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Biomedical subjects

M Ginsbourg

Publications and source records attributed to M Ginsbourg.

At least 19 recordsLinked to original sources

Purification and release from quiescence of umbilical cord blood early progenitors reveal their potential to engraft adults.

Steel factor (SF) increases the frequency of colony formation by CD34+ CD38- cycling cells, but it does not reverse the effect of an autocrine production of transforming growth factor (TGF)-beta 1 by early progenitors of the stem cell compartment. We have used optimal culture conditions supplemented with SF and anti-TGF-beta serum to estimate the proliferative capacity and ability to generate early progenitors in long-term cultures of bone marrow and umbilical cord blood cells. We estimate that the CD34+ CD38- cells from a typical umbilical cord blood sample produce equivalent numbers of granulocyte erythrocyte macrophage megakaryocyte colony-forming units (CFU), twice as many granulocyte-macrophage (GM) CFU, and three times as many erythroid burst-forming units as the same population from an average bone marrow sample used in adult transplantation. These results suggest that umbilical cord blood is a suitable source of cells for adult transplantation.

ADP-ribosyl Cyclase↗

c-fos mRNA constitutive expression by mature human megakaryocytes.

By in situ hybridization with a c-fos probe, we have shown that human bone marrow megakaryocytes cultured in the presence of 20% aplastic anemia plasma constitutively express c-fos mRNA. At day 0, megakaryocytes are mostly immature and only 3% of them are labeled. The number of labeled cells reached 23% after 12 days of culture. Interleukin 3 (IL-3) and IL-6 added together at day 10 further increased this number to 31% 2 days later. Mature labeled megakaryocytes were more numerous and more strongly labeled than immature ones. These results suggest that c-fos could play a role in megakaryocytic terminal differentiation, either in the polyploidization or in the thrombopoietic function unique to these cells.

Genes, fos↗

Simultaneous detection in the bone marrow of mammary cancer metastatic cells and of their labelling index as respective markers of the residual minimum submacroscopic disease and its proliferative condition (preliminary results).

A study of 200 patients with breast cancer carcinoma at different stages of the disease, was carried out for detecting in their bone marrow, mammary cells and their proliferative condition using a double labelling method with two types of monoclonal antibodies. The mammary cells were visualised with monoclonal antibodies raised against human breast epithelium and/or carcinoma. DNA synthetising cells (in S phase) were detected on the same slide, using a monoclonal antibody directed against an antigen associated with bromodeoxyuridine (BrdU) after cell incubation with BrdU. Mammary cells could be detected in the bone marrow of 13 out of 20 cases presenting macroscopically visible metastasis, 12 out of 20 patients at diagnosis of their disease, 90 out of 160 patients in apparent disease free condition. The labelling index was 6/13, 6/12 and 45/90 in those respective three groups of patients. The similarity of these three groups for both parameters suggests that the fate of breast carcinoma patients and their prognosis in three types (++, +-, --) is carried from the beginning of the disease. We have, with Eriguchi shown that the mammary (and other) cancer patients survival exponential curves do not express homogeneous populations but are in fact composed of three segments, the first with a rapid slope represents the acute type patients, at high risk of early relapse, the second, with a slow slope, represents the chronic type patients at risk of late relapse and the third, the slope of which is parallel to the general population life expectancy, represents the so called "cured patient".(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Relationship between proliferative activity of bone marrow micrometastasis and plasmatic level of a new cancer marker: lipid associated sialic acid (LASA) in human breast cancer.

The correlation between elevated level of a new plasma cancer marker, Lipid Associated Sialic Acid (LASA) and detection of bone marrow heterotopic epithelial cells by monoclonal antibodies using an immunocytologic technique, associated with the study of the proliferative activity of these heterotopic cells by measurement of their labelling index (LI) was analyzed in 158 samples obtained from 94 breast cancer patients. Six different groups of patients in complete remission of breast cancer, after radical treatment of the primary (minimal residual disease (MRD] were defined, according to the presence with or without proliferative activity of heterotopic cells in the bone marrow or the absence of such cells and to the level, normal or elevated of LASA in the serum of the same patient at the same time. 115 samples (73%) of the patients had an elevated LASA level at the time of the study among which 71 (45%) came from patients in which heterotopic cells were detected in the bone marrow, 32 (20%) of which with proliferative activity (LI+) 39 (25%) without (LI-). In 44 (28%) samples, no heterotopic cells were detected in the B.M. 43 samples (27%) of the patients had a normal LASA level. In 29 (18%) no heterotopic cells could be detected in the B.M. In only 14 could such cells be found, 5 with LI+, 9 with LI-. Both of these cytological and biological parameters can be useful markers of minimal residual disease and help to determine the prognosis and define optimal therapeutic strategy for curable breast cancer. Their prognostic value in predicting relapse awaits further observation with longer follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗

Cytological and immunological study of 139 patients with acute leukemia.

