Biomedical subjects

S Grell

Publications and source records attributed to S Grell.

10 recordsLinked to original sources

PubMed2001

Mental stimulation increases circulating CD4-positive T lymphocytes: a preliminary study.

To stimulate the dorsolateral frontal cortex, 12 healthy, adult, human females played contract bridge for 1.5 h between initial and final blood sample collections. Flow cytometric analyses of samples, performed in triplicate, showed a significant increase in CD4-positive T lymphocytes. The dorsolateral frontal cortical thickness is significantly and bilaterally reduced in immune-incompetent female, nude mice. Thymic transplants reverse the deficient cortical thickness and CD4-positive cell numbers.

Aged↗

PubMed1996

Interferon-alpha enhances the cytotoxic and cytostatic activities of chemotherapeutic drugs in human myeloid leukemia cells.

In comparison with chemotherapeutic drugs, IFN-alpha showed a significantly better median survival rate in CML patients; therefore, current studies focus on the identification of the proper chemotherapeutic drug, with the most effective synergistic interaction with IFN-alpha for the elimination of the human myeloid leukemia cell clone. The cytostatic and cytotoxic effects of combining IFN-alpha with each of the three chemotherapeutic drugs carboplatin, daunorubicin, and cytarabine were evaluated in three human myeloid leukemia cell lines representing different stages of differentiation: MHH225 (CD34-positive multilineage), HL-60 (promyelocytic), and U937 (monoblastic) in both liquid suspension and agar clonogenic cultures. The ED90 (the concentrations of chemotherapeutic drugs required for 90% inhibition of colony formation or cell death) in human myeloid leukemia cells were in the following order: daunorubicin > carboplatin > cytarabine, with HL-60 the most sensitive and MHH225 the least sensitive. Whereas IFN-alpha failed to decrease significantly the ED90 of cytarabine in the three human myeloid leukemia cell lines, it significantly decreased the ED90 of carboplatin and to a lesser extent daunorubicin in both liquid suspension and agar clonogenic cultures. The present results are in line with the previous results of a negative interaction between IFN-alpha and cytarabine both in vitro in K562 human leukemia and in vivo in L1210 murine leukemia, and a synergistic cytostatic interaction between IFN-alpha and carboplatin in K562 cells. The significant synergism between IFN-alpha and carboplatin was observed in all four human myeloid leukemia cell lines with various stages of differentiation and confirmed in both serum-free and serum-supplemented cultures applying different in vitro assays: liquid suspension, agar clonogenic, and capillary agar microclonogenic cultures. Thus, given the in vitro profound synergism between IFN-alpha and carboplatin in all four human myeloid leukemia cells tested, together with the in vivo significant antileukemic activity of both IFN-alpha and carboplatin in several reported clinical studies for myeloid leukemia patients, the clinical use of the combination of IFN-alpha and carboplatin in the treatment of CML patients could prolong the complete hematologic and cytogenetic responses and consequently improve the survival rate. On the other hand, given the negative interaction between IFN-alpha and cytarabine observed in myeloid leukemia cells, together with the inferior cytogenetic responses observed in CML patients treated with the combination of IFN-alpha and cytarabine, caution should be exercised against the continuous clinical use of the combination of IFN-alpha and cytarabine in treating CML patients. In conclusion, the present results suggest the use of carboplatin and to a lesser extent daunorubicin instead of cytarabine in combination with IFN-alpha for the treatment of CML patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Effect of recombinant human interferons in inducing differentiation of acute megakaryoblastic leukaemia blast cells.

The effects of interferons (IFN)-alpha, beta 2 and -gamma in inducing megakaryocytic differentiation of blast cells from a patient with acute megakaryoblastic leukaemia (AMegL) was investigated in liquid suspension culture by the increase in CD41 and CD42b expressions using monoclonal antibodies in the APAAP technique. After six days of culture, the percentage of CD41 and CD42b positive cells increased in control cultures from 15.2% and 10.6% on day 0 to 32.0 +/- 4.3% and 22.1 +/- 2.5%, respectively. The addition of IFN-alpha significantly increased the number of CD41 and CD42b positive cells by about two to three fold compared to control cultures (p < 0.01) and by about four to six fold compared to day 0 (p < 0.001) Similarly, IFN-beta 2 induced a significant increase in CD41 and CD42b positive cells. On the other hand, IFN-gamma failed to increase the number of CD41 and CD42b positive cells in comparison to control cultures on day 6 and instead stimulated a significant increase in the number of monocytes/macrophages by about ten fold compared to control cultures in IFN-gamma-treated cultures (p < 0.001). The present results suggest that megakaryocytic differentiation of blast cells in AMegL could be induced by IFN-alpha and beta 2 and support a clinical role for them in the treatment of AMegL patients. Also, the present results showed that monocytic differentiation of blast cells in AMegL could be stimulated by IFN-gamma, supporting the multipotent stem or progenitor cell origin of the AMegL subtype of acute myelogenous leukaemia.

