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Biomedical subjects

A Falus

Publications and source records attributed to A Falus.

At least 19 recordsLinked to original sources
PubMed2001

Mouse plasmacytoma: an experimental model of human multiple myeloma.

BACKGROUND AND OBJECTIVES: There is no ideal animal model for human multiple myeloma (MM). All the models resemble the human disease in some respect, but none of them fulfils all the criteria of a perfect animal model. EVIDENCE AND INFORMATION SOURCES: The pristane oil (2,6,10,12-tetramethylpentadecane)-induced mouse plasmacytoma (MPC) model is the most widely used and accepted model and has provided the most data on plasmacytomagenesis so far. This model gives the opportunity to study the role of c-myc dysregulations, the mechanisms leading to cytogenetic changes involving Ig genes, the role of chronic inflammatory factors, the role of interleukin-6 (IL-6), insulin-like growth factor-I, prostaglandins, as well as signal transduction pathways in the neoplastic process. Therapeutic agents have been successfully tested. Although MPC growth is usually restricted to the peritoneal environment, intraperitoneal injection of MPC cell suspensions can reproduce the disseminated characteristics of the human disease in recipients. The IL-6 transgene and knockout models are important tools for clarifying the role of IL-6 in the pathogenesis of MM. Transgenic mice and retroviral gene transfer facilitate the study of oncogenes in neoplastic transformation. Spontaneous development of plasmacytomas in C57BL/ KaLwRij aging mice has several advantages, mainly because the disseminated growth, the typical bone lesions and renal involvement resemble, in part, the human disease. Furthermore, this model has already proved useful in studies on the effect of bisphosphonate in the treatment of bone disease in MM. The severe combined immunodeficiency (SCID) mouse model is also very attractive. A disseminated-like disease can be reproduced in this model. Multiple osteolytic bone lesions and bone marrow involvement are generated, and conventional drugs applied in the treatment of human multiple myeloma have proven to be effective. Nevertheless, the immune system of SCID mice basically differs from that of a MM patient. PERSPECTIVES: Taken together, all these models have contributed to our understanding of MM, but demonstrate the opportuness of developing a more appropriate model of the human disease.

Animals↗
PubMed2000

Measurement of intracellular interferon-gamma and interleukin-4 in whole blood T lymphocytes from patients with systemic lupus erythematosus.

Contradictory data are available about the dominance of T-helper 1 (T(H)1), or T-helper 2 (T(H)2) cytokines in systemic lupus erythematosus (SLE). Therefore, intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production of T lymphocytes was measured in whole blood of healthy donors and active and inactive SLE patients by flow cytometry. The percentage of IFN-gamma and IL-4 positive cells was low (<1%) in unstimulated samples of the healthy controls, while that of IFN-gamma and IL-4 positive cells in the stimulated cells was 25.2+/-10.6% and 0.6+/-1.5%, respectively. No significant difference was found between SLE patients and healthy controls and between active and inactive patients in these parameters either in the unstimulated or in the stimulated samples. One patient with severe disease had as high as 11.8% IL-4 positive cells and 12.5% IFN-gamma positive cells in the stimulated samples, but after the initiation of intensive corticosteroid and cytostatic therapy, the percentage of IL-4 positive T cells decreased (4.76%) while that of IFN-gamma positive T cells increased (47.91%). We conclude that the intracellular IL-4 and IFN-gamma expression of T lymphocytes does not differ markedly between SLE patients and healthy controls, with the possible exception of severe disease, when marked IL-4 overproduction may exist beside low IFN-gamma production. Furthermore, corticosteroid and cytostatic therapy might normalize this altered IFN-gamma/IL-4 ratio.

Adult↗
PubMed2000

[Secondary cutaneous infiltration in B-cell chronic lymphocytic leukemia (B-CLL)].

Authors report here on a case presenting as B-CLL and complicated with cutaneous infiltration involving the legs and the trunk a year later. Immunohistochemic analysis and the immunoglobulin heavy chain gene rearrangement confirmed cell invasion into the skin identical with the underlying disorder. After failure of conventional chemotherapy, interferon alpha 2b therapy has been started with satisfactory result. Few cases presenting cutaneous infiltration in the course of B-CLL has already been reported in the literature. Secondary cutaneous B-cell lymphoma represents an entity of the poorest prognosis in comparison with primary cutaneous form treated with conventional therapy as well as with lymphomas lacking skin manifestations. Interferon alpha 2b therapy cleans up the skin and yields a favourable survival so it's introduction recommended in this entity. Authors summarise the characteristics of secondary cutaneous B-cell lymphomas on the basis of literature survey. According to authors investigations histidine decarboxylase activity was found to be absent from the lymphocytes infiltrating the skin in contrast to those remaining in the circulation. This seems to be a newly recognised feature of these cells. The changing character of the disease raises the possibility of an altered gene expression pattern of the cells invading the skin. Authors summarise data from the literature concerning suspected molecular mechanism of tissue invasion.

