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Biomedical subjects

G Massa

Publications and source records attributed to G Massa.

At least 109 records · Page 6Linked to original sources
PubMed1987

Marrow repopulation in mice treated with busulphan or isopropyl methane sulphonate and bone marrow.

By using karyotypic analysis of female mice treated with busulphan or isopropyl methane sulphonate (IMS), and injected with male bone marrow the donor contribution to both total marrow cellularity and spleen colony forming cells (CFU-S) was assessed for up to 6 months after transplant. In the mice treated with busulphan the marrow cells yielded metaphases of which between 40% and 83% were of donor type. Between 60% and 97% of metaphases in spleen colonies formed in irradiated mice were of donor type during the 24-week study period. In contrast, mice prepared for the transplant with IMS showed no cells of donor type at any time after transplant, neither did they possess CFU-S of donor type. We were therefore led to conclude that the donor cells made no contribution to longterm engraftment in mice prepared with IMS, whilst in those prepared with busulphan they were the predominantly active haemopoietic cells. These results are consistent with a model of haemopoiesis in which the most primitive cells reside in a 'niche' where they are resistant to the effects of IMS but susceptible to the action of busulphan. Busulphan may vacate some niches to allow engraftment by transplanted marrow, whilst IMS yields no unoccupied niches for grafted cells to occupy, and cannot therefore lead to a stable chimaerism.

Alkylating Agents↗
PubMed1987

Turner syndrome and craniosynostosis.

A girl with Turner syndrome and sagittal synostosis is described. The patient had a normal psychomotor development and no neurological impairments. Since more severe forms of craniosynostosis can occur in patients with Turner syndrome, a careful examination of the skull should be performed in all patients with this syndrome.

Craniosynostoses↗
PubMed1986

Leucovorin rescue of enteric lesions induced by high-dose methotrexate: a time-related study in mice.

In this study, different groups of mice were treated with a single high-dose of methotrexate or with a leucovorin-methotrexate association, and the changes in structure and cell types of the small intestine were studied histologically. The results suggested that leucovorin rescue diminished the degree of mitotic abatement induced by methotrexate in the first days after treatment, with better preservation of enteric structures and the cell type ratio.

Animals↗
PubMed1986

An analysis of haemopoietic and microenvironmental populations of mouse bone marrow after treatment with busulphan.

The effects of the cytotoxin busulphan (myleran) have been investigated in order to ascertain the unique nature of the lesion which it induces. It is one of only few compounds which can cause marked residual marrow dysfunction and the only drug reported to induce a marrow lesion of such magnitude that after a prolonged interval mice may die of the effects of pancytopaenia resulting from hypoplastic marrow failure. We have found that busulphan has a major microenvironmental effect as assessed by the ability of the marrow to form a complete organ in an ectopic site, which confirms existing evidence from a range of putative stromal assays. The effects upon CFU-S are known to include a selective action against certain subpopulations. Our investigation of the dose relationship of busulphan effects have shown that induction of the prolonged marrow lesion is not dependent on the dose of drug administered, or the fractionation regime employed, and is not dependent therefore on the number of CFU-S removed by the drug. The unique action of busulphan probably rests therefore in its ability to damage the microenvironment and the most primitive stem cells which are closely associated with it, if not entirely dependent on it, for their existence.

Animals↗
PubMed1986

Short stature in the "hyperimmunoglobulin E syndrome".

A boy presenting the hyperimmunoglobulin E syndrome and short stature is described. Extensive endocrine investigations could not reveal any disturbance. It is suggested that a very active immunological process might cause growth retardation in this syndrome.

Body Height↗
PubMed1984

Leucovorin protection on pluripotent hemopoietic stem cells in mice treated with high-dose methotrexate.

Haematologic effects of delayed 16 h administration of leucovorin (LV) following high-dose methotrexate (HDMTX) were analyzed in C57Bl X C3H F1 mice. Results show that 16 h administration of LV significantly reduces the toxic effects of HDMTX on hemopoietic progenitors and bone marrow cells. At 12 days after HDMTX administration, the bone marrow level of CFUs was significantly higher in HDMTX-LV treated mice than in HDMTX treated animals. In comparison with previous data obtained when LV was injected 2 h after HDMTX, the delay in administration of LV does not appear to reduce the protective effect of the vitamin.

Animals↗
PubMed1984

Cytotoxic effect of dose and schedule on normal murine hematopoietic progenitor cells following the administration of 4'-deoxydoxorubicin.

In an experimental setting, 4'-deoxydoxorubicin (4'-deoxy-DX) shows minimal cardiotoxicity as well as the marked antitumoral activity shown by doxorubicin, its parent compound. In this experimental study, the haematologic toxicity of the new anthracycline was investigated by haematopoietic precursor cell (HPC) assays using in vivo (colony-forming units - spleen, CFUs) and in vitro (CFUc-culture) methods with (C57B1 X C3H)F1 mice. Dose-survival curves and time response of HPC in situ following 4'-deoxy-DX administration were determined. In the time-related experiments, the effects of a single dose, an intermittent treatment (Days 0, 2, and 5) and a prolonged biweekly administration were studied. All dose-survival curves were exponential, with statistically significant differences between the effects on the various cell classes. CFUc appeared more sensitive than CFUs. In time-related experiments, 4'-deoxy-DX toxicity for HPC seemed to be relatively mild. However, CFUc sensitivity was again high in comparison with other populations assayed. In long-term administration, the 4-deoxy-DX effects on the haematopoietic system were also rather slight.

