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  • 1
    ISSN: 1432-0584
    Keywords: CTL-p ; Cytokines ; Limiting dilution analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experimental animal and human in vivo studies have previously demonstrated the impact of exogenous administration of various cytokines on frequencies of circulating myeloid and LAK precursor cells. For the first time we investigated whether exogenous cytokines, in the absence of antigeneic challenge, may also influence frequencies of circulating antigenspecific cytotoxic T-lymphocyte precursor cells. We further asked whether triggering of autoimmune pathways as has been reported for several cytokines can be confirmed on the cellular level by demonstration of induction of autoreactive CTL-p. Limiting dilution analysis was used to determine alloreactive CTL-p frequencies in 31 patients with nonhematologic diseases before and after short-term systemic treatment with either rIL-2 (4.8×106 IU/m2 bid), rIL-3 (2.5, 5.0 or 10.0μg/kg qd), rGM-CSF (5μ/kg qd), rIFN-gamma (200 or 400μg qd), or IFN-alpha (3 or 5×106 IU qod). Simultaneously, autoreactive CTL-p frequencies were determined by split-well analysis in 25 of these patients. We found that rIL-2 significantly expands the circulating precursor pool of alloreactive CTL (p〈0.05). rIL-3 affected CTL-p frequencies in a dosedependent fashion. Low and intermediate doses of rIL-3 did not exhibit significant effects, whereas 10μg/kg rIL-3 led to expansion of alloreactive CTL-p in the same order of magnitude as did rIL-2. This effect was statistically significant when compared with rGM-CSF (p〈0.02), which apparently had no influence on alloreactive CTL-p frequencies. In contrast to rIL-2 and rIL-3, exogenous rIFN-gamma markedly reduced the circulating precursor pool of CTL. This again was statistically significant compared with rIFN-alpha (p〈0.03), which, like rGM-CSF, did not exhibit any effects on the level of alloreactive CTL-p. Frequencies of autoreactive CTL-p were invariably below the limit of detection in our system (〈1/300000). In conclusion, these data demonstrate that (a) short-term systemic administration of rIL-2, rIL-3, and rIFN-gamma differently affects the clone size of circulating precursors of alloreactive CTL in man, while rGM-CSF and rIFN-alpha do not exhibit measurable effects, and (b) none of the cytokines administered is capable of uncovering detectable frequencies of autoreactive CTL-p.
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  • 2
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Aggressive chemotherapy of advanced myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) evolving from MDS, subacute AML and secondary AML has usually been associated with low complete remission (CR) rates, a high incidence of early death, and low disease-free survival. We therefore have initiated a phase-III trial of aggressive chemotherapy consisting of idarubicin, cytosine arabinoside, and VP-16 to improve the CR rate. Each chemotherapy cycle is followed by G-CSF to accelerate neutrophil recovery and to reduce the incidence of infections. Until now, 19 patients with high-risk AML have been entered. The CR rate is 47%, with only one death during induction. Patients achieving CR are randomized to receive either high-dose or low-dose interleukin-2 to eliminate residual leukemic cells and to prolong the duration of remission.
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  • 3
    ISSN: 1432-0584
    Keywords: Key words All-trans-retinoic acid ; Granulocyte colony-stimulating factor ; Erythropoietin ; Myelodysplastic syndrome ; Tumor necrosis factor ; TNF receptor ; Soluble IL-2 receptor ; ICAM-1 ; Transferrin receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Differentiation induction therapy is being tested in myelodysplastic syndromes to ameliorate maturation defects and to restore normal hematopoietic function. To this end, 17 patients (eight with refractory anemia, two with refractory anemia and ring sideroblasts, and seven with refractory anemia and excess of blast cells) were treated with a combination of all-trans-retinoic acid (ATRA), granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and α-tocopherol for durations of 8–16 weeks. Absolute neutrophil counts increased in all patients; platelet counts increased in five patients with discontinuation of transfusion needs in two of four transfusion-dependent patients. Stimulation of erythropoiesis was seen in eight patients with an increase in hemoglobin concentration in three, a discontinuation of transfusion requirements in another three, and a significant increase in reticulocyte counts as the only parameter in two patients. Clinically important multilineage responses with increases of hemoglobin levels or discontinuation of transfusion needs were thus seen in six patients (35.3%) with three patients having a trilineage response. Serum erythropoietin concentrations did not differ significantly between responders and nonresponders, but the erythroid response was accompanied by a rise in the serum transferrin receptor levels. In the bone marrow, the myeloid-to-erythroid ratio and the maturation index of myeloid cells increased during therapy, while the percentage of blast cells did not change. Cytogenetic analysis demonstrated the persistence of the abnormal clones. Prior to therapy, nonresponders had a significantly higher serum TNF level than responders. Serum concentrations of TNF-α and soluble TNF-α receptor significantly increased during therapy, but mainly in the patients without an erythroid and platelet response. Soluble IL-2 receptor and soluble ICAM-1 concentrations both increased. This pilot study demonstrates that treatment with ATRA/G-CSF/EPO/tocopherol is well tolerated, leading to normalization of neutrophil counts in most, and to improvement of platelets and red blood cells in a significant subgroup of patients.
