmacologic remobilization of hyperadhesive granulocytes: a new principle in "anti-inflammatory" therapy].

It is thought that the nonsteroidal anti-inflammatory drugs act through inhibition of cyclooxygenase (CO). The authors show that the pyrazolon derivatives phenylbutazone (P) and sulfinpyrazone (S) affect PMN function in a manner independent of CO inhibition. During inflammation PMN often show increased adhesiveness. Such adhesiveness can be provoked in vitro by high concentrations of chemotaxins. Preincubation (10--20 minutes) of platelet-free human PMN suspensions in heat-inactivated plasma with 100 micrograms P or S per ml completely abolished a submaximal adherence induction on Petri dishes from 4% adherent cells in the absence, to 23% in the presence, of 10(-7) M of the chemotaxin N-f-Met-Leu-Phe (FP). In vivo, premedication of rabbits with P or S prevented the FP-induced neutropenia, e.g. 10 mg/kg of S blocked a 5-minutes agranulocytosis. P and S also abrogated adherence-induced lysosomal enzyme release and FP-stimulated hexose monophosphate pathway (HMP) activity. FP-induced hyperadhesiveness impedes PMN locomotion. Preincubation of PMN with P or S reestablished random motility and allowed chemotactic migration toward activated C (as C5a) in spite of the presence of 'adhesive' concentrations of FP. The potent CO inhibitors indomethacin and aspirin had no effect on FP-induced adherence, enzyme release, neutropenia and HMP stimulation. In 3 selected patients with PMN hyperadhesiveness, correction of this adhesiveness by P paralleled clinical remission. It is concluded that P and S exert their antiinflammatory action at least in part by interfering with PMN hyperadhesiveness and lysosomal enzyme release. These effects are independent of the prostaglandin-thromboxane system, since other CO inhibitors are uneffective.

Cell Adhesion↗
PubMed1979

[Idiopathic hemochromatosis: current problems in diagnosis and therapy].

The main interest in idiopathic hemochromatosis (IH) currently centers more and more on early detection of the basic pathogenetic mechanisms of the disease, and on the prevention of organ lesions rather than therapy of the late syndrome. An understanding of the pathophysiology of this inborn error of iron metabolism, which is briefly outlined, enables the physician to motivate a still healthy potential IH patient for the simple but life-long therapeutic regimen (phlebotomy). The possible organ lesions of IH are briefly mentioned, and early recognition of arthropathy as a far from exceptional first symptom of the disease is emphasized. With regard to the detection of the latent disease, the practical value of liver biopsy, serum iron, the still debated serum ferritin, and the desferrioxamine test are discussed. Personal experience with a new and sensitive test for the screening of relatives, the cobalt absorption/excretion test, is also presented. After the recent clarification of the mode of inheritance of IH (autosomal recessive), the question arises whether heterozygote individuals, who obviously exhibit increased iron absorption, augmented transferrin saturation and an increased hepatic iron content, should also be treated prophylactically.

Adolescent↗
PubMed1979

Disparity between circulating and marginated neutrophils: evidence from studies on the granulocyte alkaline phosphatase, a marker of cell maturity.

Since circulating and marginated human granulocytes are in rapid kinetic equilibrium, cells of these two compartments have been considered to be a homogeneous population. Our studies on the relationship between neutrophil maturity and the granulocyte alkaline phosphatase (GAP) activity cast doubt on this assumption. After iv administration of hydrocortisone, 12 male volunteers showed an augmentation in circulating granulocytes of 5730 cells/mm3, accompanied by an increase of band neutrophils from 18% to 33% (p less than 0.001). During this influx phase, the GAP activity decreased by 73% when measured cytochemically and by 28% when assayed biochemically (p less than 0.001 and less than 0.01, respectively). When granulocytes were demarginated by epinephrine, the mean count increased by 38%, accompanied by a rise in the portion of segmented forms from 74% to 79% (p less than 0.005) and by an increase of the cytochemical GAP activity by 24% (p less than 0.01). Exact complementary results were obtained during an excessive transient margination, the hemodialysis neutropenia: bands increased from 24% to 54% (p less than 0.02), while the cytochemical GAP dropped by 40% (p less than 0.005). Thus, our analysis of three situations with an acute transient shift of granulocytes indicates that functionally or chronologially "older" cells have a higher GAP activity, and that the transfer of granulocyte from the circulating to the marginal pool is selective.

Adult↗
PubMed1979

Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function.

The importance of adhesion in regulating locomotion and accumulation of polymorphonuclear leukocytes (PMN) has remained vague. We found that the chemotaxis of human PMN resuspended in heat-inactivated plasma was maximal toward 1-10 nM N-formyl-met-leu-phe (f-Met-Leu-Phe), but fell below random motility toward >/= 100 nM. This impressive decrease of motility was paralleled by increased cell adherence on Petri dishes being minimal at 1 nM and maximal at >10 nM f-Met-Leu-Phe (6+/-1 and 37+/-2% [SE] adherent cells, respectively). Checked by phase-contrast microscopy, cells under stimulated adhesion lost the typical bipolar shape of moving PMN and became immobilized and highly flattened. PMN, preexposed to 250 nM f-Met-Leu-Phe and tested after washing, retained increased adhesiveness and showed extremely low random and chemotactic motility. In contrast, preexposure to 1 nM f-Met-Leu-Phe had no effect on chemotaxis. Supporting the concept that immobilizing hyperadhesiveness does not correspond to a general functional hyporesponsiveness of PMN, no depression of the initial ingestion rate was observed in the presence of 250 nM f-Met-Leu-Phe. Moreover, a close correlation was found between the induction of PMN adhesiveness and the stimulation of the hexose monophosphate pathway activity as well as of lysomal enzyme release (r >/= 0.98). Thus, "chemotactic deactivation" and "high-dose inhibition of chemotaxis" by N-formyl peptides is the consequence of increased cell adhesiveness. This phenomenon provides a mechanism for cell trapping at the inflammatory site. Conversely, if operative in circulating blood, e.g., in septicemia, it may impair PMN emigration to such sites.

Adult↗
PubMed1979

Comparison of red cell creatine level and reticulocyte count in appraising the severity of hemolytic processes.

In seeking a sensitive indicator for quantitative assessment of hemolytic disease, we found a close dependence of red cell creatine level on cell age. Studies in 21 patients with steady-state hemolysis showed high correlation (r=0.89, p less than 0.001) between reticulocyte counts and red cell creatine levels. Excluding elevation of the creatine level as a variable epiphenomenon of increased erythropoietic activity, density separation of normal red cells revealed distinctly higher creatine levels in younger cells. The reticulocyte counts and creatine levels as quantitative predictors of hemolytic processes were compared: in severe hemolytic anemias (T50Cr less than 11 days), erythrocyte survival (T50Cr) correlated well with creatine levels (r = -0.86, p less than 0.01) and, to a lesser degree, with reticulocyte counts (r = -0.72, p less than 0.05). In milder disease (T50Cr greater than 11 days), however, no correlation existed between reticulocyte counts and T50Cr, whereas the creating levels correlated closely with T50Cr (r = -0.84, p less than 0.001). Thus, on the basis of our regression equations, useful estimation of red cell survival may be obtained from single measurements of erythrocyte creatine.

Adolescent↗