Animals↗
PubMed1982

Studies on hemopoietic stem cells in mice treated with testosterone propionate and anticancer drugs.

The alleged possibility that testosterone propionate (TP) has a protective effect on hemopoietic cells submitted to the damaging effect of antitumoral drugs was studied. The bone marrow content and the proliferating fraction of CFUs were determined following a single dose on 450 mg/kg of TP. At selected times after TP injection (2 and 4 days), TP-treated mice received a single dose of azathioprine, hydroxyurea, vinblastine, cyclophosphamide, BCNU and doxorubicin. The bone marrow of CFUs were determined 24 h after drug administration. The CFUs-surviving fraction in all cases appeared similar to or lower than that found in controls not treated with TP. It seems therefore that in this experimental setting TP does not reduce the toxic effect of anticancer drugs on hemopoietic pluripotent stem cells. However, this finding does not exclude a possible protective effect of TP at different levels of hemopoiesis or when the steroid is administered with a different schedule.

Animals↗
PubMed1982

Hematopoietic precursor cells in mice treated with 4-demethoxydaunorubicin and doxorubicin.

The hematologic toxicity of 4-demethoxydaunorubicin (4-dmDNR), a new anthracycline more potent and less cardiotoxic than doxorubicin (Dx), was studied. Dose-survival curves of bone marrow hematopoietic precursor cells (HPC) in situ were determined with the use of (C57BL X C3H)F1 mice and with assays of colony-forming units--spleen, culture, and erythroid--by in vivo and in vitro methods. Time response of HPC was followed in mice treated at days 0, 2, and 5 with 0.75 mg 4-dmDNR/kg of 4.5 mg Dx/kg and in mice receiving 2.23 mg 4-dmDNR/kg or 3.96 mg Dx/kg twice a week for 4 weeks. The dose-survival curves of HPC for 4-dmDNR were exponential. Slight differences in sensitivity among assayed populations were seen. Although the doses of 4-dmDNR required to reduce the survival of HPC to 37% were similar or lower than those of Dx, following intermittent treatment with doses of 4-dmDNR with the same optimal antitumor activity as with Dx, 4-dmDNR seemed to have a lesser effect on hematopoietic progenitors and a greater effect on peripheral blood cells than did Dx. However, during prolonged administration 4-dmDNR appeared to be toxic at every hematopoietic level.

Animals↗
PubMed1982

Activity of 4'-epi-doxorubicin on normal hematopoietic precursor cells in mice.

The effects of 4'epi-doxorubicin (4'-epi-DX) on survival of in situ murine bone marrow hematopoietic precursor cells (HPC) were studied. The drug was given to (C57BL X C3H)F1 mice in increasing single doses, in repeated administration (three time in 5 days), or for a long period (twice a week for 10 weeks). Survival of colony-forming units (CFUs, spleen; CFUc, culture; and CFUe, erythroid) was assayed by in vivo and in vitro methods; dose survival curves were exponential. It appears that single doses of 4'epi-DX have a greater impact on murine HPC than single doses of the parent compound. Following repeated administrations, pluripotential stem cells recover better after the derivative than after its parent drug. During prolonged treatment, the bone marrow content of committed progenitors is depleted to a lesser extent in the animals treated with 4;-epi-DX than in those receiving DX. It is, however, possible that, following the same prolonged treatment, this difference is minimal. The conclusion, these experimental data seem to indicate that 4'-epi-DX has lower toxicity in murine HPC than DX and that this is evident mainly after repeated administrations for a short period of time.

Animals↗
PubMed1982

Effects of high-dose methotrexate and leucovorin on murine hemopoietic stem cells.

This study compares the effects of a high dose of methotrexate (HDMTX) to that of a high dose of methotrexate plus leucovorin protection on the hemopoietic stem cells in a murine model. C57BL X C3H F1 mice were treated with a single large bolus (500 mg/kg body weight) of methotrexate or with the same dose of the drug plus leucovorin administered in fractionated doses during the following 24 hr. At 1 to 2 days after the administration of HDMTX, there was a large bone marrow and spleen depopulation of pluripotent stem cells and of committed and recognizable progenitors. At 2 to 3 days, a severe fall of white blood cells and reticulocytes ensued. The recovery process of hemopoietic precursors followed alternate phases of overshooting and secondary falls. Leucovorin administration appeared to protect all stages of hemopoiesis and prevented the severe drops of bone marrow cellularity and stem cell content which followed the HDMTX bolus. However, the effect of leucovorin on peripheral blood cell reduction was less significant. After treatment with HDMTX, the recovery of bone marrow cells and the burst of splenic hemopoietic activity followed a pattern similar in both leucovorin-protected and unprotected animals, but in the former, the increase in stem cells and hemopoietic progenitors appeared to reach higher values and to last longer. In particular, the overshooting of colony-forming units, culture and erythroid, reached a higher peak in leucovorin-treated mice and was more prolonged. Our results indicate that, in HDMTX-treated mice, leucovorin protection involves the earliest stages of hemopoiesis, assuring the maintenance of a satisfactory endowment of stem and progenitor cells.

Animals↗
PubMed1980

[The significance of glycosaminoglycans in normal and pathological bile].

Mucopolysaccharidic substances have been sought in the bile of normal gall-bladders, lithiasic gallbladders and choledocic bile. The quantity of glycosaminoglycanes is much higher in lithogenous than in normal bile, but these substances are but scantily represented in coledochic bile. The significance of glycosaminoglycanes in the lithogenous process is discussed.

Bile↗