PubMed Health⌕ Search

Biomedical subjects

G Prindull

Publications and source records attributed to G Prindull.

At least 37 records · Page 2Linked to original sources
PubMed1986

Pre-CFU-f: young-type stromal stem cells in murine bone marrow following administration of DNA inhibitors.

Occurrence of young-type stromal stem cells (defined here as "pre-CFU-f") in murine bone marrow is reported in this study. Two consecutive intraperitoneal (i.p.) cytosine arabinoside (ara-C) injections were administered to C57B1 mice (2 X 200 mg/kg at 6-h intervals). Two days later the bone marrow was collected and assayed for colony-forming units-fibroblastoid (defined here as "CFU-f"). In additional experiments, ara-C-treated marrow was exposed in vitro to hydroxyurea (HU; "hydroxyurea killing test"), prior to plating, to establish the cycling state of stromal stem cells. In separate cultures of ara-C-treated marrow, replating of adherent cells was carried out up to quaternary sub-cultures. The results indicate ara-C-treated marrow produces approximately 20% "huge" fibroblastoid colonies (approximately 5 mm diameter versus 0.5-2 mm normal size); most stromal stem cells producing huge colonies are cycling cells; and adherent cells from primary ara-C-treated marrow cultures replated to secondary cultures produce adherent layers with double the number of cells than in the control secondary cultures. We conclude that the ara-C-treated murine bone marrow contains certain young-type cycling stromal stem cells which we refer to as pre-CFU-f. These stem cells produce huge fibroblastoid colonies in culture, indicating that they probably go through more cell cycles than CFU-f during the culture period. Alternatively, pre-CFU-f may have a higher self-replicative capacity than CFU-f.

Animals↗
PubMed1986

Clinical symptoms and biochemical properties of three new glucosephosphate isomerase variants.

Glucosephosphate isomerase deficiency as the cause of macrocytic congenital nonspherocytic hemolytic anemia is described in three unrelated families. The biochemical properties of the variant glucosephosphate isomerases indicate that the patients have new variants, designated as GPI Kiel, GPI Hamburg, and GPI Homburg. The severity of the clinical symptoms depended on the amount of residual GPI activity and the biochemical properties of the variant enzyme. Thus the patient with GPI Kiel (34% residual activity) whose variant GPI was slightly unstable showed a mild chronic hemolytic anemia. The patient with GPI Homburg (7% residual activity) whose variant enzyme was stable and had a reduced specific activity, suffered from severe congenital hemolytic anemia and neuromuscular symptoms. Due to the special properties of GPI Homburg, we assume that both the hematological and neuromuscular symptoms of the patient with GPI Homburg are caused by his GPI deficiency. The twins with GPI Hamburg (27% residual activity) had a distinctly unstable variant enzyme and had suffered from hemolytic crises since birth. Only GPI Homburg showed an altered electrophoretic mobility and an increased affinity for fructose-6-phosphate. The other two variants had normal values.

Adolescent↗
PubMed1985

Radiotherapy of non-metastatic ewing sarcoma.

Comparing the radiotherapy data of two groups of patients with non-metastatic Ewing sarcoma, we came to the following conclusions: intensive chemotherapy does not substitute for effective radiotherapy. Irradiation fields should be large enough to include the whole affected bone and the entire extra-osseous compartments, exempting only uninvolved epiphyses. Marginal recurrences are a major risk of the shrinking field technique. Single doses per fraction should be high and the total dose raised to the point of maximal irradiation tolerance of normal tissues.

Adolescent↗
PubMed1985

Local therapy of rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma of children and adolescents.

Local control of the primary tumour is a fundamental requirement for clinical cure. Towards this aim, the primary tumour must be diagnosed early and identified histologically. The size, extension, and spread within the patient must be defined precisely. In planning effective local therapy, additional questions must be answered including resectability, mutilation, sensitivity to radio- and chemotherapy, anticipated morbidity from therapeutic measures, etc. For osteosarcoma there is no reasonable alternative to radical surgery. Because of the 20% local recurrence rate of Ewing's sarcoma following radiotherapy, radical surgical removal of the primary tumour should be attempted whenever possible. For rhabdomyosarcoma, particularly for its embryonal histology, non-radical removal of the primary sarcoma is still compatible with a cure, provided adequate radio- and chemotherapy is also administered. Primary irradiation is indicated in radiosensitive unresectable primary tumours and may convert these into an operable state. Chemotherapy is the domain of prevention and treatment of metastatic disease. It has, however, also a proved effect on primary tumours and, in several recent protocols, precedes local therapy.

