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Biomedical subjects

F Herrmann

Publications and source records attributed to F Herrmann.

At least 199 records · Page 11Linked to original sources
PubMed1988

Yeast-expressed granulocyte-macrophage colony-stimulating factor in cancer patients: a phase ib clinical study.

The in vivo effect of yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was investigated in 29 patients with advanced malignancy in phase Ib trial. Patients were treated at six different dose levels (30-1000 micrograms/m2/day) with either daily intravenous bolus injection or 24 hours continuous infusion for 5 days or 2 weeks. Administration of rh GM-CSF resulted in a broad spectrum of dose-, route-, and schedule-dependent hematopoietic effects. Sustained infusion of rh GM-CSF elicited a maximum 17-fold average peak increase of the total white blood cell (WBC) count with mainly neutrophils, eosinophils, and monocytes accounting for this rise, and increases in bone marrow cellularity with a shift to immature myeloid elements. Elevation of lymphocytes, platelets and reticulocytes was not induced. Within one week after discontinuation of treatment the leukocytosis had disappeared. Adverse reactions encountered with rh GM-CSF seen in 65% of the patients studied were never life-threatening and always reversible. They included mild myalgias, facial flushing, low-grade fever, headache, bone discomfort, nausea, dyspnoea and transient decline of platelet counts. These results suggest that rh GM-CSF can be safely administered at the doses and schedules employed and that it can induce in vivo some of the biological effects reported in in vitro studies. Although no objective antitumour responses have been seen, the ability of rh GM-CSF to increase turnover and function of leukocytes in vivo may prevent neutropenia and infections, when GM-CSF is adjunctively added to cytotoxic cancer therapy.

Adult↗
PubMed1988

Regulation of gene expression of M-, G-, GM-, and multi-CSF in normal and malignant hematopoietic cells.

Colony stimulating factors (CSFs) are produced by a variety of cell types, including T-lymphocytes (T cells) and mononuclear phagocytes; both cell types are known to cooperatively interact to elaborate CSFs, although the specific cellular source of CSF species and mechanisms of intercellular communications in this regard are poorly understood. In this report, we investigate the specific origin of various CSF species in peripheral blood mononuclear cells (PBMC), purified T-lymphocyte and monocyte (Mo) populations. Furthermore, we assess the conditions required for stimulation of purified cell cultures to express CSF messenger RNAs (mRNAs) and proteins. In the absence of exogenous activation stimuli, human PBMC, T cells and Mo failed to produce transcripts for CSF for macrophages (M-CSF or CSF-1), for granulocytes (G-CSF), for granulocytes/macrophages (GM-CSF), and for multilineage CSF (multi-CSF or Il-3). However, after stimulation with phorbol myristate acetate (PMA) and phytohemagglutinin (PHA), mRNAs for M-, G-, GM-CSF, and multi-CSF became detectable in PBMC as early as 6 hours after initiation of cultures. Identical culture conditions resulted in synthesis of G-, and M-CSF mRNA by Mo, whereas T-lymphocytes produced GM-CSF and multi-CSF mRNA. More physiologically, when Mo were activated with interferon (IFN)-gamma or tumor necrosis factor-alpha (TNF-alpha) and T-lymphocytes were stimulated in an Mo-independent pathway, that is via triggering of the 50 kd sheep erythrocyte receptor protein employing monoclonal antibodies (mo ab) to the Tll-2- and Tll-3- defined epitopes, similar kinetics of mRNA expression were obtained. Similarly, when interleukin-1 (Il-1) receptive T cells were stimulated with Il-1, T cells transcribed functionally active GM-CSF and multi-CSF. Maximum peak activity of GM-, G-, and M-CSF protein secretion was identical for all CSF species investigated, and occurred in culture 48-72 hours after specific induction. Constitutive expression of CSFs not found in unactivated normal hematopoietic cells was, however, frequently observed in blast cell populations of patients with acute myeloblastic leukemia. Of 49 AML samples, 15 revealed G-CSF transcripts; 11, GM-CSF mRNA; and 6 samples synthesized M-CSF mRNA. Employing specific bioassays, 12 of 15 G-CSF-mRNA-producing cell populations, 8 of 11 GM-CSF-mRNA-producing cell populations, and 1 of 6 M-CSF-mRNA-synthesizing samples, demonstrated release of the respective functionally active CSFs into their culture supernatants.(ABSTRACT TRUNCATED AT 400 WORDS)

Blotting, Northern↗
PubMed1988

Constitutive expression of hematopoietic growth factor genes by acute myeloblastic leukemia cells.

