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Biomedical subjects

S E Jacobsen

Publications and source records attributed to S E Jacobsen.

105 records · Page 6Linked to original sources
PubMed1991

Stimulation of granulopoiesis by transforming growth factor beta: synergy with granulocyte/macrophage-colony-stimulating factor.

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit the growth of immature hematopoietic progenitor cells, whereas more mature, lineage-restricted progenitors are not inhibited. In contrast, in the presence of saturating concentrations of granulocyte/macrophage-colony-stimulating factor (GM-CSF), TGF-beta promoted a 3- to 5-fold increase in the number and size (greater than 0.5 mm) of bone marrow colonies in a dose-dependent manner with an ED50 of 10-20 pM; TGF-beta 1 alone had no effect. Morphological examination showed an increase in granulocyte colonies. In suspension cultures, TGF-beta 1 and GM-CSF stimulated an increase in total viable cells with markedly enhanced neutrophilic differentiation and a concomitant decrease in the number of monocytes/macrophages by day 6 in culture. Limiting dilution analysis demonstrated a 2- to 5-fold increase in the frequency of progenitor cells that responded to GM-CSF plus TGF-beta 1 vs. GM-CSF alone. Bone marrow progenitors obtained from mice 3 days after treatment with 5-fluorouracil responded to a combination of GM-CSF and TGF-beta 1, whereas either factor alone had no effect. A single-cell assay identified a progenitor cell that directly responded to TGF-beta and GM-CSF. TGF-beta increased the number of GM-CSF receptors on bone marrow cells. Thus, TGF-beta 1 can act as a bifunctional mediator of hematopoietic cell growth, and TGF-beta 1 and GM-CSF act together to stimulate granulopoiesis as measured by large granulocyte colony formation; the progenitor cell is tentatively designated granulocyte burst-forming unit.

Animals↗
PubMed1991

Characterization and regulation of RB6-8C5 antigen expression on murine bone marrow cells.

Murine bone marrow cells expressing the cell surface Ag RB6-8C5 were identified by fluorescence-activated cell-sorting analysis using a rat IgG mAb. The fluorescent intensity of RB6-8C5 was variable on bone marrow cells. This made it possible to separate bone marrow cells into distinct subpopulations, RB6-8C5neg, RB6-8C5lo, and RB6-8C5hi cells. Morphologic analysis of the sorted populations demonstrated that the Ag was expressed on myeloid cells. The expression of RB6-8C5 increases with granulocyte maturation, whereas expression is transient on cells in the monocytic lineage. The RB6-8C5hi sorted cells were enriched for end-stage neutrophils (75%), whereas the RB6-8C5lo sorted cells contained more immature myeloid cells and myelocytes (75%). Lymphocytes and macrophages were less than 5% in any RB6-8C5+ population, whereas the erythroid precursors were RB6-8C5neg. The colony forming unit culture (CFU-C) (greater than 90%) were found in the RB6-8C5neg and RB6-8C5lo populations, and all the CFU-granulocyte, erythroid, megakaryocyte, and macrophage (CFU-GEMM) and burst-forming units-erythroid (BFU-E) were in the RB6-8C5neg population. Granulocyte-macrophage-CSFR (GM-CSFR) and IL-1 alpha R were expressed on RB6-8C5hi bone marrow cells, whereas no receptors could be detected on RB6-8C5neg and RB6-8C5lo cells. The expression of the RB6-8C5 Ag can be induced on RB6-8C5neg cells in liquid culture by IL-3 and granulocyte-macrophage CSF. Thus, RB6-8C5 is a myeloid differentiation Ag whose expression can be regulated by cytokines.

Animals↗
PubMed1991

Transforming growth factor-beta trans-modulates the expression of colony stimulating factor receptors on murine hematopoietic progenitor cell lines.

