The sequence of the hemoregulatory peptide is present in Gi alpha proteins.

The hemoregulatory peptide PyroGlu-Glu-Asp-Cys-Lys (HP5b), which inhibits myelopoietic colony formation in vitro, is shown to be a sequence motif which is also part of the effector domain of Gi alpha proteins. Out of 8 synthetic peptides with sequence variations of HP5b, those with the closest similarity to the Gi alpha sequence are biologically active. The inhibitory effect appears to be dependent on the blocked N-terminus. It is postulated that these peptides may interfere with signal transduction mediated by Gi alpha proteins.

In vitro effects of insulin-like growth factor-1 (IGF-1) on proliferation and constitutive cytokine secretion by acute myelogenous leukemia blasts.

The effects of insulin-like growth factor 1 (IGF-1) on autonomous proliferation, cytokine-dependent proliferation and constitutive cytokine secretion by acute myelogenous leukemia (AML) blasts were investigated using serum-free in vitro conditions. IGF-1 enhanced AML blast proliferation independent of the presence of other exogenous cytokines only for 2 of 21 patients, but for 10 additional patients IGF-1 altered blast proliferation in the presence of certain exogenous cytokines or cytokine combinations. IGF-1 had minor effects on AML blast cytokine secretion only for a subset of the patients (decreased levels for 1 patient, increased levels for 7 patients). Our in vitro observations indicate that IGF-1 can modulate AML blast proliferation and/or cytokine secretion for a subset of patients.

In vitro culture of acute myelogenous leukemia blasts: a comparison of four different culture media.

Proliferative responses and cytokine secretion were compared when AML blasts were cultured in the three serum-free media, X-Vivo 10, X-Vivo 15, and defined serum-free medium (IMDM with mercaptoethanol, low-density lipoprotein, albumin, and transferrin) and in media containing 10% inactivated fetal bovine serum (FBS). The following AML blast functions were investigated: (a) constitutive cytokine secretion, (b) autonomous and cytokine-dependent proliferation, and (c) accessory cell function during T cell activation. Constitutive cytokine secretion and accessory cell function differed markedly when using different culture media. For the constitutive AML blast secretion of IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, no qualitative differences were seen, but quantitative differences were observed with decreased cytokine levels for cells cultured in X-Vivo 10 and X-Vivo 15. The accessory cell function of AML blasts was also decreased in the X-Vivo media, whereas differences were less pronounced when comparing AML blast proliferation. Our results clearly demonstrate that a well-characterized culture system is essential for in vitro studies of AML blast functions.

Hemoregulatory peptide (HP5b) dimer effects on normal and malignant cells in culture.

The dimer of the hemoregulatory peptide HP5b has been investigated for biological effects on various cell types in culture including mouse granulocyte-macrophage colony forming units (CFU-GM) from agar and murine long-term bone marrow culture (LTBMC). While CFU-GM were significantly stimulated in both systems, mitogen activation of mouse T, B and natural killer (NK) cells was not affected. Peptide treated mouse 3T3 fibroblasts reached a higher saturation density than controls; otherwise no effect was seen. A series of malignant cell lines was also tested. On a human glioblastoma cell line (GaMg) and rat glioma cell line (BT5C) a slight but significant stimulatory effect was found, while human mammary carcinoma cells (MCF7) were not affected. On SC1 mouse lymphoma cells a slight stimulation of cell growth was seen during the first part of exponential growth. Since HP5b acts as a stimulator for stromal cell secretion of other growth factors, supernatants from a human bone marrow stromal cell line stimulated with HP5b were tested on various cell lines. The effects of the supernatants on cell growth of the tested cell lines were not affected by HP5b treatment. Taken together with available in vivo data, the results indicate that the hemoregulatory peptide is a selective stimulator of myelopoiesis.

The ontogeny of immunological receptors in the thymus.