Adolescent↗
PubMed1985

Effects of chemotherapy on bone marrow stroma in mice with acute myelogenous leukemia. Correlation with CFU-C and CFU-D.

This study describes changes in bone marrow stroma in murine acute myelogenous leukemia (AML). The AML was induced in C57B1 mice by intravenous (i.v.) transfusion of C4198 myelogenous leukemic cells. In untreated leukemic mice, the colony-forming unit fibroblasts (CFU-F) were severely inhibited. In leukemic mice treated by three chemotherapy protocols of cytosine-arabinoside (Ara-C) and adriamycin there was a 200% increase in the life span as compared to untreated leukemic animals and marked reduction of marrow leukemic load. In these mice the stromal inhibition was temporarily relieved, expressed by peaks of CFU-F2-3 days following each protocol. In between the peaks, CFU-F decreased to subnormal levels, remaining low to the end of the disease. In normal mice administered a similar chemotherapy regimen, there were peaks of CFU-F activation after each protocol and normal levels in between the peaks. Granulocyte/macrophage progenitors (CFU-C) of leukemic-treated and normal-treated mice showed increased levels following each chemotherapy protocol. Whereas CFU-C decreased below normal levels in leukemic mice towards the end of the disease, the level of these progenitors remained high in normal mice receiving Ara-C and adriamycin. Colony-forming units in diffusion chamber (CFU-D) showed mild fluctuations in both leukemic and normal mice receiving three protocols of Ara-C and adriamycin. It is possible that despite treatment, the bone marrow stroma in leukemia becomes irreversibly deficient towards the end of the disease and cannot support the residual normal hematopoiesis.

Animals↗
PubMed1984

Bone marrow stromal deficiency in acute myeloid leukemia in mice.

A study of bone marrow stroma in acute myeloid leukemia (AML) in mice was carried out. AML was induced in C57B1 mice by i.v. inoculation of the C1498 cell line. There was a direct correlation between the marrow leukemic load and the degree of marrow stromal deficiency. This was expressed by reduced in vitro fibroblastoid colony formation. In co-cultures of normal mouse bone marrow and leukemic cells, and also in cultures of normal marrow with added conditioned medium (CM) of leukemic cells, marked inhibition of fibroblast-colony-forming units (CFU-F) from normal marrow was observed. In additional experiments, leukemic mice were treated with two consecutive injections of cytosine arabinoside (Ara-C) (2 X 200mg/kg) and sacrificed 48 h later. Bone marrow samples of treated animals formed in vitro an increased number of fibroblastoid colonies despite relatively high levels of marrow leukemia. It is concluded that: (a) there is a direct correlation between the incidence of marrow leukemic cells and the degree of stromal deficiency; (b) leukemic cells produce in vitro--and probably in vivo CFU-F inhibitory factors and (c) administration of restricted doses of cytosine arabinoside to leukemic mice reduces the marrow leukemic cell content to some extent and increases the capacity of CFU-F to form fibroblastoid colonies in vitro.

Animals↗
PubMed1983

Incidence and characteristics of colony-forming units fibroblasts (CFU-F) in the bone marrow of weanling mice treated with cytosine arabinoside and phenylhydrazine: correlation with CFU-S, progenitors of diffusion-chamber colonies (CFU-D), and CFU-C.

A study of murine adherent marrow cells (AMC) under conditions of high and low concentrations of hematopoietic stem cells and progenitors was carried out. In one group of weanling mice, decreased marrow cellularity and increased concentrations of CFU-S, CFU-D, and CFU-C were observed two days after administration of two consecutive intraperitoneal (i.p.) cytosine arabinoside (Ara-C) injections (2 x 200 ng/kg, at 6 h interval). Fibroblast colony-forming units (CFU-F) of this marrow were studied. In a second group of mice, which were given three i.p. phenylhydrazine (PHZ) injections (3 x 60 mg/kg on days 0, 1, and 3), CFU-S and CFU-C levels were unchanged or lowered 6 days after the start of PHZ administration. In these animals, however, the number of CFU-D was four times higher than in controls. The study of CFU-F in experiments of groups 1 and 2 indicated a high concentration of these progenitors in group 1 and lower concentration in group 2. Furthermore, fibroblastoid colonies produced in vitro by CFU-F of Ara-C-treated marrow were significantly larger than colonies from control marrow, and they markedly inhibited G/M colonies in split-phase agar cultures. By contrast, fibroblastoid colonies produced by PHZ-treated marrow were of regular size and did not inhibit G/M colonies from test bone marrow.