Aged↗

PubMed1989

Biphasic effect of a kappa-opioid receptor agonist on plasma oxytocin levels in rats.

The effect of the kappa-opioid receptor agonist, bremazocine, on plasma oxytocin levels in rats was measured by a sensitive radioimmunoassay. Initially, a decrease in plasma oxytocin levels was seen 30 min after injection. This was in accordance with the bremazocine inhibition of oxytocin release after submaximal electrical stimulation seen in isolated neurointermediate lobes. The initial decrease in plasma oxytocin reversed, and 4 h after injection of bremazocine a 20-fold increase in the oxytocin level was seen. The rise in plasma oxytocin was paralleled by a rise in plasma sodium. The biphasic time course of the plasma oxytocin response can be explained by a combination of an inhibition of oxytocin release from the neurohypophysis and an increased water excretion leading to an elevation in plasma sodium, which may be responsible for the late rise in plasma oxytocin. Down-regulation of the opioid receptors may also contribute to the delayed rise in plasma oxytocin.

Analgesics↗

PubMed1989

Limited diversity of T-cell receptor gamma-chain expression of murine Thy-1+ dendritic epidermal cells revealed by V gamma 3-specific monoclonal antibody.

To study the origin of and the degree of T-cell antigen receptor (TCR) diversity of Thy-1+ dendritic epidermal cells (Thy-1+ dECs) in mice, we have developed a monoclonal antibody (mAb 536) to the gamma delta TCR. mAb 536 binds to and stimulates interleukin 2 secretion from Thy-1+ dEC but not cells that express TCR composed of alpha and beta chains. mAb 536 precipitates CD3-associated gamma and delta chains from lysates of radioiodinated Thy-1+ dECs. Analysis of a panel of hybridomas that express gamma delta TCR indicated that mAb 536 defines an epitope of the variable region (V gamma 3) gene product. Flow cytometric analysis revealed that expression of V gamma 3 in the adult mouse is restricted to cells in the epidermis, where essentially all Thy-1+ cells are V gamma 3+. The majority of CD3+ cells in the 14-day fetal thymus also express V gamma 3. These results indicate that the T-cell complement in epidermis are cells that express gamma delta TCR and that the diversity of antigens recognized by the cells might be restricted by the use of a single V gamma gene segment. Finally, the data raise the intriguing possibility that Thy-1+ dECs may arise from precursors that are among the first to emerge from the developing thymus. This suggests that V gene usage during thymocyte development is highly regulated and has important consequences on the tissue localization and function of the emerging cells. As in other developing tissues, it appears that programmed and transient gene expression determines the fate of the emerging cells.

Animals↗

PubMed1988

The influence of morphine and naloxone on plasma oxytocin concentration in the rat.

Subcutaneous injections of morphine decrease the plasma oxytocin level significantly in both normohydrated rats and rats dehydrated for 24 hrs. This effect of morphine is naloxone-reversible. Injections of naloxone increase the plasma oxytocin level in a time dependent manner, when the oxytocin system is stimulated by dehydration, but have no effect on basal oxytocin level. This observation indicates liberation of an endogenous opioid, during stimulation of the neurohypophysis, leading to inhibition of the oxytocin secretion. A discrepancy in the time course between the plasma oxytocin enhancing effect and the morphine reversing effect of naloxone is observed. On the basis of this observation two different opioid receptors are suggested to be involved in the effect of naloxone on the neurohypophysis.

Animals↗

PubMed1988

Application of flow karyotyping in prenatal detection of chromosome aberrations.

