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Biomedical subjects

A Vaheri

Publications and source records attributed to A Vaheri.

At least 163 records · Page 9Linked to original sources
PubMed1995

Human epithelial cells immortalized by human papilloma viruses.

Human papillomaviruses (HPVs) are small DNA viruses capable of inducing proliferation of epithelial cells in the natural hosts. The etiologic association between HPV and many forms of human cancer, especially squamous tumors of the anogenital region, has been generally recognized. Human epithelial cells transfected by high-risk-type HPV DNA can overcome apoptosis and become immortalized, but they are not capable of anchorage-independent growth or tumorigenic in nude mice, suggesting that they are premalignant and not malignant cells. These cells, due to their genetic instability, are liable to progress to anchorage-independent growth and tumorigenicity following subsequent genetic and epigenetic events. On the other hand, because immortalized epithelial cells represent an initial step in the multistep model of human carcinogenesis in vitro, they are useful in studies on the regulation by environment factors. Immortalized epithelial cells differ from normal epithelial and malignant carcinoma cells, in their response to various cytokines and growth factors, but their response is more like that of normal cells than of malignant cells. Understanding these processes may help design new therapeutic strategies to control tumor growth.

Animals↗
PubMed1995

Hantavirus infections in Finland.

Hantaviruses cause haemorrhagic fever with renal syndrome (HFRS) and hantaviruspulmonary syndrome (HPS), and occur throughout the world. The viruses aretransmitted to humans in aerosols of rodent secretions. About 200 000 people,mainly in Eurasia, develop

Journal Article↗
PubMed1995

Expression of the alpha 2-macroglobulin receptor on human neoplastic fibroblastoid cells.

The alpha 2-macroglobulin membrane-associated receptor (alpha 2MR) has been previously detected on hepatocytes, fibroblasts, macrophages, syncytiotrophoblasts and recently on human malignant blood cells of myelomonocytic leukemia. In cells growing in vitro from human germ cell tumors alpha 2MR mRNA was detected by Northern blotting. Endocytosis of alpha 2M from culture medium was detected in these cells by indirect immunofluorescence. In cell extracts alpha 2M and its degradation products were detected by immunoblotting. The cells expressing alpha 2MR and internalizing alpha 2M were identified as fibroblasts both by their morphology and expression of vimentin intermediate filaments. The role and function of alpha 2MR receptor in the analyzed neoplastic cells of teratomatous origin is discussed.

Blotting, Northern↗
PubMed1995

Culturing of acoustic neuroma--methodological aspects.

We have been able to culture acoustic neuroma (AN) tissues by taking small tumor pieces during surgery from the cisternal or, preferably, metal part of the tumor where macroscopic tissue degeneration is not prominent. The AN pieces were transported in culture tubes to our cell laboratory where they were sliced and transferred to culture medium. The AN tissue demands a crude culture suspension containing laminin. We have been successful in culturing 15 successive ANs. The cells have different morphological features with characteristics of type Anthony A and B. Four main cell types were recognized: ameboid microglia-like cells, spindle-shaped cells, racket-shaped cells, and kite-shaped cells. However, no immortal cell line could be established. Some of the cultures were viable for up to 4 months.

Culture Media↗
PubMed1995

[Ebola virus epidemic].

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Democratic Republic of the Congo↗
PubMed1994

Altered growth behavior of human cervical epithelial cells transfected by HPV type 16 and 18 DNA.

Transfection of primary human cervical epithelial (HCE) cells with full-length HPV type 16 and 18 DNAs resulted in cell lines that could grow continuously. Four HPV DNA-immortalized cell lines were established. Morphologically the immortalized cells resembled primary HCE cells. Electron microscopy showed that they contained desmosomes and keratin filaments, which are characteristic structural components of epithelial cells. Each cell line had a unique integration pattern of HPV DNA but the transcription patterns were similar in the 3 HPV 16 DNA-immortalized cell lines. The expression patterns of viral DNA in the HPV 18 DNA-immortalized cell line were similar to that in HeLa cells, suggesting transcription of mainly early viral genes. The cell lines, unlike HeLa and SiHa carcinoma cells, did not form tumors in nude mice or grow in soft agarose, but collagen raft culture indicated that the immortalized cell lines had lost the capacity of normal differentiation compared with primary HCE cells. Morphologically, the aberrant differentiation of the immortalized cells showed great resemblance to cervical intra-epithelial neoplasia. The altered pattern of growth and differentiation of human cervical epithelial cells transfected by HPV 16 and 18 DNAs is in agreement with the view that HPV types 16 and 18 play an important role at an initial step of human cervical epithelial carcinogenesis but that co-carcinogenic factors are necessary for full malignant transformation in vivo.

Animals↗
PubMed1994

Induction of differentiation of promyelocytic NB4 cells by retinoic acid is associated with rapid increase in urokinase activity subsequently downregulated by production of inhibitors.