Animals↗
PubMed1983

Hodgkin's disease and a mediastinal tumor.

Two children are presented with Hodgkin's disease and a mediastinal mass which did not respond to polychemotherapy and radiation therapy and proved to be a benign thymic cyst. The coincidence of Hodgkin's disease with a benign thymic cyst has only been reported once before [11]. The diagnostic and therapeutic implications are discussed.

Adolescent↗
PubMed1983

Adjuvant chemotherapy in osteosarcoma - effects of cisplatinum, BCD, and fibroblast interferon in sequential combination with HD-MTX and adriamycin. Preliminary results of the COSS 80 study.

In a cooperative adjuvant chemotherapy study of osteosarcoma (COSS-80), 192 patients were registered from December 1979 to March 1982. Forty-one patients have been excluded from study because of their nonadjuvant situation, therapy-limiting clinical conditions, or inadequate diagnosis. One hundred and fifty-one patients have been randomized to receive either the drug combination bleomycin + cyclophosphamide + dactinomycin (BCD) or cisplatinum (CPL) within a course of sequential multidrug chemotherapy including adriamycin (ADR) and high dose methotrexate (HDMTX). After exclusion of 51 patients with some deviation in history and/or management 100 selected patients were randomized once more to receive in addition or not fibroblast interferon after preoperative chemotherapy and surgical removal of the primary tumor. Patients were stratified for age and sex and for site and extension of tumor as well in both randomizations. Median follow up is now 12 (1-16) months. The expected 2-year disease free survival (DFS) rate of the total doubly randomized group is 78% and of the single randomized group 76%. No difference could be discerned between recombined groups receiving BCD vs CPL or interferon vs no interferon. The effect of preoperative chemotherapy on the tumor was evaluated clinically and by histopathologic grading; 66/85 (78%) patients were judged clinically as responders with pathohistologic verification of this finding in 71% of these cases. No adverse effect arose from delaying definite surgery for preoperative chemotherapy, but initial application of chemotherapy as well as planning, preparing, and performing of the surgical procedure have been facilitated. The majority of patients received some kind of limb-salvage treatment without local recurrences so far. A statistically insignificant but intriguing tendency for a slightly higher incidence of pulmonary metastases after resection as opposed to amputation could be detected. Similar to observations in the previous study COSS-77.

Adult↗
PubMed1983

Radiosensitivity of haematopoietic stem cells (DCPC and CFU-GM) from cord blood.

The radiosensitivity of human cord blood haematopoietic stem cells was measured by assessing colony formation in methylcellulose cultures and diffusion chambers. The results show that fetal colony forming units, granulocytic, monocytic (CFU-GM), are radiosensitive: colonies formed by electron-irradiated CFU-GM, both in spontaneous and in colony stimulating factor (CSF) supplemented cultures decrease in number in an exponential fashion with increasing doses of irradiation. Do values up to 800 rads were, for highly purified fetal lymphoid cells, 160 +/- 88 rads; for whole buffy coat cells, 155 +/- 75 rads; and for buffy coat cells plus exogenous CSF: 155 +/- 77 rads. Extrapolation numbers (N) approached the value of 1. Among cord blood diffusion chambers progenitor cells (DCPC), radiosensitive and radioresistant subpopulations of myelopoietic stem cells exist, as tested over a range up to 1500 rads. Monocytopoietic CFU-D are radioresistant.

Cells, Cultured↗
PubMed1983

Sleep-related gonadotropin rhythms in children following treatment of acute leukemia: recovery of the hypothalamo-pituitary-gonadal axis after chemotherapy and CNS-irradiation.

Twelve children (5 girls and 7 boys, between the ages of 6 and 20 years) in complete remission from previous ALL who had completed their entire anti-leukemic treatment program and who had been off all chemotherapy for at least one year, were included in a study of sleep-related prolactin and gonadotropin rhythms. All the patients had received prophylactic CNS-irradiation. The patients in early puberty showed a sleep-dependent FSH rhythm. Patients in middle-to-late puberty had sleep-related FSH and LH rhythms, and estradiol and testosterone plasma concentrations were normal for their pubertal stage, suggesting recovery of the hypothalamo-pituitary-gonadal feedback system. We conclude that the neuro-endocrine axis is not permanently injured by CNS-irradiation and anti-leukemic therapy.

Adolescent↗
PubMed1982

Enhanced acceptance of regenerating bone marrow of random bred newborn mice by random bred adult mice.

