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Biomedical subjects

I Boll

Publications and source records attributed to I Boll.

At least 19 recordsLinked to original sources
PubMed1992

A long-term clinical trial of interferon alpha-therapy in essential thrombocythemia.

In a prospective clinical trial involving six patients suffering from essential thrombocythemia (ET), recombinant human interferon alpha 2b significantly and consistently lowered highly elevated peripheral platelet numbers over long time periods. One patient has now been on continuous treatment for 4 years. During the treatment phase none of the patients suffered from bleeding episodes, thrombosis or disturbances of the microcirculation. The interferon maintenance dose varies considerably from patient to patient, but it is usually much lower than the induction dose. One of the patients had to be withdrawn from the study due to interferon-specific chronic toxicity concomitant with the development of non-neutralizing interferon antibodies. With the exception of one patient, stopping interferon treatment led to an increase in peripheral platelet numbers of up to one million cells per microliter of blood within 4 to 12 weeks. We conclude that interferon alpha can correct peripheral thrombocytosis in selected patients with essential thrombocythemia over a period of years and prevent morbidity attributable to this disease.

Female↗
PubMed1991

Erythroblastopenia in two patients after splenectomy and polychemotherapy.

Acquired erythroblastopenia is a rare disorder of the hematopoietic system associated with viral infections, autoimmune diseases, and drugs. We report on two patients who became anemic due to maturation-arrest at the proerythroblast level, without alterations of white blood cell or platelet counts. Both patients had been splenectomized and had undergone chemotherapy for nephroblastoma or Hodgkin's disease, respectively, at the same pediatric oncology unit. Erythropoietin levels were elevated in both patients. Antibodies against specific viruses, particularly parvovirus B 19, could not be detected in patient sera. Both patients responded to infusions of 7 S immunoglobulin with a rapid increase of the reticulocyte counts. In both cases, complete clinical remission was observed after a duration of 5 months. Heat-inactivated serum obtained during the acute phase and after remission as well was found to be inhibitory for normal bone marrow granulocyte and erythrocyte progenitor growth in vitro. The simultaneous appearance of this rare disorder in two otherwise unrelated patients treated at the same unit prompts speculations about a viral etiology.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Nocodazole sensitivity, age-related aneuploidy, and alterations in the cell cycle during maturation of mouse oocytes.

To detect age-related alterations in the formation and function of the spindle apparatus, we examined in vitro maturing oocytes obtained from young (2-4 mo) and aged (greater than 9 mo) diestrous CBA/Ca mice. Observation of cells processed for antitubulin immunofluorescence revealed that oocytes from aged females progress faster through first maturation division than those from young animals. They are also more prone to nondisjunction, as shown by a significantly higher level of aneuploidy in C-banded cells arrested at metaphase II. The ability of oocytes to recover from treatment with a microtubule inhibitor, nocodazole, and the effect of the drug on spindle integrity and chromosome segregation were also studied. In both age groups, treatment of metaphase I oocytes with 10 microM nocodazole caused rapid and complete microtubule depolymerization and chromosome scattering. Upon recovery, oocytes from both age groups were able to reestablish a spindle apparatus, proceed through anaphase, and extrude a first polar body. However, nocodazole treatment led to a dramatic increase of aneuploidy. Unexpectedly, the relative rise in hyperploids was greater in oocytes from young mice than in those from aged mice, so that the absolute percentage of hyperploid metaphase II cells was similar in both age groups after drug treatment. Concomitantly, nocodazole exposure abolished or, at least, diminished intrinsic differences in the cell cycle and anaphase trigger present in the controls (e.g., the earlier onset of chromosome separation in oocytes from aged females). It shortened the period available for spindle formation before chromosome segregation in all oocytes. Therefore, our study implies that temporal differences in the progression of oocytes through maturation, in particular, the shortening of the time available for alignment of bivalents before chromosome separation occurs in oocytes of old females, are mainly responsible for age-related rises in aneuploidy. There is no indication that (1) the spindle apparatus of oocytes from aged mammals is more labile or susceptible to disturbances than the spindle apparatus of oocytes from young individuals or that (2) an increase in the number of univalents makes oocytes from aged mammals particularly prone to nondisjunction.

Aging↗
PubMed1988

Kinetic and morphological changes induced in human blood leucocytes by cytochalasin D and E.

The effect of increasing concentrations of cytochalasin D and E, up to toxicity, on the velocity of blood leucocytes from normal subjects was measured in vitro using a high-resolution objective and phase-contrast time-lapse photography. The dose-response effect for the two different cytochalasins differed in accordance with the different cell specificity of their membrane binding. The average velocity of granulocytes was reduced at cytochalasin D concentrations above 5 x 10(-7)M and cytochalasin E concentrations above 5 x 10(-5)M. The effect on monocytes and eosinophils was similar. In contrast the velocity of lymphocytes was not affected until cytotoxic concentrations were reached. The concentration ranges which inhibited locomotion corresponded well with the concentration ranges of the cytochalasins which have an in vitro effect on microfilaments. The concentrations which induced additional morphological changes in lymphocytes also correlate well with the concentrations found to inhibit cross-linking in vitro, as well as those known to induce morphological changes in, for example, fibroblasts in vivo. Cytotoxic effects were first observed with ten-fold higher concentrations of cytochalasin E than of cytochalasin D.