Receptors for sheep erythrocytes, for the Fc part of IgG (Fc gamma R) and IgM (Fc mu R), and for components of activated human complement C3 (C3bR and C3dR) in thymus tissue from fetuses, infants and children were studied using haemadsorption to cryostat sections in a closed chamber. Sheep erythrocytes (SE) did not adhere to sections of thymus from fetuses at 10-11 weeks of gestation, adhered weakly between 14 and 20 weeks, while they adhered in a dense monolayer in older fetuses, in infants and in children, denser in the cortex than in the medulla. Ox erythrocytes (OE), sensitized with IgG to demonstrate Fc gamma R, adhered focally to both cortical and medullary areas. The adherence was more pronounced to the sections of fetal thymus than to the sections from infants and children. OE, sensitized with IgM to demonstrate Fc mu R, adhered focally to all thymus tissue sections, preferentially to the cortex. The adherence was most pronounced in fetal thymus. SE, sensitized with IgM and coated with complement, adhered to sections of fetal thymus, but the density decreased markedly during fetal life. Indicator cells demonstrating C3bR adhered focally also to sections from infants and children, while indicator cells demonstrating C3dR did not adhere to sections from individuals older than 38 weeks of gestation. Indicator cells demonstrating C3bR and C3dR adhered both to cortex and medulla.

[Membranoproliferative glomerulonephritis]. / Membranproliferativ glomerulonefritt.

During the period 1981-1986, membranoproliferative glomerulonephritis was demonstrated in ten patients admitted to the Medical Department, Haukeland Hospital. At the time of the diagnosis all patients had proteinuria and hematuria, and six of them had renal failure. Seven patients exhibited nephrotic syndrome and three patients developed progressive renal failure during the observation period. Three patients died during the follow-up period. Four patients were treated with Cyclosporine A and corticosteroids. With this therapy the proteinuria disappeared in two of the patients with nephrotic syndrome. Immunosuppressive treatment may be tried if the disease shows signs of progression. We believe that some of these patients may benefit from cyclosporine A.

[Viral infections in immunocompromised patients]. / Virusinfeksjoner hos pasienter med immunsvikt.

An increasing number of patients are immunocompromised due to modern treatment of cancer, organ transplantations and HIV-infections. Opportunistic viral infections are common and may cause serious disease among these patients. New vaccines, immunomodulators and antiviral drugs make it possible to prevent and treat many of these infections. We review the host defence against viral infections and the most important viral infections. We also discuss prophylaxis, diagnosis and therapy.

Insulin-like Growth Factor-1 (IGF-1) is a Costimulator of the Expansion of Lineage Committed Cells Derived from Peripheral Blood Mobilized CD34(+) Cells in Multiple Myeloma Patients.

The effect of insulin-like growth factor-1 (IGF-1) on highly enriched human apheresis CD34(+) progenitor cells was investigated in vitro. The progenitor cells were mobilized by treatment with cyclophosphamide + granulocyte-colony stimulating factor (G-CSF) in patients with multiple myeloma. CD34(+) cells were cultured for 7 days in serumfree medium containing stem cell factor (SCF), granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), and this is referred to as cytokine-dependent proliferation. After 7 days of cytokine-dependent proliferation the total number of viable cells increased 1.6-8.2 times, and subsets of cells expressing the granulocyte marker CD15, the myelomonocytic marker CD64 and the erythrocyte phenotype CD71(high)/CD64(-) were detected among the in vitro cultured cells. Addition of G-CSF together with SCF + IL-3 + GM-CSF increased the number of CD15(+) and CD64(+) cells, but without altering the number of erythroid cells. IGF-1 caused a dose-dependent increase in the number of CD15(+), CD64(+) and CD71(high)/CD64(-) cells, and this increase was detected when cells were cultured in both SCF + IL-3 + GM-CSF alone and G-CSF + SCF + IL-3 + GM-CSF. A minor subset of CD34(+) cells could still be detected among in vitro cultured cells and the number of CD34(+) cells was not altered by adding G-CSF and/or IGF-1. Morphologically recognizable mature granulocytes or erythroid cells could not be detected for any of the combinations investigated. We conclude that IGF-1 can enhance the in vitro proliferation of committed progenitor cells derived from apheresis CD34(+) cells.

Insulin-like growth factor-1 (IGF-1) has a costimulatory effect on proliferation of committed progenitors derived from human umbilical cord CD34+ cells.