This paper describes the application of bivariate flow karyotyping to (1) classification of chromosomes isolated from cultures of cells taken by amniocentesis and (2) detection of numerical and structural aberrations. Chromosomes were isolated from primary cultures 2-5 wk after amniocentesis, stained with Hoechst 33258 and chromomycin A3, and analyzed using dual beam flow cytometry. Information about chromosome DNA content and DNA base composition was derived from the locations of the peaks in the flow karyotypes, each peak being produced by one or more chromosome types with similar DNA content and DNA base composition. Information about the relative frequency of each chromosome type was determined on the basis of the relative volume of the peak for that chromosome type. Cytogenetic information determined on the basis of flow karyotypes was compared with that obtained by visual analysis following G-banding. Variability among the peak means and volumes in flow karyotypes was determined from analyses of 50 normal amniocyte cultures. Numerical aberrations involving chromosomes 21, 18, and Y were detected correctly in all of 28 analyses, including eight in a blind study. Structural aberrations involving chromosomes 1, 2, 3, 6, 9-12, 13, 14, 15, 21, and 22 were detected in all of seven cultures in a blind study. Flow karyotypes proved to be insensitive to small, normally occurring chromosome polymorphisms detected by banding analysis. In addition, a few samples were erroneously scored as having numerical aberrations.

Cells, Cultured↗

PubMed1987

GABA receptor stimulation increases the release of vasopressin and oxytocin in vitro.

The release of oxytocin and vasopressin from rat neurointermediate lobes was determined in vitro. The electrically evoked release of posterior pituitary hormones was markedly potentiated by the GABA receptor agonist, isogauvacin, an effect which was abolished by the GABAA receptor antagonist bicuculline. Spontaneous hormone outflow was not affected by the substances tested. The results suggest the existence of a GABA receptor on the terminal fibres in the pituitary, facilitating the release of oxytocin and vasopressin.

Animals↗

PubMed1985

Morphine antidiuresis in conscious rats: contribution of vasopressin and blood pressure.

Intracerebroventricular injections of morphine (5-20 micrograms) produced a dose dependent antidiuresis in the conscious hydrated rat. Naloxone pretreatment completely abolished this antidiuretic effect, but pretreatment with a specific antidiuretic vasopressin antagonist did not change the morphine antidiuresis. The vasopressin concentration in the first voided urine after antidiuresis from morphine treated rats was found to be in the same range as the vasopressin concentration in urine from saline treated rats. Injections of 20 micrograms morphine intracerebroventricularly in conscious hydrated rats gave a short decrease in heart rate but not in mean arterial blood pressure. This indicates, that either liberation of vasopressin nor a fall in systemic blood pressure contribute to the morphine antidiuresis.

Animals↗

PubMedDate not supplied

Interleukin-4 inhibits proliferation of human leukemic megakaryoblast cell line MHH 225.

The effects of six recombinant human cytokines: erythropoietin, GM-CSF, G-CSF, interleukin-3, -4 and -6 on the proliferation and differentiation of a human multilineage myeloid leukemia cell line MHH 225, established from the bone marrow of an AML(M7) patient in our laboratory determined by changes in antigen expressions using monoclonal antibodies in APAAP technique were examined in liquid suspension culture. The MHH 225 cells have been growing exponentially without cytokines or conditioned media. About 90 per cent of MHH 225 cells are CD33+ CD34+ CD3- CD7- CD19- CD20- TdT- with 57.6 per cent, 28.3 per cent and 7.8 per cent of them being CD41+, glycophorin A+ and CD15+, respectively. After five days of treatment with erythropoietin, GM-CSF, G-CSF or IL-6 no change was observed in MHH 225 cell antigens expression. IL-3 (100 U/ml) induced a moderate increase in only CD13 and alpha naphthyl esterase positive cells from 6.5 +/- 1.9 per cent and 5.7 +/- 2.4 per cent in control cultures to 21.6 +/- 3.0 per cent and 19.1 +/- 2.8 per cent, respectively. On the other hand, 100 U/ml IL-4 significantly increased the number of CD13, CD15 and alpha naphthyl esterase positive cells to 48.9 +/- 5.0 per cent, 47.2 +/- 3.6 per cent and 46.1 +/- 3.0 per cent, p < 0.001, respectively. Also, 100 U/ml IL-4 decreased the number of CD41 positive cells from 57.6 +/- 2.8 per cent to only 25.9 +/- 3.6 per cent and did not change the number of CD33 or glycophorin A positive cells. The present results showed that out of the six myelopoietic growth factors tested, IL-4 was the only one to inhibit selectively the proliferation of CD33+ CD41+ leukemic megakaryoblast cells suggesting that IL-4 may have a lineage regulatory effect in favour of a myeloblastic CD33+ CD13+ CD15+ at the expense of a megakaryoblastic CD33+ CD41+ amplification in human leukemia cells and with apparently no effect on leukemic erythroblast cells. The MHH 225 cell line provides a useful tool and freely available model to scientists for studying signal transduction via IL-4 and for studies of 'lineage switch'.

Antigens, CD↗