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Biomedical subjects

E Gallo

Publications and source records attributed to E Gallo.

At least 91 records · Page 5Linked to original sources

Autologous bone marrow transplantation in acute myeloid leukemia after in-vitro purging with an anti-lacto-N-fucopentaose III antibody and rabbit complement.

Two AML patients, whose leukemic clonogenic cells totally reacted to the anti-lactofucopentaose III S4-7 monoclonal antibody (MoAb), underwent autologous bone marrow transplantation, in first complete remission, after in-vitro purging with S4-7 MoAb and complement. After ablative chemotherapy (BAVC regimen) and reinfusion of S4-7 purged cells, regeneration of marrow cells occurred with prompt recovery of granulopoiesis and erythropoiesis. A more delayed platelet recovery was observed. The two patients are in complete remission at 20 and 11 months from ABMT. The results indicate that immunologic purging with S4-7 MoAb is safe and suitable for selected AML patients undergoing ABMT.

Adolescent↗

Antigenic phenotype of myelomonocytic progenitors (CFU-GM) in chronic myeloproliferative disorders.

The antigenic phenotype of myelomonocytic progenitors [colony-forming unit granulocyte-macrophage (CFU-GM)] from 33 patients with chronic myeloproliferative disorders was investigated using four cytotoxic monoclonal antibodies. Monoclonal antibodies S3-13, S8-6, and S16-144 which recognize normal hemopoietic progenitors of different lineages reacted with almost all CFU-GM. R1B-19 monoclonal antibody identified two subpopulations of myelomonocytic progenitors (type 1 and 2 CFU-GM), as reported previously in normal subjects. In 3 of 11 patients with chronic myelogenous leukemia, in 1 of 2 patients with chronic myelomonocytic leukemia, and in 2 of 4 patients with polycythemia vera, a higher proportion of the more immature CFU-GM (type 1) was detected in bone marrow cells. The more differentiated CFU-GM (type 2) is not detectable in normal peripheral blood. By contrast, in 14 of 15 chronic myelogenous leukemia patients, in 1 of 2 chronic myelomonocytic leukemia patients and in 3 of 8 patients with idiopathic myelofibrosis, it was present in high to very high proportions. It is clear from these findings that the antigens present on normal CFU-GM are expressed in chronic myeloproliferative disorders. The proportion and distribution of type 1 and 2 CFU-GM, on the other hand, are very different from those observed in the normal subjects.

Adult↗

Cytogenetic pattern in leukemic cells of patients with constitutional chromosome anomalies.

Acquired karyotypic changes analyzed by banding techniques in 21 patients with a malignant hematologic disorder and a major constitutional chromosome anomaly, including ten patients with trisomy 21, five patients with a balanced translocation, and six patients with a sex chromosome anomaly. Detailed karyotypic findings were ascertained in 28 additional patients reported in the literature. Some striking differences were observed in the combined material of the present series and cases previously published as regards (a) distribution of morphological leukemia types among patients with different types of constitutional anomalies, and (b) incidence and type of acquired chromosomal abnormality among patients with different types of constitutional anomalies.

Adolescent↗

Release of hemopoietic factors by normal human T cell lines with either suppressor or helper activity.

We analyzed the release of activities capable of stimulating the in vitro growth of human hemopoietic progenitor cells by long-term cultured T cell growth factor (TCGF)-dependent human T lymphocytes. Seven cell lines tested produced colony-stimulating activity (CSA) as well as burst-promoting activity (BPA). The CSA stimulated primarily the growth of the cells forming colonies after 14 days of incubation. In addition the supernatants from these seven T-cell lines showed the ability to induce the in vitro growth of mixed granulocyte, erythroid, megakaryocyte, macrophage colonies (CFU-GEMM). The release of hemopoietic factors did not depend on the presence of accessory cells or phytohemagglutinin or serum during the incubation for factor production. In six of the T cell lines the majority of the cells were reactive to the OKT 8 monoclonal antibody (MoAb), whereas one cell line contained mostly OKT 4+ cells. Suppressor activity was detected in three tested OKT 8+ cell lines, while the one OKT 4+ displayed helper activity. All cell lines produced hemopoietic factors with equal efficiency. These results indicate that factors affecting human hematopoiesis are produced by normal T lymphocytes in long-term culture and this property is not related to the helper or suppressor activity of the cultured cells.