13-trans retinoic acid (13-trans RA) is an effective inducer of differentiation of acute promyelocytic (APL) cells both in vivo and in vitro. It is used in the induction of remission of patients with APL. We found, by using the promyelocytic NB4 cell line established from a patient with APL, that the induction of differentiation with RA was accompanied by modulation of the plasminogen activation system. The expression of urokinase (uPA) activity was rapidly increased in the growth medium and at the surface of cells treated with RA. The high uPA activity was counteracted both in the growth medium and at the cell surface by an increased plasminogen activator inhibitor (PAI) production and reduction of uPA synthesis. The expression of uPA receptor and PAI-2 were stimulated and persisted at 48 hours from RA addition. The simultaneous induction of CD11b suggests that differentiation results in increased production of both. APL patients often encounter episodes of disseminated intravascular coagulation that are associated with secondary fibrinolytic events. Our results suggest that downregulation of uPA activity results in the decrease of plasmin on the surface of the differentiated cells, which may reduce the occurrence of fibrinolytic episodes of patients with APL.

Cell Differentiation↗
PubMed1994

Ezrin has a COOH-terminal actin-binding site that is conserved in the ezrin protein family.

Ezrin, previously also known as cytovillin, p81, and 80K, is a cytoplasmic protein enriched in microvilli and other cell surface structures. Ezrin is postulated to have a membrane-cytoskeleton linker role. Recent findings have also revealed that the NH2-terminal domain of ezrin is associated with the plasma membrane and the COOH-terminal domain with the cytoskeleton (Algrain, M., O. Turunen, A. Vaheri, D. Louvard, and M. Arpin. 1993. J. Cell Biol. 120: 129-139). Using bacterially expressed fragments of ezrin we now demonstrate that ezrin has an actin-binding capability. We used glutathione-S-transferase fusion proteins of truncated ezrin in affinity chromatography to bind actin from the cell extract or purified rabbit muscle actin. We detected a binding site for filamentous actin that was localized to the COOH-terminal 34 amino acids of ezrin. No binding of monomeric actin was detected in the assay. The region corresponding to the COOH-terminal actin-binding site in ezrin is highly conserved in moesin, actin-capping protein radixin and EM10 protein of E. multilocularis, but not in merlin/schwannomin. Consequently, this site is a potential actin-binding site also in the other members of the protein family. Furthermore, the actin-binding site in ezrin shows sequence homology to the actin-binding site in the COOH terminus of the beta subunit of the actin-capping protein CapZ and one of the potential actin-binding sites in myosin heavy chain. The actin-binding capability of ezrin supports its proposed role as a membrane-cytoskeleton linker.

Actins↗
PubMed1994

Morphological differentiation of human SH-SY5Y neuroblastoma cells inhibits human immunodeficiency virus type 1 infection.

We have studied human immunodeficiency virus type 1 (HIV-1) infection in human SH-SY5Y neuroblastoma cells at various stages of morphological differentiation. Two days' treatment of the cells with retinoic acid (RA) or dibutyryl cAMP (db-cAMP) resulted in the appearance of elongated neurites and enhanced production of 160K to 200K neurofilament proteins as shown by indirect immunofluorescence. DNA synthesis was reduced only in RA-treated cells as detected by 5-bromo-2'-deoxyuridine incorporation. The cells were infected with two T-lymphotropic virus strains (IIIB and NDK) and two fresh isolates (39001 and 46001) from bronchoalveolar lavage samples of AIDS patients. The latter two isolates were unable to form syncytia in infected CD4-positive T-lymphoblastoid C8166 cells which was in contrast to our T-lymphotropic virus strains. Interphase in situ hybridization showed that 14 to 16% of SH-SY5Y cells become positive for HIV-1 DNA. Regardless of the virus strain, morphological differentiation of the cells with RA or db-cAMP inhibited infection by 50% at a single cell in situ resolution. Nested PCR confirmed the presence of proviral DNA in the infected cells. These results show that human neuroblastoma cells, tumour cells of neuroectodermal origin, can be infected by different HIV-1 isolates and that the infection is inhibited by neurotypic cell differentiation.

Base Sequence↗
PubMed1994

Sequences of wild Puumala virus genes show a correlation of genetic variation with geographic origin of the strains.

An experimental scheme was developed for direct sequence analysis of Puumala virus-containing specimens from wild rodents (Clethrionomys glareolus). Total RNA isolated from rodent lung tissues was reverse-transcribed in the presence of a universal 11 nucleotide primer complementary to all three viral RNA segments followed by amplification in a PCR with gene-specific primers. A full-length PCR product of approximately 1800 bp from the S segment encoding the viral nucleoprotein and a product of approximately 900 bp from the M segment (encoding the C-terminal two-thirds of the G2 protein and including the 3' non-coding region) of Puumala virus (from C. glareolus trapped in Udmurtia) were prepared and sequenced. No pronounced differences to Vero cell-grown viruses were seen. The Udmurtia/894Cg/91 strain was more closely related to the Bashkiria/CG18-20/84 strain than to the Finnish prototype strain of Puumala virus, Sotkamo/V-2969/81. Thus there is a correlation with the geographic origin of the three strains. The results indicate the occurrence of genetic drift and different selection pressures leading to (i) clustering of mutations, (ii) a lower frequency of nucleotide substitutions in the coding than in the 3' noncoding regions and (iii) a higher frequency of amino acid substitutions in G2 than in the N protein.

