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Biomedical subjects

A Balázs

Publications and source records attributed to A Balázs.

8 recordsLinked to original sources

Control of CFUc proliferation by selective endogenous inhibitors.

The susceptibility of mouse bone marrow colony forming cells (CFUc) to three different types of proliferation inhibitors in capillary semisolid agar gel was studied. GI-3, a target specific peptide containing granulocyte fraction, T4-1, an oligospecific thymic factor of proteid nature, and the alkylating cytostatics dianhydrogalactitol (DAD) inhibit myeloid colony formation as a function of concentration. The respective MED values amount to 8, 10, and 0.002 microgram/ml. When compared with this same parameter 3H-TdR incorporation into DNA of liquid bone marrow cultures showed a single fold charge for the endogenous inhibitors (GI-3, T4-1) for the cytostatic (DAD) a 3 to 4 fold lower difference. It was demonstrated, that in competitive antagonism of GI-3 and colony stimulating factor the inhibitor prevails over CSF.

Animals

In vitro sensitivity of transplantable leukemias to endogenous granuloid (GCE, GI-2) and lymphoid (T4, T4-1) inhibitors of proliferation.

The effect on cell proliferation of crude granulocyte and thymocyte extracts (GCE, T4) and of their target-specific fractions (GI-2, T4-1) was studied in cultures with transplantable subacute myeloid and lymphoid leukemia (ML, LL). In the dose rage studied (1-500 microgram/ml) each factor reduced 3H-TdR incorporation into acid-insoluble DNA of bone marrow, thymus and spleen cells with ML or LL as a function of the dose, approximately linearly. Normal bone marrow proved to be less sensitive to GCE than the ML one: according to parallel line bioassay by a factor of mu = 0.56. The reactivity of LL spleen and thymus is also higher to medium T4-1 concentrations (50-200 microgram/ml) than that of normal lymphoid populations. T4-1 inhibits 3H-TdR incorporation into the DNA of LL spleen cells submaximally in 90': this effect lasts for greater than 7 hours. Because of its more homogeneous cell composition and higher sensitivity, subacute myeloid leukemia is more suitable for screening endogenous granuloid inhibitors than are homologous normal cell cultures.

Bone Marrow Cells

Acute effect of endogenous inhibitors and exogenous cytostatics on the ultrastructure of bone marrow cells. I. Single dose of 1,2 : 5,6-dianhydrogalactitol (DAD).

The ultrastructural effects of the endogenous inhibitor, granuloid crude extract (GCE), known to control the proliferation of myeloid cells, and of the current hexitol derivative, 1,2 : 5,6-dianhydrogalactitol (DAD) were compared on the rat bone marrow. A single intraperitoneally injected LD50 dose of DAD induces the following changes in the fine structure: The mitochondria become swollen, the matrix less electron-dense, the cristae fragmentate, the ribosomes aggregate, anomalies appear in the perinuclear the cell membranes, and myelin figures and intranuclear bodies develop. Autophagy, degeneration and the phagocytotic activity of the reticulum cells is appreciable in 4 hours after treatment and increase by the 24th hour. The toxic effect of DAD is cell aspecific but in the ultrastructure its myelotropic effect manifests earlier than in erythropoiesis. In contrast, the arrest caused by a single dose of the endogenous granuloid inhibitor [2] is cell-specific and non-toxic.

Animals

Acute effect of endogenous inhibitors and exogenous cytostatics on the ultrastructure of bone marrow cells. II. Single dose of granulocyte crude extract (GCE).

The particle-free crude extract of granulocytes (GCE) contains at least three inhibitors of proliferation (M.w. greater than or equal to 70,000, approximately 11,500 and less than or equal to 4000, [5,5]). Intraperitoneal administration of a single effective mitodepressive dose (EDM = 59.4 mg/kg b.w. protein) does not damage the majority of rat bone marrow cells. The observed slight ultrastructural alterations are as follows. The cristate pattern of the mitochondria is occasionally deficient, their matrix may contain membrane shreds or myelin figures, the package of individual granules may be injured. Cytoplasmic vacuolization, autophagy are infrequent and nuclear bleb formation occurred in a single case only. The incidence of such injuries is practically the same in untreated bone marrow cells. Although GCE effectively inhibits cell proliferation, its single dose does not induce such toxic, irreversible and degenerative ultrastructural alterations as have been observed in the same system after the administration of the cytostatic dianhydrogalactitol.