Transforming growth factor beta (TGF-beta) is a potent and selective growth inhibitor of early hematopoietic progenitors and leukemic cells. The cellular mechanism(s) underlying this antiproliferative effect is, however, currently unknown. In the present study, we demonstrate that TGF-beta inhibits the expression of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3), and granulocyte-CSF (G-CSF) receptors on murine factor-dependent and independent hematopoietic progenitor cell lines without a significant change in receptor affinity. A maximum reduction in GM-CSF receptor numbers of 65% to 77% was observed by 96-hour incubation with TGF-beta. The TGF-beta induced trans-down-modulation of GM-CSF receptors was prolonged, noncytotoxic but reversible, and not due to endogenous production of GM-CSF. The TGF-beta induced reduction in CSF receptor numbers preceded TGF-beta's growth inhibitory action. In addition, the ED50 (1 to 10 pmol/L) for TGF-beta's CSF receptor modulatory and antiproliferative effect was similar. The effect of TGF-beta on cell surface CSF receptor expression was specific, because the expression of other cell surface proteins (Ly 5 and Ly 17) was not affected by TGF-beta treatment, and because other growth inhibitors (tumor necrosis factor and interferon) did not affect CSF receptor expression. These data suggest that the downregulation of the growth of hematopoietic progenitor cells by TGF-beta involves reducing the cell surface expression on growth factor receptors.

Animals↗
PubMed1991

In vivo and in vitro effects of TGF-beta 1 on normal and neoplastic haemopoiesis.

TGF-beta 1 and TGF-beta 2 are equipotent selective inhibitors of murine and human haemopoiesis in vitro. Primitive haemopoietic cells such as the high proliferative potential progenitor cell and the colony-forming unit (CFU)-GEMM are directly inhibited by TGF-beta whereas the more differentiated CFU-G, CFU-M and CFU-E are not. Recombinant TGF-beta 1 administered intraperitoneally or intravenously to mice selectively inhibits haemopoietic colony formation in a time- and dose-dependent manner to the same extent as seen in vitro. The progenitors are reversibly prevented from entering the cell cycle. This inhibitory action of TGF-beta functions on at least two levels: (1) down-modulation of the cell surface expression of receptors for growth stimulatory molecules and (2) interference with the intracellular signalling pathways of these molecules. In addition, expression of TGF-beta receptors is regulated during cytokine stimulation of haemopoiesis. Neoplastic B lymphocytes can proliferate by escaping from a TGF-beta-mediated autocrine inhibitory loop. Activation signals (e.g. phorbol esters) inhibit tumour cell growth by stimulating active TGF-beta production and inducing cell surface expression of TGF-beta receptors. These results indicate that TGF-beta may be useful as a bone marrow protective and/or an antitumour agent.

Animals↗
PubMed1991

Characterization of the Arrest in Anther Development Associated with Gibberellin Deficiency of the gib-1 Mutant of Tomato.

The role of gibberellins in flower bud development was investigated by studying the gib-1 mutant of tomato, Lycopersicon esculentum. This gibberellin-deficient mutant initiates flower buds, but floral development is not completed unless the mutant is treated with gibberellin. Treatment with other plant growth regulators does not induce normal flower development. Development of gib-1 flower buds, as measured by progress toward anthesis, ceases at a bud length of 2.5 millimeters; however, increase in size of the bud continues. Buds between 2.5 and 3.7 millimeters are developmentally arrested but still are capable of developing normally after treatment with gibberellic acid. Anthers of these developmentally arrested buds contain pollen mother cells that are in the G1 phase of premeiotic interphase. Following treatment of developmentally arrested buds with gibberellic acid, premeiotic DNA synthesis and callose accumulation in pollen mother cells are evident by 48 hours posttreatment, and within 66 hours, prophase I of meiosis- and meiosis-related changes in tapetum development are observable.

Journal Article↗
PubMed1991

Role of transforming growth factor-beta 1 in regulation of hematopoiesis.

The data presented above suggest that one possible clinical use of TGF-beta would be to protect the bone marrow from the effects of myelosuppressive chemotherapeutic drugs by preventing entry or removing primitive stem cells from the cell cycle. It may also have the additional benefit of reducing the drug-induced neutrophil nadir by stimulating granulopoiesis. The availability of large quantities of recombinant TGF-beta will allow study of the pharmacokinetics with different routes of administration, dosage effects, and details of the pleiotropic effects on other cell systems. Experiments are in progress to determine whether TGF-beta will allow the delivery of higher amounts or more frequent doses of chemotherapeutic drugs and thus allow increased antitumor efficacy in tumor-bearing animals.