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  • 4
    ISSN: 1432-0584
    Keywords: Key words Acute myeloid leukemia ; Myelodysplastic syndrome ; Secondary leukemia ; Interleukin-2 ; G-CSF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Intensive chemotherapy followed by treatment with interleukin-2 (IL-2) was evaluated in a prospective, randomized, multicenter trial including 18 patients with refractory anemia with excess of blasts in transformation (RAEB-T), 86 patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndromes, and six patients with secondary AML after previous chemotherapy. Median age was 58 years (range: 18–76 years). Forty-nine patients (45%) achieved a complete remission (CR) after two induction cycles with idarubicin, ara-C, and etoposide, 52% of them aged ≤60 years and 35% aged 〉60 years (p=0.06). After two consolidation courses, patients were randomized to four cycles of either high- or low-dose IL-2. Patients aged up to 55 years with an HLA-identical sibling donor were eligible for allogeneic bone marrow transplantation. The median relapse-free survival was 12.5 months, with a probability of ongoing CR at 6.5 years of 19%. Overall survival of all patients was 8 months, and 21 months for the CR patients. Median survival was significantly longer among patients aged ≤60 years than among the older patients (16 vs 6 months, p〈0.001). Median duration of survival and relapse-free survival were not statistically different in the two IL-2 treatment arms.
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  • 5
    ISSN: 1432-0584
    Keywords: Ph1+-ALL ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Between 1983 and 1991 the Philadelphia chromosome (Ph1) was found in bone marrow and/or peripheral blood cells of 25 adult patients with acute lymphoblastic leukemia (ALL). The Ph1 as sole anomaly was seen in 13 patients, while six patients had additional structural and another six structural and numerical aberrations. Most patients (23/25) received combination chemotherapy according to the BMFT protocols 1/81, 2/84, 3/87, and 4/89. For 25 evaluable patients two early deaths, two treatment failures, two partial remissions (PR), and 19 complete remissions (CR) after phase 1 or 2 of the induction regimen were recorded. Two of these 19 patients who achieved CR are presently disease free, whereas 17 have relapsed after a median duration of remission of 9 months. Actuarial median survival for all patients was 13 months. The probability of continuous complete remission (CCR) after 39 months, as well as that of survival after 40 months, is only 6%. Our results confirm that the presence of the Ph1 is associated with a poor prognosis in adult-ALL patients. Therefore, whenever first CR is obtained and an HLA-identical donor is available, allogeneic bone marrow transplantation (BMT) should be performed at once, the more so, since transplantation in second CR seems to offer no cure. Future studies will have to show whether an intensified cytotoxic therapy can improve the prognosis of Ph1+-ALL.
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  • 6
    ISSN: 1432-0584
    Keywords: Plasma levels ; Interleukin ; Neutropenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma levels of IL-1, IL-6, IL-8, IL1-RA, TNF alpha, and G-CSF were prospectively studied during 23 chemotherapy cycles of 20 patients suffering from acute myelogenous leukemia. Increased plasma levels of IL-6, IL-8, and G-CSF were observed in patients with febrile neutropenia and/or major infection. Plasma levels of IL-6, IL-1, TNF alpha and IL-1-RA measured 1 day before and 1 day after the onset of febrile episodes did not accurately predict the development of major infection. In contrast, IL-8 plasma levels were significantly higher in those patients who subsequently developed major infection. The question whether IL-8 plasma levels identify high risk or low risk patients with sufficient specificity and sensitivity has to be answered in large scale clinical trials.