Blast cell populations of forty nine individuals with acute myeloblastic leukemia (AML) were investigated for constitutive expression of genes for various hematopoietic growth factors. Fifteen samples constitutively exhibited messenger (m) RNA for colony stimulating factor for granulocytes (G-CSF). Eleven AML specimens produced mRNA specific for CSF for granulocyte and macrophages (GM-CSF). When probed for CSF for macrophages (M-CSF or CSF-1) specific hybridization signals became detectable in six samples. Five out of six blast cell populations transcribing M-CSF, synthesized G-, and GM-CSF mRNA's simultaneously, whereas another five leukemias transcribed G-, and GM-CSF genes exclusively. Furthermore, when specific bioassays were performed to detect secretion of biologically active CSF proteins by these leukemic blast samples, twelve out of fifteen G-CSF mRNA producing cell populations, eight out of eleven GM-CSF mRNA producing cell populations and one out of six M-CSF mRNA synthesizing samples, demonstrated release of the respective, functionally active CSF's into their culture supernatants. Our results show that gene transcription and protein secretion of hematopoietic growth factors are features that are frequently detected in leukemic myeloid blast cells and involve G-, GM-, and M-CSF. With respect to recent findings of receptiveness of leukemic colony forming cells (L-CFC) for proliferative stimuli provided by various hematopoietic growth factors, our findings point out a potential role of autocrineously produced CSF's in the pathophysiology of autonomous proliferation in AML.

Blotting, Northern↗
PubMed1987

Interferon-gamma induces expression of the interleukin 2 receptor gene in human monocytes.

Interferon-gamma induces surface expression of interleukin 2 (IL2) receptors on human monocytes and the monocytic cell line U937. Freshly prepared peripheral blood monocytes and U937 cells were found to lack detectable IL 2 mRNA, but exposure of these cells to interferon-gamma induced IL 2 receptor message at 6 h of culture. At least two IL 2 receptor transcripts were detected (3.5 and 1.5 kb) in both monocytes and U937 cells, similar in size to IL 2 receptor transcripts in activated T cells. These results show that interferon-gamma induces expression of the monocyte IL 2 receptor gene.

Cell Line↗
PubMed1987

[Is hip sonography meaningful as a screening method?].

The results of screening 162 non-selected neonates by sonography of the hips indicate that this is not a desirable screening method. Sonography is, however, indicted in neonatal groups which are considered to be at risk.

Female↗
PubMed1987

Kallikrein excretion: relationship with maturation and renal function in human neonates at different gestational ages.

Kallikrein excretion and renal function were studied on 37 one-day-old newborn infants (14 fullterm and 23 preterm infants). Preterm infants excreted less kallikrein (p less than 0.001), had lower creatinine clearance (p less than 0.02) and urinary osmolality (p less than 0.01). They had higher values on urinary volume (p less than 0.001), FENa (p less than 0.001), FEK (p less than 0.02), and free water clearance (p less than 0.01) than fullterm infants. The excretion of kallikrein correlated directly with gestational age (p less than 0.01) and body weight (p less than 0.01). No correlations were found with FENa, urinary volume, FEK or free water clearance. The values of kallikrein excretion were very low when compared with a young adult population. As kallikrein is synthesized in the distal nephron we advance as an hypothesis that the low levels of kallikrein excretion observed in newborns could be a reflection of immature distal tubular mass, and to the relative unresponsiveness of the distal nephron to hormones known to stimulate renal kallikrein such as aldosterone and antidiuretic hormone.

Creatinine↗
PubMed1987

Human granulocyte-macrophage colony-stimulating factor induces expression of the tumor necrosis factor gene by the U937 cell line and by normal human monocytes.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) exerts profound effects on the proliferation, differentiation, and effector function of myeloid lineage cells. In contrast to its growth-promoting effects on normal myeloid progenitor cells, we found that GM-CSF unexpectedly inhibited the colony growth of U937 cells in agar culture. Furthermore, medium conditioned by recombinant GM-CSF(rGM-CSF)-treated U937 cells was found to exert an inhibitory effect on subsequent U937 colony growth that was partially due to the presence of tumor necrosis factor (TNF). By Northern blot analysis, rGM-CSF was shown to induce expression of the TNF gene in U937 cells and in T-lymphocyte-depleted, monocyte-enriched peripheral blood mononuclear cells. Furthermore, rGM-CSF was observed to significantly enhance TNF secretion by monocytes stimulated with endotoxin and phorbol myristate acetate (PMA). These data suggest that some of the biological effects of GM-CSF may be amplified through the release of monokines such as TNF.

Cell Line↗
PubMed1987

Renal function in full-term newborns following neonatal asphyxia. A prospective study.

A prospective study of full-term infants with neonatal asphyxia was performed to evaluate possible alterations in renal function. Twenty-one newborns with an Apgar score less than or equal to 3 at 1 minute after birth and a control group of 20 normal infants were included. Oliguria of 12 hours or more (less than 1 ml/Kg/h) during the first 24 hours after birth was considered indication for a volume challenge test and use of diuretic. The study of renal function was effected between 24 and 48 hours after birth for asphyxiated and control infants (Period I), and was repeated between 48 and 72 hours (Period II) for the asphyxiated group only. Intrinsic acute renal failure was diagnosed in two patients, one of whom died. In 10 cases, prerenal oliguria responded promptly to volume expansion with improvement of biochemical indices in Period II. In nine cases, urine volume was not altered, and all functional parameters were comparable with those of control.