Animals

Proliferation and morphology of ascitic cells as a function of age in cell culture.

Ascitic cells in the logarithmic growth phase increase the accumulation of glycogen particles in the course of explantation into suspension culture, probably due to the increasing arrest of glycogenolytic enzymes. At this age, a part of the cells are capable of restitution by exopinocytosis of the glycogen-containing vacuoles ia formation of cytoplasmic buds. Older cells, taken from the plateau-phase, pass atypical differentiation and ageing, are less capable of hindering the abnormal accumulation of glycogen and the hypervacuolisation. As a consequence, the cells finally degenerate and die.

Animals

Ultrastructural study of the prothoracic glands of Galleria mellonella L. in the penultimate last larval, and pupal stages.

The prothoracic gland (PGL) of Galleria mellonella is a Y-shaped, paired organ, consisting of 45-50 polyploid giant cells. The PGL cells are supplied by neurosecretory axons; release of neurosecretory granules (1000-1300 A in diameter) directly on the surface of PGL cells was frequently observed. Based on ultrastructure, the last two larval instars can be divided into three phases: 1) restitutive phase immediately after moulting; 2) gradual activation in mid-intermoult as indicated by the logarithmic cell growth, decrease of nucleo-cytoplasmic ratio, increase in the number of cell organelles participating in protein synthesis, and the structural changes of these organelles; 3) "release' period preceding moulting, characterized mainly by the extreme dilatation of peripheral invaginations. From the prepupal stage onward cellular activity is asynchronous. Part of the cells already show the signs of involution, while others histolyse only after the activation phase subsequent to moulting. PGL in G. mellonella is one of the larval tissues. In the course of activation its ultrastructure changes as a function of juvenile hormone (JH) cocentration, in the absence of which it histolyses. Accordingly, it has seemed to us to be a suitable model for the cytological study of JH activity.

Axons

A multifactorial system controlling myeloid cell differentiation and division.

It has been demonstrated that mature granulocytes contain two stimulatory and three inhibitory factors of cell proliferation. Consequently, beyond the negative feedback inhibitor (chalone), myeloid cells are controlled presumably by other negative (inhibitory) and positive (stimulatory) mechanisms, in addition.

Animals

Modulative effect of endogenous granuloid inhibitors on cell proliferation.

The particle-free crude extract of differentiated granulocytes (GCE) and the GI-1, GI-2, GI-3 proliferation inhibitory fractions (M.W. larger than or equal to 70,000 approximately 11,500 and less than or equal to 4000) were studied for the effects they exert on cultured cells. As shown by the curve, in bone marrow suspension cultures, in the dose range of 0.01-10.0 microng/ml, GCE maximally inhibits 3H-TdR incorporation into the DNA for 5.5 hours. In agar-gel cultures, 1.0-5.0 microng/ml of GCE reduces both the number (by 50.6-54.8%) and the size of the colonies formed. The manifestation of the inhibitory effect of GI-1, GI-2 and GI-3 fractions requires 2.5-3.5 hours. The inhibitors designated GI-2 and GI-2 are target-cell specific but they do not reduce 3H-TdR incorporation either in thymocyte suspension or HeLa monolayer cultures. On the other hand GI-1 inhibis the proliferation in HeLa cultures, as well. These endogenous inhibitors exert their optimum effect, even in a partially purified state at 2-4 orders or magnitude lower concentrations than does 1,2/5,6-dianhydrogalactitol (DAD), a cell-aspecific inhibitor used for comparison in the same system.

Alkylating Agents