Animals↗
PubMed1987

Complement C3b receptors on erythrocytes in patients with juvenile rheumatoid arthritis.

Forty patients with juvenile rheumatoid arthritis (JRA) were examined for C3b receptor (CR1) levels on erythrocytes (by an enzyme-linked immunosorbent assay), levels of circulating immune complexes (IC) (by a polyethylene glycol precipitation-complement consumption method), C3d split products (by intermediate gel rocket immunoelectrophoresis), and HLA-A, B, and C (by microdroplet lymphocytotoxicity test). Lower CR1 levels were found predominantly among patients with JRA (mean 57%) compared with 40 age-matched controls (mean 68%) (P = 0.008). The CR1 levels differed when the JRA patients were grouped by mode of disease onset and by clinical state at the time of testing (levels in patients with pauciarticular disease were higher than those in patients with polyarticular disease, and levels in patients with polyarticular disease were higher than those in patients with systemic disease) or by sex (girls had higher levels than boys; P = 0.01). The levels of circulating IC and C3d were elevated in 25% and 40% of JRA patients, respectively, and were mutually correlated (P less than 0.05, tau = 0.20). A negative correlation was found between levels of C3d and the numbers of CR1 (P less than 0.01, tau = -0.28), but concentrations of circulating IC did not correlate with CR1 values. CR1 levels were the same in 6 HLA-B27 positive and 25 HLA-B27 negative patients. These findings do not represent conclusive evidence that the number of CR1 on erythrocytes serves as a predictor of disease severity or as an indicator of disease activity in patients with JRA.

Adolescent↗
PubMed1986

Normal distribution of complement C3b receptor (CR1) numbers on erythrocytes in blood donors: low levels are associated with HLA-B27.

Blood donors were examined for C3b receptor (CR1) levels on erythrocytes by a microtiter plate enzyme-linked immunosorbent assay and for HLA-A, -B, and -C antigens, C3 phenotypes and blood groups. The CR1 levels among 150 donors varied in the range from 24 to 130% (mean +/- 1 SD = 69.9 +/- 22.9) of an erythrocyte standard, and in accordance with a polygenic model of inheritance the distribution of CR1 was well approximated by a normal curve (chi-square goodness-of-fit test nonsignificant, p = 0.66). Low CR1 levels were associated with HLA-B27 (n = 11, p = 0.05), which was confirmed by investigation of further 20 HLA-B27-positive donors (p = 0.05). The CR1 levels were not associated with a certain C3 phenotype. Possibly, the blood group phenotype M-M + S-s+ is associated with high and the S antigen with low CR1 numbers. The relation between low CR1 numbers and HLA-B27 might be important for the understanding of the association between HLA-B27 and certain inflammatory rheumatological diseases.

Blood Donors↗
PubMed1986

Cushing's disease presenting with severe osteoporosis.

Cushing's disease is usually associated with a variety of symptoms and signs making a characteristic clinical picture. A patient with Cushing's disease due to a pituitary adenoma in whom the only striking feature was osteoporosis is presented. In addition, unusually severe hypopituitarism, was present.

Adolescent↗
PubMed1985

Acute abdomen in rheumatoid arthritis due to mesenteric arteritis. A case report and review.

A 69-year-old woman with seropositive rheumatoid arthritis since the age of 54 developed severe abdominal pain, and laparotomy was performed. Due to perforation of the ileum, there was generalised peritonitis. The histological examination showed mesenteric rheumatoid arteritis. Only a few cases like this are described in the literature. Most of the patients were males, and the mortality was high. When a patient with rheumatoid arthritis develops abdominal pain, mesenteric arteritis may be the cause. No definitive therapy is available, but prompt surgical intervention followed by anticoagulants has been recommended. For the treatment of rheumatoid vasculitis as such, corticosteroids in high doses, cyclophosphamide and plasma exchange have been used separately with beneficial effects.

Abdomen, Acute↗