Adult↗

Estrogen and progesterone receptors in the human vagina.

Estrogen (E) and progesterone (Pg) receptor (R) levels were determined in the human vagina in relation to menopausal status, day of ovarian cycle and pregnancy. The results obtained confirmed that the human vagina contains ER and, in addition, demonstrated for the first time the presence of PgR in this organ in humans. In cycling women, ER and PgR did not vary significantly during the ovarian cycle; however low (less than or equal to 10 fmoles/mg cytosol protein) concentrations of PgR were more frequently (6 out of 8 cases) detected during the secretory phase. No substantial difference was seen in ER and PgR values between anterior and posterior wall of the vagina. In postmenopausal patients the levels of ER (range: 10-83 fmoles/mg) were similar to those found in premenopause (range: 12-78 fmoles/mg). As regards PgR, the majority (14 out of 20) of vaginae were devoid of PgR, 4 had a very low (less than or equal to 6 fmoles/mg) PgR content and only 2 cases had a PgR level higher than 10 fmol/mg cytosol protein. In pregnant patients (6th to 8th week) ER were found in all vaginae, while PgR were present only in some cases (3 out of 8). It was concluded that the behavior of ER in the human vagina seems different from that in the human endometrium, since ER levels do not vary in relation to changes in the concentrations of sexual hormones in the circulation. On the contrary, PgR levels appear to depend on blood estradiol and progesterone concentration, as in other target tissues.

Adult↗

Effects of medroxyprogesterone acetate on DMBA-induced mammary tumors.

Rats with DMBA-induced mammary tumors were treated for 30 days i.m. with medroxyprogesterone acetate (MPA) at doses of 7.5, 15 or 75 mg/kg. Complete regression (disappearance of tumor) was observed in 60% and 20% of tumors from rats treated with 75 or 15 mg/kg MPA respectively. Partial regression (50% decrease in tumor area) was found in the remaining 20% of tumors from rats treated with 15 mg/kg MPA. The dose of 7.5 mg/kg MPA resulted in being devoid of effectiveness. Estrogen receptor (ER) levels were significantly reduced at all doses of MPA injected both in responsive and non-responsive tumors. However, only tumors with ER levels above 15 fmol/mg before therapy resulted in being responsive to MPA treatment. Progesterone receptors were so reduced at the end of the experiment as to not be detectable in all treated groups. It was concluded that MPA is effective as an antitumoral drug also in DMBA-induced mammary tumors and that this effect is at least in part related to ER levels before treatment.

9,10-Dimethyl-1,2-benzanthracene↗

Cytogenetic findings in acute promyelocytic leukaemia. A report of 25 cases.

Cytogenetic analyses of bone marrow cells were carried out by means of direct technique and short-term cultures in 25 acute promyelocytic leukaemia (APL) patients. 16 were affected by the hypergranular form and 9 by the M3-variant. The t(15;17) was documented at diagnosis in 15 patients. In addition, 2 cases, in which an M3 morphology and a normal karyotype on direct preparation were found at diagnosis, disclosed the chromosome anomaly in cultured cells at relapse, in concomitance with a change of blast morphology to the M3-variant. However, the t(15;17) was a consistent feature in 5 of the 15 patients with cells analysed on direct preparations only and in all cases who had successful bone marrow cultures. Overall, the 15;17 translocation was detected in 7 out of 9 patients with the M3-variant and in 8 out of 16 patients with typical M3. Whenever the chromosome preparations were made after culture, 7/7 had the translocation in the M3-V group and 5/5 in the M3 group. No obvious differences in clinical features or outcome were evident in the patients, irrespective of their cytogenetic findings.

Adolescent↗

Effects of long-term administration of high doses of medroxyprogesterone acetate on hormone receptors and target organs in the female rat.