Sixty-six children with acute lymphatic leukemia (ALL), 26 adults with ALL and 47 adults with acute myeloid leukemia (AML) were subclassified according to the classifications French-American-British (FAB) and World-Health-Organization (WHO). Nine immunological markers and 6 cytochemical stains were also used. The reproducibility of the WHO classification of the smears performed independently twice by one observer was 93%, but that between two observers only 78%. Three patients considered ALL by A were called AML by B, but all three had the common acute leukemia antigen, CALLA. In the group of 87 patients considered ALL by B, only 74 were classified ALL by A, but of the 13 non-ALL B, none had the CALLA. Ten of these thirteen patients had myeloid markers such as Philadelphia chromosomes, peroxidase or Sudan Black B positive reactions, or Fc and C3 receptors. The remaining 3 patients were non-Hodgkin lymphoma with B-cell markers. None of the 47 cases classified as AML had CALLA. Seventeen of nineteen myeloblastic leukemias (M2, FAB) had a myeloid antigen (Mag) and 13 of 15 myelomonocytic leukemias (M4, FAB) had, in addition, Fc and C3 receptors.

Acute Disease↗

Established cell lines of mouse marrow adherent cells producing differentiation factor(s) for the granulocyte-macrophage lineage.

Two continuous cell lines derived from long-term cultures of AKR mouse bone marrow adherent cells were isolated. These cell lines release colony stimulating activity (CSA), a factor that induces in vitro differentiation of granulocyte-macrophage progenitor cells. The colony forming cells and cluster forming cells in mouse marrow responsive to CSA from mouse lung conditioned medium MLCM). Colony forming cells were characterized by analysis of their density distribution after equilibrium centrifugation in density gradient. Cluster forming cells were characterized by analyzing the progeny of individual clusters after transfer to fresh semisolid culture medium containing MLCM. The results obtained indicate that the CSA from cell line conditioned medium closely compares with the CSA from MLCM in terms of the populations of colony and cluster forming cells stimulated.

Animals↗

Histoenzymatic and permeability changes in human brain adjacent to meningioma.

Cerebral specimens were removed from ten patients with meningioma. Vascular permeability was tested with sodium fluorescein and a correlative study of the oxidative and hydrolytic enzyme activity was performed. Vascular permeability change was observed in half of the specimens of cortex taken from the region of the tumor. Labeled tracer diffusion was found to be either perivascular or involved microscopic ischemic areas. Fluorescein diffusion of the edematous white matter was observed in only two specimens. Enzyme activity in walls of the blood vessels was modified in the fluorescent specimens. Alkaline phosphatase and oxidoreductase activities were decreased. Experimental results have shown a relationship between increased vascular permeability and metabolic disorder of both vascular walls and cerebral cortex. Our findings agree with Zülch's hypothesis regarding a "hemodynamic" mechanism in the formation of edema by extraneural compression.

Adenosine Triphosphatases↗

[Glial histoenzymatic study in human cerebral edema (collateral edema in glial tumors)].

Histoenzymatic study was performed on neurosurgical specimens. Two patterns of reactive astrocytes were found. Normal shape cells with perivascular processes were observed in subcortical white matter and in moderate edematous changes. Hypertrophic cells without processes were seen in severe edematous changes. The role of glia in the selective vulnerability of the white matter is discussed.

Astrocytes↗

[Histochemical correlations of vascular permeability and enzyme activity in the choroid plexus in man].

The choroid plexuses are characterized by the absence of alcaline phosphatase activity as well as the absence of any vascular barrier for proteins as revealed by fluorescein tracer observation. This correlation is interpreted as supporting the hypothesis of enzymatic control, via alcaline phosphatase, of the blood-brain barrier. Adenosine mono and triphosphatase activity, on the contrary, is identical in choroid plexus vessels and in vessels where the blood-brain barrier phenomena may be demonstrated.

Adenosine Triphosphatases↗