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  • 7
    ISSN: 1432-0584
    Keywords: Key words Plasma levels ; Interleukin ; Neutropenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Plasma levels of IL-1, IL-6, IL-8, IL1-RA, TNF alpha, and G-CSF were prospectively studied during 23 chemotherapy cycles of 20 patients suffering from acute myelogenous leukemia. Increased plasma levels of IL-6, IL-8, and G-CSF were observed in patients with febrile neutropenia and/or major infection. Plasma levels of IL-6, IL-1, TNF alpha and IL-1-RA measured 1 day before and 1 day after the onset of febrile episodes did not accurately predict the development of major infection. In contrast, IL-8 plasma levels were significantly higher in those patients who subsequently developed major infection. The question whether IL-8 plasma levels identify high risk or low risk patients with sufficient specificity and sensitivity has to be answered in large scale clinical trials.
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  • 8
    ISSN: 1438-3888
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The distribution and cover density of macroalgae (Chlorophyta, Ulvaceae) were estimated by means of aerial surveys in 1990–1992 in the Wadden Sea of Niedersachsen, an intertidal area of some 1200 km2 situated at the German North Sea coast. Each year, up to a maximum of 15% of the total area was covered by algae. The spatial distribution was heterogeneous. In some subregions the macroalgal carpets covered from 30% up to 60% of the tidal flats. The cover density was at its peak in 1990. Additionally, tentative ground truth investigations were carried out on species composition. Reviewing other reports of macroalgal mass development at various sites in Europe, it is assumed that in the German Wadden Sea the recent macroalgal blooms have to be regarded as a response to eutrophication, and will presumably remain a chronic problem for many years to come.
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  • 9
    ISSN: 1435-1536
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Summary In the 100-Mc/sec spectra of vinylidene chloridevinylacetate-copolymers lines of pentads (CH-resonance) and lines of hexads (CH2-resonance) are shown by spin-decoupling technique. The differences between these lines are strongly dependent on the type of solvent. The concentrations of pentads and hexads experimentally determined from the line intensities agree satisfactorily with the calculated values. In the calculations the parameters of copolymerizationr 1=5,00 andr 2=0,05 are used.
    Notes: Zusammenfassung In den 100-MHz-Spektren von Vinylidenchlorid-Vinylacetat-Copolymeren werden mit Spin-Entkopplung Pentadenlinien (CH-Resonanz) und Hexadenlinien (CH2-Resonanz) nachgewiesen. Die Abstände zwischen diesen Resonanzlinien hängen stark vom Lösungsmittel ab. Die experimentell aus den relativen Linienintensitäten gemessenen Pentaden-und Hexadenkonzentrationen stimmen mit berechneten Werten befriedigend überein. Bei der Rechnung wurden die Copolymerisationsparameterr 1=5,00 undr 2=0,05 zugrunde gelegt.
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  • 10
    ISSN: 1435-1536
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Summary Vinylidene chloride (VDC)-isobutylene (IB)-copolymers with IB contents between 0 and 40% are radically polymerised at 50 °C. The copolymerization parameters are determined from NMR spectra to ber 1=3.00 andr 2=0.05. The lines in the NMR spectra of the copolymers are assigned to diads, triads, tetrads, pentads and hexads. Concentrations of the monomer units and of diads, triads and tetrads in the copolymer as well as the mean lengths of the sequences are determined from the line intensities. They are compared with values calculated from copolymerization theory. The concentrations of monomer units and of diads in the copolymer as well as the mean lengths of the sequences as determined experimentally agree with calculated values within the experimental error. With triads and tetrads deviations occur. These indicate non-constant copolymerization parameters.
    Notes: Zusammenfassung Es werden Vinyliden (VDC)-Isobutylen (IB)-Copolymere radikalisch mit verschiedenem IB-Gehalt von 0–40% hergestellt. Aus den Kernresonanzspektren werden die Copolymerisationsparameter zur 1=3,00 undr 2=0,05 bestimmt. Die im Spektrum beobachteten Resonanzlinien werden Diaden, Triaden, Tetraden, Pentaden und Hexaden zugeordnet. Aus den Linienintensitäten werden die Konzentrationen der Monomereinheiten im Copolymeren, der Diaden, Triaden und Tetraden sowie mittlere Sequenzlängen bestimmt und mit nach der Copolymerisationstheorie berechneten Werten verglichen. Die gemessenen Konzentrationen der Monomereinheiten im Copolymeren, der Diaden und die mittleren Sequenzlängen stimmen mit den berechneten innerhalb der Meßgenauigkeit überein. Abweichungen treten bei Triaden und Tetraden auf. Die Abweichungen deuten auf nicht konstante Copolymerisationsparameter hin.
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