Base Sequence↗
PubMed1994

Clinical picture of nephropathia epidemica in children.

The clinical picture of nephropathia epidemica (NE) among children is poorly understood. We made a retrospective analysis of 32 patients aged 4-15 years treated in hospital for serologically verified recent NE. The most common clinical findings were high fever (100%), nausea (81%), vomiting (72%), tenderness in the kidney area (63%), abdominal pains (59%) and headache (59%). A peculiar symptom of NE, transient visual abnormalities, was found in 25% of patients. Four children had clinical bleeding and 1 had encephalitis. 44% were transiently hypertensive. Renal function was impaired in 84%, proteinuria was present in 97%, hematuria in 73% and leukocyturia in 44%. Other common laboratory findings were thrombocytopenia (87%), leukocytosis (41%), elevated ERS (74%, up to 76 mm/h) and CRP level (89%, up to 97 mg/l), elevated liver enzymes (53%) and hypoalbuminemia (50%). No child needed dialysis therapy and all recovered. NE seems to be less severe in children than in adults.

Adolescent↗
PubMed1994

Secretion of plasminogen activators by cells cultured from subretinal fluid.

Secretion of plasminogen activators was examined in 11 cells cultures from subretinal fluid of patients with retinal detachment. The plasminogen activator production was compared to 4 retinal pigment epithelial cell cultures from post-mortem donors with no known retinal pathology. Plasminogen activator activity was evaluated by zymography and was corrected for the total cell protein in the cultures. Cells from subretinal fluid had more proteolytic activity and secreted more active urokinase-type plasminogen activator than retinal pigment epithelial cells of donor origin. It is possible that cells from subretinal fluid are modulated by the conditions in subretinal fluid to secrete more urokinase-type plasminogen activator, generally considered to be a sign of invasive growth or that the subretinal fluid cultures contain other cell types than solely retinal pigment epithelial cells, such as pigmented macrophages, with an active plasminogen activator production. Alternatively, retinal pigment epithelial cells detached into the subretinal fluid may represent a selected population of retinal pigment epithelial cells with a more active extracellular proteolysis.

Adolescent↗
PubMed1994

Alpha- and gamma-interferon inhibit plasminogen activator inhibitor-1 gene expression in human retinal pigment epithelial cells.

The effect of interferons IFN-alpha and IFN-gamma on the production of plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs) was examined in human retinal pigment epithelial (RPE) cells in culture. Cultures of human RPE cells were incubated with either of the interferons for 48-96 h. The cell cultures were assayed using mRNA analysis and solid-phase immunocapture assay. Both interferons caused a marked decrease in PAI-1 mRNA expression after 48 h with no change in urokinase-type plasminogen activator (u-PA) mRNA expression. A marked decrease in PAI-1 activity and concomitant increase in u-PA activity in the culture medium appeared only after 72-96 h. We conclude that IFN-alpha and IFN-gamma stimulate plasminogen-mediated pericellular proteolysis of human RPE cells in culture by inhibiting PAI-1 gene expression.

Adolescent↗
PubMed1994

ED-A region-containing isoform of cellular fibronectin is present in dentin matrix in dentinogenesis imperfecta associated with osteogenesis imperfecta.

To elucidate the defective dentin formation in osteogenesis imperfecta (OI), we analyzed the expression of selected fibronectin (FN) isoforms in the dentin matrix of a patient with dentinogenesis imperfecta (DI) associated with OI, and in normal teeth. Frozen tooth sections were immunostained with three monoclonal antibodies (MAbs). The MAb recognizing the major cell-binding region (f-33), shared by plasma FN (pFN) and cellular FN (cFN), stained the pulp of normal adult permanent teeth intensely, while no reactivity was present in predentin, (demineralized) dentin, or dental cementum. The periodontal ligament stained unevenly. The dentin matrix of the patient with OI displayed reactive zones, alternating layerwise or concentrically with non-reactive ones. Staining throughout the connective tissue of adult oral mucosa, analyzed for the form of FN present, was intense, and in dermis, which was also studied, it was moderate. Reactivities in dental tissues with the MAb specific for the ED-A region (IST-9), included in cFN but not pFN, were similar to those with MAb f-33. The mucosal connective tissue stained weakly and dermis was negative, except that nerves and endothelia of some large blood vessels stained clearly. The MAb specific for the ED-B segment (BC-1), also included in cFN only, did not stain any of the tissues analyzed. The results suggest that, unlike mucosal and dermal FNs, FNs in the dental tissues are largely cellular, and also that dentin formation in OI may be completed by successive generations of pulpal fibroblasts differentiated into hard-tissue-forming cells.

Adult↗