Acute Kidney Injury↗
PubMed1987

Inhibition of in vitro hematopoiesis by hepatitis A virus.

Inoculation of human bone marrow with hepatitis A virus (HAV) resulted in a dose- and duration-of-incubation-dependent suppression of hematopoietic progenitor (CFU-GM, BFU-E, CFU-Mix) growth in vitro. Monocytic progenitors appeared to be least affected. While HAV inactivation by heat or beta-propiolactone and neutralization by specific antibodies completely abrogated hematopoietic inhibition, depletion of adherent bone marrow cells, and enrichment of progenitors did not alter the pattern of suppression, which also seemed to be independent of HuIFN-alpha, -beta, -gamma, and TNF. These findings support the concept that direct infection of progenitor cells by HAV may be responsible for hematologic changes commonly seen during early phases of infectious hepatitis and possibly for some cases of bone marrow failure.

Adult↗
PubMed1987

In vitro regulation of human hematopoiesis by natural killer cells: analysis at a clonal level.

We studied the effects of a series of well-characterized clones of human natural killer (NK) cells on the proliferation of highly purified normal marrow hematopoietic progenitor cells. Individual NK clones suppressed granulocyte, monocyte, erythroid, or mixed colony formation in a heterogeneous but clonally stable manner. Inhibition of colony growth required a period of close cell contact between NK cell and progenitor cell with maximum inhibition occurring after 8 to 18 hours of preincubation time. The mechanism of killing was at least partially humoral, however, as cell-free supernatants generated by NK clones "activated" by contact with a target cell also inhibited progenitor cell growth. One of the possible humoral mediators was identified as gamma-interferon by studies with specific neutralizing monoclonal antibodies. These results show that clonal NK lines can be further activated by coming in contact with hematopoietic progenitor cells, resulting in substantial inhibition of colony formation in vitro.

Antigens, Surface↗
PubMed1987

[Is hip sonography in premature infants necessary as a screening procedure?].

Screening sonography of the hip in 132 premature infants indicates that prematurity is not a risk for congenital dysplasia/dislocation of the hip. However, for reasons explained in the text, screening should be carried out before discharge from hospital. Follow-up examinations are necessary only for infants with known risk factors for dysplasia/dislocation of the hip.

Female↗
PubMed1987

Tumor necrosis factor (TNF)-alpha but not TNF-beta induces secretion of colony stimulating factor for macrophages (CSF-1) by human monocytes.

Tumor necrosis factor (TNF)-alpha has been identified as a major inducer of colony stimulating factor (CSF)-secretion by human vascular endothelial cells and fibroblasts. In the present study we assessed the capacity of TNFs to induce release of CSF-1 from highly purified peripheral blood monocyte preparations. Whereas monocytes do not accumulate CSF-1 messenger (m)RNA constitutively and consequently do not produce CSF-1 protein, CSF-1 mRNA and protein secretion became detectable, when monocytes were cultured in the presence of TNF-alpha, that was synergistically enhanced by interferon-gamma (IFN-gamma). However, under identical experimental conditions TNF-beta failed to induce monocyte CSF-1 synthesis. Cultures of monocytes in the presence of TNF-beta before addition of TNF-alpha abolished the CSF-1 inducing capacity of TNF-alpha, suggesting that TNF-beta may act as antagonist to TNF-alpha for CSF-1 production. These data point out a previously unrecognized function of TNF-alpha to modulate CSF-1 release by monocytes and demonstrate disparate biological properties of different TNF species in hematopoiesis.

Colony-Forming Units Assay↗
PubMed1986

T cell-monocyte interactions in the production of humoral factors regulating human granulopoiesis in vitro.

A variety of monocyte functions are modulated by the T cell lymphokine interferon-gamma (IFN-gamma). We assessed the capacity of IFN-gamma to induce release of granulocyte-monocyte stimulating factors (CSF-GM) from highly purified monocyte preparations. Whereas secretion of CSF-GM by monocytes is negligible in the absence of T cells, CSF-GM secretion is inducible when concentrations of IFN-gamma as low as 10 U/ml are present. This effect could be abrogated by specific neutralizing monoclonal antibody to IFN-gamma and was restricted to monocytes, as resting T cells failed to secrete detectable CSF-GM in response to IFN-gamma. The response of monocyte preparations to IFN-gamma was biphasic in that concentrations greater than 250 U/ml did not induce detectable CSF-GM activity. However, this was shown to be due to the release of a humoral inhibitor of G/M-progenitor cells, and not necessarily due to a lack of CSF-GM secretion.

Cell Communication↗