Regenerating bone marrow of newborn random bred Sabra mice (9-13 days old) was obtained by the administration of two consecutive i.p. injections of hydroxyurea (HU) (2 x 100 mg/kg body wt), three days prior to collection of the marrow cells. The bone marrow of HU-treated newborn mice was assayed for CFU-S, CFU-C and plasma-clot-diffusion-chamber (PCDC) progenitor cells. A fourfold content of CFU-S was found in the regenerating bone marrow compared with that of the control marrow, while the level of CFU-C and PCDC progenitor cells was the same in treated and untreated newborn mice. In lethally irradiated adult, random bred Sabra recipient mice, transfused with regenerating bone marrow from newborn mice, the initial survival rate was greater than in irradiated animals receiving normal newborn marrow (75% as against 50%); marrow repopulation, 10-14 days after transfusion, was also greater in the former than in the latter group of animals (1.5-2x10(6) nucleated cells per femur as compared with 08.-2x10(5)). The bone marrow of these groups of mice was assayed for CFU-S, CFU-C and PCDC progenitor cells; with a cell inoculum of 5 x 10(4) i.v., 10(5) in vitro and 5 x 10(4) per DC, respectively, pluripotent and committed stem cells were detected in the experimental group and were lacking in control recipients. Regenerating bone marrow of newborn mice was also transfused into lethally irradiated splenectomized recipients. In this experimental group there was high mortality, low marrow repopulation and lack of CFU-S (5-10 x 10(4) cell inoculum). The results of this study indicate that, despite genetic differences among random bred Sabra mice, regenerating bone marrow of newborn mice "takes better" than normal marrow in lethally irradiated recipients. Improved marrow acceptance is possibly due to the increased content of activated CFU-S and/or pre-CFU-S in the regenerating bone marrow

Age Factors↗
PubMed1982

Hemoglobin biosynthesis in juvenile erythroleukemia: evidence of imbalanced globin chain synthesis.

In three young patients with erythroleukemia in whom a partial reversion to the fetal pattern of erythropoiesis occurred there was found additionally an imbalance of globin chain synthesis. The synthesis of beta- plus gamma-chains exceeded that of the alpha-chains. In contrast, physiologic hemoglobin F production occurring in newborn infants and increased hemoglobin F production due to rapidly regenerating erythropoiesis in hereditary spherocytosis and after acute erythroblastopenia are characterized by a well balanced globin chain synthesis. These studies indicate that in distinct cases of juvenile erythroleukemia the genuine reversion to fetal erythropoiesis may be associated not only with a depression of hemoglobin synthesis but also with an imbalanced globin chain synthesis. Unlike adult cases of erythroleukemia without reversion to fetal erythropoiesis the imbalance of globin chain synthesis seems to be a more generalized phenomenon in these cases of juvenile erythroleukemia which is not confined to a particular red cell population.

Adolescent↗
PubMed1982

A comparison of spontaneous and CSF added CFU-MG colony formation in healthy, sick and hypotrophic pre-term infants.

Myelopoietic progenitor cells (CFU-MG) have been studied from peripheral blood of healthy, sick, and hypotrophic pre-term infants. Methylcellulose cultures were prepared simultaneously with and without exogenous colony stimulating factor. It was found that large numbers of circulating CFU-M are present at birth in healthy infants, smaller numbers in sick infants, and very few in hypotrophic infants. Exogenous CSF increases the number of colonies in cultures of healthy infants at birth. A limiting factor in spontaneous colony formation is the production of CSF by the cells in culture. This is particularly evident in sick infants. During the postnatal course similar levels of circulating CFUc, higher than in adult blood, are found in all three groups of pre-term infants.

Colony-Stimulating Factors↗
PubMed1982

Iodine-induced hypothyroidism and goiter following lipiodolTM lymphography.

Hypothyroid goiter is a rare but well recognized complication following long term administration of iodine containing expectorants and disinfectants in children. Only few reports exist on iodine-induced hypothyroidism after a single injection of the iodized radiopaque dye Lipiodol. A 15-year-old boy with previously normal thyroid function is described who developed hypothyroid goiter within six weeks following bipedal lymphography. Urinary iodine excretion was extremely elevated up to 18 mg/day while serum concentrations of total thyroxine were below the euthyroid range and thyrotropin levels were elevated. After oral L-thyroxine treatment the goiter disappeared. Thyroid function remained normal when treatment was discontinued after five months although iodine excretion was still 50 times higher (2.5 mg/day) than in normal age matched children. The observed alterations of the thyroid gland were caused by a long lasting Wolff-Chaikoff effect with a delayed adaptation to high iodide concentrations.

Adolescent↗