Antineoplastic Agents↗
PubMed2000

Soluble interleukin-6 receptor (sIL-6R) makes IL-6R negative T cell line respond to IL-6; it inhibits TNF production.

The receptor for interleukin-6 (IL-6) consists of two subunits: a ligand specific IL-6Ralpha and gp130 that is responsible for signal-transduction. A soluble form of the ligand specific chain was described that when complexed to IL-6 is capable of binding to the membrane-bound gp130 subunit and thus can elicit signal-transduction. This soluble receptor can act on cells that express only the gp130 but not the ligand-specific subunit of the IL-6R. This phenomenon, called trans-signaling, introduced a novel aspect of cytokine action. In this study we examined the response of Jurkat cells, that are known not to express IL-6Ralpha, to IL-6, the soluble IL-6 receptor (sIL-6R) and a covalent complex of IL-6 and sIL-6R termed Hyper-IL-6. We studied the expression of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma). The complex of IL-6+sIL-6R and Hyper-IL-6 inhibited significantly the production of TNF in a gp130-dependent manner, whereas no differences in IFN-gamma expression were found. IL-6 and sIL-6R alone were not effective. Because we did not detect major differences in the TNF mRNA levels upon treatments, we conclude that the inhibition of TNF production should occur at the post-transcriptional level. These results provide another example of trans-signaling and underline the physiological importance of sIL-6R, and in the case of Hyper-IL-6 its possible therapeutic application can also be considered.

Antigens, CD↗
PubMed2000

Exon-intron organization of the human gp130 gene.

The exon-intron organization and sequences of the exon-intron boundaries of the human gp130 transmembrane receptor gene have been determined using genomic DNAs as samples. The gp130 gene comprises 17 exons and 16 introns. The positions of the exon-intron boundaries show good correlation to the functional/homology regions of gp130. Exons 3-17 code for the gp130 protein, and each subdomain of the receptor is encoded by a set of exons. The coding potential of exons and the intron phasing of the human gp130 gene conform to the patterns observed previously for other cytokine receptor genes. This supports the notions that the gp130 gene evolved from the same ancestral gene that gave rise to other members of the cytokine receptor family.

Antigens, CD↗
PubMed2000

Effects of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine on the blood-brain barrier permeability in the rat.

Histamine plays a role in the regulation of the blood-brain barrier function. In this study, effects of N, N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE), an intracellular histamine binding site antagonist on the cerebrovascular permeability were investigated in control and post-ischemic male Wistar rats. Intravenous administration of DPPE, in a dose of 1 and 5 mg/kg, was not followed by any major clinical change, but 20 mg/kg proved to be toxic. A significantly (P<0.05) increased permeability for sodium fluorescein (MW=376) was seen in hippocampus, striatum, and cerebellum, but not in parietal cortex, of rats 2 h after the injection of 5 mg/kg DPPE, whereas no increase was measured later. There was a more intense (5- to 12-fold) and prolonged elevation in Evan's blue-labeled albumin (MW=67,000) extravasation 2, 4, and 8 h after 5 mg/kg DPPE administration in each brain region. In parietal cortex, a dose-dependent increase in albumin extravasation developed 4 h after intravenous injection of 1, 5, and 20 mg/kg DPPE, but doses applied resulted in no significant change in sodium fluorescein permeability. Cerebral ischemia-reperfusion evoked by four-vessel occlusion caused a significant (P<0.05) increase in the permeability for albumin in each region, but few changes in that of sodium fluorescein. DPPE treatment failed to prevent the ischemia-reperfusion-induced changes in the blood-brain barrier permeability. In conclusion, DPPE induced an increased permeability in the rat, which supports a role for histamine, as an intracellular messenger, in the regulation of the blood-brain barrier characteristics.

Animals↗
PubMed2000

Interleukin-6-induced production of type II acute phase proteins and expression of junB gene are downregulated by human recombinant growth hormone in vitro.

Growth hormone (GH), given therapeutically in many human diseases, is able to modulate the maturation and function of many cells of immune system. The present study demonstrates the effect of human recombinant GH on the production of acute phase proteins (APP) as well as on the gene expression of junB proto-oncogene on human hepatoma cell line, HepG2. When applied alone GH resulted in an increase in the transcription of junB proto-oncogene within 30 min. The production of alpha2-macroglobulin, haptoglobin and fibrinogen was also enhanced by rhGH treatment. However, both IL-6-stimulated junB gene expression (junB mRNA) and biosynthesis of type II APP (alpha2-macroglobulin, fibrinogen, haptoglobin) were strongly inhibited by the GH. The results indicate that GH has a modulatory role in regulating inflammation both in the absence and presence of IL-6. These findings call for further in vivo studies to determine the potential anti-inflammatory actions of GH therapy.