Cell Movement↗
PubMed1986

[Effect of different glucocorticoids on the in vitro cell kinetics of human hematopoiesis represented by a bone marrow culture and by phytohemagglutinin- and pokeweed mitogen-stimulated blood cultures].

The effect of nine glucocorticoids, DHEA, cyclohexanol and dextran sulphate on the hematopoietic proliferation was investigated. Three glucocorticoids inhibited the proliferation of normal bone marrow cells, the others enhanced it. The T-cell stimulation was not inhibited by fluorcortolone contrary to prednisolone. Specially the proliferation of acute myeloid leukemic blasts was inhibited by fluorcortolone hemisulfate, which significantly stimulated the proliferation of normal bone cells.

Blood Cells↗
PubMed1985

Interactions between lymphocytes and hematopoietic progenitor cells in normal and leukemic human bone marrow (phase contrast observations).

Single cell observations of normal and of leukemic human bone marrow cells demonstrated cell-cell interactions of lymphocytes with hematopoietic progenitor cells. In all cases lymphocytes and target cells were from the same individual. Lymphocyte-target cell interactions occurred more frequently with normal committed progenitor cells and leukemic blast cells from acute myeloid leukemia than with precursor cells of the proliferative cell pool, including myeloblasts, promonocytes, erythroblasts and megakaryocytes. Both induction of mitosis and degeneration of the progenitor cells occurred after cell-cell interaction with almost the same frequency. Acute myeloid leukemic blast cells degenerated after contact with lymphocytes with the same frequency as normal progenitor cells (i. e. in 16% of cell contacts), but especially during mitosis. In contrast, normal and regenerating bone marrow progenitor cells from myeloproliferative diseases demonstrated no degeneration after cell-cell interaction with lymphocytes during mitosis. Otherwise the induction of mitoses by lymphocyte-target cell interactions was more frequently observed in normal progenitor cells than in leukemic blasts.

Bone Marrow Cells↗
PubMed1983

[Different effects of cytostatics on cell kinetics of normal and leukemic human bone marrow in vitro].

The kinetics of the erythropoietic and of the granulocytopoietic pool of normal und leukemic human bone marrow cells were investigated in vitro under the influence of 23 cytostatic drugs. Clot cultures were evaluated up to 72 hours by differential and mitotic counting in smears stained according to Pappenheim. Based on mitotic index, caryological curve and percentage of proliferative cells different patterns of proliferation were observed: spindle poisons enhanced the mitotic index, all other investigated cytostatic drugs diminished it, but in a different degree the one of the erythroblasts, of the granuloblasts and of the leukemic blasts. The decrease of the percentage of proliferative precursors did not always correlate with the decrease of the mitotic index, because sometimes an ineffective granulocytopoiesis arised or leukemic blasts entered the Go-phase of the cell cycle. 1-asparaginase was the only drug which increased erythroblasts. Chloramphenicol was the only out of 18 drugs tested on leukemic bone marrow that decreased only the leukemic proliferation and had no influence on the normal one.

Acute Disease↗
PubMed1981

Clinical and prognostic heterogeneity of non-Hodgkin lymphomas of high-grade malignancy.

Comparison of clinical data of 64 patients with centroblastic lymphoma, 55 patients with immunoblastic lymphoma and 31 patients with lymphoblastic lymphoma not only confirmed the original assumption of high-grade malignancy as proposed by the concept of the Kiel classification but also demonstrated distinct clinical differences, particularly between lymphoblastic lymphoma and the two other entities. Rapid lymph node enlargement as well as steep fall of survival curves within the first year after diagnosis were common characteristics. Bimodal age distribution, predominance of males and early generalization of disease were typical features of lymphoblastic lymphoma; elderly patients and patients with the unclassified subtypes of lymphoblastic lymphoma exhibited the worst prognosis. Whereas patients with centroblastic and immunoblastic lymphomas showed similar distribution of age, sex and initial stage of disease, patients with immunoblastic lymphoma presented more frequently with a reduced performance status and showed a poorer response to radio- and chemotherapy resulting in a worse prognosis discernible after the first year of follow-up. Generalization during course of the disease was significantly more frequent in immunoblastic than in centroblastic lymphoma.

Adolescent↗
PubMed1980

[Morphological characterization of the myelopoietic stem cell reserves in the human].