The effects of insulin-like growth factor-1 (IGF-1) on highly enriched human umbilical cord CD34+ cells were investigated in vitro. CD34+ cells were cultured in serum-free medium containing stem cell factor (SCF), GM-CSF, and interleukin-3 (IL-3). Culture of CD34+ cells for one week in the presence of these cytokines resulted in a dose-dependent increase in total cell number. Addition of G-CSF together with SCF+IL-3+GM-CSF increased the proliferation of myelopoietic cells as determined by the number of cells expressing the myelomonocytic marker CD64 and the granulocytic marker CD15 without significantly altering the number of CD34+ cells in the cultures. In the presence of G-CSF, IGF-1 induced a dose-dependent increase in the total cell number and a moderate but significant increase in the percentages of CD15+, CD64+ cells with sustained CD34+ cell proliferation. We conclude that IGF-1 can enhance the in vitro proliferation of committed progenitor cells derived from umbilical cord CD34+ cells.

Selectivity of hemoregulatory peptide (HP5b) action in culture.

A synthetic analog of a hemoregulatory peptide associated with mature human granulocytes (HP5b) has been investigated for inhibitory effects on various cell types in culture as compared to inhibitory action on mouse and human myelopoietic colonies (CFU-gm), which occurs from 1 X 10(-13) to 1 X 10(-6) M in vitro. This includes colony formation by lymphoid T and B cells in capillary cultures, as well as mitogen activation of T, B and NK cells. At higher concentrations, i.e., above 1 X 10(-7) M, an inhibitory effect was found on colony formation. Neither the production of interleukin (IL) 3 by mitogen-activated T cells, nor the proliferation of the IL-3-dependent L/B cell line were affected by the peptide up to 1 X 10(-5) M. A slight inhibitory effect was found above 1 X 10(-9) M on mouse 3T3 fibroblasts. A series of malignant cell lines was also tested. No effect was seen between 1 X 10(-11) and 1 X 10(-7) M on human mammary carcinoma cells in culture. On Ehrlich ascites mouse mammary carcinoma cells a 30% inhibition was seen at 10(-6) M. On a human glioblastoma cell line (GaMg) no effect was seen, and on a rat glioma cell line (BT5C) an inhibitory effect was seen at 1 X 10(-7) M and above. No significant inhibition of cell growth was seen on SC1 mouse lymphoma cells from 1 X 10(-9) to 1 X 10(-5) M during 7 days of culture. The investigated normal and malignant cell types in culture were thus not inhibited in very low concentrations which act on CFU-gm. However, a variable inhibitory effect was found at higher concentrations where the inhibition of myelopoiesis was maximal and at concentrations where the inhibition is released. The hemoregulatory peptide thus seems to be a concentration-dependent selective inhibitor of myelopoiesis. The finding that various malignant cells do not respond at lower concentrations supports the possibility of using the peptide as a protector of normal cells during cancer chemotherapy.

[Research training--the work situation of research trainees at the School of Medicine, University of Bergen]. / Forskerutdanning--forskerrekruttenes arbeidssituasjon ved Det medisinske fakultet, Universitetet i Bergen.

In an investigation in spring 1989 on research training at the Medical Faculty, University of Bergen, 111 questionnaires were returned of a total of 180 distributed. 35% of the trainees were satisfied with the training, 31% not, while 30% did not know as yet. Trainees who had been full-time research fellows for two years or more (n = 33), were split in two groups with different opinions. Half of them were satisfied with the training programme, and the other half were not. The most important factor linked with the trainees' opinion of the training was personal supervision. The satisfied ones were content with supervision they had received, whereas the unsatisfied ones were not. By and large, office and laboratory conditions were adequate for the trainees, but data equipment had been supplied by many of the trainees themselves. The overall impression of this investigation is that the research training programme is working fairly well, but there is remove for improvement in the supervision of the individual trainee.

[Research training--what trainees think about future research education]. / Forskerutdanning--hva forskerrekruttene mener om fremtidens forskerutdanning.

A research training programme should have a clearly defined aim and a framework for accomplishment and contents. In Norway no such programme exists for the medical PhD. Present research training depends to a large extent on the individual student. The aim of this paper is to contribute to a discussion on the goals for a research programme and to report what research trainees and research fellows at the Medical Faculty, University of Bergen think is necessary as regards framework and content. 111 of 180 questionnaires were returned. On the average, the students preferred a research programme to last 4.0 years. 91 persons wanted the programme to contain a compulsory part lasting, on average, 5.5 months. The majority preferred no examination during this part of the programme. Most students wanted to maintain the present Norwegian standard for the medical PhD.