The changes in oestrogen, progesterone and prolactin receptor levels in target organs, and the macroscopic and microscopic modifications of uterus, ovary, adrenal and pituitary gland induced by long-term administration of high doses of medroxyprogesterone acetate (MPA) were investigated in female rats. Medroxyprogesterone acetate was injected i.m. for 30 days at daily doses of 7.5, 15 and 75 mg/kg. Oestrogen and/or progesterone-binding capacities were remarkably reduced at all doses of MPA used both in the uterus and pituitary gland. Furthermore, MPA caused a very evident reduction in the weight of pituitary glands, ovaries, adrenals and uterus. In all MPA-treated rats corpora lutea were absent from the ovaries, whereas the adrenals showed a significant reduction in the thickness of the cortex. In accordance with this, there was no evidence of ACTH-producing cells in the pituitary glands. Prolactin-producing cells were also absent, while GH-producing cells were present. Serum prolactin levels were significantly reduced at all doses of MPA used. A dramatic reduction of prolactin receptor concentrations was observed in the liver and the ovaries of MPA-treated rats. The results suggest that MPA acts as an antioestrogenic drug both by reducing the number of oestrogen receptors in target tissues and by changing the structure (and perhaps the function) of those organs (pituitary glands, ovaries and adrenals) which are, directly or indirectly, a source of oestrogens. The decreased synthesis of prolactin and the reduction of the number of prolactin receptors (which, on the contrary, are both increased by oestrogens) might be considered as additional antioestrogenic effects of MPA.

Adrenal Glands↗

Functional and phenotypic characterization of two HL60 clones resistant to dimethylsulfoxide.

Two HL60 clones (C12 and C13) totally insensitive to differentiation induction by dimethylsulfoxide (Me2SO) are described. They have been growing continuously in the presence of the inducer for more than 6 months. The morphological and cytochemical features of the two populations are quite similar to those of the original HL60 cell line, whereas a different karyotype with marked hyperploidy (modal chromosome number of 86 for C12 and 82 for C13) was detected. An antigenic pattern analogous to that of the native HL60 cell line was found in C12 and C13 populations using three monoclonal antibodies differently reactive to myeloid cells. Both clones can be induced to differentiate by retinoic acid (RA) and 12-O-tetradecanoylphorbol 13-acetate (TPA). The pattern of differentiation was assessed by morphological, cytochemical, phenotypical and functional markers. Differentiation of C12 cells by RA and TPA was similar to that observed with native HL60 cells, whereas C13 cells showed lower degrees of sensitivity to RA and TPA. The data presented suggest the existence of different mechanisms for induction of differentiation by Me2SO, RA and TPA. In addition, they are in accordance with previous observations of different degrees of inducibility to differentiation among leukemic cell populations in culture.

Cell Differentiation↗

Effects of bromocriptine and dopamine on the binding of estradiol to its uterine cytoplasmic receptors.

The in vivo and in vitro effects of bromocriptine on the binding of estradiol 17 beta to its specific uterine receptors were studied in both mature and immature rats. A single i.p. injection of bromocriptine reduced the specific estradiol-receptor interaction in adult rats, while it resulted ineffective in prepubertal animals. The effect of bromocriptine in mature rats was dose-dependent and evident only when using a dose of at least 0.70 mg/kg. Experiments in vitro also showed that in mature rats bromocriptine affected the estradiol-receptor interaction inducing a decrease in binding, which is well correlated to the concentration used. On the contrary, no effect of bromocriptine in vitro was observed when using cytosol obtained from uteri of immature rats. Very similar results were obtained in experiments in vitro when using dopamine instead of bromocriptine. Our results suggest that apparently there are two forms of estrogen receptors, one present both in prepubertal and pubertal age and the other present only in mature animals. The latter is the type of receptor sensitive to both bromocriptine and dopamine and presumably develops under the control of hormonal factors, which are only present at puberty.

Animals↗

Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives.