According to microkinomatographic observations made on single cells up to ten days in vitro, there are the following laws of growth in haematopoiesis: Small cells will increase in growth up to five times in size, with their morphologic and kinetic properties being preserved, the blood lymphocyte will grow to immunoblasts, the small pluripotent stem cell to bone-marrow histiocytes. When growing, the myelopoietic stem cell may be gradually deviated into all myelopoietic cell lines. Instead of bone-marrow histiocytes it may differentiate to promyelocytes, promonocytes or proerythroblasts, all having an equal nucleus size, when it is induced by serum factors. Apart from histiocytes these large cells are capable of differentiating to a clon of blood cells, such as granulocytes, monocytes or reticulocytes, by several successive divisions of maturity. Contrary to the stimulated lymphocyte, symmetric mitoses will frequently occur, when small pluripotent stem cells are growing to bone-marrow histiocytes to be no further differentiated. Occasionally, asymmetric divisions may also be observed, i.e. one of the daughter cells will differentiate into one of the myelopoietic lines, whereas the other one will remain a progenitor cell. Moreover, there are various pathological mitoses in all progenitor cell sizes, such as endomitosis, cytoplasm fusion after mitosis, nucleus fusion after cytoplasm conjunction or amitotic nucleus division without cytokinesis. They produce megacaryoblasts further differentiating to megacaryocytes by corresponding pathological mitoses. According to our vital observations the pluripotency of the haematopoetic stem cell is being lost step by step.

Bone Marrow Cells↗
PubMed1978

[PHA- and PWM-stimulation in acute leukaemia (author's transl)].

Peripheral blood cells from patients with acute leukaemia were stimulated in RPMI-medium with Phytohaemagglutinin (PHA) and/or Pokeweed-Mitogen (PWM). Samples of the cultures were taken at 3, 5 and 7 day intervals for cytological characterization. From 119 cultures from 65 patients 76 cultures from 47 patients could be analysed. Cultures stimulated with PHA and/or PWM showed in 43,4% a higher stimulation rate in comparison with cultures from normal persons. These findings are discussed in relation to the increased agar-colony growth growth of leukaemic cells after in vitro PHA-stimulation and transformation of blast cells.

Humans↗
PubMed1978

[Regulation of the human erythropoietic proliferation pool by the microenvironment (author's transl)].

The Effects of Various Substances in the Culture Microenvironment on the Proliferation of Erythroblasts in vitro were Studied and Evaluated by differential cell and mitosis counting in normal and pathologic bone marrow. The mitotic frequency and maturation correlated directly with the erythropoietin content of the medium and were potentiated on addition of either folic acid, etiocholanolon or cAMP. However, erythroblast proliferation was stimulated independently of erythropoietin concentration when either cobalt, and androgen or an anabolic substance was added to the medium. An iron-deficient medium prevented the maturation of erythroblasts to reticulocytes, thereby rendering erythropoiesis ineffective. The existence of an erythrocyte chalone ineffective. The existence of an erythrocyte chalone or an erythropoietin inhibitor could not be deduced from our experiments since the transformation of pluripotent to erythropoetin-sensitive stem cells is not included. A stimulation of the granulopoietic proliferation pool occurred when serum from patients with either polycythemia vera or after acute blood loss was added to the medium.

Androgens↗
PubMed1977

PHA and endotoxin stimulation of human lymphocytes separated by albumin density gradient centrifugation.

Venous blood from eight healthy subjects was divided into four fractions on a discontinuous albumin density gradient. The percentage recovery of lymphocytes was 82.3%; the purity of the lymphocyte fractions was 83.6%. The lymphocytes were cultured with PHA and Endotoxin, and the samples were analysed after 24, 48, and 72 hours. After PHA stimulation immunoblasts appeared up to 59.3% in the cultures from the 19-21% albumin fraction. After Endotoxin stimulation the maximum (75.8%) was reached in the heavy (25-27% albumin) fraction. Thus, it is concluded that the lymphocytes which can be stimulated with both the mitogens have different densities, the PHA-stimulable T lymphocytes being ligther than the Endotoxin-stimulable B lymphocytes. It is also concluded that as a mitogen Endotoxin is equal to PHA.

Adult↗
PubMed1977

[Cytoplasmic vacuoles and kinetics of bone marrow cells in alcoholism, liver cirrhosis and anemia].

Bone marrow smears show vacuoles in the cytoplasm of haematopoietic cells due to alcoholism, liver cirrhosis and anemias different origin, for example in acute leukemias, in proportion to the decreased content of haemoglobin. The cell doubling rat in vivo is not obviously impaired by the vacuolisation of the cytoplasm exactly as is the case with proliferation in vitro, although the vacuolation increases in vitro. Phase contrast observation makes visible the vacuoles without membranes and content as they appear transitorily in pinocytosis, and not as secondary lysosomes. The common cause for the formation of the vacuoles without membranes in the cytoplasm in all these pathological states could be intracellular hypoxia and acidosis.

Adolescent↗