Acute-Phase Proteins↗
PubMed2000

Role of INTERLEUKIN-6 in the pathogenesis of multiple myeloma.

Multiple myeloma (MM) is a currently incurable disease caused by the proliferation of malignant plasma cells. Although the pathogenesis of the disease still remains unclear, recent research in the biology of MM has produced new insights into the factors that control the growth and survival of myeloma cells. Among the growth factors, interleukin-6 (IL-6) has an essential role. Evidence suggests that IL-6 is not only a growth factor, but also a survival factor in MM, inhibiting apoptosis in myeloma cells. IL-6 interacts with several factors which are involved in the pathogenesis of MM, such as adhesion molecules, tumour suppressor genes and oncogenes. Considering the essential role of IL-6, it could serve as a target for new therapeutic interventions. Neutralizing the effect of IL-6 may result in a regression of tumour progression.

Cell Adhesion Molecules↗
PubMed2000

Cytokines in diseases of the endocrine system.

Cytokines, the polypeptide mediators of the immune system, were shown to exert numerous actions on endocrine functions. Bidirectional links based on the sharing of mediators and receptors between the immune and neuroendocrine systems lead to the concept of the immune-neuroendocrine system that seems to constitute an important and sophisticated regulatory system in the homeostasis. Several cytokines were found to be involved in the pathogenesis of diseases of the endocrine system. In this brief review, we attempt to present a general outline of the local actions of cytokines on cells of endocrine organs with an emphasis on disease etiology (pituitary tumours and autoimmune endocrine diseases in particular).

Animals↗
PubMed2000

Autocrine and paracrine regulation by cytokines and growth factors in melanoma.

Tumour development and progression involves the expression of oncogenes and inactivation of tumour suppressor genes, leading to the appearance of multiple malignant characteristics. Malignant melanoma cells express different growth factors and cytokines and their receptors in respective stages of tumour progression, which by autocrine and paracrine effects enable them to grow autonomously and confer competence to metastasis. Autocrine growth factors (bFGF, MGSA/GRO, IL-8 and sometimes IL-6, PDGF-A, IL-10) produced by melanoma cells stimulate proliferation of the producing cell itself, while paracrine growth factors (for example PDGF, EGF, TGF-beta, IL-1, GM-CSF, IGF-I, NGF, VEGF) modulate the microenvironment to the benefit of tumour growth and invasion. Paracrine effects include angiogenesis, stroma formation, modulation of host immune response, activation of proteolytic enzymes, adhesion or motility and metastasis formation. Some growth factors have inhibitory effects on melanocytes and early lesions (IL-1, IL-6, TGF-beta, OSM, TNF and IFN) but not on advanced stage melanomas, and in some cases they switch to autocrine stimulator (IL-6, TGF-beta). Understanding the involvement of different growth factors and cytokines in the molecular mechanism of melanoma progression will help to provide an insight into new future therapeutic approaches for melanoma.

Cell Division↗
PubMed2000

Biosynthesis of interleukin-6, an autocrine growth factor for melanoma, is regulated by melanoma-derived histamine.

Interleukin-6 is an autocrine growth factor in advanced stage melanoma and biosynthesis of IL-6 is increased by histamine in various cell lines. In our study we analysed the direct relation of histamine and IL-6 synthesis in human melanoma cell lines. All melanoma cells contained IL-6 mRNA, but only metastatic melanoma cells secreted the IL-6 protein. The H1 histamine receptor antagonist triprolidine decreased gene expression and biosynthesis of IL-6, while other histamine receptor antagonists had no effect. These data indicate that endogenous histamine has a definite role in the regulation of local IL-6, suggesting that histamine and IL-6 could be part of autocrine growth regulation of the tumor.

Glucose-6-Phosphate Isomerase↗
PubMed2000

H1 histamine receptor antagonist inhibits constitutive growth of Jurkat T cells and antigen-specific proliferation of ovalbumin-specific murine T cells.

Histamine is produced from histidine by histidine decarboxylase (HDC) in many cells including normal and malignant lymphocytes. We examined the expression of HDC and the effect of histamine receptor antagonists on the proliferation of a human T cell line, Jurkat and on antigen-driven proliferation of lymphocytes from ovalbumin-immunized mice. Our results demonstrate that HDC is inducible in Jurkat cells by anti-CD3. The H1 receptor antagonist triprolidine dose dependently inhibits proliferation of both Jurkat cells and ovalbumin-stimulated murine lymphocytes, while the H2 antagonist ranitidine was ineffective. Alpha-fluoro-methyl-histidine blocking HDC activity did not inhibit the T cell proliferation, suggesting an existing pool of histamine in T cells.

Animals↗