The effects of two progesterone derivatives, namely medroxyprogesterone acetate (MPA) and chlormadinone, and two 19-nor-testosterone derivatives, namely norgestrel and norethisterone, on the binding of oestradiol to its cytoplasmic receptors in the rat uterus were compared. In experiments performed in vivo, the rats were given a single oral dose (15 mg/kg) of one of the four progestins and killed 1, 6, 24 and 48 h later. Norgestrel, norethisterone and MPA induced a prompt and remarkable decrease in oestradiol-receptor interaction 1 h after treatment. This reduction lasted almost unchanged for 24 h in rats treated with MPA or norgestrel, but was much lower in animals given norethisterone. In the hours that followed, the effect of MPA and norgestrel began to decrease, but was still detectable after 48 h, whereas the effect of norethisterone had disappeared by this time. The effect of chlormadinone was much less than that induced by both MPA and norgestrel 1, 6 and 24 h after treatment. On the other hand, this effect was less than that caused by norethisterone 1 h after administration, equal after 6 h and much greater after 24 and 48 h. In experiments performed in vitro, the different ability of the four progestins to interfere with the capacity of oestradiol to bind to its receptors was confirmed. In conclusion, all the synthetic progestins used were able to reduce the binding of oestradiol to its cytoplasmic receptors, although there was a clear difference between the progestins in the intensity and duration of this effect. This could be one of the mechanisms by which progestins modulate the activity of oestrogens in target tissues.

Animals↗

[Albright's syndrome. Report of a case, complicated by pleural effusion and diabetes].

A case of Albright's disease in a 54-yr-old man is presented. A brief account of the nosological placement of the disease is followed by a review of the relevant literature, with particular reference to the clinical, anatomo-pathological, and aetiopathogenetic aspects. The salient points of the reported case were: 1) extensive cutaneous hyperpigmentation; 2) polyostotic fibrous dysplasia involving the skull, humeri, femurs, and pelvis; 3) voluminous bilateral costal cysts, with greater extension on the right; 4) right pleural effusion; 5) diabetes; 6) mental under-development; 7) 1/4 balanced translocation.

Bone Cysts↗

Induction of differentiation of HL-60 cells by dimethyl sulfoxide: evidence for a stochastic model not linked to the cell division cycle.

Induction of differentiation of human promyelocytic leukemia cell line HL-60 by dimethyl sulfoxide (Me2SO) was analyzed to determine the relationship between exposure time of the inducer and cell cycle. A minimum incubation time of 12 hr with Me2SO was required in order to induce differentiation in a small but significant proportion of cells. These expressed differentiation markers (morphology, phagocytosis, and nitroblue tetrazolium reduction) up to 12 hr after Me2SO was removed from the medium. For periods beyond 12 hr and as long as 120 hr of contact of HL-60 cells with the inducing agent, a linear rise in the percentage of differentiated cells was observed. The sensitivity to Me2SO of HL-60 cells synchronized by double thymidine block was examined and was found to be similar to that of nonsynchronized cells. The effect of Me2SO was not altered when incubated with cells at different phases of the cell cycle. Finally, even nonproliferating cells were sensitive to the inducing effect of Me2SO. The data are consistent with a stochastic model of induction to differentiation without having any linkage to the cell cycle.

Cell Cycle↗

Terminal differentiation of the human promyelocytic leukemia cell line, HL-60, in the absence of cell proliferation.

Induction of differentiation of the human promyelocytic leukemia cell line, HL-60, by dimethyl sulfoxide was analyzed for a requirement for cell replication. The ability of HL-60 cells to undergo terminal granulocytic differentiation as judged by nitroblue tetrazolium reduction, phagocytosis, and morphological criteria was not impaired by a total block in cellular proliferation. Retinoic acid, actinomycin D, and butyric acid also induced differentiation of HL-60 cells in the absence of cell growth. These results and the earlier demonstration that phorbol ester-induced macrophage differentiation of HL-60 occurred independently of DNA synthesis indicate that in these leukemic cells there is a dissociation of proliferation and maturation. The ability of retinoic acid to enhance differentiation of HL-60 cells was not altered in the presence of various growth-inhibiting concentrations of two clinically useful chemotherapeutic agents: hydroxyurea and 1-beta-D-arabinofuranosylcytosine. These results suggest that combination therapy in a program aimed at both inhibiting proliferation and inducing differentiation of leukemia cells could be beneficial.

Cell Cycle↗